1. NEWTON, Mass., March 1, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the Compensation Committee of Karyopharm's Board of Directors granted stock options to purchase an aggregate of 93,600 shares of Karyopharm's common stock to 11 newly-hired employees, with a grant date of February 26, 2021.  The stock options were granted as inducements material to the new employees entering into employment with Karyopharm in accordance with Nasdaq Listing Rule 5635(c)(4).

    Each of the stock options has an exercise price of $13.82 per share, the closing price of Karyopharm's common stock on February 26, 2021. Each stock option vests over four…

    NEWTON, Mass., March 1, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the Compensation Committee of Karyopharm's Board of Directors granted stock options to purchase an aggregate of 93,600 shares of Karyopharm's common stock to 11 newly-hired employees, with a grant date of February 26, 2021.  The stock options were granted as inducements material to the new employees entering into employment with Karyopharm in accordance with Nasdaq Listing Rule 5635(c)(4).

    Each of the stock options has an exercise price of $13.82 per share, the closing price of Karyopharm's common stock on February 26, 2021. Each stock option vests over four years, with 25% of the total number of shares underlying the stock option vesting on the one-year anniversary of the applicable employee's employment commencement date and 1/48th of the total number of shares vesting monthly thereafter, subject to the employee's continued service as an employee of, or other service provider to, Karyopharm through the applicable vesting dates. In addition, each stock option will be immediately exercisable in full if, on or prior to the first anniversary of the consummation of a "change in control event," the employee's employment is terminated for "good reason" by the employee or terminated without "cause" by Karyopharm (as such terms are defined in the applicable stock option agreement).

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for NEXPOVIO® (selinexor) for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

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  2. SHANGHAI and HONG KONG, Feb. 23, 2021 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, today announced that China's National Medical Products Administration (NMPA) has granted priority review to the New Drug Application (NDA) for ATG-010 (selinexor, XPOVIO®), a first-in-class selective inhibitor of nuclear export (SINE) compound, for the treatment of patients with relapsed/refractory multiple myeloma (rrMM).

    ATG-010 is the first approved SINE compound in the world. It induces the apoptosis of cancer cells in vitro and in vivo by…

    SHANGHAI and HONG KONG, Feb. 23, 2021 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, today announced that China's National Medical Products Administration (NMPA) has granted priority review to the New Drug Application (NDA) for ATG-010 (selinexor, XPOVIO®), a first-in-class selective inhibitor of nuclear export (SINE) compound, for the treatment of patients with relapsed/refractory multiple myeloma (rrMM).

    ATG-010 is the first approved SINE compound in the world. It induces the apoptosis of cancer cells in vitro and in vivo by causing the nuclear storage and activation of tumor suppressor proteins and other growth-regulating proteins, and by down-regulating the intracytoplasmic levels of various oncogenic proteins while normal cells are not affected. The US Food and Drug Administration (FDA) has approved ATG-010 (selinexor) as a novel treatment in three indications within eighteen months. Five ATG-010 regimens for patients with multiple myeloma or diffuse large B-cell lymphoma have also been added to the National Comprehensive Cancer Network (NCCN®) Guidelines. Antengene has completed patient enrollment for the registrational clinical trial in rrMM in mainland China and has submitted NDAs for ATG-010 in five APAC markets including Australia, South Korea and Singapore over the past six months.

    "ATG-010 is a novel option for the treatment of rrMM and we are pleased that it has been granted priority review by the NMPA. The target of ATG-010, XPO1, is the only proven nuclear export protein target in clinical development and we believe that ATG-010 has potential to meet the huge unmet medical needs in hematological malignancies and solid tumors." said Dr. Jay Mei, M.D., PhD., Founder, Chairman and CEO of Antengene. "rrMM still remains an incurable disease and we are excited that more patients may have access to ATG-010 earlier in the course of their treatment. We look forward to working closely with the regulatory authority to move this important indication for ATG-010 towards approval."

    "Working Procedures for Priority Review and Approval of Drug Marketing Authorization (Interim)" has been issued by the NMPA on July 7, 2020 to expedite the development and registration of drugs that provide significant clinical value. With the effective implementation of these procedures, the regulatory authority will expedite the evaluation and approval of novel drugs through a priority review pathway and facilitate earlier access of these drugs to patients in China.

    About ATG-010 (selinexor, XPOVIO®)

    ATG-010 (selinexor, XPOVIO®), a first-in-class and only-in-class oral selective inhibitor of nuclear export (SINE) compound discovered and developed by Karyopharm Therapeutics Inc. (NASDAQ:KPTI), is currently being developed by Antengene, which has the exclusive development and commercial rights in certain Asia-Pacific markets, including Greater China, South Korea, Australia, New Zealand and the ASEAN countries.

    In July 2019, the US Food and Drug Administration (FDA) approved selinexor (XPOVIO®) in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM) and in June 2020 approved selinexor (XPOVIO®) as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). In December 2020, selinexor (XPOVIO®) also received FDA approval as a combination treatment for multiple myeloma after at least one prior therapy. A Marketing Authorization Application (MAA) has also been submitted to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same rrMM indication. Selinexor (XPOVIO®) is so far the first and only oral SINE compound approved by the FDA and is the first drug approved for the treatment of both MM and DLBCL. Selinexor (XPOVIO®) is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer. In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene's partner, Karyopharm, presented positive results from the Phase 3 randomized, double blind, placebo controlled, cross-over SEAL trial evaluating single agent, oral selinexor (XPOVIO®) versus matching placebo in patients with liposarcoma. Karyopharm also announced that the ongoing Phase 3 SIENDO trial of selinexor (XPOVIO®) in patients with endometrial cancer passed the planned interim futility analysis and the Data and Safety Monitoring Board (DSMB) recommended the trial should proceed as planned without any modifications. Top-line SIENDO trial results are expected in the second half of 2021.

    About Antengene

    Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage Asia-Pacific biopharmaceutical company focused on innovative oncology medicines. Antengene aims to provide the most advanced anti-cancer drugs to patients in China, the Asia Pacific Region and around the world. Since its establishment, Antengene has built a pipeline of 12 clinical and pre-clinical stage assets and obtained 12 investigational new drug approvals in Asia Pacific. The vision of Antengene is to "Treat Patients Beyond Borders". Antengene aims to address significant unmet medical needs by discovering, developing and commercializing first-in-class/best-in-class therapeutics.

    Forward-looking statements

    The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

    *XPOVIO® is a registered trademark of Karyopharm Therapeutics Inc.;

    NCCN® is a registered trademark of National Comprehensive Cancer Network.

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  3. NEWTON, Mass., Feb. 17, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that Michael Kauffman, MD, PhD, Chief Executive Officer, will participate in a fireside chat at SVB Leerink's 10th Annual Global Healthcare Conference and at the Barclays Global Healthcare Conference.  Details regarding these upcoming virtual investor conferences are below.

    SVB Leerink 10th Annual Global Healthcare Conference
    Date: Wednesday, February 24, 2021
    Time: 1:00 PM Eastern Time

    Barclays Global Healthcare Conference
    Date: Tuesday, March 9, 2021
    Time: 9:10 AM Eastern Time

    A live webcast of the fireside chats can be accessed under "Events & Presentations" in the…

    NEWTON, Mass., Feb. 17, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that Michael Kauffman, MD, PhD, Chief Executive Officer, will participate in a fireside chat at SVB Leerink's 10th Annual Global Healthcare Conference and at the Barclays Global Healthcare Conference.  Details regarding these upcoming virtual investor conferences are below.

    SVB Leerink 10th Annual Global Healthcare Conference

    Date: Wednesday, February 24, 2021

    Time: 1:00 PM Eastern Time

    Barclays Global Healthcare Conference

    Date: Tuesday, March 9, 2021

    Time: 9:10 AM Eastern Time

    A live webcast of the fireside chats can be accessed under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. A replay of the webcast will be archived on the Company's website for 30 days following each fireside chat.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for NEXPOVIO® (selinexor) for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

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  4. NEWTON, Mass., Feb. 11, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today reported financial results for the fourth quarter and full year ended December 31, 2020. In addition, Karyopharm highlighted select corporate milestones, including details regarding the ongoing U.S. commercialization of XPOVIO® (selinexor), regulatory progress in Europe, and provided an overview of its key clinical development programs.

    "Karyopharm made substantial progress in 2020 towards its mission of improving the lives of patients with cancer, marked by the FDA approval of XPOVIO in two additional oncology indications: relapsed or refractory diffuse large B-cell lymphoma…

    NEWTON, Mass., Feb. 11, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today reported financial results for the fourth quarter and full year ended December 31, 2020. In addition, Karyopharm highlighted select corporate milestones, including details regarding the ongoing U.S. commercialization of XPOVIO® (selinexor), regulatory progress in Europe, and provided an overview of its key clinical development programs.

    "Karyopharm made substantial progress in 2020 towards its mission of improving the lives of patients with cancer, marked by the FDA approval of XPOVIO in two additional oncology indications: relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and multiple myeloma in patients who have received at least one prior therapy," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "In addition, we were particularly encouraged that the National Comprehensive Cancer Network® (NCCN) added three different XPOVIO combination regimens to its Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for previously treated multiple myeloma. As we begin to execute our plans for 2021, we are focused on the commercial expansion of XPOVIO into the second- and third-line treatment settings for multiple myeloma, a significantly increased addressable patient population. We are also progressing the international expansion of NEXPOVIO® (selinexor), with a European Commission (EC) regulatory decision expected by April 2021 following the recent positive opinion issued from the Committee for Medicinal Products for Human Use (CHMP). In parallel to our commercial efforts in the hematology space, our clinical development of XPOVIO in solid tumor indications continues to advance, with top-line data from the Phase 3 SIENDO study in endometrial cancer expected in the second half of 2021."

    Fourth Quarter 2020 and Recent Highlights

    XPOVIO in Multiple Myeloma and DLBCL

    • XPOVIO Receives Early Approval from the FDA for Patients with Multiple Myeloma After At Least One Prior Therapy. On December 18, 2020, the FDA approved once-weekly, oral XPOVIO in combination with once-weekly Velcade® (bortezomib) and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy, which became commercially available in the U.S. immediately following approval. Karyopharm is leveraging its existing commercial infrastructure to market this third oncology indication, which significantly expands the addressable patient population to the 2nd and 3rd line treatment settings and extends the anticipated duration of treatment as compared to patients currently receiving XPOVIO in the penta-refractory treatment setting.
    • XPOVIO U.S. Commercialization. Oral XPOVIO became commercially available to patients with penta-refractory multiple myeloma in July 2019 and to patients with relapsed or refractory DLBCL in June 2020. During the fourth quarter of 2020, XPOVIO generated net product sales of $20.2 million, representing a 5% decrease compared to the third quarter of 2020. Net sales for the fourth quarter were largely driven by prescription demand from both academic and community-based oncologists for patients with penta-refractory multiple myeloma. Sales were affected by the surge in U.S. COVID-19 cases late in 2020 impacting both patient visits to their healthcare providers, as well as reduced in-person access for Karyopharm's commercial team to its physician customers. Additionally, increased competition, specifically in the penta-refractory multiple myeloma setting, also contributed to the sales pressure in the quarter.



      In the fourth quarter of 2020, approximately 1,000 XPOVIO prescriptions were filled, with prescription demand higher in December 2020 compared to either October or November 2020. Over 170 new physician prescribing accounts were added in the fourth quarter of 2020, which included both myeloma and DLBCL treating physicians. Finally, based on data from specialty pharmacies, prescription refill rates for XPOVIO remained consistent compared to the third quarter of 2020 with the average number of prescriptions per patient estimated at 2.9 by the end of December 2020, compared to 2.0 at the end of December 2019.



      On a quarterly basis, Karyopharm expects XPOVIO sales to return to growth beginning in the first quarter of 2021, compared to the fourth quarter of 2020, following the expanded U.S. FDA approval of XPOVIO as a treatment for patients with multiple myeloma after at least one prior therapy.
    • Three XPOVIO Treatment Regimens Added to National Comprehensive Cancer Network® Guidelines. In December 2020, the NCCN added three different XPOVIO combination regimens to its Clinical Practice Guidelines in Oncology for previously treated multiple myeloma. The XPOVIO regimens added to the NCCN guidelines include: (i) selinexor / bortezomib / dexamethasone (once-weekly); (ii) selinexor / daratumumab / dexamethasone; and (iii) selinexor / pomalidomide / dexamethasone, which is an all-oral treatment regimen. The NCCN Guidelines are a comprehensive set of guidelines detailing the sequential management decisions and interventions that currently apply to 97% of cancers affecting patients in the U.S. and are intended to ensure that all patients receive preventive, diagnostic, treatment, and supportive services that will most likely lead to optimal outcomes.
    • Positive CHMP Opinion for NEXPOVIO® (selinexor) for Multiple Myeloma. In January 2021, the European Medicines Agency's (EMA) CHMP adopted a positive opinion recommending the conditional approval for NEXPOVIO (the expected brand name for selinexor in Europe) in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy. The Company expects a final decision from the EC on its NEXPOVIO marketing authorization application by April 2021. Karyopharm also intends to submit a second regulatory filing to the EMA (Type II variation) based on the data from the confirmatory Phase 3 BOSTON study by April 2021.
    • First Patient Dosed in Phase 2/3 Confirmatory Study in DLBCL. In February 2021, the first patient was dosed in the Phase 2/3 XPORT-DLBCL-030 study of XPOVIO in patients with DLBCL. As part of XPOVIO's accelerated approval in DLBCL, XPORT-DLBCL-030 study will serve as the confirmatory study for this indication. This study will assess the effect of XPOVIO or placebo added to a standard backbone immunochemotherapy of rituximab gemcitabine-dexamethasone-platinum (R-GDP) in patients who have had one to three prior treatments for DLBCL.
    • Myeloma and DLBCL Data Presented at the American Society of Hematology (ASH) 2020 Annual Meeting. Multiple data presentations highlighting XPOVIO were presented at the ASH 2020 Annual Meeting held December 5-8, 2020 and continue to reinforce the broad potential clinical utility of XPOVIO. This included updated data from the Pomalyst® (pomalidomide), Kyprolis®(carfilzomib) and Revlimid® (lenalidomide) arms of the Phase 1b/2 STOMP study evaluating XPOVIO in combination with backbone therapies in patients with relapsed or refractory multiple myeloma, which continued to demonstrate favorable response rates and durability. Several new subgroup analyses from the Phase 3 BOSTON study were also presented and demonstrated XPOVIO is effective and well tolerated regardless of prior lines of treatment, including prior treatment with a proteasome inhibitor or lenalidomide, and across several important patient subgroups, including those with high risk cytogenetics, the elderly and the frail. A subgroup analyses of the Phase 2b SADAL study in DLBCL were also presented that highlighted XPOVIO's positive efficacy and safety in patients stratified by age and renal function at baseline.
    • Phase 3 BOSTON Study Results Published in The Lancet. In November 2020, the results of the Phase 3 BOSTON study evaluating XPOVIO in patients with relapsed or refractory multiple myeloma were published in The Lancet. The BOSTON study evaluated once-weekly XPOVIO in combination with once-weekly Velcade® and low-dose dexamethasone (XVd) against standard twice-weekly Velcade® plus dexamethasone (Vd) in adult patients with multiple myeloma who had received one to three prior lines of therapy. The BOSTON study met its primary endpoint with a median progression-free survival (PFS) in the XVd arm of 13.93 months compared to 9.46 months in the Vd arm, representing a 4.47 month (47%) increase in median PFS (hazard ratio HR=0.70; p=0.0075). The XVd group also demonstrated a significantly greater overall response rate compared to the Vd group (76.4% vs. 62.3%, p=0.0012). Additionally, peripheral neuropathy rates were significantly lower on the XVd arm compared to the Vd arm (32.3% vs. 47.1%; p=0.0010).

    XPOVIO in Development for Solid Tumors

    • Phase 3 SIENDO Study in Endometrial Cancer Passes Interim Futility Analysis. In November 2020, Karyopharm announced that, following a pre-specified interim futility analysis for the ongoing Phase 3 SIENDO study, the Data and Safety Monitoring Board (DSMB) recommended that the study should continue as planned without the need to add additional patients to the trial or to amend the study protocol. The SIENDO study is an ongoing multicenter, blinded, placebo-controlled, randomized Phase 3 study evaluating the efficacy and safety for front-line maintenance therapy with XPOVIO in patients with advanced or recurrent endometrial cancer. Participants with primary stage IV or recurrent disease who had a partial or complete response after a single line of at least 12 weeks of standard taxane-platinum combination chemotherapy are randomized in a 2:1 manner to receive either maintenance therapy of 80mg of XPOVIO taken once per week or placebo, until disease progression. Top-line data from the SIENDO study is expected in the second half of 2021.
    • Positive Phase 3 SEAL Data Evaluating XPOVIO in Liposarcoma Presented. In November 2020, positive results from the Phase 3 portion of the randomized, double blind, placebo-controlled, cross-over, SEAL study evaluating single agent, oral XPOVIO versus placebo in patients with advanced unresectable dedifferentiated liposarcoma were presented at the Connective Tissue Oncology Society (CTOS) 2020 Annual Meeting. The SEAL study met its primary endpoint of a statistically significant increase in median PFS. The median PFS in the XPOVIO arm of the Phase 3 portion of the SEAL study was 2.83 months compared to 2.07 months in the placebo arm (HR=0.70; p=0.023). These data indicate that treatment with XPOVIO reduced the risk of disease progression or death by approximately 30%, compared to placebo. The estimated 6-month PFS survival probability was 23.9% on the XPOVIO arm compared to 13.9% on placebo. Additionally, the 12-month PFS survival probability was 8.4% on the XPOVIO arm compared to 2% on the placebo arm. Karyopharm no longer intends to submit a New Drug Application to the FDA in the first quarter of 2021 and plans to submit the results for publication and apply for compendia listings for this very uncommon cancer.

    Corporate Updates

    • Continued Progress Towards the International Expansion of XPOVIO. In February 2021, the Israeli Ministry of Health, Israel's regulatory agency responsible for the approval of new medicines, issued a principal approval letter for XPOVIO as a treatment for patients with either multiple myeloma or diffuse large B-cell lymphoma. Additionally, in December 2020, Karyopharm signed an exclusive distribution agreement for the commercialization of XPOVIO in Canada with FORUS Therapeutics Inc. Under the terms of the agreement, Karyopharm received an upfront payment of $5.0 million and is eligible to receive additional payments if certain prespecified regulatory and commercial milestones are achieved, as well as double-digit royalties on future net sales of XPOVIO in Canada. Separately, Karyopharm's partner in the Asia-Pacific region, Antengene Therapeutics Limited, filed for regulatory approval of selinexor in both multiple myeloma and DLBCL indications in Australia, Singapore and South Korea in December 2020, which triggered approximately $10.0 million in milestone payments to Karyopharm.
    • New Appointment to Board of Directors. In December 2020, Karyopharm appointed Chen Schor, MBA, to its Board of Directors. Mr. Schor has led biotechnology companies across all stages, from formation and early stage discovery to leading a publicly traded multi-product company with significant external partnerships. He currently serves as President and Chief Executive Officer and a member of the board of directors of Adicet Bio, Inc.

    Full Year and Fourth Quarter 2020 Financial Results       

    Net product revenue: Net product revenue for the fourth quarter of 2020 was $20.2 million, compared to $17.7 million for the fourth quarter of 2019. Net product revenue for the year ended December 31, 2020 was $76.2 million, compared to $30.5 million for the year ended 2019.

    License and other revenue: License and other revenue for the fourth quarter of 2020 was $14.9 million, compared to $0.4 million for the fourth quarter of 2019. This increase was driven by approximately $10.0 million in milestone payments associated with regulatory filings in Asia from Antengene Therapeutics Limited, as well as a $5.0 million upfront payment from FORUS Therapeutics Inc. upon the execution of a commercial distribution agreement for Canada. License and other revenue in 2020 were $31.9 million, compared to $10.4 million in 2019.

    Cost of sales: Cost of sales for the fourth quarter of 2020 were $1.1 million, compared to $1.4 million for the fourth quarter of 2019. Cost of sales for the year ended December 31, 2020 were $2.7 million, compared to $2.4 million for the year ended December 31, 2019. Cost of sales reflects the costs of XPOVIO units sold and third-party royalties on net product revenue.

    Research and development (R&D) expenses: R&D expenses for the fourth quarter of 2020 were $37.2 million, compared to $31.6 million for the fourth quarter of 2019. R&D expenses for 2020 were $150.8 million, compared to $122.3 million for 2019. The increase in R&D expenses in 2020 compared to 2019 was primarily attributable to costs incurred related to our COVID-19 trial activity, which are not expected to be incurred in 2021, and continued activity in our other ongoing clinical trials.

    Selling, general and administrative (SG&A) expenses:  SG&A expenses for the fourth quarter of 2020 were $33.9 million, compared to $28.4 million for the fourth quarter of 2019. SG&A expenses for the year ended December 31, 2020 were $126.4 million, compared to $105.4 million for the year ended December 31, 2019. The increase in SG&A expenses compared to the prior year was due primarily to activities to support the U.S. commercialization of XPOVIO, including the launches of XPOVIO as a treatment for patients with relapsed or refractory DLBCL and in combination with once-weekly Velcade® and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.

    Interest expense: Interest expense for the fourth quarter of 2020 was $7.1 million, compared to $6.5 million for the fourth quarter of 2019. Interest expense for the full year 2020 was $27.1 million, compared to $15.6 million for the full year 2019. The increase in interest expense was primarily attributable to the imputed interest on the deferred royalty obligation Karyopharm has with HealthCare Royalty Partners.

    Net loss: Karyopharm reported a net loss of $43.4 million, or $0.59 per share, for the fourth quarter of 2020, compared to a net loss of $48.6 million, or $0.76 per share, for the fourth quarter of 2019. Net loss includes non-cash stock-based compensation expense of $6.3 million and $3.6 million for the fourth quarter of 2020 and 2019, respectively. Karyopharm reported a net loss of $196.3 million, or $2.72 per share, for the year ended December 31, 2020, compared to a net loss of $199.6 million, or $3.22 per share, for the year ended December 31, 2019. Net loss includes non-cash stock-based compensation expense of $24.4 million and $15.3 million for the years ended December 31, 2020 and 2019, respectively.

    Cash position: Cash, cash equivalents, restricted cash and investments as of December 31, 2020 totaled $276.7 million, compared to $265.8 million as of December 31, 2019.

    2021 Financial Outlook

    Based on its current operating plans, Karyopharm expects its non-GAAP R&D and SG&A expenses, excluding stock-based compensation expense, for the year ending December 31, 2021 to be in the range of $280 million to $300 million.

    The Company expects that its existing cash, cash equivalents and investments, and the revenue it expects to generate from XPOVIO product sales, as well as revenue generated from its license agreements, will be sufficient to fund its planned operations into late 2022.

    Non-GAAP Financial Information

    Karyopharm uses a non-GAAP financial measure, including R&D and SG&A expenses, to provide operating expense guidance. Non-GAAP R&D and SG&A expenses exclude stock-based compensation expense. Karyopharm believes this non-GAAP financial measure is useful to investors because it provides greater transparency regarding Karyopharm's operating performance as it excludes non-cash stock compensation expense. This non-GAAP financial measure should not be considered a substitute or an alternative to GAAP R&D and SG&A expenses and should not be considered a measure of Karyopharm's liquidity. Instead, non-GAAP R&D and SG&A expenses should only be used to supplement an understanding of Karyopharm's operating results as reported under GAAP.

    Conference Call Information

    Karyopharm will host a conference call today, Thursday, February 11, 2021, at 8:30 a.m. Eastern Time, to discuss the fourth quarter and full year 2020 financial results, recent accomplishments, clinical developments and business plans. To access the conference call, please dial (888) 349-0102 (local) or (412) 902-4299 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. An archived webcast will be available on the Company's website approximately two hours after the event.

    About XPOVIO® (selinexor)

    XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm's supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA on December 18, 2020. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email: 

    XPOVIO® (selinexor) is a prescription medicine approved:

    • In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
    • In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).
    • For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

    SELECT IMPORTANT SAFETY INFORMATION

    Warnings and Precautions

    • Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
    • Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
    • Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
    • Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
    • Serious Infection: Monitor for infection and treat promptly.
    • Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
    • Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
    • Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.

    Adverse Reactions

    • The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
    • The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
    • The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection(21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.

    Use In Specific Populations

    Lactation: Advise not to breastfeed.

    For additional product information, including full prescribing information, please visit www.XPOVIO.com.

    To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1–888–209–9326 or FDA at 1–800–FDA–1088 or www.fda.gov/medwatch. 

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for NEXPOVIO® (selinexor) for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's guidance on its 2021 non-GAAP research and development and selling, general and administrative expenses; expectations and plans relating to XPOVIO for the treatment of patients with relapsed or refractory multiple myeloma or relapsed or refractory diffuse large B-cell lymphoma; commercialization of XPOVIO or any of its drug candidates and the commercial performance of XPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; and the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the European Union as a result of data from the STORM study or confirmatory approval in the European Union based on the BOSTON study in patients with multiple myeloma; or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

    XPOVIO®(selinexor) is a registered trademark of Karyopharm Therapeutics Inc. Any other trademarks referred to in this presentation are the property of their respective owners.

     

    KARYOPHARM THERAPEUTICS INC.

    CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS

    (unaudited)

    (in thousands, except per share amounts)







    Three Months Ended

    December 31,





    Year Ended

    December 31,







    2020





    2019





    2020





    2019



    Revenues:

































    Product revenue, net



    $

    20,218





    $

    17,719





    $

    76,210





    $

    30,540



    License and other revenue





    14,882







    377







    31,875







    10,353



    Total revenues





    35,100







    18,096







    108,085







    40,893



    Operating expenses:

































    Cost of sales





    1,052







    1,394







    2,705







    2,407



    Research and development





    37,185







    31,579







    150,813







    122,340



    Selling, general and administrative





    33,929







    28,389







    126,417







    105,421



    Total operating expenses





    72,166







    61,362







    279,935







    230,168



    Loss from operations





    (37,066)







    (43,266)







    (171,850)







    (189,275)



    Other income (expense):

































    Interest income





    396







    1,102







    2,820







    5,422



    Interest expense





    (7,072)







    (6,467)







    (27,140)







    (15,647)



    Other income (expense), net





    383







    (14)







    206







    (50)



    Total other expense, net





    (6,293)







    (5,379)







    (24,114)







    (10,275)



    Loss before income taxes





    (43,359)







    (48,645)







    (195,964)







    (199,550)



    Income tax provision





    (62)







    (2)







    (309)







    (40)



    Net loss



    $

    (43,421)





    $

    (48,647)





    $

    (196,273)





    $

    (199,590)



    Net loss per share—basic and diluted



    $

    (0.59)





    $

    (0.76)





    $

    (2.72)





    $

    (3.22)



    Weighted-average number of common shares outstanding used in net loss per share—basic and diluted





    73,727







    63,908







    72,044







    61,955



     

     

    KARYOPHARM THERAPEUTICS INC.

    CONDENSED CONSOLIDATED BALANCE SHEETS

    (unaudited)

    (in thousands)







    December 31,

    2020





    December 31,

    2019



    Assets

















    Cash, cash equivalents and investments



    $

    273,455





    $

    263,972



    Restricted cash





    3,203







    1,831



    Accounts receivable





    12,881







    7,862



    Property and equipment, net





    2,219







    3,046



    Other assets





    21,292







    18,252



    Total assets



    $

    313,050





    $

    294,963



    Liabilities and stockholders' equity

















    Deferred revenue



    $

    297





    $

    4,533



    Convertible senior notes





    117,928







    109,857



    Deferred royalty obligation





    73,088







    73,588



    Other liabilities





    71,191







    57,211



    Total liabilities





    262,504







    245,189



    Total stockholders' equity





    50,546







    49,774



    Total liabilities and stockholders' equity; 73,923 and 65,370 shares issued and outstanding at December 31, 2020 and December 31, 2019, respectively



    $

    313,050





    $

    294,963



     

    Cision View original content:http://www.prnewswire.com/news-releases/karyopharm-reports-fourth-quarter-and-full-year-2020-financial-results-and-highlights-recent-company-progress-301226477.html

    SOURCE Karyopharm Therapeutics Inc.

    View Full Article Hide Full Article
  5. NEWTON, Mass., Feb. 4, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that it will report fourth quarter and full year 2020 financial results on Thursday, February 11, 2021. Karyopharm's management team will host a conference call and audio webcast at 8:30 a.m. ET on Thursday, February 11, 2021, to discuss the financial results and other company updates.

    To access the conference call, please dial (888) 349-0102 (local) or (412) 902-4299 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call will be available under "Events & Presentations…

    NEWTON, Mass., Feb. 4, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that it will report fourth quarter and full year 2020 financial results on Thursday, February 11, 2021. Karyopharm's management team will host a conference call and audio webcast at 8:30 a.m. ET on Thursday, February 11, 2021, to discuss the financial results and other company updates.

    To access the conference call, please dial (888) 349-0102 (local) or (412) 902-4299 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. An archived webcast will be available on the Company's website approximately two hours after the event.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    Cision View original content:http://www.prnewswire.com/news-releases/karyopharm-to-report-fourth-quarter-and-full-year-2020-financial-results-on-february-11-2021-301222257.html

    SOURCE Karyopharm Therapeutics Inc.

    View Full Article Hide Full Article
  6. NEWTON, Mass., Feb. 4, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that its partner Promedico Ltd., a member of the Neopharm Group, has received a principal approval letter from the Israeli Ministry of Health, Israel's regulatory agency responsible for the approval of new medicines, granting the approval of XPOVIO® (selinexor) for the treatment of patients with either multiple myeloma or diffuse large B-cell lymphoma (DLBCL). The approved indications for XPOVIO are a) in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma who have received at least three prior therapies and…

    NEWTON, Mass., Feb. 4, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that its partner Promedico Ltd., a member of the Neopharm Group, has received a principal approval letter from the Israeli Ministry of Health, Israel's regulatory agency responsible for the approval of new medicines, granting the approval of XPOVIO® (selinexor) for the treatment of patients with either multiple myeloma or diffuse large B-cell lymphoma (DLBCL). The approved indications for XPOVIO are a) in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor, at least one immunomodulatory agent, and an anti-CD38 monoclonal antibody, and b) for the treatment of adult patients with relapsed or refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy.

    Karyopharm expects Promedico to receive a registration license providing commercial and marketing authorization for XPOVIO in Israel during the second quarter of 2021. Separately, today's announcement follows Karyopharm's recently announced adoption of a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use recommending conditional approval for NEXPOVIO® (selinexor) in combination with dexamethasone for the treatment of multiple myeloma in patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy. Karyopharm expects to receive a final decision from the European Commission by April 2021.

    "The approval of XPOVIO in Israel represents its first regulatory approval outside the United States and is a tremendous milestone for both Karyopharm and the patients we hope to serve in the future," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "The approval of XPOVIO in Israel further demonstrates our commitment to expand XPOVIO's reach to cancer patients across the globe who are in need of novel therapies. We look forward to continuing to work closely with our dedicated partner, Promedico, and its world-class team to bring XPOVIO to patients in Israel."

    Karyopharm has previously entered into an exclusive distribution agreement with Promedico, a member of the Neopharm Group, a leader in launching and marketing novel therapies in Israel, for the commercialization of XPOVIO® (selinexor) in Israel and the Palestinian Authority.

    About XPOVIO® (selinexor)

    XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm's supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA on December 18, 2020. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email: 

    XPOVIO® (selinexor) is a prescription medicine approved in the U.S.:

    • In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
    • In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).
    • For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

    SELECT IMPORTANT SAFETY INFORMATION

    Warnings and Precautions

    • Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
    • Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
    • Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
    • Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
    • Serious Infection: Monitor for infection and treat promptly.
    • Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
    • Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
    • Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.

    Adverse Reactions

    • The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
    • The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
    • The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection(21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.

    Use In Specific Populations

    Lactation: Advise not to breastfeed.

    For additional product information, including full prescribing information, please visit www.XPOVIO.com.

    To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1–888–209–9326 or FDA at 1–800–FDA–1088 or www.fda.gov/medwatch. 

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for NEXPOVIO® (selinexor) for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    About Neopharm Group

    Established in 1941, Neopharm is one of Israel's leading providers of innovative integrated solutions across the pharmaceutical, medical and healthcare markets. Neopharm focuses on the sale and marketing of novel groundbreaking specialty and orphan medications as well as home healthcare services in Israel via partnerships with the world's leading multinational bio-pharma companies. Neopharm is the partner-of-choice and one-stop-shop for multinational bio-pharma companies seeking to enter or expand their business in the Israeli pharmaceutical, medical and biotechnology markets and is proud of its best-in-class platform, reputation and track- record of success for launching and marketing groundbreaking novel therapies in Israel.

    For more information, please visit http://www.promedico.co.il/en/

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's expectations and plans relating to XPOVIO/NEXPOVIO for the treatment of patients with relapsed or refractory multiple myeloma and/or relapsed or refractory diffuse large B-cell lymphoma; commercialization of XPOVIO/NEXPOVIO or any of its drug candidates and the commercial performance of XPOVIO/NEXPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; and the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO/NEXPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the European Union as a result of data from the STORM study or confirmatory approval in the European Union based on the BOSTON study in patients with multiple myeloma; or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any product or product candidate. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

    XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc. Velcade® is a registered trademark of Takeda Pharmaceutical Company Limited.

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  7. NEWTON, Mass., Feb. 1, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the Compensation Committee of Karyopharm's Board of Directors granted stock options to purchase an aggregate of 165,500 shares of Karyopharm's common stock to 31 newly-hired employees, with a grant date of January 29, 2021.  The stock options were granted as inducements material to the new employees entering into employment with Karyopharm in accordance with Nasdaq Listing Rule 5635(c)(4).

    Each of the stock options has an exercise price of $15.23 per share, the closing price of Karyopharm's common stock on January 29, 2021. Each stock option vests over four years…

    NEWTON, Mass., Feb. 1, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the Compensation Committee of Karyopharm's Board of Directors granted stock options to purchase an aggregate of 165,500 shares of Karyopharm's common stock to 31 newly-hired employees, with a grant date of January 29, 2021.  The stock options were granted as inducements material to the new employees entering into employment with Karyopharm in accordance with Nasdaq Listing Rule 5635(c)(4).

    Each of the stock options has an exercise price of $15.23 per share, the closing price of Karyopharm's common stock on January 29, 2021. Each stock option vests over four years, with 25% of the total number of shares underlying the stock option vesting on the one-year anniversary of the applicable employee's employment commencement date and 1/48th of the total number of shares vesting monthly thereafter, subject to the employee's continued service as an employee of, or other service provider to, Karyopharm through the applicable vesting dates. In addition, each stock option will be immediately exercisable in full if, on or prior to the first anniversary of the consummation of a "change in control event," the employee's employment is terminated for "good reason" by the employee or terminated without "cause" by Karyopharm (as such terms are defined in the applicable stock option agreement).

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for NEXPOVIO® (selinexor) for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

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  8. NEWTON, Mass., Jan. 29, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the conditional approval for NEXPOVIO® (selinexor) in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

    The positive CHMP opinion is a scientific…

    NEWTON, Mass., Jan. 29, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the conditional approval for NEXPOVIO® (selinexor) in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

    The positive CHMP opinion is a scientific recommendation for marketing authorization and one of the final steps before the European Commission (EC) makes a decision on Karyopharm's marketing authorization application (MAA). An EC marketing authorization through the centralized procedure is valid in all 27 European Union member countries as well as the European Economic Area countries Iceland, Liechtenstein and Norway.

    "We are delighted that the CHMP has adopted a positive opinion for NEXPOVIO, which could lead to Karyopharm's first regulatory approval in Europe," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "This positive opinion highlights the CHMP's recognition of the positive clinical benefit-risk profile for oral NEXPOVIO and takes Karyopharm one step closer to bringing this important medicine to European patients in need of novel multiple myeloma treatment options. We look forward to the European Commission's final decision on the NEXPOVIO MAA, which is expected by April of 2021."

    The MAA is supported by data from the Phase 2b STORM study which evaluated selinexor in patients with heavily pretreated, triple class refractory multiple myeloma and published in the New England Journal of Medicine (Chari, et al.) in August 2019. 

    Karyopharm intends to submit a second regulatory filing to the EMA (Type II variation) by April 2021 based on the data from the confirmatory Phase 3 BOSTON study, which evaluated once-weekly NEXPOVIO in combination with once-weekly Velcade® and low-dose dexamethasone in patients with multiple myeloma after at least one prior therapy with the goal of further expanding the global reach of NEXPOVIO to additional patients in need of new treatment options.

    About the Phase 2b STORM Pivotal Trial

    The Phase 2b STORM trial (Selinexor Treatment of Refractory Myeloma) was an international, multi-center, single-arm, open-label study which enrolled 122 patients (Part 2 of the trial) with heavily pretreated, triple class refractory multiple myeloma. Patients in the trial had a median of seven previous therapeutic regimens, including a median of 10 unique antimyeloma agents. 

    For the study's primary endpoint, oral selinexor achieved an overall response rate of 26% (95% confidence interval [CI], 19, 35) and the trial therefore met its primary endpoint. Minimal response per IMWG criteria was observed in 16 (13%) patients and 48 patients (39%) had stable disease.  All responses were adjudicated by an Independent Review Committee. The median overall survival was 8.6 months in the total population studied and 15.6 months in patients who had a minimal response or better.   

    Karyopharm's request for conditional approval in Europe is based upon the same patient population that served as the basis for XPOVIO's accelerated FDA approval in the U.S.  Specifically, it includes the efficacy and safety data from a pre-specified sub-group analysis of 83 patients in the STORM study whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab, as the benefit-risk ratio appeared to be greater in this more heavily pre-treated population than in the overall trial population. The overall response rate in this patient population was 25.3%. 

    The most common adverse reactions (≥20%) were thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.

    About Multiple Myeloma in Europe

    Multiple myeloma (MM) is an incurable cancer with significant morbidity and the second most common hematologic malignancy. In 2020, there were approximately 51,000 new cases and 32,000 deaths from MM in Europe1. While the treatment of MM has improved over the last 20 years, and overall survival has increased considerably, the disease remains incurable, and nearly all patients will eventually relapse and develop disease that is refractory to all approved anti-MM therapies. Therefore, there continues to be a high unmet medical need for new therapies, particularly those with novel mechanisms of action.

    About NEXPOVIO® (selinexor)

    NEXPOVIO®, which is marketed as XPOVIO® in the U.S., is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. NEXPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). NEXPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. XPOVIO is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. A Marketing Authorization Application for NEXPOVIO for patients with penta-refractory multiple myeloma is also currently under review by the European Medicines Agency and received a positive CHMP opinion in January 2021. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email:

    For additional product information, including full prescribing information, please visit www.XPOVIO.com.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for NEXPOVIO™ (selinexor) for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's expectations and plans relating to XPOVIO/NEXPOVIO for the treatment of patients with relapsed or refractory multiple myeloma and/or relapsed or refractory diffuse large B-cell lymphoma; commercialization of XPOVIO/NEXPOVIO or any of its drug candidates and the commercial performance of XPOVIO/NEXPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; and the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO/NEXPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the European Union as a result of data from the STORM study or confirmatory approval in the European Union based on the BOSTON study in patients with multiple myeloma; or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any product or product candidate. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

    XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc. Velcade® is a registered trademark of Takeda Pharmaceutical Company Limited.

    References

    1  World Health Organization. 2020. https://gco.iarc.fr/today/data/factsheets/cancers/35-Multiple-myeloma-fact-sheet.pdf

     

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  9. SHANGHAI and HONG KONG, Jan. 27, 2021 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced that the National Medical Products Administration (NMPA) accepted its New Drug Application (NDA) for ATG-010 (Selinexor, XPOVIO®), a first-in-class oral selective inhibitor of nuclear export (SINE) compound, for the treatment of patients with relapsed/refractory multiple myeloma (rrMM). This is the fifth NDA for ATG-010 submitted by Antengene, after the four NDAs recently submitted in Australia, South Korea, Singapore and Hong Kong in…

    SHANGHAI and HONG KONG, Jan. 27, 2021 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced that the National Medical Products Administration (NMPA) accepted its New Drug Application (NDA) for ATG-010 (Selinexor, XPOVIO®), a first-in-class oral selective inhibitor of nuclear export (SINE) compound, for the treatment of patients with relapsed/refractory multiple myeloma (rrMM). This is the fifth NDA for ATG-010 submitted by Antengene, after the four NDAs recently submitted in Australia, South Korea, Singapore and Hong Kong in the Asia Pacific region, and also the first NDA of SINE compounds in mainland China, a step closer to providing a novel option to Chinese patients diagnosed with hematological malignancies.

    Antengene has recently submitted NDAs in multiple markets for ATG-010 across three indications for multiple myeloma and diffuse large B-cell lymphoma. Recently, the National Comprehensive Cancer Network (NCCN®) has also added five ATG-010 regimens to its guidelines for multiple myeloma or diffuse large B-cell lymphoma. ATG-010 is the first approved SINE compound in the world. It induces the apoptosis of cancer cells in vitro and in vivo by causing the nuclear storage and activation of tumor suppressor proteins and other growth-regulating proteins, and by down-regulating the intracytoplasmic levels of various oncogenic proteins while normal cells are not affected. Clinical studies have demonstrated that ATG-010 has clinical effects in multiple types of hematological and solid tumors with manageable safety profile.

    "We are delighted to see the acceptance of the NDA submission in China for ATG-010 in rrMM, which marks another important milestone and one step closer to bringing ATG-010 to patients in China." said Dr. Jay Mei, M.D., Ph.D., Founder, Chairman and CEO of Antengene. "In addition to its effectiveness in hematological malignancies, there are several clinical trials in multiple solid tumor indications with ATG-010 including a global Phase 3 trial in endometrial cancer (SIENDO) and a Phase 3 trial in liposarcoma (SEAL) which have shown encouraging results. We continue to prepare to commercialize ATG-010 in China and across the APAC region so that cancer patients can benefit from this novel cancer medicine."

    About ATG-010 (selinexor, XPOVIO®)

    ATG-010 (selinexor, XPOVIO®), a first-in-class and only-in-class oral selective inhibitor of nuclear export (SINE) compound discovered and developed by Karyopharm Therapeutics Inc. (NASDAQ:KPTI), is currently being developed by Antengene, which has the exclusive development and commercial rights in certain Asia-Pacific markets, including Greater China, South Korea, Australia, New Zealand and the ASEAN countries.

    In July 2019, the US Food and Drug Administration (FDA) approved selinexor (XPOVIO®) in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM) and in June 2020 approved selinexor (XPOVIO®) as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). In December 2020, selinexor (XPOVIO®) also received FDA approval as a combination treatment for multiple myeloma after at least one prior therapy. A Marketing Authorization Application (MAA) has also been submitted to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same rrMM indication. Selinexor (XPOVIO®) is so far the first and only oral SINE compound approved by the FDA and is the first drug approved for the treatment of both MM and DLBCL. Selinexor (XPOVIO®) is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer. In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene's partner, Karyopharm, presented positive results from the Phase 3 randomized, double blind, placebo controlled, cross-over SEAL trial evaluating single agent, oral selinexor (XPOVIO®) versus matching placebo in patients with liposarcoma. Karyopharm also announced that the ongoing Phase 3 SIENDO trial of selinexor (XPOVIO®) in patients with endometrial cancer passed the planned interim futility analysis and the Data and Safety Monitoring Board (DSMB) recommended the trial should proceed as planned without any modifications. Top-line SIENDO trial results are expected in the second half of 2021.

    About Antengene

    Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage Asia-Pacific biopharmaceutical company focused on innovative oncology medicines. Antengene aims to provide the most advanced anti-cancer drugs to patients in China, the Asia Pacific Region and around the world. Since its establishment, Antengene has built a pipeline of 12 clinical and pre-clinical stage assets and obtained 12 investigational new drug approvals in Asia Pacific. The vision of Antengene is to "Treat Patients Beyond Borders". Antengene aims to address significant unmet medical needs by discovering, developing and commercializing first-in-class/best-in-class therapeutics.

    Forward-looking statements

    The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

    *XPOVIO® is a registered trademark of Karyopharm Therapeutics Inc..

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    SOURCE Antengene Corporation Limited

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  10. TORONTO, Jan. 27, 2021 /CNW Telbec/ - FORUS Therapeutics launches today, bringing a new pharmaceutical company onto the Canadian landscape. With a highly-experienced and proven team, an FDA-approved product already in its pipeline, and significant financial investment secured, the Toronto-based company looks to bring innovative cancer therapies to Canadian patients, new treatment tools for caregivers and physicians, and in the future, be a preferred partner for emerging Canadian-based research companies.

    To support its launch, FORUS has raised approximately $20 million from investors that include adMare BioInnovations, Canada's global life sciences venture, and sophisticated international and institutional investors.

    FORUS has also secured an exclusive Canadian distribution agreement with Karyopharm Therapeutics Inc. (NASDAQ:KPTI) for the commercialization of XPOVIO® (selinexor), an FDA-approved cancer medicine for adults with Multiple Myeloma and Lymphoma. "We are thrilled to launch on the heels of our first licensing agreement to deliver a novel cancer treatment for Canadians," said Kevin Leshuk, Founder and President of FORUS.

    Multiple Myeloma is the second most common blood cancer. Every year, 3,400 Canadians are diagnosed with Multiple Myeloma, and sadly 1,600 die from the disease. FORUS will submit XPOVIO® to Health Canada for approval in the coming months.

    "We are investing in and supporting the launch of FORUS to address a major gap in the Canadian life sciences ecosystem," said Gordon C. McCauley, President and CEO of adMare BioInnovations. "We have an abundance of world-leading health research, a growing industry to translate that research into new therapeutics, but we have limited home-grown companies to bring these innovations directly to Canadian patients. FORUS begins to fill this gap by connecting medical innovations with the healthcare and patient communities across the country."

    "We're turning the traditional start-up model upside down," said Leshuk. Biopharmaceutical start-ups typically begin with early research, then undergo an arduous process of translating the research into a product, which can take at least a decade and have high associated failure rates. In this case, FORUS is starting on strong footing with an FDA-approved product already in place, considerable investment, and an experienced team. The company will move quickly to identify and secure development partnerships with Canadian research companies and globally-sourced innovations.

    Leshuk brings over 25 years of experience in the pharmaceutical industry. He and the FORUS founding team have delivered significant financial returns; and since 2009, secured 12 Health Canada approvals, including five in Multiple Myeloma. The FORUS goal is to continue this track record of success and bring important new medicines to Canadians to actively contribute to the Canadian life sciences innovation ecosystem.

    About FORUS Therapeutics

    FORUS Therapeutics is a Canadian biopharmaceutical company dedicated to advancing differentiated, novel medicines for hematologic malignancies and other forms of cancer. Our mission is to bring solutions to cancer patients, caregivers, physicians and our partners by accelerating unique and important treatments that meaningfully enhance life. forustherapeutics.com

    About adMare BioInnovations

    adMare BioInnovations is Canada's global life sciences venture, building the Canadian life sciences industry from sea to sea. We do this by sourcing therapeutically and commercially promising research from leading academic and biotech partners to create new companies of scale, providing specialized expertise, infrastructure, and capital to help existing companies scale up, and drive the growth of those companies into Canadian anchors by training the next generation of highly qualified personnel. adMare's ~20 portfolio companies have attracted more than $1.15 billion in investment and have a combined worth of over $2.3 billion. admarebio.com

    SOURCE adMare BioInnovations

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  11. NEWTON, Mass., Jan. 11, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced preliminary unaudited fourth quarter and full year 2020 total revenue estimates including net product sales for XPOVIO, the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) medicine, and provided additional updates on XPOVIO's commercial progress.

    Based on preliminary unaudited financial information, Karyopharm expects total revenues for the fourth quarter of 2020 to be between $35.0 million and $36.0 million and between $108.0 million and 109.0 million for the full year of 2020. Additionally, Karyopharm expects net product sales of XPOVIO…

    NEWTON, Mass., Jan. 11, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced preliminary unaudited fourth quarter and full year 2020 total revenue estimates including net product sales for XPOVIO, the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) medicine, and provided additional updates on XPOVIO's commercial progress.

    Based on preliminary unaudited financial information, Karyopharm expects total revenues for the fourth quarter of 2020 to be between $35.0 million and $36.0 million and between $108.0 million and 109.0 million for the full year of 2020. Additionally, Karyopharm expects net product sales of XPOVIO to be between $20.0 million and $20.5 million during the fourth quarter and between $76.0 million and $76.5 million for the full year 2020. Net sales for the fourth quarter were largely driven by prescription demand from both academic and community-based oncologists for patients with penta-refractory multiple myeloma. Additional sales were also generated from patients with diffuse large B-cell lymphoma (DLBCL). Finally, approximately $15 million of license revenue was also recognized in the fourth quarter following progress made toward the international expansion for XPOVIO.

    XPOVIO sales in the fourth quarter of 2020 were approximately 4-6% lower than the third quarter of 2020. Sales were affected by the recent surge in U.S. COVID-19 cases impacting both patient visits to their healthcare providers, as well as reduced in-person access for Karyopharm's commercial team to its physician customers. Additionally, increased competition, specifically in the penta-refractory multiple myeloma setting, also contributed to the sales pressure in the quarter. Importantly, XPOVIO prescription demand was higher in December 2020 compared to either October or November 2020. On a quarterly basis, Karyopharm expects XPOVIO sales to return to growth beginning in the first quarter of 2021 as compared to the fourth quarter of 2020 following the expanded FDA approval of XPOVIO granted in late December and the related commercial launch which began immediately thereafter.

    These updates will be discussed during a webcast presentation at the 39th Annual J.P. Morgan Healthcare Conference to be held on Monday, January 11, 2021 at 4:30 p.m. ET. A live webcast of the presentation and Q&A session can be accessed under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. A replay of the webcast will be archived on the Company's website for 30 days following the presentation.

    "2020 was a pivotal year for Karyopharm as XPOVIO received two FDA approvals, including for the treatment of patients with relapsed or refractory DLBCL, as well as in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "Our most recent FDA approval in multiple myeloma, received in late December 2020, substantially broadens the existing label for XPOVIO and allows Karyopharm to offer a new, highly active, treatment option to a significantly expanded patient population. Importantly, the regimen of once-weekly, oral XPOVIO with once-weekly bortezomib and dexamethasone has the potential to meet a current treatment gap for patients with multiple myeloma in need of new therapeutic options."

    Additional Progress Made Toward International Expansion

    Karyopharm also today announced its entry into an exclusive distribution agreement for the commercialization of XPOVIO in Canada with FORUS Therapeutics Inc., a new Canadian biopharmaceutical company that has extensive knowledge, expertise and demonstrated capabilities in advancing important medicines for Canadian cancer patients.

    Under the terms of the agreement, Karyopharm received an upfront payment of approximately $5 million in December 2020 and is eligible to receive additional payments if certain prespecified regulatory and commercial milestones are achieved by FORUS Therapeutics. Karyopharm is also eligible to receive double-digit royalties on future net sales of XPOVIO in Canada. In exchange, FORUS Therapeutics received the exclusive rights to commercialize XPOVIO in Canada and is responsible for all regulatory filings and obligations required for registering XPOVIO. Karyopharm has retained the exclusive production rights and will supply finished product to FORUS Therapeutics for commercial use in Canada.

    Additional regulatory progress was also made by Karyopharm's partner Antengene Therapeutics Limited, which filed for regulatory approval of selinexor in both multiple myeloma and DLBCL indications in Australia, Singapore and South Korea in December 2020. These filings triggered approximately $10 million in milestone payments to Karyopharm, which together with the $5 million upfront payment from FORUS Therapeutics, resulted in the recognition of approximately $15 million of license revenue during the fourth quarter of 2020.

    Finally, Karyopharm has previously submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) requesting conditional approval for XPOVIO in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma based on the results of the Phase 2b STORM study. Based on ongoing discussions with EMA's Committee for Medicinal Products for Human Use (CHMP), Karyopharm now expects a final opinion on the MAA by February 2021. Following receipt of CHMP's opinion, Karyopharm expects to submit a second MAA based on the data from the BOSTON study shortly thereafter.

    Cash Position and 2021 Financial Guidance

    Unaudited cash, cash equivalents, restricted cash and investments as of December 31, 2020 totaled approximately $277.0 million, compared to $265.8 million as of December 31, 2019.

    The Company intends to provide 2021 financial guidance on non-GAAP research and development expenses and selling, general and administrative expenses in February 2021 in connection with the final financial results for the fourth quarter of 2020 and the audited financial results for full year 2020.

    The financial information presented in this press release may be adjusted as a result of the completion of customary quarterly and annual review and audit procedures, and the Company's actual financial results may differ materially from the preliminary estimated financial information set forth above.

    About XPOVIO® (selinexor)

    XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm's supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA on December 18, 2020. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email: 

    XPOVIO® (selinexor) is a prescription medicine approved:

    • In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
    • In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd).
    • For the treatment of adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

    SELECT IMPORTANT SAFETY INFORMATION

    Warnings and Precautions

    • Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.

    • Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors. 

    • Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care. 

    • Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.

    • Serious Infection: Monitor for infection and treat promptly.

    • Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.

    • Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.

    • Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.

    Adverse Reactions

    • The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.

    • The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.

    • The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection(21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.

    Use In Specific Populations

    Lactation: Advise not to breastfeed.

    For additional product information, including full prescribing information, please visit www.XPOVIO.com.

    To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's preliminary financial information for fourth quarter and full year 2020; Karyopharm's plans to provide guidance on its 2021 non-GAAP research and development and selling, general and administrative expenses; expectations and plans relating to XPOVIO for the treatment of patients with relapsed or refractory multiple myeloma or relapsed or refractory diffuse large B-cell lymphoma; commercialization of XPOVIO or any of its drug candidates and the commercial performance of XPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; and the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the European Union as a result of data from the STORM study or confirmatory approval in the European Union based on the BOSTON study in patients with multiple myeloma; or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any product or product candidate. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

    XPOVIO®(selinexor) is a registered trademark of Karyopharm Therapeutics Inc. Velcade® is a registered trademark of Takeda Pharmaceutical Company Limited.

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  12. SHANGHAI and HONG KONG, Jan. 4, 2021 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced that it submitted an Investigational New Drug (IND) application to the National Medical Products Administration (NMPA) for ATG-010 (selinexor) in the treatment of Endometrial Cancer. This is a global Phase 3, multicenter, randomized, double-blind trial (SIENDO) aiming to evaluate the efficacy of ATG-010 compared to placebo as maintenance therapy in patients with advanced or recurrent endometrial cancer after combination chemotherapy and…

    SHANGHAI and HONG KONG, Jan. 4, 2021 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced that it submitted an Investigational New Drug (IND) application to the National Medical Products Administration (NMPA) for ATG-010 (selinexor) in the treatment of Endometrial Cancer. This is a global Phase 3, multicenter, randomized, double-blind trial (SIENDO) aiming to evaluate the efficacy of ATG-010 compared to placebo as maintenance therapy in patients with advanced or recurrent endometrial cancer after combination chemotherapy and is being conducted at approximately 80 investigative sites around the world, including North America, Europe and Asia.

    Endometrial cancer is the most common cancer of the female reproductive tract and for patients who progress following initial chemotherapy there are limited treatment options with poor prognosis. The highest incidence rates are reported in developed countries and some economically developed areas of China. In recent years, with an increase in the prevalence of obesity, diabetes and hypertension, the incidence and mortality rate of endometrial cancer has been increasing with a trend towards younger women.

    ATG-010 is a first-in-class and only-in-class oral selective inhibitor of nuclear export, developed by Antengene and Karyopharm Therapeutics Inc. (NASDAQ:KPTI). It has been approved by the US Food and Drug Administration (FDA) for use in both multiple myeloma and diffuse large B-cell lymphoma, which are two major indications in hematological malignancies. In addition, the Phase 3 SIENDO trial of ATG-010 in patients with endometrial cancer has passed the planned interim futility analysis and the Data and Safety Monitoring Board (DSMB) recommended the trial should proceed as planned without any modification.

    "The positive data of the Phase 3 SEAL trial in liposarcoma and the ongoing Phase 3 SIENDO trial in endometrial cancer which just passed the interim analysis have suggested substantial potential of ATG-010 across multiple solid tumors. Filing an IND with the NMPA in China is an important step in the clinical development of ATG-010 as we expect to explore additional therapeutic areas of our novel oral drug candidate," said Dr. Jay Mei, Founder, Chairman and CEO of Antengene. "We look forward to initiating the Phase 3 global trial in patients with advanced or recurrent endometrial cancer in China, to provide Chinese patients with better treatment options."

    Professor Qi Zhou from the Gynecological Oncology Center of Chongqing University Cancer Hospital, the leading clinical investigator, said: "R&D capability in China has improved significantly in recent years. There are more innovative anti-tumor drugs moving towards clinical research and commercialization, and they are widely used in clinical practice. The emergence of targeted and immunotherapy drugs effectively improved the prognosis of patients. I look forward to advancing the research of ATG-010, a first-in-class selective nuclear export inhibitor, with Antengene, to improve the effect and increase the accessibility of treatment, so that patients can benefit from clinical results as soon as possible."

    About ATG-010 (selinexor, XPOVIO®)

    ATG-010 (selinexor, XPOVIO®), a first-in-class and only-in-class oral selective inhibitor of nuclear export compound discovered and developed by Karyopharm, is currently being developed by Antengene, which has the exclusive development and commercial rights in certain Asia-Pacific markets, including the Greater China, South Korea, Australia, New Zealand and the ASEAN countries. In July 2019, the US Food and Drug Administration (FDA) approved ATG-010 in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM) and in June 2020 approved ATG-010 as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). A Marketing Authorization Application (MAA) has also been submitted to the European Medicines Agency (EMA) with a request for conditional approval of ATG-010 in this same rrMM indication. On December 18, 2020, the supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA. ATG-010 is so far the first and only oral SINE compound approved by the FDA and is the first drug approved for the treatment of both MM and DLBCL. ATG-010 is also being evaluated in several other mid-and later-Phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer. In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene's partner, Karyopharm, presented positive results from the Phase 3 randomized, double blind, placebo controlled, cross-over SEAL trial evaluating single agent, oral ATG-010 versus matching placebo in patients with liposarcoma. Karyopharm also recently announced that the ongoing Phase 3 SIENDO trial of ATG-010 in patients with endometrial cancer passed the planned interim futility analysis and the Data and Safety Monitoring Board (DSMB) recommended the trial should proceed as planned without any modifications. Top-line SIENDO trial results are expected in the second half of 2021.

    Antengene is conducting two registrational Phase 2 clinical trials of ATG-010 in China for relapsed/refractory multiple myeloma (MARCH) and for relapsed/refractory diffuse large B-cell lymphoma (SEARCH), and has initiated clinical trials for high prevalence cancer types in the Asia Pacific region including peripheral T-cell lymphoma and NK/T-cell lymphoma (TOUCH) and KRAS-mutant non-small cell lung cancer (TRUMP).

    About Antengene

    Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage Asia-Pacific biopharmaceutical company focused on innovative oncology medicines. Antengene aims to provide the most advanced anti-cancer drugs to patients in China, the Asia Pacific Region and around the world. Since its establishment, Antengene has built a pipeline of 12 clinical and pre-clinical stage assets and obtained 11 investigational new drug approvals in Asia Pacific. The vision of Antengene is to "Treat Patients Beyond Borders". Antengene aims to address significant unmet medical needs by discovering, developing and commercializing first-in-class/best-in-class therapeutics.

    Forward-looking statements

    The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

    * XPOVIO® is a registered trademark of Karyopharm Therapeutics Inc..

     

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  13. NEWTON, Mass., Jan. 4, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the Compensation Committee of Karyopharm's Board of Directors granted stock options to purchase an aggregate of 50,500 shares of Karyopharm's common stock to 12 newly-hired employees, with a grant date of December 31, 2020. The stock options were granted as inducements material to the new employees entering into employment with Karyopharm in accordance with Nasdaq Listing Rule 5635(c)(4).

    Each of the stock options has an exercise price of $15.48 per share, the closing price of Karyopharm's common stock on December 31, 2020. Each stock option vests over four years…

    NEWTON, Mass., Jan. 4, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the Compensation Committee of Karyopharm's Board of Directors granted stock options to purchase an aggregate of 50,500 shares of Karyopharm's common stock to 12 newly-hired employees, with a grant date of December 31, 2020. The stock options were granted as inducements material to the new employees entering into employment with Karyopharm in accordance with Nasdaq Listing Rule 5635(c)(4).

    Each of the stock options has an exercise price of $15.48 per share, the closing price of Karyopharm's common stock on December 31, 2020. Each stock option vests over four years, with 25% of the total number of shares underlying the stock option vesting on the one-year anniversary of the applicable employee's employment commencement date and 1/48th of the total number of shares vesting monthly thereafter, subject to the employee's continued service as an employee of, or other service provider to, Karyopharm through the applicable vesting dates. In addition, each stock option will be immediately exercisable in full if, on or prior to the first anniversary of the consummation of a "change in control event," the employee's employment is terminated for "good reason" by the employee or terminated without "cause" by Karyopharm (as such terms are defined in the applicable stock option agreement).

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma and in December 2020 in combination with Velcade® (bortezomib) and dexamethasone as a treatment for patients with multiple myeloma after at least one prior therapy. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

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  14. NEWTON, Mass., Jan. 4, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that Michael Kauffman, MD, PhD, Chief Executive Officer, will present at the 39th Annual J.P. Morgan Healthcare Conference. The conference is being conducted in a virtual format and the presentation will take place on Monday, January 11 at 4:30 p.m. ET, followed by a question and answer breakout session at 4:50 p.m. ET.

    A live webcast of the presentation and breakout session can be accessed under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. A replay of the webcast will be archived…

    NEWTON, Mass., Jan. 4, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that Michael Kauffman, MD, PhD, Chief Executive Officer, will present at the 39th Annual J.P. Morgan Healthcare Conference. The conference is being conducted in a virtual format and the presentation will take place on Monday, January 11 at 4:30 p.m. ET, followed by a question and answer breakout session at 4:50 p.m. ET.

    A live webcast of the presentation and breakout session can be accessed under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. A replay of the webcast will be archived on the Company's website for 30 days following the presentation.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), is approved in the U.S. in multiple hematologic malignancy indications, including in combination with Velcade® (bortezomib) and dexamethasone for the treatment of patients with multiple myeloma after at least one prior therapy, in combination with dexamethasone for the treatment of patients with heavily pretreated multiple myeloma and as a monotherapy for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

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  15. SHANGHAI and HONG KONG, Jan. 3, 2021 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced that it has submitted a New Drug Application (NDA) with Orphan Drug Designation (ODD) to the South Korean Ministry of Food and Drug Safety (MFDS) for ATG-010 (selinexor, XPOVIO®) in combination with low dose dexamethasone for the treatment of adult patients with relapsed/refractory multiple myeloma (rrMM) and for ATG-010 (selinexor, XPOVIO®) as monotherapy to treat adult patients with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). ATG-010…

    SHANGHAI and HONG KONG, Jan. 3, 2021 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced that it has submitted a New Drug Application (NDA) with Orphan Drug Designation (ODD) to the South Korean Ministry of Food and Drug Safety (MFDS) for ATG-010 (selinexor, XPOVIO®) in combination with low dose dexamethasone for the treatment of adult patients with relapsed/refractory multiple myeloma (rrMM) and for ATG-010 (selinexor, XPOVIO®) as monotherapy to treat adult patients with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). ATG-010 (selinexor, XPOVIO®) was granted orphan drug designation in South Korea in October 2020 and our US partner Karyopharm received U.S. Food and Drug Administration (FDA) approval for the treatment of patients with multiple myeloma after at least one prior therapy on December 18, 2020.

    The NDA submission includes positive data from the pivotal STORM and SADAL studies, which both demonstrated significant and meaningful efficacy with a manageable safety profile for ATG-010 (selinexor, XPOVIO®). The STORM study is a Phase 2b, open-label, single-arm study evaluating ATG-010 (selinexor, XPOVIO®) plus low-dose dexamethasone in patients with rrMM who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody. The SADAL study is a Phase 2b, open label study evaluating ATG-010 (selinexor, XPOVIO®) in patients with rrDLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, who have received at least two prior therapies. 

    ATG-010 (selinexor, XPOVIO®) is a first-in-class and only-in-class oral selective inhibitor of nuclear export (SINE) and it is the first drug approved by the FDA for use in both multiple myeloma and diffuse large B-cell lymphoma. In December 2020, the National Comprehensive Cancer Network (NCCN®) added three different triplet ATG-010 (selinexor, XPOVIO®) combination regimens, including SVd (selinexor, bortezomib and dexamethasone), SPd (selinexor, pomalidomide and dexamethasone) and SDd (selinexor, daratumumab and dexamethasone) to its Clinical Practice Guidelines in Oncology (NCCN® Guidelines) for previously treated multiple myeloma in the US. Antengene has submitted NDAs to the Health Sciences Authority (HSA) of Singapore and to the Australian Therapeutic Goods Administration (TGA) for ATG-010 in patients with rrMM and in patients with rrDLBCL.

    "The incidence of blood cancers increases with age, yet many healthcare providers still do not have sufficient innovative therapies available to help people with hematological malignancies, such as rrMM and rrDLBCL," Dr. Jay Mei, Founder, Chairman and CEO of Antengene said, "We are excited about the regulatory filing of ATG-010 in APAC markets, including South Korea. We believe that oral ATG-010 will expand and improve treatment options for hematological malignancies and therefore presents a significant advancement for patients requiring treatment of these life threatening diseases."

    About ATG-010 (selinexor, XPOVIO®)

    ATG-010 (selinexor, XPOVIO®), a first-in-class and only-in-class oral selective inhibitor of nuclear export compound discovered and developed by Karyopharm Therapeutics Inc. (NASDAQ:KPTI), is currently being developed by Antengene, which has the exclusive development and commercial rights in certain Asia-Pacific markets, including the Greater China, South Korea, Australia, New Zealand and the ASEAN countries. In July 2019, the US Food and Drug Administration (FDA) approved selinexor (XPOVIO®) in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM) and in June 2020 approved selinexor (XPOVIO®) as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). A Marketing Authorization Application (MAA) has also been submitted to the European Medicines Agency (EMA) with a request for conditional approval of selinexor (XPOVIO®) in this same rrMM indication. On December 18, 2020, the supplemental New Drug Application (sNDA) with a request for an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA. Selinexor (XPOVIO®) is so far the first and only oral SINE compound approved by the FDA and is the first drug approved by the FDA for the treatment of both MM and DLBCL. Selinexor (XPOVIO®) is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer. In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene's partner, Karyopharm, presented positive results from the Phase 3 randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral selinexor (XPOVIO®) versus matching placebo in patients with liposarcoma. Karyopharm also recently announced that the ongoing Phase 3 SIENDO study of selinexor (XPOVIO®) in patients with endometrial cancer passed the planned interim futility analysis and the Data and Safety Monitoring Board (DSMB) recommended the study should proceed as planned without any modifications. Top-line SIENDO study results are expected in the second half of 2021.

    Antengene is conducting two registrational Phase 2 clinical trials of ATG-010 (selinexor, XPOVIO®) in China for relapsed/refractory multiple myeloma (MARCH) and for relapsed/refractory diffuse large B-cell lymphoma (SEARCH), and has initiated clinical trials for high prevalence cancer types in the Asia Pacific region including peripheral T-cell lymphoma and NK/T-cell lymphoma (TOUCH) and KRAS-mutant non-small cell lung cancer (TRUMP).

    About Antengene

    Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage Asia-Pacific biopharmaceutical company focused on innovative oncology medicines. Antengene aims to provide the most advanced anti-cancer drugs to patients in China, the Asia Pacific Region and around the world. Since its establishment, Antengene has built a pipeline of 12 clinical and pre-clinical stage assets and obtained 11 investigational new drug approvals in Asia Pacific. The vision of Antengene is to "Treat Patients Beyond Borders". Antengene aims to address significant unmet medical needs by discovering, developing and commercializing first-in-class/best-in-class therapeutics.

    Forward-looking statements

    The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

    * XPOVIO® is a registered trademark of Karyopharm Therapeutics Inc.;

    NCCN® is a registered trademark of National Comprehensive Cancer Network.

    Cision View original content:http://www.prnewswire.com/news-releases/antengene-submits-nda-for-atg-010-selinexor-in-south-korea-for-rrmm-and-rrdlbcl-301199927.html

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  16. SHANGHAI and HONG KONG, Dec. 20, 2020 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) submitted by its partner Karyopharm Therapeutics Inc. (NASDAQ:KPTI) for oral XPOVIO® (selinexor, ATG-010), a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) medicine, in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. This indication was approved three months ahead of its March Prescription Drug User Fee Act (PDUFA) date based on the result of a confirmatory Phase 3 BOSTON study.

    XPOVIO® was…

    SHANGHAI and HONG KONG, Dec. 20, 2020 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) submitted by its partner Karyopharm Therapeutics Inc. (NASDAQ:KPTI) for oral XPOVIO® (selinexor, ATG-010), a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) medicine, in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. This indication was approved three months ahead of its March Prescription Drug User Fee Act (PDUFA) date based on the result of a confirmatory Phase 3 BOSTON study.

    XPOVIO® was previously approved under the FDA's Accelerated Approval Program for the treatment of adult patients with relapsed or refractory multiple myeloma (rrMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

    XPOVIO®, a first-in-class and only-in-class oral SINE compound, and now the first and only drug approved by FDA for use in both multiple myeloma and diffuse large B-cell lymphoma, discovered and developed by Karyopharm, is currently being developed by Antengene, who has the exclusive development and commercial rights in certain Asia-Pacific markets, including China. In December 2020, National Comprehensive Cancer Network (NCCN®) added three different XPOVIO® combination regimens to its Clinical Practice Guidelines in Oncology (NCCN® Guidelines) for previously treated multiple myeloma.

    Antengene has conducted two Phase 2 registrational clinical trials of XPOVIO® in China for relapsed or refractory multiple myeloma (MARCH) and for relapsed or refractory diffuse large B-cell lymphoma (SEARCH). A Phase 3 randomized, controlled, open-label and multicenter BENCH trial has also received the IND approval from the National Medical Products Administration (NMPA) in China. Antengene is working on making XPOVIO® commercially available in Asia Pacific regions and has submitted the New Drug Applications (NDAs) for XPOVIO® to the Health Sciences Authority (HSA) of Singapore and the Australian Therapeutic Goods Administration (TGA) for three indications, including the treatment of patients with multiple myeloma who have received at least one prior therapy.

     "This is the third approved indication for XPOVIO®, highlighting its potential of clinical application and broad market prospects. XPOVIO® offers patients with rrMM and their physicians the first oral SINE compound and makes more treatment options available to cancer patients with critical unmet medical needs." Dr. Jay Mei, M.D., Ph.D., Founder, Chairman and CEO of Antengene said, "We plan to launch XPOVIO® as soon as possible for the treatment of patients with rrMM and rrDLBCL in APAC following regulatory approvals, by leveraging our established commercial infrastructure and seasoned international team."

    About the Phase 3 BOSTON Study

    The approval of XPOVIO® in combination with once-weekly bortezomib plus low-dose dexamethasone (SVd) is supported by the results of the multi-center, Phase 3, randomized study, which evaluated 402 adult patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy. The study was designed to compare the efficacy, safety and certain health-related quality of life parameters of once-weekly XPOVIO® (selinexor) in combination with once-weekly bortezomib plus low-dose dexamethasone (SVd) versus twice-weekly bortezomib plus dexamethasone (Vd). The primary endpoint of the study was progression-free survival (PFS) and key secondary endpoints included overall response rate (ORR), rate of peripheral neuropathy, and others. Additionally, the BOSTON study allowed for patients on the Vd control arm to crossover to the SVd arm following objective (quantitative) progression of disease verified by an Independent Review Committee (IRC). The BOSTON study was conducted at over 150 clinical sites internationally.

    Although the study had one of the highest proportions of patients with high-risk cytogenetics (~50%) as compared with other bortezomib-based studies in previously treated myeloma, the median PFS in the SVd arm was 13.9 months compared to 9.5 months in the Vd arm, representing a 4.4 month increase in median PFS (hazard ratio [HR] of 0.70; p=0.0075). The SVd group also demonstrated a significantly greater ORR compared to the Vd group (76.4% vs. 62.3%, p=0.0012). Importantly, SVd therapy compared to Vd therapy showed consistent PFS benefit and higher ORR across several important subgroups.

    In addition, the following results favored SVd therapy as compared to Vd therapy:

    • SVd therapy demonstrated a significantly higher rate of deep responses, defined as ≥ Very Good Partial Response compared to Vd therapy (44.6% vs. 32.4%) as well as a longer median duration of response (20.3 months vs. 12.9 months). Additionally, 17% of patients on the SVd arm achieved a Complete Response or a Stringent Complete Response as compared to 10% of patients receiving Vd therapy. All responses were confirmed by an IRC.

    • Peripheral neuropathy (PN) rates were significantly lower on SVd compared to Vd (32% vs. 47%). In addition, PN rates ≥ Grade 2 were also significantly lower in the SVd arm compared to Vd (21% vs. 34%).

    The most common adverse reactions were cytopenias, along with gastrointestinal and constitutional symptoms and were consistent with those previously reported from other selinexor studies. Most adverse reactions were manageable with dose modifications and/or standard supportive care. The most common non-hematologic adverse reactions were nausea (50%), fatigue (42%), decreased appetite (35%), and diarrhea (32%) and were mostly Grade 1 and 2 events. The most common Grade 3 and 4 adverse reactions were thrombocytopenia (43%), lymphopenia (38%), anemia (17%), and fatigue (13%).

    About XPOVIO® (selinexor, ATG-010)

    XPOVIO® (selinexor, ATG-010), a first-in-class and only-in-class oral selective inhibitor of nuclear export compound discovered and developed by Karyopharm, is currently being developed by Antengene, who has the exclusive development and commercial rights in certain Asia-Pacific markets, including China. In July 2019, the US Food and Drug Administration (FDA) approved Selinexor (XPOVIO®) in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM) and in June 2020 approved selinexor (XPOVIO®) as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). A Marketing Authorization Application (MAA) has also been submitted to the European Medicines Agency (EMA) with a request for conditional approval of selinexor (XPOVIO®) in this same rrMM indication. On December 18, 2020, the supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA. Selinexor (XPOVIO®) is so far the first and only oral SINE compound approved by the FDA. Selinexor (XPOVIO®) is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer. In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene's partner, Karyopharm, presented positive results from the Phase 3 randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral selinexor (XPOVIO®) versus matching placebo in patients with liposarcoma. Karyopharm also recently announced that the ongoing Phase 3 SIENDO study of selinexor (XPOVIO®) in patients with endometrial cancer passed planned interim futility analysis and that Data and Safety Monitoring Board (DSMB) recommended the study should proceed as planned without any modifications. Top-line SIENDO study results are expected in the second half of 2021.

    Antengene is conducting two registrational Phase 2 clinical trials of selinexor (XPOVIO®) in China for relapsed refractory multiple myeloma (MARCH) and for relapsed refractory diffuse large B-cell lymphoma (SEARCH), and has initiated clinical trials for high prevalence cancer types in the Asia Pacific region including peripheral T-cell lymphoma and NK/T-cell lymphoma (TOUCH) and KRAS-mutant non-small cell lung cancer (TRUMP).

    About Antengene

    Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage Asia-Pacific biopharmaceutical company focused on innovative oncology medicines. Antengene aims to provide the most advanced anti-cancer drugs to patients in China, the Asia Pacific Region and around the world. Since its establishment, Antengene has built a pipeline of 12 clinical and pre-clinical stage assets and obtained 11 investigational new drug approvals in Asia Pacific. The vision of Antengene is to "Treat Patients Beyond Borders". Antengene aims to address significant unmet medical needs by discovering, developing and commercializing first-in-class/best-in-class therapeutics.

    Forward-looking Statements

    The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

    *XPOVIO® is a registered trademark of Karyopharm Therapeutics Inc.;

    NCCN® is a registered trademark of National Comprehensive Cancer Network.

    Cision View original content:http://www.prnewswire.com/news-releases/antengene-announces-its-us-partner-karyopharm-therapeutics-inc-has-received-fda-approval-of-xpovio-selinexor-as-a-treatment-for-patients-with-multiple-myeloma-after-at-least-one-prior-therapy-301196488.html

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  17. NEWTON, Mass., Dec. 18, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the U.S. Food and Drug Administration (FDA) has approved XPOVIO® (selinexor), the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) medicine, in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. XPOVIO was previously approved under the FDA's Accelerated Approval Program for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at…

    NEWTON, Mass., Dec. 18, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the U.S. Food and Drug Administration (FDA) has approved XPOVIO® (selinexor), the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) medicine, in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. XPOVIO was previously approved under the FDA's Accelerated Approval Program for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

    "Today's U.S. approval broadens the existing label for XPOVIO and allows Karyopharm to offer a new, highly active, treatment option to a significantly expanded patient population," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "We believe the expanded reach of XPOVIO will address a critical need for patients with multiple myeloma given its novel mechanism of action, convenient oral administration and established rapid and sustained efficacy profile. The XPOVIO label expansion approval was supported by the pivotal Phase 3 BOSTON study, which was recently published in The Lancet. This approval was made possible by the patients, caregivers and physicians who participated in the clinical development of XPOVIO, as well as our global, dedicated Karyopharm team that has worked tirelessly to advance this innovative therapy to the greater multiple myeloma community."

    "New treatments for multiple myeloma remain a critical need for both patients and their treating physicians," said Paul Richardson, MD, Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute and co-senior author of the BOSTON study publication. "Selinexor with once weekly bortezomib-dexamethasone (SVd) demonstrated encouraging and highly significant results in the Phase 3 BOSTON study, including a 47% improvement in progression-free survival versus standard twice weekly bortezomib-dexamethasone (Vd). Patients receiving SVd had approximately 35% fewer clinic visits compared to those receiving the standard, twice-weekly Vd regimen, thus receiving 40% less bortezomib and 25% less dexamethasone as compared with the control arm in the first 24 weeks of therapy. This once-weekly dosing feature helps makes the SVd regimen attractively simple. Importantly, patients achieved a significantly higher overall response of 76% with once-weekly SVd compared with the standard control arm therapy, and higher response rates were observed regardless of prior therapies received, the presence of high-risk cytogenetics, renal impairment or advanced age. Finally, adverse events with SVd were important but generally self-limiting, reversible, and proved manageable with dose modifications and aggressive supportive care, as well as generating significantly lower rates of peripheral neuropathy compared to the control group. As the only approved nuclear export inhibitor that has demonstrated a strong synergistic effect with a proteasome inhibitor such as bortezomib, selinexor has, in my opinion, the potential to meet a current treatment gap for our multiple myeloma patients in need of new therapeutic options."

    "We plan to immediately launch XPOVIO in this earlier-line indication by leveraging our established commercial infrastructure and growing account base of academic institutions and community-based oncology practices," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "In parallel to our commercial initiatives in the U.S., we continue to collaborate with the European Medicines Agency (EMA) on the Marketing Authorization Application (MAA) of XPOVIO with the goal of further growing the global reach of XPOVIO to more patients in need."

    In addition to multiple myeloma, XPOVIO is also approved for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy.

    About the Phase 3 BOSTON Study

    The FDA approval of XPOVIO's expanded indication is supported by the results of the BOSTON study, a multi-center, Phase 3, randomized study (NCT03110562), which evaluated 402 adult patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy. The study was designed to compare the efficacy, safety and certain health-related quality of life parameters of once-weekly XPOVIO (selinexor) in combination with once-weekly Velcade® (bortezomib) plus low-dose dexamethasone (SVd) versus twice-weekly Velcade® plus dexamethasone (Vd). The primary endpoint of the study was progression-free survival (PFS) and key secondary endpoints included overall response rate (ORR), rate of peripheral neuropathy, and others. Additionally, the BOSTON study allowed for patients on the Vd control arm to crossover to the SVd arm following objective (quantitative) progression of disease verified by an Independent Review Committee (IRC). The BOSTON study was conducted at over 150 clinical sites internationally.

    Although the study had one of the highest proportions of patients with high-risk cytogenetics (~50%) as compared with other Velcade-based studies in previously treated multiple myeloma, the median PFS in the SVd arm was 13.9 months compared to 9.5 months in the Vd arm, representing a 4.4 month (47%) increase in median PFS (hazard ratio of 0.70; p=0.0075). The SVd arm also demonstrated a significantly greater ORR compared to the Vd arm (76.4% vs. 62.3%, p=0.0012). Importantly, SVd therapy compared to Vd therapy showed consistent PFS benefit and higher ORR across several important subgroups.

    In addition, the following results favored SVd therapy as compared to Vd therapy:

    • SVd therapy demonstrated a significantly higher rate of deep responses, defined as ≥ Very Good Partial Response compared to Vd therapy (44.6% vs. 32.4%) as well as a longer median duration of response (20.3 months vs. 12.9 months). Additionally, 17% of patients on the SVd arm achieved a Complete Response or a Stringent Complete Response as compared to 10% of patients receiving Vd therapy. All responses were confirmed by an IRC.
    • Peripheral neuropathy (PN) rates were significantly lower on SVd compared to Vd (32% vs. 47%). In addition, PN rates ≥ Grade 2 were also significantly lower in the SVd arm compared to the Vd arm (21% vs. 34%).

    The most common adverse reactions were cytopenias, along with gastrointestinal and constitutional symptoms and were consistent with those previously reported from other selinexor studies. Most adverse reactions were manageable with dose modifications and/or standard supportive care. The most common non-hematologic adverse reactions were fatigue (59%), nausea (50%), decreased appetite (35%), and diarrhea (32%) and were mostly Grade 1 and 2 events. The most common Grade 3 and 4 adverse reactions were thrombocytopenia (43%), lymphopenia (38%), fatigue (28%) and anemia (17%).

    The full results from the BOSTON study were recently published in The Lancet and can be found here.

    Conference Call Information

    Karyopharm will host a conference call today, Friday, December 18, 2020, at 1:00 p.m. Eastern Time, to discuss the FDA's approval of the expanded XPOVIO label. To access the conference call, please dial (877) 870-4263 (local) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. An archived webcast will be available on the Company's website approximately two hours after the event.

    About Multiple Myeloma

    According to the National Cancer Institute (NCI), multiple myeloma is one of the most common types of blood cancer in the U.S. with more than 32,000 new cases each year and over 140,000 patients living with the disease. It is most frequently diagnosed among people aged 65-74 years old. Despite recent therapeutic advances, there is currently no cure and most patients' disease will typically progress following treatment with currently available therapies. According to the NCI, nearly 13,000 deaths due to multiple myeloma are expected in the U.S. in 2020.

    About XPOVIO® (selinexor)

    XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm's supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA on December 18, 2020. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email: 

    IMPORTANT SAFETY INFORMATION

    Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma.

    Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of bleeding. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

    Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection.

    Monitor more frequently during the first 3 months of treatment. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

    Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients.

    Nausea/Vomiting/Diarrhea: Provide prophylactic antiemetics or treatment as needed.

    Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment and provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

    Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. 

    Monitor sodium level at baseline and throughout treatment.

    Serious Infection: XPOVIO can cause serious and fatal infections. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

    Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.

    Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

    Advise patients to refrain from driving and engaging in hazardous occupations or activities until the neurological toxicity fully resolves. Institute fall precautions as appropriate.

    Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

    Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

    Cataracts: New onset or exacerbation of cataract has occurred during treatment with XPOVIO. The incidence of new onset or worsening cataract requiring clinical intervention was reported.

    ADVERSE REACTIONS

    The most common adverse reactions (ARs) (≥20%) in patients with multiple myeloma who received SVd were fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract, and vomiting.

    Grade 3-4 laboratory abnormalities (≥10%) were thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia.

    Fatal ARs occurred in 6% of patients within 30 days of last treatment. Serious ARs occurred in 52% of patients. Treatment discontinuation rate due to ARs was 19%. The most frequent ARs requiring permanent discontinuation in >2% of patients included fatigue, nausea, thrombocytopenia, decreased appetite, peripheral neuropathy and vomiting. Adverse reactions led to XPOVIO dose interruption in 83% of patients and dose reduction in 64% of patients.

    USE IN SPECIFIC POPULATIONS

    No overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥65 years old had a higher incidence of discontinuation due to an adverse reaction (AR) and a higher incidence of serious ARs than younger patients.

    The effect of end-stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.

    Please see full Prescribing Information.

    To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma and in December 2020 in combination with Velcade® (bortezomib) and dexamethasone as a treatment for patients with multiple myeloma after at least one prior therapy. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's expectations and plans relating to XPOVIO for the treatment of patients with relapsed or refractory multiple myeloma or relapsed or refractory diffuse large B-cell lymphoma; commercialization of XPOVIO or any of its drug candidates and the commercial performance of XPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; and the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the European Union as a result of data from the STORM study or confirmatory approval in the European Union based on the BOSTON study in patients with multiple myeloma; or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any product or product candidate. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

    XPOVIO®(selinexor) is a registered trademark of Karyopharm Therapeutics Inc. Velcade® is a registered trademark of Takeda Pharmaceutical Company Limited.

    Cision View original content:http://www.prnewswire.com/news-releases/karyopharm-announces-fda-approval-of-xpovio-selinexor-as-a-treatment-for-patients-with-multiple-myeloma-after-at-least-one-prior-therapy-301196120.html

    SOURCE Karyopharm Therapeutics Inc.

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  18. SHANGHAI and HONG KONG, Dec.18, 2020 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced that the National Medical Products Administration (NMPA) has approved the Investigational New Drug (IND) application for ATG-010 (selinexor), an oral Selective Inhibitor of Nuclear Export compound, in combination with bortezomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma (rrMM) in China.

    The trial is a Phase 3 randomized, controlled, open-label, multicenter clinical trial, aiming to evaluate…

    SHANGHAI and HONG KONG, Dec.18, 2020 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced that the National Medical Products Administration (NMPA) has approved the Investigational New Drug (IND) application for ATG-010 (selinexor), an oral Selective Inhibitor of Nuclear Export compound, in combination with bortezomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma (rrMM) in China.

    The trial is a Phase 3 randomized, controlled, open-label, multicenter clinical trial, aiming to evaluate the efficacy and safety of ATG-010, bortezomib and dexamethasone (SVd) regimen against bortezomib and dexamethasone (Vd) regimen in Chinese adult patients with rrMM who have received one to three prior lines of therapy. A total of 150 patients will be randomized in a 2:1 ratio to receive SVd or Vd treatment.

    ATG-010 is a first-in-class and only-in-class oral selective inhibitor of nuclear export (SINE) and the first and only drug approved by the Food and Drug Administration (FDA) for use in both relapsed/refractory multiple myeloma and diffuse large B-cell lymphoma. In December 2020, National Comprehensive Cancer Network (NCCN®) added three different ATG-010 combination regimens to its Clinical Practice Guidelines in Oncology (NCCN ® Guidelines) for previously treated multiple myeloma, including SVd, SDd and SPd. In China, Antengene is conducting a Phase 2 registrational clinical trial of ATG-010 for rrMM (MARCH).

    "The NMPA approval of BENCH trial demonstrates our ability to efficiently execute, and marks a great start of Antegene's first Phase 3 registrational trial to validate SVd regimen's efficacy and safety (as evidenced in the global BOSTON trial) in Chinese population." said Dr. Jay Mei, Founder, Chairman and CEO of Antengene. "Since becoming a public company, our clear focus has been on advancing the clinical development of ATG-010. We will initiate immediately our Phase 3 trial of ATG-010 for rrMM patients in China and believe the unique and novel MoA of ATG-010 will provide physicians new treatment options for more oncology indications."

    About ATG-010 (selinexor, XPOVIO®)

    ATG-010 (selinexor, XPOVIO®) is a first-in-class and only-in-class oral selective inhibitor of nuclear export compound, developed by Antengene and Karyopharm Therapeutics Inc. (NASDAQ:KPTI). In July 2019, the US Food and Drug Administration (FDA) approved ATG-010 in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM) and in June 2020 approved ATG-010 as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). ATG-010 is so far the first and only oral SINE compound approved by the FDA. ATG-010 is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer. In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene's partner, Karyopharm Therapeutics, presented positive results from the Phase 3 randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral ATG-010 versus matching placebo in patients with liposarcoma. Karyopharm also recently announced that the ongoing Phase 3 SIENDO study of ATG-010 in patients with endometrial cancer passed planned interim futility analysis and that Data and Safety Monitoring Board (DSMB) recommended the study should proceed as planned without any modifications. Top-line SIENDO study results are expected in the second half of 2021.

    Antengene is conducting two Phase 2 registrational clinical trials of ATG-010 in China for relapsed refractory multiple myeloma (MARCH) and for relapsed refractory diffuse large B-cell lymphoma (SEARCH), and has initiated clinical trials for high prevalence cancer types in the Asia Pacific region including peripheral T-cell lymphoma and NK/T-cell lymphoma (TOUCH) and KRAS-mutant non-small cell lung cancer (TRUMP).

    About Antengene

    Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage Asia-Pacific biopharmaceutical company focused on innovative oncology medicines. Antengene aims to provide the most advanced anti-cancer drugs to patients in China, the Asia Pacific Region and around the world. Since its establishment, Antengene has built a pipeline of 12 clinical and pre-clinical stage assets, obtained 11 investigational new drug approvals and has 9 ongoing cross-regional clinical trials in Asia Pacific. The vision of Antengene is to "Treat Patients Beyond Borders". Antengene aims to address significant unmet medical needs by discovering, developing and commercializing first-in-class/best-in-class therapeutics.

    Forward-looking statements

    The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

    *XPOVIO® is a registered trademark of Karyopharm Therapeutics Inc.;

    NCCN® is a registered trademark of National Comprehensive Cancer Network;

    SVd: selinexor, bortezomib and dexamethasone;

    SDd: selinexor, daratumumab and dexamethasone;

    SPd: selinexor, pomalidomide and dexamethasone.

    Cision View original content:http://www.prnewswire.com/news-releases/antengene-announces-approval-of-ind-application-in-china-for-a-phase-3-clinical-trial-of-atg-010-selinexor-in-combination-with-bortezomib-and-dexamethasone-svd-for-the-treatment-of-rrmm-301195807.html

    SOURCE Antengene Corporation Limited

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  19. NEWTON, Mass., Dec. 11, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the National Comprehensive Cancer Network® (NCCN) added three different XPOVIO® (selinexor) combination regimens to its Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for previously treated multiple myeloma. The XPOVIO regimens added to the NCCN guidelines, include: (i) selinexor / bortezomib / dexamethasone (once-weekly) (SVd); (ii) selinexor / daratumumab / dexamethasone (SDd); and (iii) selinexor / pomalidomide / dexamethasone (SPd), which is an all-oral treatment regimen. Importantly, the once weekly SVd regimen received a Category 1 recommendation…

    NEWTON, Mass., Dec. 11, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the National Comprehensive Cancer Network® (NCCN) added three different XPOVIO® (selinexor) combination regimens to its Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for previously treated multiple myeloma. The XPOVIO regimens added to the NCCN guidelines, include: (i) selinexor / bortezomib / dexamethasone (once-weekly) (SVd); (ii) selinexor / daratumumab / dexamethasone (SDd); and (iii) selinexor / pomalidomide / dexamethasone (SPd), which is an all-oral treatment regimen. Importantly, the once weekly SVd regimen received a Category 1 recommendation, which represents the highest designation assigned by NCCN indicating the recommendation is based upon high-level evidence and that there is uniform NCCN consensus that the intervention is appropriate.

    "We are honored to have XPOVIO receive this important recognition through its addition to the NCCN Guidelines," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "The NCCN Guidelines are utilized by healthcare providers across the country to inform optimal treatment decision making. The inclusion of three different XPOVIO combination regimens into these guidelines further validates the importance XPOVIO may have in the future multiple myeloma treatment landscape."  

    The NCCN is a not-for-profit alliance of 30 leading cancer centers devoted to patient care, research, and education. The NCCN Guidelines are a comprehensive set of guidelines detailing the sequential management decisions and interventions that currently apply to 97% of cancers affecting patients in the U.S and are intended to ensure that all patients receive preventive, diagnostic, treatment, and supportive services that will most likely lead to optimal outcomes.

    Karyopharm's supplemental New Drug Application requesting approval for XPOVIO as a treatment for patients with multiple myeloma who have received one prior line of therapy has been assigned an FDA action date of March 19, 2021 under the Prescription Drug User-Fee Act.

    About XPOVIO® (selinexor)

    XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm's supplemental New Drug Application (sNDA) requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy has been accepted for filing by the FDA. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email: 

    IMPORTANT SAFETY INFORMATION

    Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.

    Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

    Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. Neutropenia and febrile neutropenia occurred in patients with MM and in patients with DLBCL.

    Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).

    Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.

    Nausea/Vomiting: Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.

    Diarrhea: Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration, and replace electrolytes as clinically indicated.

    Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

    Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia developed in patients with MM and in patients with DLBCL.

    Monitor sodium level at baseline and throughout treatment. Monitor more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.

    Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

    Monitor for signs and symptoms of infection, and evaluate and treat promptly.

    Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.

    Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

    Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.

    Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

    Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

    ADVERSE REACTIONS

    The most common adverse reactions (ARs) in ≥20% of patients with MM are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

    The most common ARs, excluding laboratory abnormalities, in ≥20% of patients with DLBCL are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in ≥15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥5% were thrombocytopenia, lymphopenia, and neutropenia.

    In patients with MM, fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia.

    In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection. Discontinuation due to ARs occurred in 17% of patients.

    USE IN SPECIFIC POPULATIONS

    In MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥75 years old had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.

    Clinical studies in patients with relapsed or refractory DLBCL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

    The effect of end-stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.

    To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    Please see XPOVIO Full Prescribing Information available at www.XPOVIO.com.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's expectations and plans relating to XPOVIO for the treatment of patients with relapsed or refractory multiple myeloma or relapsed or refractory diffuse large B-cell lymphoma; commercialization of XPOVIO or any of its drug candidates and the commercial performance of XPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the E.U. as a result of data from the STORM study or confirmatory approval in the U.S. or E.U. based on the BOSTON study in patients with multiple myeloma or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for indications in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

     

    Cision View original content:http://www.prnewswire.com/news-releases/karyopharm-announces-national-comprehensive-cancer-network-adds-three-xpovio-selinexor-treatment-regimens-to-its-clinical-practice-guidelines-in-oncology-for-multiple-myeloma-301191344.html

    SOURCE Karyopharm Therapeutics Inc.

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  20. SHANGHAI and HONG KONG, Dec. 10, 2020 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced that the National Medical Products Administration (NMPA) has accepted the Investigational New Drug (IND) application for ATG-010 (selinexor), an oral Selective Inhibitor of Nuclear Export (SINE) compound, in combination with bortezomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma (rrMM) in China.

    The trial is a randomized, controlled, open-label, multicenter, Phase 3 trial, aiming to evaluate the…

    SHANGHAI and HONG KONG, Dec. 10, 2020 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced that the National Medical Products Administration (NMPA) has accepted the Investigational New Drug (IND) application for ATG-010 (selinexor), an oral Selective Inhibitor of Nuclear Export (SINE) compound, in combination with bortezomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma (rrMM) in China.

    The trial is a randomized, controlled, open-label, multicenter, Phase 3 trial, aiming to evaluate the efficacy and safety of ATG-010, bortezomib and dexamethasone (SVd) regimen against bortezomib and dexamethasone (Vd) regimen in Chinese adult patients with rrMM who have received one to three prior lines of therapy. A total of 150 patients will be randomized in a 2:1 ratio to receive SVd or Vd treatment.

    ATG-010 is a first-in-class and only-in-class oral selective inhibitor of nuclear export (SINE) and it is now the first and only drug approved by the Food and Drug Administration (FDA) for use in both multiple myeloma and diffuse large B-cell lymphoma. In China, Antengene is conducting a registrational Phase 2 clinical trial of ATG-010 for rrMM (MARCH). The trial is expected to complete enrollment by the end of 2020.

    "The result of the BOSTON study has demonstrated that the SVd regimen reduced the risk of disease progression or death with lower doses of bortezomib and dexamethasone in the triplet combination when compared to the standard Vd regimen. Addition of ATG-010 to Vd may be more convenient and provides a more significant therapeutic effect in patients with rrMM." said Dr. Jay Mei, Founder, Chairman and CEO of Antengene. "This planned Phase 3 trial, which is the registrational study based on BOSTON, is going to validate the SVd regimen's efficacy and safety in Chinese population."

    About ATG-010 (selinexor, XPOVIO®)

    ATG-010 (selinexor, XPOVIO®) is a first-in-class and only-in-class oral selective inhibitor of nuclear export compound, developed by Antengene and Karyopharm Therapeutics Inc. (NASDAQ:KPTI). In July 2019, the US Food and Drug Administration (FDA) approved ATG-010 in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM) and in June 2020 approved ATG-010 as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). ATG-010 is so far the first and only oral SINE compound approved by the FDA. ATG-010 is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer. In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene's partner, Karyopharm Therapeutics, presented positive results from the Phase 3 randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral ATG-010 versus matching placebo in patients with liposarcoma. Karyopharm also recently announced that the ongoing Phase 3 SIENDO study of ATG-010 in patients with endometrial cancer passed planned interim futility analysis and that Data and Safety Monitoring Board (DSMB) recommended the study should proceed as planned without any modifications. Top-line SIENDO study results are expected in the second half of 2021.

    Antengene is conducting two registrational Phase 2 clinical trials of ATG-010 in China for relapsed refractory multiple myeloma (MARCH) and for relapsed refractory diffuse large B-cell lymphoma (SEARCH), and has initiated clinical trials for high prevalence cancer types in the Asia Pacific region including peripheral T-cell lymphoma and NK/T-cell lymphoma (TOUCH) and KRAS-mutant non-small cell lung cancer (TRUMP).

    About Antengene

    Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage Asia-Pacific biopharmaceutical company focused on innovative oncology medicines. Antengene aims to provide the most advanced anti-cancer drugs to patients in China, the Asia Pacific Region and around the world. Since its establishment, Antengene has built a pipeline of 12 clinical and pre-clinical stage assets, obtained 10 investigational new drug approvals and has 9 ongoing cross-regional clinical trials in Asia Pacific. The vision of Antengene is to "Treat Patients Beyond Borders". Antengene aims to address significant unmet medical needs by discovering, developing and commercializing first-in-class/best-in-class therapeutics.

    Forward-looking statements

    The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

    XPOVIO® is a registered trademark of Karyopharm Therapeutics Inc.

    BOSTON study is initiated by Karyopharm Therapeutics Inc., the study aims to evaluate selinexor in combination with bortezomib and dexamethasone (SVd) compared to standard bortezomib plus dexamethasone (Vd) in patients with multiple myeloma who have received one to three prior lines of therapy.

    Cision View original content:http://www.prnewswire.com/news-releases/antengene-announces-acceptance-of-ind-application-in-china-for-a-phase-3-clinical-trial-of-atg-010-selinexor-in-combination-with-bortezomib-and-dexamethasone-svd-for-the-treatment-of-rrmm-301190334.html

    SOURCE Antengene Corporation Limited

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  21. NEWTON, Mass., Dec. 7, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced an oral presentation highlighting data related to XPOVIO® (selinexor), the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, was presented at the American Society of Hematology (ASH) 2020 Annual Meeting taking place virtually December 5-8, 2020. The presentation featured new data from a randomized, investigator-sponsored Phase 2 study evaluating combination chemotherapy with or without XPOVIO in newly diagnosed older adults with acute myeloid leukemia (AML).

    "AML is an aggressive form of blood cancer that begins in the bone marrow…

    NEWTON, Mass., Dec. 7, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced an oral presentation highlighting data related to XPOVIO® (selinexor), the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, was presented at the American Society of Hematology (ASH) 2020 Annual Meeting taking place virtually December 5-8, 2020. The presentation featured new data from a randomized, investigator-sponsored Phase 2 study evaluating combination chemotherapy with or without XPOVIO in newly diagnosed older adults with acute myeloid leukemia (AML).

    "AML is an aggressive form of blood cancer that begins in the bone marrow and is frequently characterized by resistance to currently available therapies, especially in elderly patients," said Timothy S. Pardee, M.D., Ph.D., Associate Professor, Hematology and Oncology, Wake Forest School of Medicine and lead author of the presentation. "The data presented today at ASH 2020, show that XPOVIO in combination with standard induction and consolidation chemotherapy appears highly active in older patients with de novo AML. Despite the small size of the study, XPOVIO in combination was associated with a significant survival improvement and a higher overall response rate than standard chemotherapy alone. In addition, accompanying preclinical work suggests that XPOVIO may increase response to cytarabine, one of the standard chemotherapy drugs used to treat AML, by interfering with nuclear-mitochondrial communication. As novel approaches to treating patients with AML are desperately needed, we look forward to further evaluating this active regimen."

    "AML is the most common form of acute leukemia in adults and unfortunately, very little improvement has been made in recent years in terms of improving long-term patient outcomes," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "We are extremely pleased to see such striking results from the combination of XPOVIO and standard chemotherapy in newly diagnosed older patients with AML. We believe the data presented at ASH 2020 may encourage interest from the cancer research community to further evaluate the potential use of XPOVIO as a combination drug partner with other standard treatments in older patients with AML."

    New Data from Phase 2 Study of XPOVIO in Combination with Chemotherapy in Older Patients with AML

    In this randomized Phase 2 study, researchers evaluated standard intensive chemotherapy (the "7+3" regimen because it consists of cytarabine continuously for seven days, along with short infusions of an anthracycline drug on each of the first three days) with or without XPOVIO in newly diagnosed patients with AML who were 60 years of age or older. Responding patients could go on to receive high dose cytarabine consolidation therapy with or without XPOVIO as per initial randomization. Patients in the XPOVIO arm who completed all consolidation could then move to maintenance therapy with XPOVIO alone. Induction therapy consisted of cytarabine (by continuous infusion for seven days) and daunorubicin (on days 1-3). Consolidation consisted of cytarabine therapy. XPOVIO was dosed orally at 60mg twice weekly during induction and consolidation and once weekly during maintenance.

    The following table is a summary of the efficacy results:

    Cohort

    All (n=28)

    Standard Arm

    (n=7)

    XPOVIO Arm

    (n=21)

    Median overall survival (days)



    265

    839

    Median progression-free survival (days)



    108

    558

    Residual disease on nadir marrow

    19% (5/27)

    50% (3/6)

    10% (2/21)

    Complete remission (CR)

    68% (19/28)

    43% (3/7)

    76% (16/21)

    MRD negative CR

    81% (13/16)

    n/a

    81% (13/16)

    Overall response (CR+CRi)

    75% (21/28)

    43% (3/7)

    86% (18/21)

    No CR/CRi

    26% (7/28)

    57% (4/7)

    14% (3/21)

    Went on to transplant

    29% (8/28)

    14% (1/7)

    33% (7/21)

    Relapsed after CR

    24% (5/21)

    33% (1/3)

    22% (4/18)

    Key: CR=complete remission; CRi=complete remission with incomplete count recovery)

    Diarrhea was the most common treatment-related adverse event (AE), resulting in dose modifications and dose holding. Additionally, seven patients (33%) on the XPOVIO arm experienced prolonged thrombocytopenia. Sixty-day mortality was 10% (2/21) of patients on the XPOVIO arm compared to 14% (1/7) of patients on the standard of care arm.

    These results suggest that a 7+3 regimen in combination with XPOVIO has a manageable safety profile and is highly active in patients aged 60 and older. XPOVIO provided a statistically significant survival benefit (839 days versus 265 days; p=0.0472) in this small, randomized trial; ORR was also significantly improved on the XPOVIO arm.

    In addition to the Phase 2 clinical research, preclinical studies were also conducted with murine AML cell lines to assess the mechanisms of chemo-sensitization. The results of this preclinical research showed that XPOVIO induces retention of topoisomerase II in the nucleus increasing sensitivity to anthracyclines (which block topoisomerase II), and significantly sensitizes cell lines to cytarabine. Existing research shows that AML cells increase mitochondrial oxygen consumption in response to cytarabine, which in turn leads to resistance. The ability of XPOVIO to interfere with this response was assessed. When co-treated with both cytarabine and XPOVIO, the treated AML cells showed a diminished mitochondrial oxygen response.

    Details for the ASH 2020 presentations are as follows:

    Title: Frontline selinexor and chemotherapy is highly active in older adults with Acute Myeloid Leukemia (AML)

    Presenter: Timothy Pardee, Wake Forest School of Medicine

    Abstract #: 633

    Session: 615. Acute Myeloid Leukemia: Commercially Available Therapy, excluding Transplantation: Commercially Available Therapy, excluding Transplantation II

    Date and Time: Monday, December 7, 2020, 11:45 a.m. ET

    Location: Channel 12 (Virtual Meeting)

    A PDF copy of this presentation are available here.

    Virtual Investor and Analyst Event Conference Call and Webcast

    Karyopharm will host a conference call and on Tuesday, December 8, 2020, at 1:00 p.m. Eastern Time, to review highlights from the ASH 2020 data presentations. The event will feature recognized myeloma and leukemia experts James Berenson, MD, Founder, President and Medical and Scientific Director of the Institute for Myeloma and Bone Cancer Research, and Dr. Timothy Pardee, MD, PhD, FACP, Wake Forest School of Medicine, along with members of the Karyopharm executive leadership team. To access the event, please dial (877) 870-4263 (local) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. An archived webcast will be available on the Company's website approximately two hours after the event.

    About XPOVIO® (selinexor)

    XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm's supplemental New Drug Application (sNDA) requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy has been accepted for filing by the FDA. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email:

    IMPORTANT SAFETY INFORMATION

    Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.

    Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

    Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. Neutropenia and febrile neutropenia occurred in patients with MM and in patients with DLBCL.

    Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).

    Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.

    Nausea/Vomiting: Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.

    Diarrhea: Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration, and replace electrolytes as clinically indicated.

    Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

    Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia developed in patients with MM and in patients with DLBCL.

    Monitor sodium level at baseline and throughout treatment. Monitor more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.

    Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

    Monitor for signs and symptoms of infection, and evaluate and treat promptly.

    Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.

    Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

    Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.

    Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

    Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

    ADVERSE REACTIONS

    The most common adverse reactions in ≥20% of patients with MM are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

    The most common ARs, excluding laboratory abnormalities, in ≥20% of patients with DLBCL are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in ≥15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥5% were thrombocytopenia, lymphopenia, and neutropenia.

    In patients with MM, fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia.

    In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection. Discontinuation due to ARs occurred in 17% of patients.

    USE IN SPECIFIC POPULATIONS

    In MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥75 years old had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.

    Clinical studies in patients with relapsed or refractory DLBCL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

    The effect of end-stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.

    Please see full Prescribing Information.

    To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's expectations and plans relating to XPOVIO for the treatment of patients with AML; commercialization of XPOVIO or any of its drug candidates and the commercial performance of XPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; and the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the E.U. as a result of data from the STORM study or confirmatory approval in the U.S. or E.U. based on the BOSTON study in patients with multiple myeloma; or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for indications in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

    Cision View original content:http://www.prnewswire.com/news-releases/karyopharm-announces-presentation-of-new-xpovio-selinexor-data-in-patients-with-acute-myeloid-leukemia-at-the-american-society-of-hematology-2020-annual-meeting-301187650.html

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  22. NEWTON, Mass., Dec. 7, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that over twenty presentations related to XPOVIO® (selinexor), the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, were presented at the American Society of Hematology (ASH) 2020 Annual Meeting taking place virtually December 5-8, 2020. These presentations included:

    • An oral presentation highlighted updated data from the Pomalyst® (pomalidomide) arm of the Phase 1b/2 STOMP study evaluating XPOVIO in combination with backbone therapies in patients with relapsed or refractory multiple myeloma;
    • Updated data from the Kyprolis®(carfilzomib…

    NEWTON, Mass., Dec. 7, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that over twenty presentations related to XPOVIO® (selinexor), the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, were presented at the American Society of Hematology (ASH) 2020 Annual Meeting taking place virtually December 5-8, 2020. These presentations included:

    • An oral presentation highlighted updated data from the Pomalyst® (pomalidomide) arm of the Phase 1b/2 STOMP study evaluating XPOVIO in combination with backbone therapies in patients with relapsed or refractory multiple myeloma;
    • Updated data from the Kyprolis®(carfilzomib) and Revlimid® (lenalidomide) arms of the STOMP study;
    • Several new subgroup analyses from the pivotal Phase 3 BOSTON study evaluating once weekly XPOVIO in combination with once weekly Velcade® (bortezomib) and low-dose dexamethasone (SVd) versus standard twice weekly Velcade® with dexamethasone (Vd) in adult patients with multiple myeloma following one to three prior lines of therapy;
    • New subgroup analyses from the Phase 2b SADAL study evaluating XPOVIO in relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

    "The highlights of our ASH data this year include updated data from multiple arms of the STOMP study where once weekly oral XPOVIO continues to demonstrate compelling and durable responses in important patient subgroups when combined with approved multiple myeloma therapies. We believe that XPOVIO has the potential to be an important combination partner for future multiple myeloma treatment regimens," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "Several presentations were also given describing subgroup analyses from the Phase 3 BOSTON study. Collectively, these analyses show that XPOVIO is effective and well tolerated regardless of prior lines of treatment, including prior treatment with a proteasome inhibitor or lenalidomide, and across several important patient subgroups including those with high risk cytogenetics and the elderly and the frail. Notably, the highest progression free survival (PFS) seen across these subgroups came from patients who were naïve to proteasome inhibitor therapy whose median PFS had not yet been reached, as well as from those who had previously been treated with only one prior therapy who demonstrated a median PFS of 16.6 months in the SVd arm compared to 10.6 months in the Vd arm. A supplemental New Drug Application seeking approval for XPOVIO for the patient population studied in the BOSTON study is currently being reviewed by the U.S. Food and Drug Administration and has been assigned a target Prescription Drug User Fee Act action date of March 19, 2021. If approved, we expect to launch in the expanded indication immediately thereafter."

    Updated Data from Phase 1b/2 STOMP Study Evaluating the All Oral Regimen of XPOVIO in Combination with Pomalyst® and Low-dose Dexamethasone (SPd) in Patients with Relapsed or Refractory Multiple Myeloma

    In this all oral arm of the Phase 1b/2 STOMP study, XPOVIO is being evaluated in combination with Pomalyst® and low-dose dexamethasone in patients with relapsed or refractory multiple myeloma who received at least two prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD). Of note, 25% of the population enrolled in the study had previously received Darzalex®. The recommended Phase 2 dose (RP2D) was determined to be XPOVIO 60mg orally once-weekly, Pomalyst® 4mg orally once-daily and dexamethasone orally (40mg once weekly or 20mg twice weekly). The following table is a summary of the efficacy results:



    Best Responses1 in Evaluable SPd Patients as of November 14, 20202

    Category

    N

    ORR

    CR

    VGPR

    PR

    Median PFS

    Pomalyst®  naïve or non-refractory

    46

    25 (54%)

    1 (2%)

    9 (20%)3

    15 (33%)4

    12.3 months

    Pomalyst®  refractory

    14

    5 (36%)

    -

    1 (7%)

    4 (29%)

    Not reported

    RP2D

    20

    12 (60%)

    -

    6 (30%)

    6 (30%)

    Not reached5

    All patients

    60

    30 (50%)

    1 (2%)

    10 (17%)

    19 (32%)

    12.2 months

















    Key: ORR=Overall Response Rate (CR+VGPR+PR); CR=Complete Response; VGPR=Very Good Partial Response; PR=Partial Response

    1 Responses were adjudicated according to the International Myeloma Working Group (IMWG) criteria

    2 Based on interim unaudited data

    3 Two VGPRs were unconfirmed

    4 One PR was unconfirmed

    5 Median follow-up time for 20 patients at the RP2D was 2.5 months; median follow-up time for all 60 patients was 12.2 months

    Among the patients evaluated for safety as of the data cutoff date, the most common treatment-related adverse events (AEs) were cytopenias, along with gastrointestinal and constitutional symptoms; most were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (60%), fatigue (51%), decreased appetite (44%), weight loss (38%) and diarrhea (29%), and were primarily grade 1 and 2 events. As expected, the most common treatment-related Grade 3 and 4 AEs were neutropenia (54%), anemia (33%), and thrombocytopenia (32%).

    Based on these Phase 2 results, a Phase 3 study investigating the SPd combination (XPORT-MM-031) is planned to begin in 2021. Historical clinical trials evaluating the efficacy of Pomalyst® and low-dose dexamethasone in less heavily pretreated populations (i.e., without prior Darzalex® therapy) have demonstrated an overall response rate of 29% and median PFS of 3.6 months, as highlighted in the Pomalyst® U.S. Full Prescribing Information.

    Updated Data from Phase 1b/2 STOMP Study Evaluating XPOVIO in Combination with Kyprolis® and Low-dose Dexamethasone (SKd) in Patients with Relapsed or Refractory Multiple Myeloma

    In this arm of the Phase 1b/2 STOMP study, oral XPOVIO is being evaluated in combination with Kyprolis® and low-dose dexamethasone in patients with relapsed or refractory multiple myeloma who have received at least two prior therapies, including a PI, one or more IMiDs (e.g., Revlimid® or Pomalyst®) or Darzalex®. In these heavily pretreated patients, 100% had previously received Velcade®, 96% had previously received Revlimid®, 67% had previously received Pomalyst® and 63% had previously received Darzalex®. The RP2D was determined to be XPOVIO 80mg orally once-weekly, Kyprolis® 56mg/m2 once-weekly and dexamethasone (40mg orally once weekly or 20mg twice weekly) and enrollment continues using this regimen. The following table is a summary of the efficacy results:

    Best Responses1 in Evaluable SKd Patients as of October 1, 20202

    Category

    N

    ORR

    CR

    VGPR

    PR

    All

    24

    18 (75%)

    5 (21%)

    8 (33%)

    5 (21%)

    1 Responses were adjudicated according to the IMWG criteria

    2 Based on interim unaudited data

    Median PFS was 23.7 months for all patients.

    Among the patients evaluated for safety as of the data cutoff date, the most common treatment-related AEs were cytopenias, along with gastrointestinal, constitutional and other symptoms; most were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (71%), fatigue (58%), decreased appetite (50%) and weight loss (46%), and were mostly Grade 1 and 2 events. As expected, the most common treatment-related Grade ≥3 AEs included thrombocytopenia (58%), anemia (21%) and leukopenia (13%).

    These results indicate that the once weekly combination of SKd can induce responses in the majority of patients with heavily pretreated double or triple class refractory myeloma.

    Updated Data from Phase 1b/2 STOMP Study Evaluating the All Oral Regimen of XPOVIO in Combination with Revlimid® and Low-dose Dexamethasone (SRd) in Patients with Newly Diagnosed and Relapsed or Refractory (RR) Multiple Myeloma

    In this all oral arm of the Phase 1b/2 STOMP study, XPOVIO is being evaluated in combination with Revlimid® and low-dose dexamethasone in patients with newly diagnosed or previously treated multiple myeloma. The previously treated patients received at least one prior therapy, which may include prior Revlimid®, as long as the patient's myeloma was not refractory to Revlimid®. The RP2D was determined to be XPOVIO (60mg orally, once-weekly), Revlimid® (25mg orally, once daily), and dexamethasone (40mg orally, once weekly or 20mg twice weekly). The following table is a summary of the efficacy results:

    Best Responses1 in Evaluable SRd Patients as of October 1, 20202

    Category

    N

    ORR

    CR

    VGPR

    PR

    Revlimid®-naïve RR myeloma

    12

    11 (92%)

    1 (8%)

    4 (33%)

    6 (50%)3

    Revlimid®-treated/refractory myeloma

    8

    1 (13%)

    -

    -

    1 (13%)

    Newly diagnosed (efficacy evaluable)

    74

    7 (100%)

    1 (14%)

    4 (57%)5

    2 (29%)

    1 Responses were adjudicated according to the IMWG criteria

    2 Based on interim unaudited data

    3 Two PRs were unconfirmed 

    4 One patient's efficacy not evaluable due to withdrawal of consent during cycle 1

    5 One VGPR was unconfirmed

    Responses are highly durable with four relapsed or refractory patients remaining on study with PFS of greater than 35 months and two newly diagnosed patients remaining on study with PFS of greater than 24 months.

    Among the newly diagnosed patients evaluable for safety, the most common treatment-related AEs were cytopenias, along with gastrointestinal and constitutional symptoms; most were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were fatigue (63%), weight loss (63%), diarrhea (63%), nausea (50%) and insomnia (38%) and were mostly Grade 1 and 2 events. The most common Grade ≥3 AEs were neutropenia (75%), anemia (50%) and thrombocytopenia (38%).

    Among the relapsed or refractory patients evaluable for safety, the most common treatment-related AEs were cytopenias, along with gastrointestinal and constitutional symptoms; most were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (58%), fatigue (54%), decreased appetite (50%), weight loss (42%), and diarrhea (33%), and were mostly Grade 1 and 2 events. The most common Grade ≥3 AEs were thrombocytopenia (63%), neutropenia (63%), anemia (17%) and fatigue (17%).

    These data show that the all oral regimen of weekly selinexor with standard Revlimid® and dexamethasone induces high response rates with good tolerability.

    Phase 3 BOSTON Study Subgroup Analyses in Multiple Myeloma Following One to Three Prior Lines of Therapy

    The pivotal Phase 3 BOSTON study evaluated once weekly XPOVIO in combination with once weekly Velcade® and low-dose dexamethasone (SVd) versus standard twice weekly Velcade® and moderate dose dexamethasone (Vd) in adult patients with multiple myeloma following one to three prior lines of therapy. Karyopharm previously reported positive data from this study which were recently published in the Lancet. The subgroup analyses presented at ASH 2020 include evaluations of the safety and efficacy of XPOVIO (i) in patients previously treated with PIs, (ii) according to the number of prior lines of therapy or prior treatment with Revlimid®, (iii) in patients with high risk cytogenetics, and (iv) based on age (patients younger than 65 years old versus older than 65 years old) or by frailty level (frail versus fit).

    • Patients previously treated with PIs. Among the 402 patients treated in the BOSTON study, 307 (76%) had prior treatment with a PI (e.g., Velcade®) and 95 (24%) were PI naïve. Among patients who were PI-naïve, median PFS was not yet reached for patients receiving SVd versus 9.7 months for patients on the Vd arm (HR 0.26; p=0.0003). In patients previously treated with a PI, SVd improved PFS relative to Vd with an HR of 0.78 (p=0.057). Among patients who only had a Velcade® based induction regimen prior to autologous stem cell transplant (ASCT), SVd provided a PFS benefit compared to Vd with an HR of 0.58 (p=0.06). ORR was significantly improved with SVd in PI-treated patients (77% versus 60%; p=0.0006). The ≥VGPR rate was 41.9% in patients on SVd versus 29.6% on Vd (p=0.012) and 53.2% on SVd versus 41.7% on Vd (p=0.131) in the prior PI and PI naïve groups, respectively. Non-peripheral neuropathy (PN) AEs were higher with SVd, however, most of these AEs were reversible and treatable; PN AEs were consistently higher in all subgroups on Vd as compared with SVd. These results suggest that SVd is an active, convenient regimen and may have a particularly strong benefit in patients with previously treated myeloma who have not yet received a PI or had a Velcade®-based ASCT induction regimen. Importantly, although the doses of Velcade® and dexamethasone were substantially lower on the SVd arm as compared with the Vd arm, SVd still conferred benefits over Vd in patients who had previously received Velcade®.
    • Prior lines of therapy and prior treatment with Revlimid®. Among the 402 patients treated in the BOSTON study, 154 (38%) had previously received Revlimid® and 204 (51%) had received at least two prior lines of therapy. This analysis demonstrated that SVd was active regardless of prior Revlimid® treatment with a PFS HR of 0.63 (p=0.017) among patients with prior Revlimid® treatment who received SVd compared to patients treated with Vd. Notably, patients who had only received one prior therapy prior to enrolling in the BOSTON study achieved a PFS of 16.6 months on SVd compared to 10.6 months for Vd (HR 0.63; p=0.015). Also, regardless of prior treatment, SVd was associated with significantly lower rates of Grade 2 or higher PN compared to Vd. AEs of Grade ≥3 were more commonly reported in the SVd treatment arm than in the Vd arm, however, most non-PN AEs were reversable and treatable and major organ toxicities were not common. These results suggest that, if approved, SVd may offer an effective and convenient treatment option for patients with previously treated multiple myeloma, including those that have been treated with Revlimid®. SVd may confer its strongest benefits to patients who have received a single line of therapy including Revlimid®, though it was numerically superior in all of the subgroups evaluated.
    • Patients with high risk cytogenetics. Among the 402 patients treated in the BOSTON study, 141 (35%) had high risk cytogenetics, defined as patients with at least one abnormality (i.e., chr(17p) deletion, t(4;14), t(14;16), or amplification with ≥4 copies of chr(1q21)) in ≥10% of screened plasma cells. This analysis demonstrated that SVd was superior to Vd in patients with high risk multiple myeloma, including in patients with one cytogenetic abnormality, two or more abnormalities and in patients with a chr(17p) deletion (i.e., patients with myeloma missing one copy of the p53 tumor suppressor protein). In patients with one cytogenetic abnormality, patients treated with SVd achieved a PFS of 10.2 months compared to 8.6 months for Vd treated patients (HR 0.69; p=0.08) while patients with ≥2 cytogenetic abnormalities treated with SVd achieved a PFS of 15.5 months compared to 5.9 months for Vd treated patients (HR 0.54; p=0.09). The safety profile of SVd and Vd in both higher risk and standard risk groups were consistent with the overall BOSTON population. Non-PN AEs were higher with SVd and most of the AEs were reversible. These results suggest that SVd is an effective and safe regimen and, if approved, may be an important treatment option for patients with high risk multiple myeloma.
    • Patients stratified by age (<65 or ≥65) and frailty. Among the 402 patients treated in the BOSTON study, 241 (60%) were at least age 65 and 130 (32%) were characterized as frail. This analysis demonstrated that both elderly and frail patients benefited from SVd compared to Vd. Elderly patients treated with SVd achieved a PFS of 21.0 months compared to 9.4 months for Vd treated patients (HR 0.55; p=0.002). SVd also provided a statistically significant PFS benefit in frail patients: 13.9 months for SVd treated patients compared to 9.4 months for Vd treated patients, (HR 0.69; p=0.08). Overall, SVd prolonged PFS, improved response rates and had lower rates of PN regardless of age and frailty score compared to Vd. Non-PN AEs were higher with SVd and most of the AEs were reversible and treatable. These results suggest that SVd, if approved, may be an effective and well tolerated treatment option for patients with previously treated multiple myeloma, including those who are elderly or frail.

    Phase 2b SADAL Study in Patients with relapsed or refractory DLBCL Subgroup Analyses

    The Phase 2b SADAL study evaluated twice weekly XPOVIO in adult patients with relapsed or refractory DLBCL, not otherwise specified, who had received at least two prior therapies. Karyopharm previously reported positive data from this study and the data were published in The Lancet Haematology. The subgroup analyses presented at ASH 2020 included evaluations of the safety and efficacy of XPOVIO in patients stratified by (i) age and (ii) renal function at baseline. An additional poster was also presented highlighting the results of a study in which researchers investigated molecular markers of response to XPOVIO in patients treated on the SADAL study.

    • Patients stratified by age (<65 or ≥65). Among the 134 patients treated in the SADAL study, 82 (61%) were at least age 65. This analysis demonstrated that patients ≥65 years old had similar clinical benefit to those <65 years old when treated with XPOVIO. There was no statistical difference in ORR in patients <65 years old versus ≥65 years old. Median duration of response was also similar at 9.7 months in the <65 years old patient group compared to 9.2 months in the ≥65 years old patient group. The incidence of treatment-related AEs was comparable between both groups. The most common Grade ≥3 AEs in <65 vs ≥65 years old patients were thrombocytopenia (42.3% vs 39.0%), nausea (3.8% vs 7.3%), and fatigue (5.8% vs 13.4%). These results suggest that XPOVIO is an active, convenient oral option for patients with relapsed or refractory DLBCL, including the elderly.
    • Patients stratified by renal function at baseline. Among the 134 patients treated in the SADAL study, 37 (28%) had low creatinine clearance (CrCl) defined as CrCl of ≤60mL/min. This analysis demonstrated that XPOVIO had similar response rates in patients regardless of severity of renal function. Treatment with XPOVIO demonstrated a similar ORR in patients with a baseline reduced CrCl (29.7%) compared to normal CrCl (28.9%). Overall survival was also comparable in patients with reduced versus normal renal function: 7.8 vs 9.1 months. The incidence of treatment-related AEs was comparable between both groups. The most common Grade ≥3 treatment-related AEs for patients with reduced versus normal renal function were thrombocytopenia (45.9% vs. 38.1%), nausea (5.4% vs. 6.2%), and fatigue (8.1% vs. 11.3%).These results suggest that XPOVIO is an important option for patients with relapsed or refractory DLBCL, including patients with renal dysfunction.

    PDF copies of all of these presentations are available here.

    Virtual Investor and Analyst Event Conference Call and Webcast

    Karyopharm will host a conference call and webcast tomorrow, Tuesday, December 8, 2020, from 1:00 to 2:30 p.m. Eastern Time, to review highlights from the ASH 2020 data presentations. The event will feature recognized myeloma and leukemia experts James Berenson, MD, Founder, President and Medical and Scientific Director of the Institute for Myeloma and Bone Cancer Research, and Dr. Timothy Pardee, MD, PhD, FACP, Wake Forest School of Medicine, along with members of the Karyopharm executive leadership team. To access the event, please dial (877) 870-4263 (local) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. An archived webcast will be available on the Company's website approximately two hours after the event.

    About XPOVIO® (selinexor)

    XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm's supplemental New Drug Application (sNDA) requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy has been accepted for filing by the FDA. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email:

    IMPORTANT SAFETY INFORMATION

    Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.

    Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

    Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. Neutropenia and febrile neutropenia occurred in patients with MM and in patients with DLBCL.

    Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).

    Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.

    Nausea/Vomiting: Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.

    Diarrhea: Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration, and replace electrolytes as clinically indicated.

    Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

    Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia developed in patients with MM and in patients with DLBCL.

    Monitor sodium level at baseline and throughout treatment. Monitor more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.

    Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

    Monitor for signs and symptoms of infection, and evaluate and treat promptly.

    Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.

    Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

    Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.

    Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

    Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

    ADVERSE REACTIONS

    The most common adverse reactions in ≥20% of patients with MM are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

    The most common ARs, excluding laboratory abnormalities, in ≥20% of patients with DLBCL are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in ≥15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥5% were thrombocytopenia, lymphopenia, and neutropenia.

    In patients with MM, fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia.

    In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection. Discontinuation due to ARs occurred in 17% of patients.

    USE IN SPECIFIC POPULATIONS

    In MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥75 years old had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.

    Clinical studies in patients with relapsed or refractory DLBCL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

    The effect of end-stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.

    Please see full Prescribing Information.

    To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's expectations and plans relating to XPOVIO for the treatment of patients with relapsed or refractory multiple myeloma or relapsed or refractory diffuse large B-cell lymphoma; commercialization of XPOVIO or any of its drug candidates and the commercial performance of XPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the E.U. as a result of data from the STORM study or confirmatory approval in the U.S. or E.U. based on the BOSTON study in patients with multiple myeloma or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for indications in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

    Velcade® is a registered trademark of Takeda Pharmaceutical Company Limited

    Revlimid® and Pomalyst® are registered trademarks of Celgene Corporation

    Kyprolis® is a registered trademark of Onyx Pharmaceuticals, Inc.

    Cision View original content:http://www.prnewswire.com/news-releases/karyopharm-presents-xpovio-selinexor-data-in-multiple-myeloma-and-diffuse-large-b-cell-lymphoma-at-the-american-society-of-hematology-2020-annual-meeting-301187571.html

    SOURCE Karyopharm Therapeutics Inc.

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  23. SHANGHAI and HONG KONG, Dec. 6, 2020 /PRNewswire/ --  Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced that the National Medical Products Administration (NMPA) has accepted the Investigational New Drug (IND) application for ATG-010 (selinexor) combined with R-GDP (SR-GDP) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). The trial is a global Phase 2/3, multicenter, randomized study aiming to evaluate the safety and efficacy of ATG-010 in combination with R-GDP (SR-GDP) in patients with rrDLBCL (Code: XPORT-DLBCL-030…

    SHANGHAI and HONG KONG, Dec. 6, 2020 /PRNewswire/ --  Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced that the National Medical Products Administration (NMPA) has accepted the Investigational New Drug (IND) application for ATG-010 (selinexor) combined with R-GDP (SR-GDP) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). The trial is a global Phase 2/3, multicenter, randomized study aiming to evaluate the safety and efficacy of ATG-010 in combination with R-GDP (SR-GDP) in patients with rrDLBCL (Code: XPORT-DLBCL-030).

    ATG-010 is a first-in-class and only-in-class oral selective inhibitor of nuclear export, developed by Antengene and Karyopharm Therapeutics Inc. (NASDAQ:KPTI). In July 2019, the US Food and Drug Administration (FDA) approved ATG-010 in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM). After its initial approval of rrMM, FDA approved ATG-010 as a single-agent for the treatment of rrDLBCL in June 2020. In China, Antengene is conducting a registrational Phase 2 clinical trial to evaluate the efficacy and safety of ATG-010 in the treatment of patients with rrDLBCL who have received at least 2 but no more than 5 previous systemic regimens and the first patient was dosed in April 2020.

    The Phase 2 part of the study aims to identify the optimal dose of ATG-010 (40mg or 60mg) in combination with R-GDP and will also evaluate the SR-GDP regimen against an active R-GDP comparator arm. The Phase 3 part of the study contains three arms and aims to evaluate the selected optimal dose of ATG-010 in combination with R-GDP for up to 6 cycles followed by continuous ATG-010 (SR-GDP→S) until disease progression versus the selected optimal dose of ATG-010 in combination with R-GDP for up to 6 cycles followed by placebo (SR-GDP→P) until disease progression and versus standard R-GDP with matching placebo for up to 6 cycles followed by placebo (PR-GDP→P) until disease progression. The study will be conducted at multiple international centers across 11 countries, including China, U.S., Europe, Australia and other countries. Up to 501 patients will be enrolled and treated in the Phase 2/3 study.

    "The submission of NDAs for ATG-010 in multiple APAC markets in the past few weeks has marked a significant milestone for Antengene as our lead product candidate, ATG-010, advances towards commercial stage. This IND acceptance of ATG-010 in a new therapy for rrDLBCL marks another important milestone for Antengene, demonstrating our commitment to bringing innovative oncology therapies to cancer patients worldwide." Dr. Jay Mei, Founder, Chairman and CEO of Antengene, commented, "We look forward to harnessing the power of Antengeners to extend the lives and improve the quality of life of patients by discovering, developing and commercializing novel therapies."

    About ATG-010 (selinexor, XPOVIO®)

    ATG-010 (selinexor, XPOVIO®) is a first-in-class and only-in-class oral selective inhibitor of nuclear export compound, developed by Antengene and Karyopharm Therapeutics Inc. (NASDAQ:KPTI). In July 2019, the US Food and Drug Administration (FDA) approved ATG-010 in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM) and in June 2020 approved ATG-010 as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). ATG-010 is so far the first and only oral SINE compound approved by the FDA. ATG-010 is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer. In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene's partner, Karyopharm Therapeutics, presented positive results from the Phase 3 randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral ATG-010 versus matching placebo in patients with liposarcoma. Karyopharm also recently announced that the ongoing Phase 3 SIENDO study of ATG-010 in patients with endometrial cancer passed planned interim futility analysis and that Data and Safety Monitoring Board (DSMB) recommended the study should proceed as planned without any modifications. Top-line SIENDO study results are expected in the second half of 2021.

    Antengene is conducting two registrational Phase 2 clinical trials of ATG-010 in China for relapsed refractory multiple myeloma (MARCH) and for relapsed refractory diffuse large B-cell lymphoma (SEARCH), and has initiated clinical trials for high prevalence cancer types in the Asia Pacific region including peripheral T-cell lymphoma and NK/T-cell lymphoma (TOUCH) and KRAS-mutant non-small cell lung cancer (TRUMP).

    About Antengene

    Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage Asia-Pacific biopharmaceutical company focused on innovative oncology medicines. Antengene aims to provide the most advanced anti-cancer drugs to patients in China, the Asia Pacific Region and around the world. Since its establishment, Antengene has built a pipeline of 12 clinical and pre-clinical stage assets, obtained 10 investigational new drug approvals and has 9 ongoing cross-regional clinical trials in Asia Pacific. The vision of Antengene is to "Treat Patients Beyond Borders". Antengene aims to address significant unmet medical needs by discovering, developing and commercializing first-in-class/best-in-class therapeutics.

    Forward-looking statements

    The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

    XPORT-DLBCL-030 was initiated by Karyopharm Therapeutics Inc.;

    XPOVIO® is a registered trademark of Karyopharm Therapeutics Inc.;

    R-GDP: Rituximab, Gemcitabine, Dexamethasone and Cisplatin.

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  24. SHANGHAI and HONG KONG, Dec. 3, 2020 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced it has submitted new drug applications ("NDA(s)") for XPOVIO® (selinexor, ATG-010) to the Health Sciences Authority of Singapore and to the Australian Therapeutic Goods Administration for three indications: the treatment of adult patients with relapsed or refractory multiple myeloma ("rrMM") who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory…

    SHANGHAI and HONG KONG, Dec. 3, 2020 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, announced it has submitted new drug applications ("NDA(s)") for XPOVIO® (selinexor, ATG-010) to the Health Sciences Authority of Singapore and to the Australian Therapeutic Goods Administration for three indications: the treatment of adult patients with relapsed or refractory multiple myeloma ("rrMM") who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody; and in combination with bortezomib and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior line of therapy; and for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma ("rrDLBCL"), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. Australian Therapeutic Goods Administration has accepted the NDA of Antengene on December 2, 2020.

    A new drug application (NDA) for XPOVIO® (selinexor) has also been submitted to the Hong Kong Department of Health for the treatment of adult patients with rrMM who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

    In South Korea, XPOVIO® (selinexor) has been granted orphan drug designation for the treatment of adult patients with rrMM who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody and for the treatment of adult patients with rrDLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. 

    XPOVIO® (selinexor, ATG-010) is a first-in-class and only-in-class oral selective inhibitor of nuclear export, developed by Antengene and Karyopharm Therapeutics Inc. (NASDAQ:KPTI). In July 2019, the US Food and Drug Administration (FDA) approved XPOVIO® (selinexor) in combination with low-dose dexamethasone for the treatment of rrMM. After its initial approval of rrMM, FDA approved XPOVIO® (selinexor) as a single-agent for the treatment of rrDLBCL in June 2020.

    In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene's partner, Karyopharm Therapeutics, presented positive results from the Phase 3 portion of the randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral XPOVIO® (selinexor) versus matching placebo in patients with liposarcoma. Karyopharm also recently announced that the ongoing phase 3 SIENDO study of XPOVIO® (selinexor) in patients with endometrial cancer passed planned interim futility analysis and that Data and Safety Monitoring Board (DSMB) recommended the study should proceed as planned without any modifications. Top-line SIENDO study results are expected in the second half of 2021.

    About XPOVIO®

    XPOVIO® is a first-in-class and only-in-class oral selective inhibitor of nuclear export compound, developed by Antengene and Karyopharm Therapeutics Inc. (NASDAQ:KPTI). In July 2019, the US Food and Drug Administration (FDA) approved XPOVIO® in combination with low-dose dexamethasone for the treatment of relapsed or refractory multiple myeloma (rrMM) and in June 2020 approved XPOVIO® as a single-agent for the treatment of relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL). XPOVIO® is so far the first and only oral SINE compound approved by the FDA. XPOVIO® is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer.

    Antengene is conducting two registrational Phase 2 clinical trials of XPOVIO® in China for relapsed refractory multiple myeloma (MARCH) and for relapsed refractory diffuse large B-cell lymphoma (SEARCH), and has initiated clinical trials for high prevalence cancer types in the Asia Pacific region including peripheral T-cell lymphoma and NK/T-cell lymphoma (TOUCH) and KRAS-mutant non-small cell lung cancer (TRUMP).

    About Antengene

    Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage Asia-Pacific biopharmaceutical company focused on innovative oncology medicines. Antengene aims to provide the most advanced anti-cancer drugs to patients in China, the Asia Pacific Region and around the world. Since its establishment, Antengene has built a pipeline of 12 clinical and pre-clinical stage assets, obtained 10 investigational new drug approvals and has 9 ongoing cross-regional clinical trials in Asia Pacific. The vision of Antengene is to "Treat Patients Beyond Borders". Antengene aims to address significant unmet medical needs by discovering, developing and commercializing first-in-class/best-in-class therapeutics.

    Forward-looking statements

    The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development.

    * XPOVIO® is a registered trademark of Karyopharm Therapeutics Inc.

     

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  25. NEWTON, Mass., Dec. 1, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that it will host a virtual investor and analyst event to discuss the Company's pipeline of clinical programs and highlights from the data presentations being given at the American Society of Hematology (ASH) 2020 Annual Meeting. This Karyopharm-sponsored event is scheduled for Tuesday, December 8, 2020 from 1:00 - 2:30 p.m. ET.

    The Karyopharm management team will be joined by a group of recognized multiple myeloma, diffuse large B-cell Lymphoma and leukemia experts to provide additional external context and participate in the Q&A portion of the call.

    To access the…

    NEWTON, Mass., Dec. 1, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that it will host a virtual investor and analyst event to discuss the Company's pipeline of clinical programs and highlights from the data presentations being given at the American Society of Hematology (ASH) 2020 Annual Meeting. This Karyopharm-sponsored event is scheduled for Tuesday, December 8, 2020 from 1:00 - 2:30 p.m. ET.

    The Karyopharm management team will be joined by a group of recognized multiple myeloma, diffuse large B-cell Lymphoma and leukemia experts to provide additional external context and participate in the Q&A portion of the call.

    To access the event, please dial (877) 870-4263 (local) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call.  A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. An archived webcast will be available on the Company's website approximately two hours after the event.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com

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  26. NEWTON, Mass., Nov. 25, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that following a pre-specified interim futility analysis for the ongoing Phase 3 SIENDO study, the Data and Safety Monitoring Board (DSMB) has recommended that the study should continue, as previously planned, without the need for adding additional patients to the trial or amending the study protocol.

    "We are very excited that the SIENDO study has passed its planned futility analysis and that the study will continue as planned," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "We believe this is an encouraging development for…

    NEWTON, Mass., Nov. 25, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that following a pre-specified interim futility analysis for the ongoing Phase 3 SIENDO study, the Data and Safety Monitoring Board (DSMB) has recommended that the study should continue, as previously planned, without the need for adding additional patients to the trial or amending the study protocol.

    "We are very excited that the SIENDO study has passed its planned futility analysis and that the study will continue as planned," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "We believe this is an encouraging development for the study, and more importantly, for patients and families in need of novel treatment options for advanced or recurrent endometrial cancer. There are currently no approved therapies in the maintenance setting for patients with advanced endometrial cancer, making the future trial results from the SIENDO study, particularly important. We expect to report top-line data from this study in the second half of 2021."

    The SIENDO study is an ongoing multicenter, blinded, placebo-controlled, randomized Phase 3 study evaluating the efficacy and safety for front-line maintenance therapy with XPOVIO in patients with advanced or recurrent endometrial cancer. Participants with primary stage IV or recurrent disease who had a partial or complete response after a single line of at least 12 weeks of standard taxane-platinum combination chemotherapy are randomized in a 2:1 manner to receive either maintenance therapy of 80mg of XPOVIO taken once per week or placebo, until disease progression. The study is expected to enroll approximately 248 patients. The primary endpoint in the study is progression free survival (PFS) with the goal of the study demonstrating a hazard ratio of 0.6. As of the date of the planned futility analysis, approximately 109 patients had been enrolled in the trial.

    About XPOVIO® (selinexor)

    XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm's supplemental New Drug Application (sNDA) requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy has been accepted for filing by the FDA. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email: 

    IMPORTANT SAFETY INFORMATION

    Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.

    Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

    Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. Neutropenia and febrile neutropenia occurred in patients with MM and in patients with DLBCL.

    Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).

    Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.

    Nausea/Vomiting: Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.

    Diarrhea: Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration, and replace electrolytes as clinically indicated.

    Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

    Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia developed in patients with MM and in patients with DLBCL.

    Monitor sodium level at baseline and throughout treatment. Monitor more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.

    Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

    Monitor for signs and symptoms of infection, and evaluate and treat promptly.

    Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.

    Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

    Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.

    Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

    Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

    ADVERSE REACTIONS

    The most common adverse reactions (ARs) in ≥20% of patients with MM are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

    The most common ARs, excluding laboratory abnormalities, in ≥20% of patients with DLBCL are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in ≥15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥5% were thrombocytopenia, lymphopenia, and neutropenia.

    In patients with MM, fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia.

    In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection. Discontinuation due to ARs occurred in 17% of patients.

    USE IN SPECIFIC POPULATIONS

    In MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥75 years old had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.

    Clinical studies in patients with relapsed or refractory DLBCL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

    The effect of end-stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.

    To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    Please see XPOVIO Full Prescribing Information available at www.XPOVIO.com.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's expectations and plans relating to XPOVIO for the treatment of patients with advanced endometrial cancer; commercialization of XPOVIO or any of its drug candidates and the commercial performance of XPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; and the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the E.U. as a result of data from the STORM study or confirmatory approval in the U.S. or EU based on the BOSTON study in patients with relapsed or refractory multiple myeloma; or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for diseases in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

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  27. NEWTON, Mass., Nov. 20, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today reported it will present positive results from the Phase 3 portion of the randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral XPOVIO® (selinexor) versus matching placebo in patients with liposarcoma at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020). As previously reported, the SEAL study met its primary endpoint of a statistically significant increase in median progression-free survival (PFS) in patients with advanced unresectable dedifferentiated liposarcoma following at least two prior therapies.

    "Dedifferentiated…

    NEWTON, Mass., Nov. 20, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today reported it will present positive results from the Phase 3 portion of the randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral XPOVIO® (selinexor) versus matching placebo in patients with liposarcoma at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020). As previously reported, the SEAL study met its primary endpoint of a statistically significant increase in median progression-free survival (PFS) in patients with advanced unresectable dedifferentiated liposarcoma following at least two prior therapies.

    "Dedifferentiated liposarcoma is a particularly aggressive cancer that arises in the body's fat tissue and is typically associated with high rates of metastatic recurrence and mortality. Unfortunately, there are few effective treatment options available for patients with advanced disease," said Mrinal M. Gounder, MD, Attending Physician, Sarcoma Service and Developmental Therapeutics Service, Memorial Sloan Kettering Cancer Center, and lead investigator of the SEAL study. "The data presented at CTOS 2020 demonstrated that patients treated with XPOVIO experienced a statistically significant improvement in median PFS compared to placebo in patients with at least two prior therapies. Extending PFS is an important clinical goal for these patients because the rapid progression of this disease often translates into early mortality."

    "We are delighted to share these significant results from the Phase 3 portion of the SEAL study, the first, late-stage clinical data for XPOVIO in a solid tumor indication," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "We believe these data strongly support our goal of developing twice-weekly XPOVIO as an effective, convenient, novel oral therapy that can extend PFS for patients with advanced unresectable dedifferentiated liposarcoma. We are especially excited by these data because XPOVIO is the first oral therapy to show activity in patients with previously treated liposarcoma.  We look forward to submitting a New Drug Application to the U.S. Food and Drug Administration (FDA) during the first quarter of 2021, requesting approval of XPOVIO to treat the patient population studied in SEAL.  If approved, XPOVIO would represent the first oral, non-chemotherapy agent available for patients with dedifferentiated liposarcoma."

    Results from the Phase 3 Portion of the Phase2/3 SEAL Study

    The median PFS in the XPOVIO arm of the Phase 3 portion of the SEAL study was 2.83 months compared to 2.07 months in the placebo arm (hazard ratio (HR)=0.70; p=0.023). These data indicate that treatment with XPOVIO reduced the risk of disease progression or death by approximately 30%, compared to placebo. The estimated 6-month PFS survival probability was 23.9% on the selinexor arm compared to 13.9% on placebo. Additionally, the 12-month PFS survival probability was 8.4% on the selinexor arm compared to 2% on the placebo arm.  Finally, 7.5% of patients on the selinexor arm had a 15% or greater reduction in their disease burden as measured by target lesion size while none of the patients on the placebo arm achieved this level of reduction. The trial allowed patients on placebo with objective progression to cross over to the XPOVIO treatment arm. The median overall survival for patients who received XPOVIO was 9.99 months compared to 9.07 months for patients who never crossed over to the XPOVIO treatment arm (HR=0.69; p=0.122).

    The most common treatment-related adverse events (AEs) were cytopenias, along with gastrointestinal and constitutional symptoms and were consistent with those previously reported from other selinexor studies. Most AEs were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (81%), decreased appetite (60%), fatigue (51%), and vomiting (49%) and were mostly Grade 1 and 2 events. The most common Grade 3 and 4 treatment-related AEs were anemia (19%), hyponatremia (11%), thrombocytopenia (10%) and asthenia (10%).

    XPOVIO is currently approved by the FDA as a treatment for patients with relapsed or refractory multiple myeloma and relapsed or refractory diffuse large B-cell lymphoma (DLBCL). XPOVIO is currently the only XPO1 inhibitor approved by the FDA and has been extensively tested in clinical trials across numerous cancer indications worldwide since 2012. Karyopharm has also submitted a supplemental New Drug Application (sNDA) for XPOVIO that is currently under review by the FDA for the expansion of XPOVIO's label to include XPOVIO as a treatment for patients with multiple myeloma after at least one prior line of therapy. The sNDA has been assigned an action date by the FDA of March 19, 2021 under the Prescription Drug User Fee Act. The full Prescribing Information for XPOVIO is available at www.XPOVIO.com.

    Details for the oral presentation at CTOS 2020 are as follows:

    Title: A Phase 2/3, Randomized, Double-Blind, Cross-Over Study of Selinexor Versus Placebo in Advanced Unresectable Dedifferentiated Liposarcoma (DDLS)

    Presenter: Mrinal Gounder, MD, Memorial Sloan Kettering Cancer Center

    Paper #: 20

    Session: 7. Liposarcoma

    Date and Time: Friday, November 20, 2020, 10:30 a.m. to 11:30 a.m. ET

    Conference Call Information

    Karyopharm will host a conference call today, Friday, November 20, 2020, at 12:00 p.m. Eastern Time, to discuss the results from the SEAL study. The call will feature Dr. Gounder and another recognized sarcoma expert Sant P. Chawla, MD, FRACP, Director of the Sarcoma Oncology Center, Santa Monica, CA, along with members of the Karyopharm executive leadership team. To access the conference call, please dial (877) 870-4263 (local) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with slides, will be available under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. An archived webcast will be available on the Company's website approximately two hours after the event.

    About the SEAL Study

    SEAL (Selinexor in Advanced Liposarcoma) is a Phase 2/3, randomized, double blind, placebo controlled, multicenter study (NCT02606461) designed to evaluate the efficacy and safety of twice-weekly, 60mg fixed dose of XPOVIO (selinexor) in patients with advanced unresectable dedifferentiated liposarcoma following at least two prior therapies. The Phase 2 portion of the study enrolled approximately 57 patients (1:1 randomization) and the Phase 3 portion enrolled approximately 285 patients (2:1 randomization). Patients on the placebo arm with confirmed progressive disease were permitted to cross over to the XPOVIO treatment arm. The primary endpoint of the study is PFS.

    About Liposarcoma

    Liposarcoma is a rare type of cancer that occurs in the fat cells in the body, most often in the muscles of the limbs or abdomen. Dedifferentiated liposarcoma (DDLS) is a high grade type of liposarcoma that grows more aggressively than a low grade, well differentiated liposarcoma and is associated with poorer prognosis.1 Liposarcoma accounts for approximately 20% of all soft tissue sarcomas2. In liposarcoma, the risk of recurrence and metastasis increases with higher grade disease.3

    About XPOVIO® (selinexor)

    XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm's supplemental New Drug Application (sNDA) requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy has been accepted for filing by the FDA. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email: 

    IMPORTANT SAFETY INFORMATION

    Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.

    Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

    Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. Neutropenia and febrile neutropenia occurred in patients with MM and in patients with DLBCL.

    Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).

    Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.

    Nausea/Vomiting: Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.

    Diarrhea: Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration, and replace electrolytes as clinically indicated.

    Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

    Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia developed in patients with MM and in patients with DLBCL.

    Monitor sodium level at baseline and throughout treatment. Monitor more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.

    Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

    Monitor for signs and symptoms of infection, and evaluate and treat promptly.

    Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.

    Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

    Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.

    Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

    Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

    ADVERSE REACTIONS

    The most common adverse reactions (ARs) in ≥20% of patients with MM are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

    The most common ARs, excluding laboratory abnormalities, in ≥20% of patients with DLBCL are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in ≥15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥5% were thrombocytopenia, lymphopenia, and neutropenia.

    In patients with MM, fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia.

    In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection. Discontinuation due to ARs occurred in 17% of patients.

    USE IN SPECIFIC POPULATIONS

    In MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥75 years old had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.

    Clinical studies in patients with relapsed or refractory DLBCL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

    The effect of end-stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.

    To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    Please see XPOVIO Full Prescribing Information available at www.XPOVIO.com.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's expectations and plans relating to XPOVIO for the treatment of patients with advanced unresectable dedifferentiated liposarcoma; commercialization of XPOVIO or any of its drug candidates and the commercial performance of XPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; and the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the E.U. as a result of data from the STORM study or confirmatory approval in the U.S. or EU based on the BOSTON study in patients with relapsed or refractory multiple myeloma; or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for diseases in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

    References

    1Livingston, J.A., et al. Role of chemotherapy in dedifferentiated liposarcoma of the retroperitoneum: defining the benefit and challenges of the standard. Sci Rep 7, 11836 (2017).

    https://doi.org/10.1038/s41598-017-12132-w 

    2 https://pubmed.ncbi.nlm.nih.gov/25115417/

    3 http://sarcomahelp.org/liposarcoma.html 

    Cision View original content:http://www.prnewswire.com/news-releases/karyopharm-reports-positive-phase-3-seal-data-in-oral-presentation-at-the-connective-tissue-oncology-society-2020-annual-meeting-301177797.html

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  28. NEWTON, Mass., Nov. 12, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the results of the Phase 3 BOSTON (Bortezomib, Selinexor and Dexamethasone) study evaluating XPOVIO in patients with relapsed or refractory multiple myeloma were published online in The Lancet. The BOSTON study evaluated once weekly XPOVIO, the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, in combination with once weekly Velcade® (bortezomib) and low-dose dexamethasone against standard twice weekly Velcade in adult patients with multiple myeloma who had received one to three prior lines of therapy.

    "The results from the…

    NEWTON, Mass., Nov. 12, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the results of the Phase 3 BOSTON (Bortezomib, Selinexor and Dexamethasone) study evaluating XPOVIO in patients with relapsed or refractory multiple myeloma were published online in The Lancet. The BOSTON study evaluated once weekly XPOVIO, the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, in combination with once weekly Velcade® (bortezomib) and low-dose dexamethasone against standard twice weekly Velcade in adult patients with multiple myeloma who had received one to three prior lines of therapy.

    "The results from the BOSTON study published in The Lancet demonstrate that the once-weekly regimen of XPOVIO and Velcade®, with low-dose dexamethasone (SVd) reduced the risk of disease progression or death by 30% and induced a higher rate of overall and deep responses compared to patients receiving a standard twice-weekly Velcade® and low-dose dexamethasone regimen (Vd). This was observed despite  approximately 40% less Velcade®, 25% less dexamethasone and approximately 35% fewer clinic visits on the SVd arm as compared with the standard Vd therapy arm.  Encouragingly, the efficacy of the SVd regimen was consistent and noteworthy across several key subgroups, including patients who were frail or 65 years and older, patients with high-risk cytogenetics, patients with moderate renal impairment and patients who had either prior bortezomib or lenalidomide treatment," said Dr. Paul Richardson, MD, Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute and co-senior author of the manuscript.  

    "Despite the enrollment of 50% of patients with high risk cytogenetics, a particularly difficult to treat population, the SVd regimen demonstrated a 47% improvement in progression-free survival as compared to the Vd regimen and an overall response rate of 76.4%. Additionally, the rate and severity of peripheral neuropathy, a key treatment-limiting side effect commonly seen with Velcade® therapy, was significantly lower on the SVd arm compared to the Vd arm and may lead to improved patient quality of life," said Sundar Jagannath, MD, Director of the Center of Excellence for Multiple Myeloma and Professor of Medicine, Hematology and Medical Oncology, at the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, and an investigator in the BOSTON study.

    "We are honored to have the Phase 3 BOSTON data selected for publication in such a highly esteemed medical journal and to be shared with the global oncology community," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "We believe the successful outcome of this study represents an important advancement for myeloma patients and we are sincerely grateful to all of the patients and investigators who participated in the BOSTON study. While XPOVIO received accelerated FDA approval last year for patients with penta-refractory multiple myeloma, a supplemental New Drug Application requesting approval for XPOVIO as a treatment for patients with multiple myeloma who have received one prior line of therapy has been accepted by the FDA and assigned a PDUFA action date of March 19, 2021.  We are working closely with the regulatory authorities in both the U.S. and Europe to make this potential new treatment option, with a completely novel mechanism of action, available to patients as quickly as possible, if approved."

    Once-weekly SVd is a novel, effective and convenient triplet therapy that utilizes approximately 40% less Velcade® and 25% less dexamethasone and requires approximately 35% fewer clinic visits during the first 24 weeks of treatment compared to the standard Vd regimen. Because Velcade® is given as a subcutaneous injection rather than as an infusion, clinic visits may be shorter with the SVd regimen than with other non-Velcade® regimens that may be employed to treat relapsed multiple myeloma and require intravenous infusions.

    The Phase 3 BOSTON Study Results as Published in the Lancet

    The published BOSTON study results are based on the multi-center, Phase 3, randomized study (NCT03110562), which evaluated 402 adult patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy. The study was designed to compare the efficacy, safety and certain health-related quality of life parameters of once-weekly selinexor in combination with once-weekly Velcade® (bortezomib) plus low-dose dexamethasone (SVd) versus twice-weekly Velcade® plus low-dose dexamethasone (Vd). The primary endpoint of the study was progression-free survival (PFS) and key secondary endpoints included overall response rate (ORR), rate of peripheral neuropathy, and others. Additionally, the BOSTON study allowed for patients on the Vd control arm to crossover to the SVd arm following objective (quantitative) progression of disease verified by an Independent Review Committee (IRC). The BOSTON study was conducted at over 150 clinical sites internationally.

    Although the study had one of the highest proportions of patients with high-risk cytogenetics (~50%) as compared with other Velcade-based studies in previously treated myeloma, the median PFS in the SVd arm was 13.93 months compared to 9.46 months in the Vd arm, representing a 4.47 month (47%) increase in median PFS (hazard ratio[HR]=0.70; p=0.0075). The SVd group also demonstrated a significantly greater ORR compared to the Vd group (76.4% vs. 62.3%, p=0.0012). Patients who had received only one prior line of therapy also demonstrated a higher ORR on the SVd arm as compared to the Vd arm (80.8% vs. 65.7%, p=0.0082). Importantly, SVd therapy compared to Vd therapy showed consistent PFS benefit and higher ORR across several important subgroups.

    In addition, the following results favored SVd therapy as compared to Vd therapy:

    SVd therapy demonstrated a significantly higher rate of deep responses, defined as ≥ Very Good Partial Response compared to Vd therapy (44.6% vs. 32.4%) as well as a longer median duration of response (20.3 months vs. 12.9 months). Additionally, 16.9% of patients on the SVd arm achieved a Complete Response or a Stringent Complete Response as compared to 10.6% of patients receiving Vd therapy.  All responses were confirmed by an IRC.

    Data at the time of analysis showed a trend toward an overall survival (OS) benefit associated with SVd therapy with fewer deaths, numerically, reported on the SVd arm (47 vs. 62). Median OS for the SVd arm had not yet been reached as of the data cut-off date of February 18, 2020, while the median OS for the Vd arm was 25.0 months. The median OS for the SVd arm will be reported once it is reached and becomes available.

    Peripheral neuropathy (PN) rates were significantly lower on SVd compared to Vd (32.3% vs. 47.1%; p=0.0010). In addition, PN rates of grade ≥2 were also significantly lower in the SVd arm compared to Vd (21.0% vs. 34.3%, P=0.0013).

    The most common treatment-emergent adverse events (AEs) were cytopenias, along with gastrointestinal and constitutional symptoms and were consistent with those previously reported from other selinexor studies. Most AEs were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (50%), fatigue (42%), decreased appetite (35%), and diarrhea (32%) and were mostly Grade 1 and 2 events. The most common Grade 3 and 4 treatment-related AEs were thrombocytopenia (39%), anemia (16%), and fatigue (13%).

    About Multiple Myeloma

    According to the National Cancer Institute (NCI), multiple myeloma is one of the most common types of blood cancer in the U.S. with more than 32,000 new cases each year and over 140,000 patients living with the disease. It is most frequently diagnosed among people aged 65-74 years old. Despite recent therapeutic advances, there is currently no cure and most patients' disease will typically progress following treatment with currently available therapies. According to the NCI, nearly 13,000 deaths due to multiple myeloma are expected in the U.S. in 2020.

    About XPOVIO® (selinexor)

    XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm's supplemental New Drug Application (sNDA) requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy has been accepted for filing by the FDA. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email: 

    IMPORTANT SAFETY INFORMATION

    Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.

    Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

    Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. Neutropenia and febrile neutropenia occurred in patients with MM and in patients with DLBCL.

    Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).

    Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.

    Nausea/Vomiting: Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.

    Diarrhea: Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration, and replace electrolytes as clinically indicated.

    Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

    Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia developed in patients with MM and in patients with DLBCL.

    Monitor sodium level at baseline and throughout treatment. Monitor more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.

    Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

    Monitor for signs and symptoms of infection, and evaluate and treat promptly.

    Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.

    Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

    Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.  

    Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

    Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

    ADVERSE REACTIONS

    The most common adverse reactions in ≥20% of patients with MM are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

    The most common ARs, excluding laboratory abnormalities, in ≥20% of patients with DLBCL are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in ≥15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥5% were thrombocytopenia, lymphopenia, and neutropenia.

    In patients with MM, fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia.

    In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection.  Discontinuation due to ARs occurred in 17% of patients.

    USE IN SPECIFIC POPULATIONS

    In MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥75 years old had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.

    Clinical studies in patients with relapsed or refractory DLBCL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

    The effect of end-stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.

    Please see full Prescribing Information.

    To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's expectations and plans relating to XPOVIO for the treatment of patients with relapsed or refractory multiple myeloma or relapsed or refractory diffuse large B-cell lymphoma; commercialization of XPOVIO or any of its drug candidates and the commercial performance of XPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the E.U. as a result of data from the STORM study or confirmatory approval in the U.S. or E.U. based on the BOSTON study in patients with multiple myeloma or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for indications in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2,, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

    Velcade® is a registered trademark of Takeda Pharmaceutical Company Limited.

    Cision View original content:http://www.prnewswire.com/news-releases/karyopharm-announces-publication-of-xpovio-selinexor-phase-3-boston-study-results-in-the-lancet-301172456.html

    SOURCE Karyopharm Therapeutics Inc.

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  29. NEWTON, Mass., Nov. 10, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that Michael Kauffman, MD, PhD, Chief Executive Officer of Karyopharm, will participate in a fireside chat at the Jefferies 2020 Virtual London Healthcare Conference on Tuesday, November 17, 2020 at 1:45 p.m. ET.

    A live webcast of the fireside chat can be accessed under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. A replay of the webcast will be archived on the Company's website for 90 days following the fireside chat.

    About Karyopharm Therapeutics
    Karyopharm Therapeutics Inc. (NASDAQ…

    NEWTON, Mass., Nov. 10, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that Michael Kauffman, MD, PhD, Chief Executive Officer of Karyopharm, will participate in a fireside chat at the Jefferies 2020 Virtual London Healthcare Conference on Tuesday, November 17, 2020 at 1:45 p.m. ET.

    A live webcast of the fireside chat can be accessed under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. A replay of the webcast will be archived on the Company's website for 90 days following the fireside chat.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.   

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    SOURCE Karyopharm Therapeutics Inc.

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  30. NEWTON, Mass., Nov. 4, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that twenty-one abstracts have been selected for virtual presentation, including two oral presentations, at the upcoming American Society of Hematology (ASH) 2020 Annual Meeting taking place December 5-8, 2020. Key abstracts to be presented at the meeting will feature clinical data for XPOVIO® (selinexor), the Company's first in class, oral SINE compound, including: (i) updated data from the Pomalyst® (pomalidomide), Kyprolis® (carfilzomib) and Revlimid® (lenalidomide) arms of the Phase 1b/2 STOMP study evaluating XPOVIO in combination with backbone therapies…

    NEWTON, Mass., Nov. 4, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that twenty-one abstracts have been selected for virtual presentation, including two oral presentations, at the upcoming American Society of Hematology (ASH) 2020 Annual Meeting taking place December 5-8, 2020. Key abstracts to be presented at the meeting will feature clinical data for XPOVIO® (selinexor), the Company's first in class, oral SINE compound, including: (i) updated data from the Pomalyst® (pomalidomide), Kyprolis® (carfilzomib) and Revlimid® (lenalidomide) arms of the Phase 1b/2 STOMP study evaluating XPOVIO in combination with backbone therapies in patients with relapsed or refractory multiple myeloma; (ii) several new subgroup analyses from the pivotal Phase 3 BOSTON study evaluating once weekly XPOVIO in combination with once weekly Velcade® (bortezomib) and low-dose dexamethasone against standard twice weekly Velcade in adult patients with multiple myeloma who had received one to three prior lines of therapy; and (iii) new subgroup analyses from the Phase 2b SADAL study evaluating XPOVIO in relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

    "Our tradition of having a strong presence at the ASH annual meeting continues this year and we are excited to share important clinical data from a variety of our XPOVIO clinical studies," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "In total, twenty-one abstracts have been selected, including an oral presentation highlighting the all-oral regimen of XPOVIO and Pomalyst® from the ongoing STOMP study. Additionally, updated data from two other arms of the STOMP study will also be presented, including the arm investigating XPOVIO and Kyprolis® as well as the arm investigating XPOVIO and Revlimid®. In all three arms, the response rates and safety profile continue to be encouraging. In addition, we look forward to several poster presentations describing a variety of subanalyses from the Phase 3 BOSTON study in important subgroups such as older, frail patients, patients previously treated with proteasome inhibitors, and patients with high risk cytogenetics, among others."

    Karyopharm plans to host a virtual investor and analyst event to discuss the Company's pipeline of clinical programs and highlights from the ASH 2020 data presentations. Details for this event, including date, time, and log-in information will be announced in the coming weeks. A live webcast of the presentation will be accessed under "Events & Presentations" in the Investors section of the Company's website at http://investors.karyopharm.com/events-presentations. A replay of the webcast will be archived on the Company's website for 90 days following the event.

    Details for the ASH 2020 presentations are as follows:

    XPOVIO (selinexor) – Company-Sponsored Studies – Oral Presentation – Multiple Myeloma

    Title: Selinexor in combination with pomalidomide and dexamethasone (SPd) for treatment of patients with relapsed refractory multiple myeloma (RRMM).

    Presenter: Christine Chen, Princess Margaret Cancer Centre

    Abstract #: 726

    Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation; Novel Approaches for Relapsed/Refractory Myeloma and Amyloidosis

    Date and Time: Monday, December 7, 2020, 1:30 p.m. to 3:00 p.m. ET

    Location: Channel 10 (Virtual Meeting)

    XPOVIO (selinexor) – Company-Sponsored Studies – Poster Presentations – Multiple Myeloma

    Title: Selinexor in combination with carfilzomib and dexamethasone, all once weekly (SKd), for patients with relapsed/refractory multiple myeloma

    Presenter: Cristina Gasparetto, Duke University Medical Center

    Abstract #: 1366

    Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster I

    Date and Time: Saturday, December 5, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location: Poster Hall (Virtual Meeting)

    Title: Selinexor, lenalidomide and dexamethasone (SRd) for patients with relapsed/refractory and newly diagnosed multiple myeloma

    Presenter: Darrell White, Dalhousie University

    Abstract #: 1393

    Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster I

    Date and Time: Saturday, December 5, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location: Poster Hall (Virtual Meeting)

    Title: Effect of prior treatment with proteasome inhibitors on the efficacy and safety of once-weekly selinexor, bortezomib, and dexamethasone in comparison with twice weekly bortezomib and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis from the BOSTON study

    Presenter: Maria Mateos, University Hospital of Salamanca

    Abstract #: 2297

    Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster II

    Date and Time: Sunday, December 6, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location: Poster Hall (Virtual Meeting)

    Title: Impact of prior therapies on the safety and efficacy of once-weekly selinexor, bortezomib, and dexamethasone compared with twice-weekly bortezomib and dexamethasone in relapsed ore refractory multiple myeloma: results from the BOSTON study

    Presenter: Maria Mateos, University Hospital of Salamanca

    Abstract #: 3245

    Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster III

    Date and Time: Monday, December 7, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location:  Poster Hall (Virtual Meeting)

    Title: Once weekly selinexor, bortezomib, and dexamethasone versus twice weekly bortezomib and dexamethasone in relapsed ore refractory multiple myeloma: age and frailty subgroup analyses from the phase 3 BOSTON study

    Presenter: Harold Auner, Imperial College London

    Abstract #: 3215

    Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster III

    Date and Time: Monday, December 7, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location:  Poster Hall (Virtual Meeting)

    Title: Once weekly selinexor, bortezomib, and dexamethasone (SVd) versus twice weekly bortezomib and dexamethasone (Vd) in relapsed or refractory multiple myeloma: high-risk cytogenetic risk planned subgroup analyses from the phase 3 BOSTON study

    Presenter: Shambavi Richard, Mount Sanai Hospital

    Abstract #: 1385

    Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster I

    Date and Time: Saturday, December 5, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location: Poster Hall (Virtual Meeting)

    Title: Peripheral neuropathy symptoms, pain and functioning in relapsed or refractory MM patients treated with selinexor, bortezomib, and dexamethasone

    Presenter: Larysa Sanchez, Icahn School of Medicine at Mount Sinai

    Abstract #: 3489

    Session: 906. Outcomes Research—Malignant Conditions (Myeloid Disease): Poster III

    Date and Time: Monday, December 7, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location:  Poster Hall (Virtual Meeting)

    XPOVIO (selinexor) – Company-Sponsored – Poster Presentations – Lymphoma

    Title: Effect of age on the efficacy and safety of single agent oral selinexor in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL): a post-hoc analysis from the SADAL pivotal study

    Presenter: Marie Maerevoet, Institut Jules Bordet

    Abstract #: 1201

    Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Poster I

    Date and Time: Saturday, December 5, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location:  Poster Hall (Virtual Meeting)

    Title: Selinexor efficacy and safety are independent of renal function in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL): a post-hoc analysis from the pivotal phase 2b SADAL study

    Presenter: Jason Westin, The University of Texas MD Anderson Cancer Center

    Abstract #: 1384

    Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster I

    Date and Time: Saturday, December 5, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location: Poster Hall (Virtual Meeting)

    Title: A six-protein activity signature defines favorable response to selinexor treatment for patients with diffuse large B-cell lymphoma (DLBCL)

    Presenter: Christopher Walker, Karyopharm Therapeutics

    Abstract #: 2125

    Session: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Retrospective/Observational Studies: Poster II

    Date and Time: Sunday, December 6, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location: Poster Hall (Virtual Meeting)

    XPOVIO (selinexor) – Investigator-Sponsored – Oral Presentations – Lymphoma

    Title: Inhibiting the Nuclear Exporter XPO1 and the Antiapoptotic Factor BCL2 Is Synergistic in XPO1 Mutant and Wildtype Lymphoma

    Presenter: Justin Taylor, University of Miami 

    Abstract #: 526

    Session: 605. Molecular Pharmacology, Drug Resistance—Lymphoid and Other Diseases: Molecular pharmacology and drug resistance mechanisms in lymphoproliferative disorders

    Date and Time: Monday, December 7, 2020 ; 7:00 a.m. to 8:30 a.m.

    Location: Channel 8 (Virtual Meeting)

    XPOVIO (selinexor) – Investigator-Sponsored – Poster Presentations – Lymphoma

    Title: Selinexor in combination with R-CHOP for frontline treatment of non-Hodgkin lymphoma: results of a phase 1b study

    Presenter: Erlene Seymour, Wayne State University 

    Abstract #: 2109

    Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Poster II

    Date and Time: Sunday, December 6, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location: Poster Hall (Virtual Meeting)

    Title: A Phase I Investigator Sponsored Trial of Selinexor (KPT-330) and Rituximab, Ifosfamide, Carboplatin and Etoposide in Patients with Relapsed or Refractory Aggressive B-Cell Lymphomas

    Presenter: Sarah Rutherford, Weill Cornell Medicine

    Abstract #: 2104

    Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Poster II

    Date and Time: Sunday, December 6, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location: Poster Hall (Virtual Meeting)

    Title: XPO1 Relieves MYC-Induced Replication Stress Limiting the Immunogenicity of DLBCL Cells

    Presenter: Rossella Marullo, Weill Cornell Medicine

    Abstract #: 2018

    Session: 621. Lymphoma—Genetic/Epigenetic Biology: Poster II

    Date and Time: Sunday, December 6, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location: Poster Hall (Virtual Meeting)

    Title: The Expression of Chromosome Region Maintenance Protein 1 (CRM1) in Large Cell Lymphoma

    Presenter: Jithma Abeykoon, Mayo Clinic

    Abstract #: 2132

    Session: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Retrospective/Observational Studies: Poster II

    Date and Time: Sunday, December 6, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location: Poster Hall (Virtual Meeting)

    XPOVIO (selinexor) – Investigator-Sponsored – Poster Presentations – Leukemia

    Title: Frontline selinexor and chemotherapy is highly active in older adults with AML

    Presenter: Timothy Pardee, Wake Forest School of Medicine

    Abstract #: 633

    Session: 615. Acute Myeloid Leukemia: Commercially Available Therapy, excluding Transplantation: Commercially Available Therapy, excluding Transplantation II

    Date and Time: Monday, December 7, 2020, 11:45 a.m. ET

    Location: Channel 12 (Virtual Meeting)

    Title: Exportin-1 (XPO1) Inhibition Sequesters p53 from MDM2 and MDM4 and Is Highly Synergistic with MDM2 Inhibition in Inducing Apoptosis in Wild-Type p53 Acute Myeloid Leukemias

    Presenter: Yuki Nishida, MD Anderson Cancer Center

    Abstract #: 2775

    Session: 603. Oncogenes and Tumor Suppressors: Poster III

    Date and Time: Monday, December 7, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location: Poster Hall (Virtual Meeting)

    XPOVIO (selinexor) – Investigator-Sponsored – Poster Presentations – Other

    Title: CRISPR/Cas9 Chemogenetic Profiling Identifies Candidate Biomarker Genes That Modulate Sensitivity to Selinexor

    Presenter: Bert Kwanten, KU Leuven

    Abstract #: 965

    Session: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Poster I

    Date and Time: Saturday, December 5, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location: Poster Hall (Virtual Meeting)

    Title: Salicylates Potentiate and Broaden CRM1 Inhibitor Anti-Tumor Activity Via S-Phase Arrest and Impaired DNA-Damage Repair

    Presenter: Jithma Abeykoon, Mayo Clinic

    Abstract #: 171

    Session: 625. Lymphoma: Pre-Clinical—Chemotherapy and Biologic Agents: Novel Approaches to Overcome Resistance

    Date and Time: Saturday, December 5, 2020, 12:00 p.m. ET

    Location: Channel 7 (Virtual Meeting)

    KPT-9274 – Investigator-Sponsored – Poster Presentations – Other

    Title: Nicotinamide Phosphoribosyltransferase Inhibitors Induce Apoptosis of AML Stem Cells through Dysregulation of Lipid Metabolism

    Presenter: Amit Subedi, Princess Margaret Cancer Center

    Abstract #: 2777

    Session: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Poster III

    Date and Time: Monday, December 7, 2020, 7:00 a.m. to 3:30 p.m. ET

    Location: Poster Hall (Virtual Meeting)

    About XPOVIO® (selinexor)

    XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm's supplemental New Drug Application (sNDA) requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy has been accepted for filing by the FDA. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email:

    IMPORTANT SAFETY INFORMATION

    Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.

    Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

    Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. Neutropenia and febrile neutropenia occurred in patients with MM and in patients with DLBCL.

    Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).

    Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.

    Nausea/Vomiting: Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.

    Diarrhea: Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration, and replace electrolytes as clinically indicated.

    Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

    Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia developed in patients with MM and in patients with DLBCL.

    Monitor sodium level at baseline and throughout treatment. Monitor more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.

    Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

    Monitor for signs and symptoms of infection, and evaluate and treat promptly.

    Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.

    Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

    Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.

    Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

    Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

    ADVERSE REACTIONS

    The most common adverse reactions (ARs) in ≥20% of patients with MM are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

    The most common ARs, excluding laboratory abnormalities, in ≥20% of patients with DLBCL are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in ≥15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥5% were thrombocytopenia, lymphopenia, and neutropenia.

    In patients with MM, fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia.

    In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection. Discontinuation due to ARs occurred in 17% of patients.

    USE IN SPECIFIC POPULATIONS

    In MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥75 years old had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.

    Clinical studies in patients with relapsed or refractory DLBCL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

    The effect of end-stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.

    To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    Please see XPOVIO Full Prescribing Information available at www.XPOVIO.com.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.  

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's beliefs regarding the ability of selinexor to treat patients with multiple myeloma, diffuse large B-cell lymphoma, solid tumors and other diseases and expectations related to future clinical development and potential regulatory submissions of XPOVIO. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the E.U. as a result of data from the STORM study or confirmatory approval in the U.S. or EU based on the BOSTON study in patients with relapsed or refractory multiple myeloma; or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for diseases in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

    Velcade® is a registered trademark of Takeda Pharmaceutical Company Limited

    Revlimid® and Pomalyst® are registered trademarks of Celgene Corporation

    Kyprolis® is a registered trademark of Onyx Pharmaceuticals, Inc.

     

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  31. NEWTON, Mass., Nov. 3, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the Compensation Committee of Karyopharm's Board of Directors granted stock options to purchase an aggregate of 86,900 shares of Karyopharm's common stock to 13 newly-hired employees, with a grant date of October 30, 2020.  The stock options were granted as inducements material to the new employees entering into employment with Karyopharm in accordance with Nasdaq Listing Rule 5635(c)(4).

    Each of the stock options has an exercise price of $14.82 per share, the closing price of Karyopharm's common stock on October 30, 2020. Each stock option vests over four years…

    NEWTON, Mass., Nov. 3, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that the Compensation Committee of Karyopharm's Board of Directors granted stock options to purchase an aggregate of 86,900 shares of Karyopharm's common stock to 13 newly-hired employees, with a grant date of October 30, 2020.  The stock options were granted as inducements material to the new employees entering into employment with Karyopharm in accordance with Nasdaq Listing Rule 5635(c)(4).

    Each of the stock options has an exercise price of $14.82 per share, the closing price of Karyopharm's common stock on October 30, 2020. Each stock option vests over four years, with 25% of the total number of shares underlying the stock option vesting on the one-year anniversary of the applicable employee's employment commencement date and 1/48th of the total number of shares vesting monthly thereafter, subject to the employee's continued service as an employee of, or other service provider to, Karyopharm through the applicable vesting dates. In addition, each stock option will be immediately exercisable in full if, on or prior to the first anniversary of the consummation of a "change in control event," the employee's employment is terminated for "good reason" by the employee or terminated without "cause" by Karyopharm (as such terms are defined in the applicable stock option agreement).

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    Cision View original content:http://www.prnewswire.com/news-releases/karyopharm-therapeutics-reports-inducement-grants-under-nasdaq-listing-rule-5635c4-301165422.html

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  32. NEWTON, Mass., Nov. 2, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today reported financial results for the quarter ended September 30, 2020. In addition, Karyopharm highlighted select corporate milestones, including details regarding the ongoing U.S. commercialization of XPOVIO® (selinexor), and provided an overview of its key clinical development programs.

    "We are delighted to share the significant top-line results from the Phase 3 portion of the SEAL study, the first, late-stage clinical data for XPOVIO in a solid tumor indication," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "The top-line results from…

    NEWTON, Mass., Nov. 2, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today reported financial results for the quarter ended September 30, 2020. In addition, Karyopharm highlighted select corporate milestones, including details regarding the ongoing U.S. commercialization of XPOVIO® (selinexor), and provided an overview of its key clinical development programs.

    "We are delighted to share the significant top-line results from the Phase 3 portion of the SEAL study, the first, late-stage clinical data for XPOVIO in a solid tumor indication," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "The top-line results from the SEAL study are particularly encouraging as advanced dedifferentiated liposarcoma represents a very difficult to treat cancer with no established standard of care and limited treatment options available to patients. XPOVIO may be particularly promising as it represents the first oral therapy to show activity in patients with previously treated liposarcoma. We look forward to presenting the detailed results at the upcoming Connective Tissue Oncology Society (CTOS) Annual Meeting and plan to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2021 requesting approval of XPOVIO to treat the patient population studied in SEAL. If approved, XPOVIO would represent the first oral, non-chemotherapy agent available for patients with dedifferentiated liposarcoma. The encouraging data from the SEAL study also provide additional rationale for advancing the clinical development of XPOVIO in other solid tumor indications, including in endometrial, glioblastoma, lung and other cancers where Karyopharm is currently conducting clinical studies."

    Commenting on additional milestones achieved in the third quarter of 2020, Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm added, "Karyopharm achieved another strong quarter for XPOVIO sales, which grew approximately 15% compared to the second quarter of 2020. Sales growth was driven primarily by an increase in new multiple myeloma and diffuse large B-cell lymphoma (DLBCL) patient starts. Looking forward, we plan to continue our ongoing support for our supplemental New Drug Application (sNDA) seeking approval for XPOVIO as a treatment for patients with multiple myeloma after at least one prior line of therapy, for which the FDA has assigned a target Prescription Drug User Fee Act (PDUFA) action date of March 19, 2021."

    Third Quarter 2020 and Recent Highlights

    XPOVIO in Multiple Myeloma and DLBCL

    • XPOVIO U.S. Commercialization. Oral XPOVIO became commercially available to patients with penta-refractory multiple myeloma in July 2019 and to patients with relapsed or refractory DLBCL in June 2020. During the third quarter of 2020, XPOVIO generated net product sales of $21.3 million, representing a 15% increase compared to the second quarter of 2020. XPOVIO sales growth was primarily driven by an increase in new multiple myeloma patient starts compared to the second quarter of 2020. XPOVIO sales also benefited from the initial commercial launch in patients with relapsed or refractory DLBCL. In the third quarter of 2020, approximately 1,100 XPOVIO prescriptions were filled, which represented the highest quarterly level to date and was 15% higher than in the second quarter of 2020. Over 200 new physician prescribing accounts were added in the third quarter of 2020, which included both myeloma and DLBCL treating physicians. Finally, based on data from specialty pharmacies, prescription refill rates for XPOVIO continued to grow with the average number of prescriptions per patient reaching 2.9 by the end of September 2020, compared to 2.0 at the end of December 2019.
    • FDA Accepts sNDA Seeking Expanded Indication For Patients with Previously Treated Multiple Myeloma. The FDA assigned a PDUFA action date of March 19, 2021 for Karyopharm's sNDA seeking approval for XPOVIO for the treatment of adult patients with multiple myeloma after at least one line of prior therapy. If approved, the Company expects to launch the expanded indication immediately thereafter. The sNDA is supported by the positive data from the pivotal Phase 3 BOSTON study, which was reported at the American Society of Clinical Oncology (ASCO) 2020 annual meeting. The BOSTON study evaluated once-weekly XPOVIO in combination with once-weekly Velcade® (bortezomib) and low-dose dexamethasone (SVd) compared to standard twice-weekly Velcade plus low-dose dexamethasone (Vd) in patients with multiple myeloma who have received one to three prior lines of therapy. The BOSTON study met its primary endpoint with a significant increase in median progression-free survival (PFS) in patients with multiple myeloma following one to three prior lines of therapy. The median PFS in the SVd arm was 13.93 months compared to 9.46 months in the Vd arm, representing a 4.47 month (47%) increase in median PFS (hazard ratio=0.70; p=0.0075). There were no new safety signals on the SVd arm, and deaths were numerically lower on the SVd arm (N=47) as compared with the Vd arm (N=62).
    • Regulatory Strategy Update in Europe. In January 2019, Karyopharm submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) requesting conditional approval for XPOVIO in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma based on the results of the Phase 2b STORM study. In January 2020, Karyopharm was granted a three-month extension from the EMA's Committee for Medicinal Products for Human Use (CHMP) to provide additional time to respond to the CHMP's outstanding questions, primarily related to re-monitoring certain clinical data. Due to the COVID-19 pandemic and the resulting disruption at many clinical sites, re-monitoring activities requested by CHMP delayed the review timelines in Europe. Karyopharm submitted the final requested re-monitoring data in September 2020 and in October 2020, Karyopharm received a further updated list of outstanding issues from the CHMP summarizing the remaining topics for Karyopharm to address and indicating that the CHMP intends to consult its Scientific Advisory Group for additional advice [in the fourth quarter of 2020]. Karyopharm continues to expect to receive an opinion from CHMP with respect to the MAA before the end of 2020. In addition, contingent upon and following receipt of CHMP's opinion, we expect to submit a MAA based on data from the BOSTON study before the end of 2020.

    XPOVIO in Development for Solid Tumors

    • Twice-Weekly XPOVIO Demonstrates a Statistically Significant Reduction in the Risk of Disease Progression or Death Compared to Placebo; Hazard Ratio=0.70, p=0.023. In November 2020, Karyopharm announced positive top-line results from the Phase 3 portion of the randomized, double blind, placebo controlled, cross-over, SEAL study evaluating single agent, oral XPOVIO versus placebo in patients with advanced unresectable dedifferentiated liposarcoma. The SEAL study met its primary endpoint of a statistically significant increase in PFS; hazard ratio=0.70; p=0.023. Among those patients who received XPOVIO, there was a trend towards an improvement in the median overall survival compared to those patients who began on the placebo arm of the study and never crossed over to the XPOVIO treatment arm. The safety profile for XPOVIO was consistent with previous clinical studies with fewer hematologic and infectious adverse events as compared to XPOVIO studies in patients with multiple myeloma and DLBCL. The clinical data from this study have been selected for an oral presentation at the CTOS Annual Meeting on November 20, 2020 at 10:30 AM ET. Additionally, Karyopharm intends to use the data from the SEAL study to submit an NDA to the FDA in the first quarter of 2021 requesting approval of XPOVIO to treat the patient population studied in SEAL.
    • Clinical Data from Advanced Solid Tumor Studies Presented at the European Society for Medical Oncology (ESMO) Virtual Congress. In September 2020, encouraging clinical data from investigator-sponsored studies evaluating XPOVIO in combination with established cancer therapies were presented at ESMO. Clinical data from XPOVIO studies included: (i) combination data with pembrolizumab for the treatment of melanoma, (ii) combination data with carboplatin and paclitaxel for the treatment of advanced or metastatic solid tumors, and (iii) combination data with topotecan for the treatment of advanced or metastatic solid tumors. The Company believes that the encouraging results from these combination studies warrant further research into the potential utility of XPOVIO in solid tumors and will help Karyopharm further prioritize future clinical development activities.

    Low Dose Selinexor in Development for COVID-19

    • Presented Phase 2 Data at COVID-19 Focused Medical Meeting. Selinexor data was highlighted recently in an oral presentation at the International Society for Influenza and Other Respiratory Virus Diseases Antiviral Group (ISIRV-AVG) Virtual Conference on Therapeutics for COVID-19. While the results of the Phase 2 study demonstrated encouraging anti-viral and anti-inflammatory activity in an important subset of treated patients, the trial was discontinued following an interim analysis which indicated that the trial was unlikely to meet its pre-specified primary endpoint. While the FDA's opinion was that the benefit-risk ratio for this study was not favorable, Karyopharm is encouraged by the potential mechanistic activity of XPO1 inhibition and believes these results warrant further research of XPO1 inhibitors in COVID-19 and other infectious diseases.

    Corporate Updates

    • Sharon Shacham, Winner of EY Entrepreneur of the Year® 2020 New England Award. In October 2020, Karyopharm's founder, Dr. Sharon Shacham, was selected as a winner in the EY Entrepreneur of the Year 2020 New England Awards Program. For more than 30 years, this award has served as one of the world's most prestigious business awards recognizing entrepreneurs who have disrupted industries, created new product categories and successfully brought innovations that have transformed our world. Dr. Shacham was recognized for her scientific research that led to the development and FDA approval of XPOVIO, as well as for leading Karyopharm from its inception to what is now a global pharmaceutical company focused on the discovery, development, and commercialization of novel medicines for patients with cancer and other major diseases.
    • Christy J. Oliger Appointed to the Board. In August 2020, Karyopharm appointed Christy J. Oliger to its Board of Directors. Ms. Oliger is the former Senior Vice President of the Oncology Business Unit at Genentech, a leading biotechnology company dedicated to pursuing groundbreaking science to discover and develop medicines for people with serious and life-threatening diseases. Ms. Oliger served in a wide variety of commercial leadership positions at Genentech from 2000 until 2020. Ms. Oliger's strategic expertise and counsel will be critical to Karyopharm as it continues to expand the global development and commercialization of XPOVIO into new patient populations and potential new indications.

    Third Quarter 2020 Financial Results

    Net product revenue: Net product revenue for the third quarter of 2020 was $21.3 million, compared to $12.8 million for the third quarter of 2019.

    License and other revenue: License and other revenue for the third quarter of 2020 was negligible, compared to $0.3 million for the third quarter of 2019.

    Cost of sales: Cost of sales totaled $0.4 million for the third quarter of 2020, compared to $1.0 million for the third quarter of 2019. Cost of sales reflects the costs of XPOVIO units sold and third-party royalties on net product revenue.

    Research and development (R&D) expenses: R&D expenses for the third quarter of 2020 were $37.0 million, compared to $26.3 million for the third quarter of 2019. The increase in R&D expenses compared to the third quarter of last year was primarily attributable to COVID-19 trial activity and continued activity in our other ongoing clinical trials.

    Selling, general and administrative (SG&A) expenses: For the third quarter of 2020, SG&A expenses were $31.0 million, compared to $25.3 million for the third quarter of 2019. The increase in SG&A expenses compared to the third quarter of last year was due primarily to activities to support the U.S. commercialization of XPOVIO, including the launch of XPOVIO as a treatment for patients with relapsed or refractory DLBCL.

    Interest expense: Interest expense for the third quarter of 2020 was $6.8 million, compared to $3.1 million for the third quarter of 2019. The increase in interest expense was primarily attributable to the imputed interest on the deferred royalty obligation Karyopharm has with HealthCare Royalty Partners.

    Net loss: Karyopharm reported a net loss of $53.5 million, or $0.73 per share, for the third quarter of 2020, compared to a net loss of $41.4 million, or $0.67 per share, for the third quarter of 2019. Net loss included non-cash stock-based compensation expense of $6.5 million and $3.7 million for the third quarters of 2020 and 2019, respectively.

    Cash position: Cash, cash equivalents, restricted cash and investments as of September 30, 2020 totaled $304.2 million, compared to $265.8 million as of December 31, 2019.

    2020 Financial Outlook

    Based on its current operating plans, Karyopharm continues to expect its non-GAAP R&D and SG&A expenses, which excludes stock-based compensation expense, for the full year 2020 to be in the range of $240.0 million to $260.0 million. Karyopharm has not reconciled the full year 2020 outlook for non-GAAP R&D and SG&A expenses to full year 2020 outlook for GAAP R&D and SG&A expenses because Karyopharm cannot reliably predict without unreasonable efforts the timing or amount of the factors that substantially contribute to the projection of stock compensation expense, which is excluded from the full year 2020 outlook for non-GAAP R&D and SG&A expenses.

    The Company expects that its existing cash, cash equivalents and investments, and the revenue it expects to generate from XPOVIO product sales, will be sufficient to fund its planned operations into the second half of 2022.

    Non-GAAP Financial Information

    Karyopharm uses a non-GAAP financial measure, including R&D and SG&A expenses, to provide operating expense guidance. Non-GAAP R&D and SG&A expenses exclude stock-based compensation expense. Karyopharm believes this non-GAAP financial measure is useful to investors because it provides greater transparency regarding Karyopharm's operating performance as it excludes non-cash stock compensation expense. This non-GAAP financial measure should not be considered a substitute or an alternative to GAAP R&D and SG&A expenses and should not be considered a measure of Karyopharm's liquidity. Instead, non-GAAP R&D and SG&A expenses should only be used to supplement an understanding of Karyopharm's operating results as reported under GAAP.

    Conference Call Information

    Karyopharm will host a conference call today, Monday, November 2, 2020, at 4:30 p.m. Eastern Time, to discuss the third quarter 2020 financial results, recent accomplishments, clinical developments and business plans. To access the conference call, please dial (877) 870-4263 (local) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. An archived webcast will be available on the Company's website approximately two hours after the event.

    About XPOVIO® (selinexor)

    XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm's supplemental New Drug Application (sNDA) requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy has been accepted for filing by the FDA. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email: 

    IMPORTANT SAFETY INFORMATION

    Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.

    Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

    Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. Neutropenia and febrile neutropenia occurred in patients with MM and in patients with DLBCL.

    Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).

    Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.

    Nausea/Vomiting: Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.

    Diarrhea: Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration, and replace electrolytes as clinically indicated.

    Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

    Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia developed in patients with MM and in patients with DLBCL.

    Monitor sodium level at baseline and throughout treatment. Monitor more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.

    Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

    Monitor for signs and symptoms of infection, and evaluate and treat promptly.

    Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.

    Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

    Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.

    Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

    Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

    ADVERSE REACTIONS

    The most common adverse reactions (ARs) in ≥20% of patients with MM are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

    The most common ARs, excluding laboratory abnormalities, in ≥20% of patients with DLBCL are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in ≥15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥5% were thrombocytopenia, lymphopenia, and neutropenia.

    In patients with MM, fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia.

    In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection. Discontinuation due to ARs occurred in 17% of patients.

    USE IN SPECIFIC POPULATIONS

    In MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥75 years old had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.

    Clinical studies in patients with relapsed or refractory DLBCL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

    The effect of end-stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.

    To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    Please see XPOVIO Full Prescribing Information available at www.XPOVIO.com.

    About Karyopharm Therapeutics

    Karyopharm Therapeutics Inc. (NASDAQ:KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies and dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's expectations and plans relating to XPOVIO for the treatment of patients with relapsed or refractory multiple myeloma or relapsed or refractory diffuse large B-cell lymphoma; commercialization of XPOVIO or any of its drug candidates and the commercial performance of XPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor; Karyopharm's collaboration efforts with third-parties; 2020 financial expectations, including forecasted non-GAAP R&D and SG&A expenses; and expectations of the sufficiency of Karyopharm's existing cash and investments. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO; that regulators will agree that selinexor qualifies for conditional approval in the E.U. as a result of data from the STORM study or confirmatory approval in the U.S. or EU based on the BOSTON study in patients with relapsed or refractory multiple myeloma; or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for diseases in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended June 30, 2020, which was filed with the Securities and Exchange Commission (SEC) on August 4, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

    Velcade® is a registered trademark of Takeda Pharmaceutical Company Limited.

     

    KARYOPHARM THERAPEUTICS INC.

    CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS

    (unaudited)

    (in thousands, except per share amounts)







    Three Months Ended

    September 30,





    Nine Months Ended

    September 30,







    2020





    2019





    2020





    2019



    Revenues:

































    Product revenue, net



    $

    21,330





    $

    12,821





    $

    55,992





    $

    12,821



    License and other revenue





    3







    328







    16,993







    9,976



    Total revenues





    21,333







    13,149







    72,985







    22,797



    Operating expenses:

































    Cost of sales





    438







    1,013







    1,653







    1,013



    Research and development





    37,037







    26,270







    113,628







    90,761



    Selling, general and administrative





    30,967







    25,267







    92,488







    77,032



    Total operating expenses





    68,442







    52,550







    207,769







    168,806



    Loss from operations





    (47,109)







    (39,401)







    (134,784)







    (146,009)



    Other income (expense):

































    Interest income





    600







    1,137







    2,424







    4,320



    Interest expense





    (6,801)







    (3,093)







    (20,068)







    (9,180)



    Other (expense) income, net





    (141)







    10







    (177)







    (36)



    Total other expense, net





    (6,342)







    (1,946)







    (17,821)







    (4,896)



    Loss before income taxes





    (53,451)







    (41,347)







    (152,605)







    (150,905)



    Income tax provision





    (44)







    (20)







    (247)







    (38)



    Net loss



    $

    (53,495)





    $

    (41,367)





    $

    (152,852)





    $

    (150,943)



    Net loss per share—basic and diluted



    $

    (0.73)





    $

    (0.67)





    $

    (2.14)





    $

    (2.46)



    Weighted-average number of common shares outstanding

    used in net loss per share—basic and diluted





    73,466







    62,093







    71,479







    61,297



     

    KARYOPHARM THERAPEUTICS INC.

    CONDENSED CONSOLIDATED BALANCE SHEETS

    (unaudited)

    (in thousands)







    September 30,

    2020





    December 31,

    2019



    Assets

















    Cash, cash equivalents and investments



    $

    302,415





    $

    263,972



    Restricted cash





    1,806







    1,831



    Accounts receivable





    11,062







    7,862



    Property and equipment, net





    2,357







    3,046



    Other assets





    19,947







    18,252



    Total assets



    $

    337,587





    $

    294,963



    Liabilities and stockholders' equity

















    Deferred revenue



    $

    297





    $

    4,533



    Convertible senior notes





    115,802







    109,857



    Deferred royalty obligation





    73,588







    73,588



    Other liabilities





    64,130







    57,211



    Total liabilities





    253,817







    245,189



    Total stockholders' equity





    83,770







    49,774



    Total liabilities and stockholders' equity; 73,528 and 65,370 shares

    issued and outstanding at September 30, 2020 and December 31, 2019,

    respectively



    $

    337,587





    $

    294,963



     

    Cision View original content:http://www.prnewswire.com/news-releases/karyopharm-reports-third-quarter-2020-financial-results-and-highlights-recent-company-progress-301165209.html

    SOURCE Karyopharm Therapeutics Inc.

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  33. NEWTON, Mass., Nov. 2, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced positive top-line results from the Phase 3 portion of the randomized, double blind, placebo controlled, cross-over, SEAL study evaluating single agent, oral XPOVIO® (selinexor) versus matching placebo in patients with advanced unresectable dedifferentiated liposarcoma. The SEAL study met its primary endpoint of a statistically significant increase in progression-free survival (PFS); hazard ratio=0.70; p=0.023. These data indicate that treatment with XPOVIO reduced the risk of disease progression or death by approximately 30%, compared to placebo. The trial…

    NEWTON, Mass., Nov. 2, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (NASDAQ:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced positive top-line results from the Phase 3 portion of the randomized, double blind, placebo controlled, cross-over, SEAL study evaluating single agent, oral XPOVIO® (selinexor) versus matching placebo in patients with advanced unresectable dedifferentiated liposarcoma. The SEAL study met its primary endpoint of a statistically significant increase in progression-free survival (PFS); hazard ratio=0.70; p=0.023. These data indicate that treatment with XPOVIO reduced the risk of disease progression or death by approximately 30%, compared to placebo. The trial allowed patients on placebo with objective progression to cross over to the XPOVIO treatment arm. Among those patients who received XPOVIO, there was a trend towards an improvement in the median overall survival compared to those patients who began on the placebo arm of the study and never crossed over to the XPOVIO treatment arm. The safety profile for XPOVIO was consistent with previous clinical studies with fewer hematologic and infectious adverse events as compared to XPOVIO studies in patients with multiple myeloma and diffuse large B-cell lymphoma (DLBCL).

    The detailed results from the SEAL study will be presented virtually in an oral presentation at the Connective Tissue Oncology Society (CTOS) Annual Meeting on Friday, November 20, 2020 at 10:30 AM ET.

    "We are delighted to share these significant top-line results from the Phase 3 portion of the SEAL study, the first, late-stage clinical data for XPOVIO in a solid tumor indication," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "The top-line results from the SEAL study are particularly encouraging as advanced dedifferentiated liposarcoma represents a very difficult to treat cancer with no established standard of care and limited treatment options available to patients. XPOVIO may be particularly promising as it represents the first oral therapy to show activity in patients with previously treated liposarcoma. We look forward to presenting the detailed results at the upcoming CTOS Annual Meeting and plan to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2021 requesting the approval of XPOVIO to treat the patient population studied in SEAL. If approved, XPOVIO would represent the first oral, non-chemotherapy agent available for patients with dedifferentiated liposarcoma. The encouraging data from the SEAL study also provide additional rationale for advancing the clinical development of XPOVIO in other solid tumor indications, including in endometrial, glioblastoma, lung and other cancers where Karyopharm is currently conducting clinical studies."

    XPOVIO is currently approved by the FDA as a treatment for patients with relapsed or refractory multiple myeloma and relapsed or refractory DLBCL. XPOVIO is currently the only XPO1 inhibitor approved by the FDA and has been extensively tested in clinical trials across numerous cancer indications worldwide since 2012. Karyopharm has also submitted a supplemental New Drug Application (sNDA) for XPOVIO that is currently under review by the FDA for the expansion of XPOVIO's label to include XPOVIO as a treatment for patients with multiple myeloma after at least one prior line of therapy. The sNDA has been assigned an action date by the FDA of March 19, 2021 under the Prescription Drug User Fee Act (PDUFA).The full Prescribing Information for XPOVIO is available at www.XPOVIO.com.

    About the SEAL Study

    SEAL (Selinexor in Advanced Liposarcoma) is a Phase 2/3, randomized, double blind, placebo controlled, multicenter study (NCT02606461) designed to evaluate the efficacy and safety of twice-weekly, 60mg fixed dose of XPOVIO (selinexor) in patients with advanced unresectable dedifferentiated liposarcoma following at least two prior therapies. The Phase 2 portion of the study enrolled approximately 57 patients (1:1 randomization) and the Phase 3 portion enrolled approximately 285 patients (2:1 randomization). Patients on the placebo arm with confirmed progressive disease were permitted to cross over to the XPOVIO treatment arm. The primary endpoint of the study is PFS.

    Conference Call Information

    Karyopharm will host a conference call on November 20, 2020, at 12:00 p.m. Eastern Time, to discuss the results from the SEAL study. To access the conference call, please dial (877) 870-4263 (local) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call will be available under "Events & Presentations" in the Investor section of the Company's website, http://investors.karyopharm.com/events-presentations. An archived webcast will be available on the Company's website approximately two hours after the event.

    About XPOVIO® (selinexor)

    XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm's supplemental New Drug Application (sNDA) requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy has been accepted for filing by the FDA. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

    For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:

    Tel: +1 (888) 209-9326

    Email: 

    IMPORTANT SAFETY INFORMATION

    Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.

    Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

    Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. Neutropenia and febrile neutropenia occurred in patients with MM and in patients with DLBCL.

    Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).

    Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.

    Nausea/Vomiting: Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.

    Diarrhea: Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide standard anti-diarrheal agents, administer int