1. Presentations to be webcast on www.exelixis.com

    Exelixis, Inc. (NASDAQ:EXEL) today announced that Michael M. Morrissey, Ph.D., the company's President and Chief Executive Officer will participate in fireside chats at the following virtual investor conferences in March:

    • Cowen 41st Annual Healthcare Conference: Exelixis is scheduled to present at 2:40 PM EST / 11:40 AM PST on Monday, March 1, 2021.
    • Barclays Global Healthcare Conference 2021: Exelixis is scheduled to present at 11:30 AM EST / 8:30 AM PST on Tuesday, March 9, 2021.
    • Oppenheimer 31st Annual Healthcare Conference: Exelixis is scheduled to present at 11:20 AM EDT / 8:20 AM PDT on Tuesday, March 16, 2021.

    To access the webcast links, log onto www.exelixis.com and proceed to…

    Presentations to be webcast on www.exelixis.com

    Exelixis, Inc. (NASDAQ:EXEL) today announced that Michael M. Morrissey, Ph.D., the company's President and Chief Executive Officer will participate in fireside chats at the following virtual investor conferences in March:

    • Cowen 41st Annual Healthcare Conference: Exelixis is scheduled to present at 2:40 PM EST / 11:40 AM PST on Monday, March 1, 2021.
    • Barclays Global Healthcare Conference 2021: Exelixis is scheduled to present at 11:30 AM EST / 8:30 AM PST on Tuesday, March 9, 2021.
    • Oppenheimer 31st Annual Healthcare Conference: Exelixis is scheduled to present at 11:20 AM EDT / 8:20 AM PDT on Tuesday, March 16, 2021.

    To access the webcast links, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the presentations to ensure adequate time for any software download that may be required to listen to the webcasts. Replays will also be available at the same location for 14 days.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a registered Japanese trademark.

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  2. U.S. FDA designation based on an interim analysis of the phase 3 COSMIC-311 pivotal trial, in which cabozantinib demonstrated significant improvement in progression-free survival –

    Exelixis expects to submit supplementary New Drug Application in 2021 –

    Exelixis, Inc. (NASDAQ:EXEL) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to cabozantinib (CABOMETYX®) as a potential treatment for patients with differentiated thyroid cancer (DTC) that has progressed following prior therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). The FDA's Breakthrough Therapy Designation aims to expedite the development and review of drugs that are intended to treat…

    U.S. FDA designation based on an interim analysis of the phase 3 COSMIC-311 pivotal trial, in which cabozantinib demonstrated significant improvement in progression-free survival –

    Exelixis expects to submit supplementary New Drug Application in 2021 –

    Exelixis, Inc. (NASDAQ:EXEL) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to cabozantinib (CABOMETYX®) as a potential treatment for patients with differentiated thyroid cancer (DTC) that has progressed following prior therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). The FDA's Breakthrough Therapy Designation aims to expedite the development and review of drugs that are intended to treat serious or life-threatening diseases. To qualify for this designation, preliminary clinical evidence must indicate that the drug may demonstrate substantial improvement on at least one clinically significant endpoint over existing therapies.

    "Receiving Breakthrough Therapy Designation is a testament to both the urgent need for effective treatments for patients with differentiated thyroid cancer who progressed after prior therapy and the promising data demonstrating cabozantinib significantly improved progression-free survival for these patients," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "We look forward to submitting our regulatory application in 2021 and to working closely with the FDA during the review process, with the goal of bringing cabozantinib to this patient population with a high unmet medical need for whom there is currently no available standard of care."

    In December 2020, Exelixis announced that at a planned interim analysis, the phase 3 COSMIC-311 pivotal trial met the co-primary endpoint, demonstrating a significant reduction in the risk of disease progression or death of 78% with cabozantinib versus placebo (HR 0.22, 96% CI 0.13 – 0.36; p<0.0001) in patients with radioactive iodine-refractory differentiated thyroid cancer who have progressed after up to two prior VEGFR-targeted therapies. The safety profile was consistent with that previously observed for cabozantinib.

    About COSMIC-311

    COSMIC-311 is a multicenter, randomized, double-blind, placebo-controlled phase 3 pivotal trial that aimed to enroll approximately 300 patients at 150 sites globally. Patients were randomized in a 2:1 ratio to receive either cabozantinib 60 mg or placebo once daily. The co-primary endpoints are progression-free survival and objective response rate. More information about this trial is available at ClinicalTrials.gov.

    About Differentiated Thyroid Cancer

    Approximately 44,000 new cases of thyroid cancer will be diagnosed in the U.S. in 2021.1 Nearly three out of four of these cases will be in women, and the disease is more commonly diagnosed at a younger age compared to most other adult cancers.1 While cancerous thyroid tumors include differentiated, medullary and anaplastic forms, differentiated thyroid tumors make up about 90 percent of cases.1 These include papillary, follicular and Hürthle cell cancer.1 Differentiated thyroid cancer is typically treated with surgery followed by ablation of the remaining thyroid tissue with radioiodine, but approximately 5% to 15% of cases are resistant to radioiodine treatment. 2,3 For these patients, life expectancy is only three to six years from the time metastatic lesions are detected.4,5,6

    About CABOMETYX® (cabozantinib)

    In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with HCC who have been previously treated with sorafenib; and for patients with advanced RCC as a first-line treatment in combination with nivolumab. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

    CABOMETYX is not indicated for radioiodine-refractory differentiated thyroid cancer.

    IMPORTANT SAFETY INFORMATION

    WARNINGS AND PRECAUTIONS

    Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

    Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

    Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

    Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

    Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

    Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

    Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.

    Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

    With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab.

    Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab depending on severity.

    Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.

    Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

    Proteinuria: Proteinuria was observed in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

    Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

    Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

    Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

    Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

    ADVERSE REACTIONS

    The most common (≥20%) adverse reactions are:

    CABOMETYX as a single agent: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation, and dysphonia.

    CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

    DRUG INTERACTIONS

    Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

    Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John's wort.

    USE IN SPECIFIC POPULATIONS

    Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

    Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

    Please see accompanying full Prescribing Information https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf.

    You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery — all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Forward-Looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: the therapeutic potential of cabozantinib as a treatment for patients with DTC that has progressed following prior therapy and who are radioactive iodine-refractory; the regulatory review process, including Exelixis' plans to submit a supplementary New Drug Application in 2021; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere, including the risk that the FDA may not approve cabozantinib as a treatment for patients with previously treated radioactive iodine-refractory DTC in a timely fashion, if at all; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating cabozantinib; the continuing COVID-19 pandemic and its impact on Exelixis' product development and commercial activities; Exelixis' ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions; and other factors affecting Exelixis and its partners to obtain regulatory approval for cabozantinib in new indications discussed under the caption "Risk Factors" in Exelixis' Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 10, 2021, and in Exelixis' future filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a Japanese trademark.


    1 American Cancer Society. About Thyroid Cancer. Available at: https://www.cancer.org/cancer/thyroid-cancer/about.html. Accessed February 2021.

    2 Cooper DS, et al. 2009. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 19:1167–1214.

    3 Worden F. 2014. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer. Ther Adv Med Oncol. 6:267–279.

    4 Xing M, Haugen BR, Schlumberger M. 2013. Progress in molecular-based management of differentiated thyroid cancer. Lancet. 381:1058–1069.

    5 Pacini F, et al. 2012. Radioactive iodine-refractory differentiated thyroid cancer: unmet needs and future directions. Expert Rev Endocrinol Metab. 7:541–554.

    6 Durante C, et al. 2006. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 91:2892–2899.

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  3. - Presentation to be webcast on www.exelixis.com -

    Exelixis, Inc. (NASDAQ:EXEL) today announced that Michael M. Morrissey, Ph.D., the company's President and Chief Executive Officer will participate in a fireside chat as part of the SVB Leerink 10th Annual Global Healthcare Conference on Friday, February 26, 2021 at 1:00 PM EST / 10:00 AM PST. Due to the ongoing COVID-19 pandemic, the conference will be held as a virtual event.

    To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to…

    - Presentation to be webcast on www.exelixis.com -

    Exelixis, Inc. (NASDAQ:EXEL) today announced that Michael M. Morrissey, Ph.D., the company's President and Chief Executive Officer will participate in a fireside chat as part of the SVB Leerink 10th Annual Global Healthcare Conference on Friday, February 26, 2021 at 1:00 PM EST / 10:00 AM PST. Due to the ongoing COVID-19 pandemic, the conference will be held as a virtual event.

    To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast. A replay will also be available at the same location for 14 days.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a registered Japanese trademark.

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  4. – Results of phase 2 trial show CABOMETYX significantly improved progression-free survival versus current guideline-preferred therapy –

    – Data to be presented during the 2021 American Society of Clinical Oncology's Genitourinary Cancers Symposium and simultaneously published in The Lancet

    Exelixis, Inc. (NASDAQ:EXEL) today announced positive phase 2 results for CABOMETYX® (cabozantinib) compared with sunitinib, the current preferred therapy according to U.S. cancer treatment guidelines,1 in patients with metastatic papillary renal cell carcinoma (PRCC), a form of kidney cancer. The data from the S1500 trial (also called "PAPMET"), which was designed and managed by SWOG Cancer Research Network, will be presented on Saturday, February 13…

    – Results of phase 2 trial show CABOMETYX significantly improved progression-free survival versus current guideline-preferred therapy –

    – Data to be presented during the 2021 American Society of Clinical Oncology's Genitourinary Cancers Symposium and simultaneously published in The Lancet

    Exelixis, Inc. (NASDAQ:EXEL) today announced positive phase 2 results for CABOMETYX® (cabozantinib) compared with sunitinib, the current preferred therapy according to U.S. cancer treatment guidelines,1 in patients with metastatic papillary renal cell carcinoma (PRCC), a form of kidney cancer. The data from the S1500 trial (also called "PAPMET"), which was designed and managed by SWOG Cancer Research Network, will be presented on Saturday, February 13th during the Oral Abstract Session: Renal Cell Cancer at 10:00 – 11:15 a.m. PT at the 2021 American Society of Clinical Oncology's Genitourinary Cancers Symposium (ASCO GU), which is being held virtually, February 11-13, 2021. The findings will be simultaneously published in The Lancet.

    "This is the first randomized trial specific to metastatic papillary renal cell carcinoma to show a clinically and statistically significant benefit with a targeted therapy, CABOMETYX, over an existing standard of care," said Dr. Sumanta Pal, Clinical Professor and Co-Director of the Kidney Cancer Program, City of Hope, and SWOG's principal investigator for the study. "The progression-free survival benefit seen in this trial is a meaningful improvement for patients with this form of kidney cancer. Based on these findings, there is strong evidence for the use of CABOMETYX in this setting."

    "The PAPMET trial was sponsored by the National Cancer Institute's drug development program in the Cancer Therapy Evaluation Program, which facilitates collaborations between pharmaceutical companies as well as collaborations between companies and academic investigators. In the case of PAPMET, the National Cancer Institute brought Exelixis, AstraZeneca and Pfizer together with oncologists from SWOG to organize this trial to define which of the tested therapies is most effective for patients with papillary renal cell carcinoma," said Dr. John Wright, Associate Branch Chief, Investigational Drug Branch, CTEP, NCI.

    In the new findings, CABOMETYX demonstrated significant improvement in progression-free survival (PFS), the trial's primary endpoint, and objective response rate (ORR) compared with sunitinib. Median PFS was 9.0 months (95% CI: 6-12) with CABOMETYX (n=44) versus 5.6 months (95% CI: 3-7) with sunitinib (n=46) (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.37 to 0.97; p=0.019). ORR was 23% for CABOMETYX versus 4% for sunitinib (p=0.010). Median overall survival was 20.0 months for cabozantinib and 16.4 months for sunitinib (HR 0.84; 95% CI: 0.47 to 1.51; p=0.28), which did not reach statistical significance. Enrollment into additional arms of the study examining the use of crizotinib or savolitinib was halted early based on predefined interim futility analyses comparing these agents with the sunitinib arm.

    "We're excited to build on the demonstrated history of CABOMETYX's clinically meaningful and statistically significant benefits for patients with renal cell carcinoma with these data that support its efficacy in patients with papillary renal cell carcinoma, who are often not the focus of major clinical trials for kidney cancer," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "The ability of CABOMETYX to inhibit MET, which is frequently altered in this tumor type, encouraged additional research into its potential benefits. It's gratifying to see these positive results of the PAPMET trial, which may help physicians choose an appropriate therapy for their patients with advanced papillary renal cell carcinoma."

    The discontinuation rate of study medications due to treatment-related adverse events was 24% for sunitinib and 23% for CABOMETYX. The most common grade 3 or 4 adverse events with CABOMETYX were hypertension (32%), hand-foot syndrome (20%) and fatigue (13%). The most common grade 3 or 4 adverse events with sunitinib were hypertension (17%), anemia (13%) and decrease in white blood cell count (11%). One death, secondary to a thromboembolic event, within 30 days of the last dose of study medication was reported for a patient receiving CABOMETYX.

    More information about this trial is available at ClinicalTrials.gov.

    About the SWOG S1500 Clinical Trial

    SWOG S1500 (NCT02761057), also called PAPMET, was a randomized phase 2 trial comparing cabozantinib, crizotinib and savolitinib to sunitinib, a VEGF-directed multikinase inhibitor and current standard of care for patients with advanced or metastatic PRCC. The study was supported by the National Cancer Institute (NCI), part of the National Institutes of Health, designed and led by the SWOG Cancer Research Network under the leadership of Dr. Pal, and conducted through the NCI National Clinical Trials Network. The goal of the trial was to determine whether MET-directed therapy improves clinical outcomes relative to conventional VEGF-directed agents. Exelixis provided the cabozantinib for the trial under a Cooperative Research and Development Agreement with the NCI.

    Patients with pathologically verified PRCC (type I, II, or not otherwise specified) were randomized 1:1:1:1 to the control arm of sunitinib or one of three investigational arms: CABOMETYX, crizotinib and savolitinib. CABOMETYX was orally administered at 60 mg daily, with dose reductions to 40 mg and 20 mg permitted. Enrolled patients could have received up to one prior therapy. Prior therapy was received by 10 patients (7%), and the most common prior therapy was the combination of nivolumab with ipilimumab (4 patients). The primary endpoint was PFS, defined as the time from randomization to the time of radiographic or clinical progression, symptomatic deterioration or death from any cause, whichever occurred first. Secondary endpoints included objective response rate and overall survival, defined as the time from randomization to death from any cause, and safety evaluation.

    About Papillary Renal Cell Carcinoma

    PRCC accounts for about 15% of all renal cell carcinomas.2,3 Genomic and molecular characterization of PRCC has implicated MET signaling as a key driver of this cancer.2,4 Targeting VEGFR and other tyrosine kinases, including MET and AXL, has led to improved outcomes in RCC as compared with sunitinib, and further supported the investigation of MET targeting tyrosine kinase inhibitors in PRCC.

    The American Cancer Society's 2021 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.5 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 13%.4 Approximately 32,000 patients in the U.S. and 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2021.6

    About CABOMETYX® (cabozantinib)

    In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; and for patients with advanced RCC as a first-line treatment in combination with nivolumab. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

    IMPORTANT SAFETY INFORMATION

    WARNINGS AND PRECAUTIONS

    Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

    Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

    Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

    Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

    Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

    Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

    Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.

    Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

    With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab.

    Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab depending on severity.

    Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.

    Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

    Proteinuria: Proteinuria was observed in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

    Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

    Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

    Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

    Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

    ADVERSE REACTIONS

    The most common (≥20%) adverse reactions are:

    CABOMETYX as a single agent: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation, and dysphonia.

    CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

    DRUG INTERACTIONS

    Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

    Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John's wort.

    USE IN SPECIFIC POPULATIONS

    Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

    Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

    Please see accompanying full Prescribing Information https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf.

    You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Forward-Looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: the presentation of data from the PAPMET study at ASCO GU and simultaneous publication of such data in The Lancet; the therapeutic potential of CABOMETYX for patients with advanced papillary RCC; the potential for the PAPMET data results to help inform physician treatment plans for patients with advanced papillary RCC; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the availability of data at the referenced times; the potential failure of cabozantinib to demonstrate safety and/or efficacy in future trials; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating CABOMETYX; Exelixis' continuing compliance with applicable legal and regulatory requirements; Exelixis' dependence on third-party vendors for the development, manufacture and supply of cabozantinib; Exelixis' ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions, including as a result of the COVID-19 pandemic; and other factors affecting Exelixis and its development programs discussed under the caption "Risk Factors" in Exelixis' Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 10, 2021, and in Exelixis' future filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a Japanese trademark.

    ________________________

    1 NCCN Guidelines Version 2.2021 Kidney Cancer. Available at: https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf. Accessed February 2021.

    2 Zhang T, Gong J, Maia MC, Pal SK. Systemic Therapy for Non-Clear Cell Renal Cell Carcinoma. Am Soc Clin Oncol Educ Book 2017;37:337–42.

    3 Cancer Genome Atlas Research Network, Linehan WM, Spellman PT, et al. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma. N Engl J Med 2016;374(2):135–45.

    4 Pal SK, Ali SM, Yakirevich E, et al. Characterization of Clinical Cases of Advanced Papillary Renal Cell Carcinoma via Comprehensive Genomic Profiling. Eur Urol 2018;73(1):71–8.

    5 American Cancer Society: Cancer Facts & Figures 2021. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf. Accessed February 2021.

    6 Decision Resources Report: Renal Cell Carcinoma. October 2014 (internal data on file).

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  5. – Study demonstrated objective response rates of 38% in all patients, 62.5% in patients with renal cell carcinoma and 42.4% in patients with urothelial carcinoma –

    – Data to be presented during the 2021 American Society of Clinical Oncology's Genitourinary Cancers Symposium –

    Exelixis, Inc. (NASDAQ:EXEL) today announced positive final data for a phase 1 trial sponsored and conducted by the U.S. National Cancer Institute (NCI), including seven expansion cohorts, evaluating cabozantinib in combination with either nivolumab or nivolumab plus ipilimumab in patients with refractory metastatic genitourinary (GU) tumors. The data will be presented as part of the Rapid Abstract Session: Urothelial Carcinoma and Rare Tumors from 2:15 p.m. – 3:05 p.m…

    – Study demonstrated objective response rates of 38% in all patients, 62.5% in patients with renal cell carcinoma and 42.4% in patients with urothelial carcinoma –

    – Data to be presented during the 2021 American Society of Clinical Oncology's Genitourinary Cancers Symposium –

    Exelixis, Inc. (NASDAQ:EXEL) today announced positive final data for a phase 1 trial sponsored and conducted by the U.S. National Cancer Institute (NCI), including seven expansion cohorts, evaluating cabozantinib in combination with either nivolumab or nivolumab plus ipilimumab in patients with refractory metastatic genitourinary (GU) tumors. The data will be presented as part of the Rapid Abstract Session: Urothelial Carcinoma and Rare Tumors from 2:15 p.m. – 3:05 p.m. PT on Friday, February 12 at the 2021 American Society of Clinical Oncology's Genitourinary Cancers Symposium (ASCO GU), which is being held virtually, February 11-13, 2021.

    In the study, cabozantinib in combination with either nivolumab alone (n=64) or nivolumab plus ipilimumab (n=56) demonstrated an objective response rate (ORR) for all evaluable patients (n=108) of 38%, with an 11.1% complete response (CR) rate per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

    For the 33 patients with previously treated metastatic urothelial carcinoma (UC), the ORR was 42.4%, and the CR rate was 21%. The ORR for the 16 patients with previously treated metastatic renal cell carcinoma (RCC) was 62.5%. The ORR was 20% for patients with urachal adenocarcinoma (n=15), 85.7% for squamous cell carcinoma of the bladder (n=7) and 44.4% for penile carcinoma (n=9).

    The median overall survival for the entire population was 15.9 months. Median progression-free survival was 5.5 months, and median duration of response was 22.8 months.

    "We see a significant level of anti-tumor activity with an acceptable tolerability profile for the combination of cabozantinib with nivolumab or nivolumab and ipilimumab for this early phase trial across a broad range of GU malignancies," said Andrea Apolo, M.D., Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health and the principal investigator of the trial. "This phase 1 study's early results provided important information for the development of the phase 3 CheckMate -9ER study sponsored by Bristol Myers Squibb, of cabozantinib plus nivolumab versus sunitinib that recently reported improved progression-free survival, overall response, and overall response rate, leading to last month's U.S. approval of the combination therapy of cabozantinib and nivolumab in first-line advanced renal cell carcinoma. The additional activity seen in other GU tumors support further research into the potential of cabozantinib combinations with immune checkpoint inhibitors in other advanced, intractable GU cancers."

    "These clinical data were the result of a productive collaboration between the investigators leading the trial, NCI-CTEP, the trial sponsor, and both Exelixis and Bristol Myers Squibb. We would like to thank the patients who generously agreed to participate in the trial," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "The combination of cabozantinib with immune checkpoint inhibitors continues to demonstrate positive outcomes for patients with difficult-to-treat advanced genitourinary malignancies such as renal cell and urothelial carcinomas. Going forward, we will continue our work to uncover the potential of cabozantinib in combination with immunotherapies to provide further treatment options to patients with cancer in need."

    Treatment-related grade 3 or 4 adverse events (>5% of patients) observed in the doublet cabozantinib and nivolumab group included fatigue (13%), hypertension (13%), dehydration (6%) and thromboembolic event (6%). Immune-related grade 3 or 4 adverse events (>5% of patients) were not observed in this group. Treatment-related grade 3 or 4 adverse events (>5% of patients) observed in the triplet cabozantinib plus nivolumab and ipilimumab group included fatigue (16%), hypertension (11%), dehydration (5.3%) and thromboembolic event (5.3%). Immune-related grade 3 or 4 adverse events (>5% of patients) for this group included hepatitis (7%) and colitis (7%).

    About the Trial

    The trial was sponsored by the U.S. NCI through Cooperative Research and Development Agreements between the NCI's Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment and Diagnosis, and both Exelixis and Bristol Myers Squibb. Andrea Apolo, M.D., of the NCI's Genitourinary Malignancies Branch, is the principal investigator. The trial was conducted by the NCI and includes centers from its Experimental Therapeutics Clinical Trials Network.

    This open label, non-randomized phase 1 trial was divided into two parts: a dose-escalation phase and an expansion cohort phase. The primary endpoint of the phase 1 trial was to determine the dose-limiting toxicity and recommended doses of the doublet and triplet combinations for later stage clinical studies. The secondary endpoint is ORR as assessed per RECIST version 1.1.

    Once the recommended doses were determined for the combinations of cabozantinib plus nivolumab and of cabozantinib plus nivolumab and ipilimumab, the trial enrolled seven subsequent expansion cohorts. The cabozantinib plus nivolumab expansion cohorts included patients with UC, RCC, bladder adenocarcinoma and other rare metastatic GU tumors. The cabozantinib plus nivolumab and ipilimumab expansion cohorts included UC, RCC and penile carcinoma. The objectives of the trial were to determine the clinical activity, safety and tolerability of both combinations in multiple metastatic GU tumors.

    The recommended phase 2 doses determined for the combination of cabozantinib plus nivolumab were cabozantinib 40 mg daily and 3 mg/kg of nivolumab every two weeks. The recommended phase 2 doses determined for the combination of cabozantinib plus nivolumab and ipilimumab were cabozantinib 40 mg daily, 3 mg/kg of nivolumab every two weeks and 1 mg/kg ipilimumab every three weeks.

    More information about the trial is available at ClinicalTrials.gov.

    About Genitourinary Cancers

    Genitourinary cancers are those that affect the urinary tract, bladder, kidneys, ureter, prostate, testicles, penis or adrenal glands — parts of the body involved in reproduction and excretion — and include RCC, castration-resistant prostate cancer (CRPC) and UC.1

    The American Cancer Society's (ACS) 2021 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.2 Clear cell RCC is the most common type of kidney cancer in adults.3 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 13%.2 Approximately 32,000 patients in the U.S. and over 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2021, with nearly 15,000 patients in need of a first-line treatment in the U.S.4

    According to the ACS, in 2021, approximately 250,000 new cases of prostate cancer will be diagnosed, and 34,000 people will die from the disease.2 Prostate cancer that has spread beyond the prostate and does not respond to androgen-suppression therapies — a common treatment for prostate cancer — is known as metastatic CRPC.5 Researchers estimate that in 2020, 43,000 people were diagnosed with metastatic CRPC, which has a median survival of less than two years.6,7,8

    Urothelial cancers encompass carcinomas of the bladder, ureter and renal pelvis at a ratio of 50:3:1, respectively.9 Bladder cancer occurs mainly in older people, with 90% of patients aged 55 or older.10 With an estimated 84,000 new cases expected to be diagnosed in 2021, bladder cancer accounts for about 5% of all new cases of cancer in the U.S. each year.11 It is the fourth most common cancer in men.2

    About CABOMETYX® (cabozantinib)

    In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib; and for patients with advanced RCC as a first-line treatment in combination with nivolumab. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

    IMPORTANT SAFETY INFORMATION

    WARNINGS AND PRECAUTIONS

    Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

    Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

    Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

    Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

    Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

    Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

    Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.

    Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

    With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab.

    Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab depending on severity.

    Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.

    Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

    Proteinuria: Proteinuria was observed in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

    Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

    Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

    Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

    Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

    ADVERSE REACTIONS

    The most common (≥20%) adverse reactions are:

    CABOMETYX as a single agent: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation, and dysphonia.

    CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

    DRUG INTERACTIONS

    Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

    Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John's wort.

    USE IN SPECIFIC POPULATIONS

    Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

    Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

    Please see accompanying full Prescribing Information https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf.

    You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Forward-Looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: the presentation of data from a phase 1 study evaluating cabozantinib in combination with either nivolumab or nivolumab plus ipilimumab in patients with refractory metastatic GU tumors at ASCO GU; the therapeutic potential of cabozantinib combinations with immune checkpoint inhibitors in advanced, intractable GU cancers; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the availability of data at the referenced times; the potential failure of cabozantinib to demonstrate safety and/or efficacy in future trials; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating CABOMETYX; Exelixis' continuing compliance with applicable legal and regulatory requirements; Exelixis' dependence on third-party vendors for the development, manufacture and supply of cabozantinib; Exelixis' ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions, including as a result of the COVID-19 pandemic; and other factors affecting Exelixis and its development programs discussed under the caption "Risk Factors" in Exelixis' Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 10, 2021, and in Exelixis' future filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a Japanese trademark.

    1 National Cancer Institute Dictionary of Cancer Terms. Genitourinary System. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/genitourinary-system. Accessed February 2021.

    2 American Cancer Society: Cancer Facts & Figures 2021. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf Accessed February 2021.

    3 Jonasch, E., Gao, J., Rathmell, W., Renal cell carcinoma. BMJ. 2014; 349:g4797.

    4 Decision Resources Report: Renal Cell Carcinoma. October 2014 (internal data on file).

    5 American Society of Clinical Oncology. Cancer.Net. Treatment of Metastatic Castration-Resistant Prostate Cancer. September 8, 2014. Available at: https://www.cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/treatment-metastatic-castration-resistant-prostate-cancer. Accessed February 2021.

    6 Scher, H.I., Solo, K., Valant, J., Todd, M.B., Mehra, M. Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model. PLOS ONE. 2015; 10: e0139440.

    7 American Urological Association. Prostate Cancer: Castration Resistant Guideline. 2018. Available at: https://www.auanet.org/guidelines/prostate-cancer-castration-resistant-guideline. Accessed February 2021.

    8 Moreira, D. M., Howard, L. E., Sourbeer, K. N., et al. Predicting Time From Metastasis to Overall Survival in Castration-Resistant Prostate Cancer: Results From SEARCH. Clin Genitourin Cancer. 2017; 15: 60–66.e2.

    9 Hurwitz, M. et al. Urothelial and Kidney Cancers. Cancer Management. http://www.cancernetwork.com/cancer-management/urothelial-and-kidney-cancers. Accessed February 2021.

    10 American Cancer Society. Bladder Cancer Key Statistics. https://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-key-statistics. Accessed February 2021.

    11 National Cancer Institute. SEER Stat Fact Sheets: Bladder Cancer. https://seer.cancer.gov/statfacts/html/urinb.html. Accessed February 2021.

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  6. - Total Revenues of $270.1 Million for the Fourth Quarter of 2020, $987.5 Million for the Full Year 2020 -

    - GAAP Diluted EPS of $0.09 for the Fourth Quarter of 2020, $0.35 for the Full Year 2020 -

    - Non-GAAP Diluted EPS of $0.14 for the Fourth Quarter of 2020, $0.61 for the Full Year 2020 -

    - Conference Call and Webcast Today at 5:00 PM Eastern Time -

    Exelixis, Inc. (NASDAQ:EXEL) today reported financial results for the fourth quarter and full year 2020 and provided an update on progress toward achieving key corporate objectives, as well as commercial, clinical and pipeline development milestones.

    "I'm very proud of the Exelixis team's execution in the fourth quarter and full year 2020 as we advanced all components of our business to…

    - Total Revenues of $270.1 Million for the Fourth Quarter of 2020, $987.5 Million for the Full Year 2020 -

    - GAAP Diluted EPS of $0.09 for the Fourth Quarter of 2020, $0.35 for the Full Year 2020 -

    - Non-GAAP Diluted EPS of $0.14 for the Fourth Quarter of 2020, $0.61 for the Full Year 2020 -

    - Conference Call and Webcast Today at 5:00 PM Eastern Time -

    Exelixis, Inc. (NASDAQ:EXEL) today reported financial results for the fourth quarter and full year 2020 and provided an update on progress toward achieving key corporate objectives, as well as commercial, clinical and pipeline development milestones.

    "I'm very proud of the Exelixis team's execution in the fourth quarter and full year 2020 as we advanced all components of our business to enable top-line revenue growth in 2021 and beyond," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "Following the strong commercial performance of cabozantinib in the fourth quarter of 2020, Exelixis maintained momentum into 2021 with the FDA approval and launch of CABOMETYX in combination with OPDIVO as a first-line treatment for advanced renal cell carcinoma, based on the CheckMate -9ER study. Our commercial team is now hard at work bringing this important new combination therapy to every eligible patient that may benefit from this potentially best-in-class regimen."

    Dr. Morrissey continued: "Looking ahead, we believe Exelixis is well positioned to deliver significant revenue growth as we pursue additional regulatory approvals for cabozantinib to benefit more patients and work towards a multi-billion-dollar franchise. In parallel, we're focused on the rapid development of XL092, with plans to advance this next-generation oral tyrosine kinase inhibitor into pivotal trials this year. We also continue to make significant progress on our early-stage pipeline, having recently begun phase 1 development of XL102, our small molecule CDK7 inhibitor, and plan to file an Investigational New Drug application for XB002, our first antibody-drug conjugate, once the drug product release assays are finalized. With significant commercial opportunities and as our growing pipeline of small molecules and biologics matures, we are quickly working toward expanding our oncology product portfolio to further our mission to help cancer patients recover stronger and live longer."

    Fourth Quarter and Full Year 2020 Financial Results

    Total revenues for the quarter and year ended December 31, 2020 were $270.1 million and $987.5 million, respectively, compared to $240.3 million and $967.8 million for the comparable periods in 2019.

    Total revenues for the quarter and year ended December 31, 2020 included net product revenues of $200.4 million and $741.6 million, respectively, compared to $194.9 million and $760.0 million for the comparable periods in 2019. The decrease in net product revenues for the full year 2020 was due to a decrease in sales volumes, which was partially offset by an increase in the average selling price.

    Collaboration revenues, composed of license revenues and collaboration services revenues, were $69.7 million and $246.0 million for the quarter and year ended December 31, 2020, respectively, compared to $45.4 million and $207.8 million for the comparable periods in 2019. The increases in collaboration revenues were primarily related to increases in milestone related revenues and development cost reimbursements earned, and higher royalty revenues for the sales of cabozantinib outside of the U.S. generated by Exelixis' collaboration partners, Ipsen Pharma SAS (Ipsen) and Takeda Pharmaceutical Company Limited (Takeda).

    Research and development expenses for the quarter and year ended December 31, 2020 were $154.3 million and $547.9 million, respectively, compared to $94.4 million and $337.0 million for the comparable periods in 2019. The increases in research and development expenses were primarily related to increases in clinical trial costs, license and other collaboration costs, personnel expenses and stock-based compensation expense.

    Selling, general and administrative expenses for the quarter and year ended December 31, 2020 were $82.4 million and $293.4 million, respectively, compared to $58.0 million and $228.2 million for the comparable periods in 2019. The increases in selling, general and administrative expenses were primarily related to increases in stock-based compensation expense, corporate giving and personnel expenses.

    Provision for (benefit from) income taxes for the quarter and year ended December 31, 2020 was $(0.3) million and $19.1 million, respectively, compared to $16.3 million and $77.1 million for the comparable periods in 2019, primarily due to a decrease in pre-tax income.

    GAAP net income for the quarter ended December 31, 2020 was $28.4 million, or $0.09 per share, basic and diluted, compared to GAAP net income of $68.7 million, or $0.23 per share, basic and $0.22 per share, diluted, for the comparable period in 2019. GAAP net income for the year ended December 31, 2020 was $111.8 million, or $0.36 per share, basic and $0.35 per share, diluted, compared to GAAP net income of $321.0 million, or $1.06 per share, basic and $1.02 per share, diluted, for the year ended December 31, 2019.

    Non-GAAP net income for the quarter ended December 31, 2020 was $43.3 million, or $0.14 per share, basic and diluted, compared to non-GAAP net income of $81.0 million, or $0.27 per share, basic and $0.26 per share, diluted, for the comparable period in 2019. Non-GAAP net income for the year ended December 31, 2020 was $193.3 million, or $0.63 per share, basic and $0.61 per share, diluted, compared to non-GAAP net income of $364.9 million, or $1.21 per share, basic and $1.16 per share, diluted, for the year ended December 31, 2019. Non-GAAP net income excludes stock-based compensation, adjusted for the related income tax effect.

    Cash and investments were $1.5 billion at December 31, 2020, compared to $1.4 billion at December 31, 2019.

    Non-GAAP Financial Measures

    To supplement Exelixis' financial results presented in accordance with U.S. Generally Accepted Accounting Principles (GAAP), Exelixis presents non-GAAP net income (and the related per share measures), which excludes from GAAP net income (and the related per share measures) stock-based compensation expense, adjusted for the related income tax effect for all periods presented.

    Exelixis believes that the presentation of these non-GAAP financial measures provides useful supplementary information to, and facilitates additional analysis by, investors. In particular, Exelixis believes that these non-GAAP financial measures, when considered together with its financial information prepared in accordance with GAAP, can enhance investors' and analysts' ability to meaningfully compare Exelixis' results from period to period, and to identify operating trends in Exelixis' business. Exelixis has excluded stock-based compensation expense, adjusted for the related income tax effect, because it is a non-cash item that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. Exelixis also regularly uses these non-GAAP financial measures internally to understand, manage and evaluate its business and to make operating decisions.

    These non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. Exelixis encourages investors to carefully consider its results under GAAP, as well as its supplemental non-GAAP financial information and the reconciliation between these presentations, to more fully understand Exelixis' business. Reconciliations between GAAP and non-GAAP results are presented in the tables of this release.

    2021 Financial Guidance

    Exelixis is providing the following financial guidance for fiscal year 2021:

    Total revenues

     

    $1,150 million - $1,250 million

    Net product revenues

     

    $950 million - $1,050 million

    Cost of goods sold

     

    Approximately 5% - 6% of net product revenue

    Research and development expenses (1)

     

    $600 million - $650 million

    Selling, general and administrative expenses (2)

     

    $375 million - $425 million

    Effective tax rate

     

    20% - 22%

    Cash and investments (3)

     

    $1.6 billion - $1.7 billion

    (1)

    Includes $45 million of non-cash stock-based compensation expense.

    (2)

    Includes $60 million of non-cash stock-based compensation expense.

    (3)

    This cash and investments guidance does not include any potential new business development activity.

    Cabozantinib Highlights

    Cabozantinib Franchise Net Product Revenues and Royalties. Net product revenues generated by the cabozantinib franchise in the U.S. were $200.4 million during the fourth quarter of 2020, with net product revenues of $196.3 million from CABOMETYX® (cabozantinib) and $4.0 million from COMETRIQ® (cabozantinib). For the year ended December 31, 2020, net product revenues generated by the cabozantinib franchise in the U.S. were $741.6 million, with net product revenues of $718.7 million from CABOMETYX and $22.9 million from COMETRIQ. Based upon cabozantinib-related revenues generated by Exelixis' collaboration partners during the quarter and year ended December 31, 2020, Exelixis earned $23.3 million and $78.4 million, respectively, in royalty revenues. In 2020, global cabozantinib franchise net revenue generated by Exelixis and its partners exceeded $1.0 billion.

    U.S. Food and Drug Administration (FDA) Approves CABOMETYX in Combination with OPDIVO® (nivolumab) for Advanced Renal Cell Carcinoma (RCC). In January 2021, Exelixis announced that the FDA approved its supplemental New Drug Application (sNDA) for CABOMETYX in combination with Bristol Myers Squibb's (BMS) OPDIVO as a first-line treatment of patients with advanced RCC. The approval is based on positive results of the CheckMate -9ER phase 3 pivotal trial, which met its primary endpoint of significantly improving progression-free survival (PFS) and secondary endpoints of overall survival and objective response rate. Exelixis announced the submission of this sNDA in August 2020. In October 2020, the FDA accepted the filing, granting the application Priority Review designation.

    Supplemental Applications Submitted for CABOMETYX in Combination with OPDIVO in European Union and Japan for the Treatment of Advanced Metastatic RCC. In September 2020, Exelixis announced that its collaboration partner Ipsen and BMS had each submitted type II variation applications for CABOMETYX in combination with OPDIVO for the treatment of metastatic RCC to the European Medicines Agency (EMA), which was validated by the EMA on September 12, 2020. In October 2020, Exelixis announced that its collaboration partner Takeda, along with Ono Pharmaceuticals Co., Ltd., submitted a supplemental application to the Japanese Ministry of Health, Labour and Welfare (MHLW) for Manufacturing and Marketing Approval of CABOMETYX in combination with OPDIVO for the treatment of patients with unresectable, advanced or metastatic RCC. Both applications are also based on the results from the CheckMate -9ER study.

    Exelixis' Partner Takeda Receives Approval in Japan for CABOMETYX for the Treatment of Unresectable Hepatocellular Carcinoma (HCC) That Has Progressed After Prior Cancer Chemotherapy. In November 2020, Exelixis announced that its collaboration partner Takeda received approval from the Japanese MHLW to manufacture and market CABOMETYX as a treatment for patients with unresectable HCC that has progressed after prior cancer chemotherapy. Takeda's application was based on the results of two clinical trials in patients with advanced HCC who had received prior systemic therapy: CELESTIAL, a global, randomized, placebo-controlled, double-blind phase 3 clinical trial; and Cabozantinib-2003, a phase 2 clinical bridging trial conducted in Japan. Exelixis received a $15.0 million milestone payment from Takeda upon the first commercial sale of CABOMETYX for unresectable HCC, which occurred in the fourth quarter of 2020.

    Announcement of Top-line Results from Pivotal Phase 3 COSMIC-311 Trial of Cabozantinib in Patients with Previously Treated Radioiodine (RAI)-Refractory Differentiated Thyroid Cancer (DTC). In December 2020, Exelixis announced that COSMIC-311, the phase 3 pivotal trial evaluating cabozantinib versus placebo in patients with RAI-refractory DTC who have progressed after up to two prior vascular endothelial growth factor receptor-targeted therapies, met the co-primary endpoint of demonstrating significant improvement in PFS with a hazard ratio of 0.22 (96% confidence interval 0.13 – 0.36; p<0.0001). Based on these positive results, Exelixis intends to file an sNDA for cabozantinib monotherapy in a DTC indication in 2021.

    Cabozantinib Data at the 2021 American Society of Clinical Oncology's Genitourinary Cancers Symposium (ASCO GU 2021). Later this week, cabozantinib will be the subject of multiple data presentations at ASCO GU 2021, which is being held virtually from February 11-13. Planned presentations include: updated trial results with extended follow-up and patient-reported outcomes from the CheckMate -9ER trial; results from the SWOG S1500 trial ("PAPMET") of cabozantinib versus sunitinib in metastatic papillary RCC; data from an international study of cabozantinib in RCC patients with brain metastases; and final data from the phase 1 trial, including seven expansion cohorts, evaluating cabozantinib in combination with either nivolumab or nivolumab plus ipilimumab in patients with refractory metastatic genitourinary tumors.

    Pipeline Highlights

    Presentations of Data for XL092 and AUR102 at the 32nd EORTC-NCI-AACR (ENA) Symposium on Molecular Targets and Cancer Therapeutics. In October 2020, Exelixis presented the preclinical profile and initial clinical pharmacokinetics (PK) for XL092 at the ENA Symposium. The poster discussion presentation included preclinical results demonstrating robust target and tumor growth inhibition, as well as increased efficacy for XL092 when combined with an immune checkpoint inhibitor (ICI). PK data from the ongoing phase 1 trial suggested a significantly shorter PK half-life for XL092 as compared to cabozantinib. Also at the ENA Symposium, Aurigene Discovery Technologies Limited (Aurigene) presented promising preclinical data for AUR102, its novel inhibitor of cyclin-dependent kinase 7 (CDK7), including potent anti-tumor activity in a large panel of cancer cell lines. In December 2020, Exelixis in-licensed AUR102; now known as XL102, the compound is the subject of an active Investigational New Drug application (IND) and an ongoing phase 1 clinical trial.

    Enrollment of First Patient in Phase 1 Trial Cohort Evaluating XL092 in Combination with Atezolizumab in Patients with Advanced Solid Tumors. In October 2020, Exelixis announced enrollment of the first patient into the dose-escalation cohort of the combination arm of the phase 1 trial evaluating the safety, tolerability, PK and preliminary anti-tumor activity of XL092, both alone and in combination with atezolizumab, in patients with advanced solid tumors. Initiated in February 2019, the dose-escalation evaluation of the XL092 monotherapy arm of the phase 1 trial is ongoing. Once the recommended doses of both single-agent XL092 and XL092 in combination with atezolizumab are established, the trial will begin to enroll expansion cohorts for patients with clear cell and non-clear cell RCC, hormone-receptor positive breast cancer and metastatic castration-resistant prostate cancer (mCRPC).

    Exelixis In-Licenses Tissue Factor-Targeting Antibody-Drug Conjugate (ADC) Program from Collaborator Iconic Therapeutics, Inc. (Iconic). In December 2020, Exelixis and Iconic announced that Exelixis exercised its exclusive option to in-license Iconic's lead oncology ADC program under the companies' May 2019 collaboration agreement. As a result, Exelixis assumed responsibility for all subsequent clinical development, manufacturing and commercialization of the Tissue Factor-targeting ADC known as XB002 (formerly ICON-2). Exelixis plans to file an IND with the FDA for XB002 once drug product release assays are finalized and, pending the FDA's acceptance of the IND, initiate a phase 1 clinical trial.

    Exelixis In-Licenses Novel CDK7 Inhibitor from Collaborator Aurigene, Files IND and Initiates Phase 1 Clinical Trial in Advanced Solid Tumors. In December 2020, Exelixis and Aurigene announced that Exelixis exercised its exclusive option to in-license XL102 under the companies' July 2019 collaboration agreement. As a result, Exelixis assumed responsibility for all subsequent clinical development, manufacturing and commercialization of XL102. Following the FDA's acceptance of Exelixis' IND, in January 2021, Exelixis initiated a phase 1 clinical trial evaluating XL102, both as a single agent and in combination with other anti-cancer agents, for the treatment of patients with inoperable, locally advanced or metastatic solid tumors.

    Corporate Updates

    Inclusion in Fortune's 100 Fastest-Growing Companies List. In November 2020, Exelixis was named to Fortune's 100 Fastest-Growing Companies list, which ranks companies that are traded on a major U.S. stock exchange by their revenue growth rate, EPS growth rate and three-year annualized total return for the period ended June 30, 2020. In its first year on the list, Exelixis ranked 17th overall and was the third-highest biopharmaceutical company.

    Exelixis Outlines Key Priorities and Anticipated Milestones for 2021. In January 2021, Exelixis announced its key priorities and anticipated milestones for 2021, including: the commercial launch of CABOMETYX in combination with OPDIVO as a first-line treatment of patients with advanced RCC; potential sNDA submissions for CABOMETYX in DTC, HCC and mCRPC; progress and enrollment in the COSMIC and CONTACT clinical studies evaluating cabozantinib as a single agent or in combination with ICIs; expanded clinical development activities for XL092; and multiple INDs for preclinical assets. Exelixis presented the details of its key priorities and anticipated milestones at the 39th Annual J.P. Morgan Healthcare Conference.

    Exelixis and Adagene Inc. (Adagene) Enter into Collaboration and License Agreement to Develop Novel Masked ADC Therapies with Improved Safety and Efficacy Profiles. In February 2021, Exelixis and Adagene announced a collaboration and license agreement under which Exelixis will utilize Adagene's SAFEbody™ technology platform to generate masked versions of monoclonal antibodies from Exelixis' growing preclinical pipeline for the development of ADCs or other innovative biologics against Exelixis-nominated targets. Under the terms of the agreement, Exelixis will make an upfront payment of $11.0 million in exchange for an exclusive, worldwide license to develop and commercialize any potential ADC products generated by Adagene with respect to an initial target, as well as a second target Exelixis may nominate during the collaboration term. Adagene will be eligible for development, regulatory and commercialization milestones, as well as royalties on net sales of products developed around each of these targets.

    Basis of Presentation

    Exelixis has adopted a 52- or 53-week fiscal year that generally ends on the Friday closest to December 31st. For convenience, references in this press release as of and for the fiscal periods ended January 1, 2021 and January 3, 2020 are indicated as being as of and for the periods ended December 31, 2020 and December 31, 2019, respectively. The periods ended December 31, 2020 were a 13-week fiscal quarter and a 52-week fiscal year, as compared to a 14-week fiscal quarter and a 53-week fiscal year for the comparable periods in 2019.

    Conference Call and Webcast

    Exelixis management will discuss the company's financial results for the fourth quarter and full year 2020 and provide a general business update during a conference call beginning at 5:00 p.m. EST / 2:00 p.m. PST today, Wednesday, February 10, 2021.

    To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the conference call to ensure adequate time for any software download that may be required to listen to the webcast. Alternatively, please call 855-793-2457 (domestic) or 631-485-4921 (international) and provide the conference call passcode 5481036 to join by phone.

    A telephone replay will be available until 8:00 p.m. EST on February 12, 2021. Access numbers for the telephone replay are: 855-859-2056 (domestic) and 404-537-3406 (international); the passcode is 5481036. A webcast replay will also be archived on www.exelixis.com for one year.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery - all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Forward-Looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: Exelixis' potential for top-line revenue growth in 2021 and beyond; Exelixis' pursuit of additional regulatory approvals for cabozantinib and work towards a multi-billion dollar franchise; the potential for the combination of CABOMETYX and OPDIVO to be a best-in-class regimen in first-line RCC; Exelixis' development plans for XL092; Exelixis' regulatory and development plans for XB002; Exelixis' 2021 financial guidance; Exelixis' plans to file an sNDA for cabozantinib monotherapy in a DTC indication in 2021; Exelixis' immediate and potential future financial obligations under the collaboration and license agreement with Adagene; planned cabozantinib presentations at ASCO GU 2021; Exelixis' key priorities and anticipated milestones for 2021; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the continuing COVID-19 pandemic and its impact on Exelixis' clinical trial, drug discovery and commercial activities; the degree of market acceptance of CABOMETYX and other Exelixis products in the indications for which they are approved and in the territories where they are approved, and Exelixis' and its partners' ability to obtain or maintain coverage and reimbursement for these products; the effectiveness of CABOMETYX and other Exelixis products in comparison to competing products; the level of costs associated with Exelixis' commercialization, research and development, in-licensing or acquisition of product candidates, and other activities; Exelixis' ability to maintain and scale adequate sales, marketing, market access and product distribution capabilities for its products or to enter into and maintain agreements with third parties to do so; the availability of data at the referenced times; the potential failure of cabozantinib and other Exelixis product candidates, both alone and in combination with other therapies, to demonstrate safety and/or efficacy in clinical testing; uncertainties inherent in the drug discovery and product development process; Exelixis' dependence on its relationships with its collaboration partners, including their pursuit of regulatory approvals for partnered compounds in new indications, their adherence to their obligations under relevant collaboration agreements and the level of their investment in the resources necessary to complete clinical trials or successfully commercialize partnered compounds in the territories where they are approved; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis' continuing compliance with applicable legal and regulatory requirements; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating cabozantinib and other Exelixis products; Exelixis' dependence on third-party vendors for the development, manufacture and supply of its products and product candidates; Exelixis' ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of Exelixis' marketed products; changes in economic and business conditions; and other factors discussed under the caption "Risk Factors" in Exelixis' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 5, 2020, and in Exelixis' future filings with the SEC, including, without limitation, Exelixis' Annual Report on Form 10-K expected to be filed with the SEC in February 2021. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks.

    MINNEBRO is a registered Japanese trademark.

    OPDIVO is a registered trademark of Bristol-Myers Squibb Company.

    -see attached financial tables-

    EXELIXIS, INC.

    CONDENSED CONSOLIDATED STATEMENTS OF INCOME

    (in thousands, except per share amounts)

    (unaudited)

     

     

    Three Months Ended December 31,

     

    Year Ended December 31,

     

    2020

     

    2019

     

    2020

     

    2019

    Revenues:

     

     

     

     

     

     

     

    Net product revenues

    $

    200,353

     

     

     

    $

    194,926

     

     

     

    $

    741,550

     

     

    $

    759,950

     

    License revenues

    53,977

     

     

     

    33,471

     

     

     

    167,295

     

     

    165,914

     

    Collaboration services revenues

    15,722

     

     

     

    11,913

     

     

     

    78,693

     

     

    41,911

     

    Total revenues

    270,052

     

     

     

    240,310

     

     

     

    987,538

     

     

    967,775

     

    Operating expenses:

     

     

     

     

     

     

     

    Cost of goods sold

    9,037

     

     

     

    10,520

     

     

     

    36,272

     

     

    33,097

     

    Research and development

    154,279

     

     

     

    94,448

     

     

     

    547,851

     

     

    336,964

     

    Selling, general and administrative

    82,439

     

     

     

    58,026

     

     

     

    293,355

     

     

    228,244

     

    Total operating expenses

    245,755

     

     

     

    162,994

     

     

     

    877,478

     

     

    598,305

     

    Income from operations

    24,297

     

     

     

    77,316

     

     

     

    110,060

     

     

    369,470

     

    Interest income

    3,489

     

     

     

    7,706

     

     

     

    19,865

     

     

    27,959

     

    Other income (expense), net

    341

     

     

     

    (8

    )

     

     

    912

     

     

    680

     

    Income before income taxes

    28,127

     

     

     

    85,014

     

     

     

    130,837

     

     

    398,109

     

    Provision for (benefit from) income taxes

    (261

    )

     

     

    16,271

     

     

     

    19,056

     

     

    77,097

     

    Net income

    $

    28,388

     

     

     

    $

    68,743

     

     

     

    $

    111,781

     

     

    $

    321,012

     

    Net income per share:

     

     

     

     

     

     

     

    Basic

    $

    0.09

     

     

     

    $

    0.23

     

     

     

    $

    0.36

     

     

    $

    1.06

     

    Diluted

    $

    0.09

     

     

     

    $

    0.22

     

     

     

    $

    0.35

     

     

    $

    1.02

     

    Weighted-average common shares outstanding:

     

     

     

     

     

     

     

    Basic

    310,774

     

     

     

    304,338

     

     

     

    308,271

     

     

    302,584

     

    Diluted

    319,519

     

     

     

    315,030

     

     

     

    318,001

     

     

    315,009

     

    EXELIXIS, INC.

    CONDENSED CONSOLIDATED BALANCE SHEET DATA

    (in thousands)

    (unaudited)

     

     

    December 31, 2020

     

    December 31, 2019

    Cash and investments

    $

    1,538,842

     

     

    $

    1,388,628

     

    Working capital

    $

    1,240,737

     

     

    $

    868,444

     

    Total assets

    $

    2,137,333

     

     

    $

    1,885,670

     

    Total stockholders' equity

    $

    1,879,113

     

     

    $

    1,685,970

     

    EXELIXIS, INC.

    RECONCILIATION OF GAAP NET INCOME TO NON-GAAP NET INCOME

    (in thousands, except per share amounts)

    (unaudited)

     

     

    Three Months Ended December 31,

     

    Year Ended December 31,

     

    2020

     

    2019

     

    2020

     

    2019

    GAAP net income

    $

    28,388

     

     

     

    $

    68,743

     

     

     

    $

    111,781

     

     

     

    $

    321,012

     

     

    Adjustments:

     

     

     

     

     

     

     

    Stock-based compensation - research and development expenses (1)

    7,064

     

     

     

    5,629

     

     

     

    37,198

     

     

     

    19,374

     

     

    Stock-based compensation - selling, general and administrative expenses (1)

    12,215

     

     

     

    10,226

     

     

     

    67,872

     

     

     

    37,228

     

     

    Income tax effect of the above adjustments

    (4,347

    )

     

     

    (3,567

    )

     

     

    (23,542

    )

     

     

    (12,715

    )

     

    Non-GAAP net income

    $

    43,320

     

     

     

    $

    81,031

     

     

     

    $

    193,309

     

     

     

    $

    364,899

     

     

    GAAP net income per share:

     

     

     

     

     

     

     

    Basic

    $

    0.09

     

     

     

    $

    0.23

     

     

     

    $

    0.36

     

     

     

    $

    1.06

     

     

    Diluted

    $

    0.09

     

     

     

    $

    0.22

     

     

     

    $

    0.35

     

     

     

    $

    1.02

     

     

    Non-GAAP net income per share:

     

     

     

     

     

     

     

    Basic

    $

    0.14

     

     

     

    $

    0.27

     

     

     

    $

    0.63

     

     

     

    $

    1.21

     

     

    Diluted

    $

    0.14

     

     

     

    $

    0.26

     

     

     

    $

    0.61

     

     

     

    $

    1.16

     

     

    Weighted-average common shares outstanding:

     

     

     

     

     

     

     

    Basic

    310,774

     

     

     

    304,338

     

     

     

    308,271

     

     

     

    302,584

     

     

    Diluted

    319,519

     

     

     

    315,030

     

     

     

    318,001

     

     

     

    315,009

     

     

     

    ____________________

    (1)

    Non-cash stock-based compensation expense used for GAAP reporting in accordance with Accounting Standards Codification Topic 718, Compensation—Stock Compensation.

     

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  7. - Online event will be accessible at www.exelixis.com -

    Exelixis, Inc. (NASDAQ:EXEL) will host an investor briefing to discuss data presented at the American Society of Clinical Oncology's 2021 Genitourinary Cancers Symposium (ASCO GU 2021). The online-only event will be held on Saturday, February 13, 2021, beginning at 5:30 p.m. EST / 2:30 p.m. PST.

    During the briefing, Exelixis management and invited guests from the clinical community will discuss and provide context for cabozantinib clinical data presented at ASCO GU 2021, including updated results with extended follow-up data from CheckMate -9ER, the phase 3 pivotal trial evaluating CABOMETYX® (cabozantinib) in combination with OPDIVO® (nivolumab) compared with sunitinib as first-line…

    - Online event will be accessible at www.exelixis.com -

    Exelixis, Inc. (NASDAQ:EXEL) will host an investor briefing to discuss data presented at the American Society of Clinical Oncology's 2021 Genitourinary Cancers Symposium (ASCO GU 2021). The online-only event will be held on Saturday, February 13, 2021, beginning at 5:30 p.m. EST / 2:30 p.m. PST.

    During the briefing, Exelixis management and invited guests from the clinical community will discuss and provide context for cabozantinib clinical data presented at ASCO GU 2021, including updated results with extended follow-up data from CheckMate -9ER, the phase 3 pivotal trial evaluating CABOMETYX® (cabozantinib) in combination with OPDIVO® (nivolumab) compared with sunitinib as first-line treatment in patients with advanced or metastatic renal cell carcinoma (RCC). The investor briefing is also expected to include discussion of other ASCO GU 2021 data sets evaluating the use of cabozantinib in treatment settings for RCC and other genitourinary cancers.

    To access the investor briefing, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the event to ensure adequate time for any software download that may be required to view the webcast. After the event concludes, a replay will be available at that same location for a minimum of one year.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a registered Japanese trademark.

    OPDIVO® is a registered trademark of Bristol-Myers Squibb Company.

    View Full Article Hide Full Article
  8. – Results of retrospective analysis demonstrate a 61% intracranial response rate in patients with progressing brain metastases –

    – Data to be presented during the 2021 American Society of Clinical Oncology's Genitourinary Cancers Symposium –

    Exelixis, Inc. (NASDAQ:EXEL) today announced results from a retrospective analysis evaluating CABOMETYX® (cabozantinib) activity in brain metastases in patients with renal cell carcinoma (RCC). The findings will be presented as part of the Poster Session: Renal Cell Cancer at the 2021 American Society of Clinical Oncology's Genitourinary Cancers Symposium (ASCO GU), which is being held virtually, February 11-13, 2021. All posters will be available on demand beginning at 5:00 a.m. PT on Thursday, February…

    – Results of retrospective analysis demonstrate a 61% intracranial response rate in patients with progressing brain metastases –

    – Data to be presented during the 2021 American Society of Clinical Oncology's Genitourinary Cancers Symposium –

    Exelixis, Inc. (NASDAQ:EXEL) today announced results from a retrospective analysis evaluating CABOMETYX® (cabozantinib) activity in brain metastases in patients with renal cell carcinoma (RCC). The findings will be presented as part of the Poster Session: Renal Cell Cancer at the 2021 American Society of Clinical Oncology's Genitourinary Cancers Symposium (ASCO GU), which is being held virtually, February 11-13, 2021. All posters will be available on demand beginning at 5:00 a.m. PT on Thursday, February 11.

    In this retrospective analysis of medical records from patients with metastatic RCC with brain metastases, an intracranial response rate of 61% (95% CI: 39%-80%), including a complete response rate of 13%, was seen for patients with progressing intracranial metastases at baseline (Cohort 1; n=25) who were treated with CABOMETYX. Patients without progressing intracranial metastases (Cohort 2; n=44) had an intracranial response rate of 57% (95% CI: 41%-72%). The rate of brain disease progression at six months was 16% for patients with progressive brain disease at baseline and 9% for those without. Median overall survival was 14.7 months for Cohort 1 and 14.1. months for Cohort 2. The reported safety data are consistent with the known safety profile for CABOMETYX.

    "With these exciting results, oral systemic cabozantinib is showing intriguing activity on brain metastases in renal cell carcinoma," said Dr. Toni Choueiri, Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and the Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School. "The high intracranial response rates seen in this retrospective analysis suggest cabozantinib has the potential for helping patients with difficult-to-treat brain lesions from kidney cancer. We look forward to building on these encouraging findings through the ongoing phase 2 CABRAMET trial (NCT03967522) led by our French colleagues, which is prospectively evaluating cabozantinib in patients with brain metastases from renal cell carcinoma."

    "Brain metastases resulting from renal cell carcinoma are especially difficult to treat, as the blood-brain barrier poses a challenge for therapies to reach their targets," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "These encouraging results including a high intracranial response rate, suggest CABOMETYX may reduce the size of brain metastases, without neurological toxicity, and thereby may be of interest to physicians treating kidney cancer patients with brain metastases."

    About the Study

    For this retrospective study, sponsored by the Dana-Farber Cancer Institute, consecutive medical records from patients with metastatic RCC with brain metastases who had been treated with cabozantinib monotherapy across 15 institutions in the United States (ten centers), Belgium (three centers), Spain (one center) and France (one center) were reviewed.

    Patients were divided into two cohorts based on the presence (n=25) or absence (n=44) of progressing intracranial metastases at start of CABOMETYX therapy. Most patients (87%) were International Metastatic RCC Database Consortium (IMDC) intermediate/poor risk, and 75% had been previously treated. Prior brain-directed therapy was received by 65% of patients with progressing brain metatstases and by 93% of those without. All patients were treated with CABOMETYX. Four patients were not included in the intracranial analysis due to brain lesion size under 5 mm.

    About RCC

    The American Cancer Society's 2021 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common form of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 13%.1 Approximately 32,000 patients in the U.S. and 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2021.3

    About 70% of RCC cases are known as "clear cell" carcinomas, based on histology.4 The majority of clear cell RCC tumors have below-normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.5,6 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.7,8,9,10 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.6,7

    About CABOMETYX® (cabozantinib)

    In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with HCC who have been previously treated with sorafenib; and for patients with advanced RCC as a first-line treatment in combination with nivolumab. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

    Important Safety Information

    Warnings and Precautions

    Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

    Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

    Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

    Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

    Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

    Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

    Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.

    Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

    With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab.

    Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab depending on severity.

    Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.

    Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

    Proteinuria: Proteinuria was observed in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

    Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

    Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

    Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

    Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

    ADVERSE REACTIONS

    The most common (≥20%) adverse reactions are:

    CABOMETYX as a single agent: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation, and dysphonia.

    CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

    DRUG INTERACTIONS

    Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

    Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John's wort.

    USE IN SPECIFIC POPULATIONS

    Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

    Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

    Please see accompanying full Prescribing Information https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.

    You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Forward-Looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: the presentation of data from a retrospective analysis evaluating CABOMETYX activity in brain metastases in patients with RCC at ASCO GU; the therapeutic potential of CABOMETYX for patients with difficult-to-treat brain lesions from kidney cancer; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the availability of data at the referenced times; the potential failure of cabozantinib to demonstrate safety and/or efficacy in future trials; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating CABOMETYX; Exelixis' continuing compliance with applicable legal and regulatory requirements; Exelixis' dependence on third-party vendors for the development, manufacture and supply of cabozantinib; Exelixis' ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions, including as a result of the COVID-19 pandemic; and other factors affecting Exelixis and its development programs discussed under the caption "Risk Factors" in Exelixis' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 5, 2020, and in Exelixis' future filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a Japanese trademark.

    1 American Cancer Society: Cancer Facts & Figures 2021. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf. Accessed February 2021.

    2 Jonasch, E., Gao, J., Rathmell, W., Renal cell carcinoma. BMJ. 2014; 349:g4797.

    3 Decision Resources Report: Renal Cell Carcinoma. October 2014 (internal data on file).

    4 American Cancer Society: What is Kidney Cancer? Available at: https://www.cancer.org/cancer/kidney-cancer/about/what-is-kidney-cancer.html. Accessed February 2021.

    5 Harshman, L., and Choueiri, T. Targeting the hepatocyte growth factor/c-Met signaling pathway in renal cell carcinoma. Cancer J. 2013; 19:316-323.

    6 Rankin, et al. Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET. Proc Natl Acad Sci USA. 2014; 111:13373-13378.

    7 Zhou, L., Liu, X-D., Sun, M., et al. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma. Oncogene. 2016; 35:2687-2697.

    8 Koochekpour, et al. The von Hippel-Lindau tumor suppressor gene inhibits hepatocyte growth factor/scatter factor-induced invasion and branching morphogenesis in renal carcinoma cells. Mol Cell Biol. 1999; 19:5902–5912.

    9 Takahashi, A., Sasaki, H., Kim, S., et al. Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. Cancer Res. 1994; 54:4233-4237.

    10 Nakagawa, M., Emoto, A., Hanada, T., Nasu, N., Nomura, Y. Tubulogenesis by microvascular endothelial cells is mediated by vascular endothelial growth factor (VEGF) in renal cell carcinoma. Br J Urol. 1997; 79:681-687.

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  9. With a median follow-up of two years, OPDIVO in combination with CABOMETYX continues to demonstrate superior progression-free survival, overall survival and objective response rate compared to sunitinib

    Patients treated with OPDIVO in combination with CABOMETYX report significantly improved health-related quality of life in a separate analysis from CheckMate -9ER

    Data showing ongoing efficacy benefits and patient-reported outcomes will be presented at the 2021 Genitourinary Cancers Symposium

    Bristol Myers Squibb (NYSE:BMY) and Exelixis, Inc. (NASDAQ:EXEL) today announced results from new analyses from the pivotal Phase 3 CheckMate -9ER trial, demonstrating clinically meaningful, sustained efficacy benefits as well as quality of life improvements…

    With a median follow-up of two years, OPDIVO in combination with CABOMETYX continues to demonstrate superior progression-free survival, overall survival and objective response rate compared to sunitinib

    Patients treated with OPDIVO in combination with CABOMETYX report significantly improved health-related quality of life in a separate analysis from CheckMate -9ER

    Data showing ongoing efficacy benefits and patient-reported outcomes will be presented at the 2021 Genitourinary Cancers Symposium

    Bristol Myers Squibb (NYSE:BMY) and Exelixis, Inc. (NASDAQ:EXEL) today announced results from new analyses from the pivotal Phase 3 CheckMate -9ER trial, demonstrating clinically meaningful, sustained efficacy benefits as well as quality of life improvements with the combination of OPDIVO® (nivolumab) and CABOMETYX® (cabozantinib) compared to sunitinib in the first-line treatment of advanced renal cell carcinoma (RCC). These data will be presented in two posters at the virtual American Society of Clinical Oncology (ASCO) 2021 Genitourinary Cancers Symposium from February 11 to 13, 2021 and featured in the Poster Highlights Session on February 13, 2021 from 9:00 a.m. – 9:45 a.m. EST.

    Abstract #308: Nivolumab + cabozantinib (NIVO+CABO) vs. sunitinib (SUN) for advanced renal cell carcinoma (aRCC): outcomes by sarcomatoid histology and updated trial results with extended follow-up of CheckMate -9ER (Motzer, et. al.)

    With a median follow-up of two years (23.5 months), OPDIVO in combination with CABOMETYX continued to show superior progression-free survival (PFS), objective response rate (ORR) and overall survival (OS) versus sunitinib, with a low rate of treatment-related adverse events (TRAEs) leading to discontinuation. No new safety signals were identified with extended follow-up. Across the full study population:

    • PFS: The combination doubled median PFS (17.0 months vs. 8.3 months, respectively; HR 0.52; 95% CI: 0.43 to 0.64), the trial's primary endpoint, compared to sunitinib.
    • ORR: Nearly twice as many patients responded to OPDIVO in combination with CABOMETYX vs. sunitinib (54.8% vs. 28.4%).
    • OS: OPDIVO in combination with CABOMETYX maintained improvements in OS, demonstrating a 34% reduction in the risk of death compared to sunitinib (HR: 0.66; 95% CI: 0.50 to 0.87).
    • Disease control rate: In an exploratory analysis, the combination was associated with a disease control rate (including complete response, partial response and stable disease) of 88.2% vs. 69.9% with sunitinib.
    • Complete response (CR): The CR rate, also exploratory, for OPDIVO in combination with CABOMETYX was 9.3% compared to 4.3% with sunitinib.
    • TRAE discontinuations: Among patients treated with OPDIVO and CABOMETYX, 6.6% discontinued both agents due to TRAEs, 9.7% discontinued OPDIVO only and 7.2% discontinued CABOMETYX only.

    In an exploratory subgroup analysis of 75 patients with sarcomatoid features, the combination of OPDIVO and CABOMETYX showed benefit in this population typically associated with a poor prognosis, reducing the risk of death by 64% vs. sunitinib (HR 0.36; 95% CI: 0.17 to 0.79) and demonstrating both superior PFS (10.3 months vs. 4.2 months) and ORR (55.9% vs. 22.0%).

    Abstract #285: Patient-reported outcomes of patients with advanced renal cell carcinoma (aRCC) treated with first-line nivolumab plus cabozantinib versus sunitinib: the CheckMate -9ER trial (Cella, et. al.)

    In a separate analysis from the CheckMate -9ER trial conducted with 18.1 months of median follow-up, patients treated with the combination of OPDIVO and CABOMETYX reported statistically significant health-related quality of life benefits. Treatment with OPDIVO in combination with CABOMETYX was associated with a lower treatment burden, decreased risk of deterioration and a reduction of disease-related symptoms compared to sunitinib. These exploratory outcomes were measured using Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), a quality of life tool specific to kidney cancer, and EQ-5D-3L instruments.

    "There is a continued need for new therapies that show benefit across subgroups of patients with advanced renal cell carcinoma," said Robert Motzer, M.D., Kidney Cancer Section Head, Genitourinary Oncology Service, and Jack and Dorothy Byrne Chair in Clinical Oncology, Memorial Sloan Kettering Cancer Center. "In CheckMate -9ER, nivolumab in combination with cabozantinib doubled progression-free survival, increased overall survival and response rate and, in an exploratory analysis, showed impressive disease control, and these promising efficacy results were sustained with extended follow-up. Also of note, patients in this study reported significant quality of life improvements, which are important for patients undergoing treatment for this challenging disease."

    "These additional data from CheckMate -9ER provide strong evidence that OPDIVO in combination with CABOMETYX may help patients achieve and maintain control of their disease," said Dana Walker, M.D., M.S.C.E., vice president, development program lead, genitourinary cancers, Bristol Myers Squibb. "This regimen brings together two proven agents in advanced renal cell carcinoma, and we believe it will play an important role alongside other first-line treatment options. We look forward to the potential to build on our heritage of transforming patient outcomes with OPDIVO-based combinations across a wide range of tumor types."

    "The overall survival benefit and quality-of-life measures reported in these findings continue to show improvement with the combination of CABOMETYX and OPDIVO after an extended follow-up of two years," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "These new findings from CheckMate -9ER and the recent FDA approval of the combination regimen are extremely encouraging as we further explore the potential of CABOMETYX in combination with immunotherapies to help more patients with difficult-to-treat tumor types."

    OPDIVO in combination with CABOMETYX was approved for the first-line treatment of advanced RCC by the U.S. Food and Drug Administration (FDA) in January 2021, and further applications are under review with health authorities globally.

    Bristol Myers Squibb and Exelixis thank the patients and investigators involved in the CheckMate -9ER clinical trial.

    About CheckMate -9ER

    CheckMate -9ER is an open-label, randomized, multi-national Phase 3 trial evaluating patients with previously untreated advanced or metastatic renal cell carcinoma (RCC). A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1≥1%) were randomized to receive OPDIVO plus CABOMETYX (n=323) vs. sunitinib (n=328). The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS) and objective response rate (ORR). The primary efficacy analysis is comparing the doublet combination vs. sunitinib in all randomized patients. The trial is sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.

    About Renal Cell Carcinoma

    Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, accounting for more than 179,000 deaths worldwide each year. RCC is approximately twice as common in men as in women, with the highest rates of the disease in North America and Europe. The five-year survival rate for those diagnosed with metastatic, or advanced, kidney cancer is 13%.

    Bristol Myers Squibb: Creating a Better Future for People with Cancer

    Bristol Myers Squibb is inspired by a single vision — transforming patients' lives through science. The goal of the company's cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient's life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

    About OPDIVO®

    Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body's own immune system to help restore anti-tumor immune response. By harnessing the body's own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

    Opdivo's leading global development program is based on Bristol Myers Squibb's scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

    In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company's Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

    About CABOMETYX® (cabozantinib)

    In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with HCC who have been previously treated with sorafenib; and for patients with advanced RCC as a first-line treatment in combination with nivolumab. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

    OPDIVO® INDICATIONS

    OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of patients with unresectable or metastatic melanoma.

    OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

    OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

    OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

    OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

    OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

    OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of patients with intermediate or poor risk advanced renal cell carcinoma (RCC).

    OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

    OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

    OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

    OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

    OPDIVO® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

    OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

    OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

    OPDIVO® (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

    OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

    OPDIVO® (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

    OPDIVO® (nivolumab) is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

    OPDIVO® IMPORTANT SAFETY INFORMATION

    Severe and Fatal Immune-Mediated Adverse Reactions

    Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

    Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

    Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

    Immune-Mediated Pneumonitis

    OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%). In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 10% (5/49) of patients. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 3.9% (26/666) of patients, including Grade 3 (1.4%) and Grade 2 (2.6%). In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, immune-mediated pneumonitis occurred in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3 (3.5%), and Grade 2 (4.0%). Four patients (0.7%) died due to pneumonitis.

    In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO, including Grade 3 (n=1) and Grade 2 (n=12).

    Immune-Mediated Colitis

    OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated colitis occurred in 9% (60/666) of patients, including Grade 3 (4.4%) and Grade 2 (3.7%).

    In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated colitis occurred in 12% (62/511) of patients, including Grade 3-5 (7%) and Grade 2 (5%).

    Immune-Mediated Hepatitis and Hepatotoxicity

    OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%). In patients receiving OPDIVO monotherapy in Checkmate 040, immune-mediated hepatitis requiring systemic corticosteroids occurred in 5% (8/154) of patients. In patients receiving OPDIVO 1 mg/ kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), Grade 3 (4.9%), and Grade 2 (0.4%).

    In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated hepatitis occurred in 4.1% (21/511) of patients, including Grade 3-5 (1.6%) and Grade 2 (2.5%).

    OPDIVO in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to OPDIVO alone. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. In patients receiving OPDIVO and cabozantinib, Grades 3 and 4 increased ALT or AST were seen in 11% of patients.

    Immune-Mediated Endocrinopathies

    OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.

    In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456), including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, adrenal insufficiency occurred in 7% (48/666) of patients, including Grade 4 (0.3%), Grade 3 (2.5%), and Grade 2 (4.1%). In patients receiving OPDIVO and cabozantinib, adrenal insufficiency occurred in 4.7% (15/320) of patients, including Grade 3 (2.2%) and Grade 2 (1.9%).

    In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456), including Grade 3 (2.4%) and Grade 2 (6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypophysitis occurred in 4.4% (29/666) of patients, including Grade 4 (0.3%), Grade 3 (2.4%), and Grade 2 (0.9%).

    In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, thyroiditis occurred in 2.7% (22/666) of patients, including Grade 3 (4.5%) and Grade 2 (2.2%).

    In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3 (0.9%) and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hyperthyroidism occurred in 12% (80/666) of patients, including Grade 3 (0.6%) and Grade 2 (4.5%).

    In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypothyroidism occurred in 18% (122/666) of patients, including Grade 3 (0.6%) and Grade 2 (11%).

    In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3 (0.3%), and Grade 2 (0.9%).

    In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, Grade 2-5 immune-mediated endocrinopathies occurred in 4% (21/511) of patients. Severe to life-threatening (Grade 3-4) endocrinopathies occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. Six of the 9 patients were hospitalized for severe endocrinopathies. Moderate (Grade 2) endocrinopathy occurred in 12 patients (2.3%), including hypothyroidism, adrenal insufficiency, hypopituitarism, hyperthyroidism and Cushing's syndrome.

    Immune-Mediated Nephritis with Renal Dysfunction

    OPDIVO and YERVOY can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated nephritis with renal dysfunction occurred in 4.1% (27/666) of patients, including Grade 4 (0.6%), Grade 3 (1.1%), and Grade 2 (2.2%).

    Immune-Mediated Dermatologic Adverse Reactions

    OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.

    YERVOY can cause immune-mediated rash or dermatitis, including bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/ exfoliative rashes.

    Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

    In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients, including Grade 3 (1.1%) and Grade 2 (2.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated rash occurred in 28% (127/456) of patients, including Grade 3 (4.8%) and Grade 2 (10%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated rash occurred in 16% (108/666) of patients, including Grade 3 (3.5%) and Grade 2 (4.2%).

    In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated rash occurred in 15% (76/511) of patients, including Grade 3-5 (2.5%) and Grade 2 (12%).

    Other Immune-Mediated Adverse Reactions

    The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO monotherapy or OPDIVO in combination with YERVOY or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica; endocrine: hypoparathyroidism; other (hematologic/immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

    In addition to the immune-mediated adverse reactions listed above, across clinical trials of YERVOY monotherapy or in combination with OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1% of patients unless otherwise specified: nervous system: autoimmune neuropathy (2%), myasthenic syndrome/myasthenia gravis, motor dysfunction; cardiovascular: angiopathy, temporal arteritis; ocular: blepharitis, episcleritis, orbital myositis, scleritis; gastrointestinal: pancreatitis (1.3%); other (hematologic/immune): conjunctivitis, cytopenias (2.5%), eosinophilia (2.1%), erythema multiforme, hypersensitivity vasculitis, neurosensory hypoacusis, psoriasis.

    Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, which has been observed in patients receiving OPDIVO and YERVOY, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.

    Infusion-Related Reactions

    OPDIVO and YERVOY can cause severe infusion-related reactions. Discontinue OPDIVO and YERVOY in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO. In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 8% (4/49) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related reactions occurred in 5.1% (28/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, infusion-related reactions occurred in 4.2% (5/119) of patients. In MPM patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, infusion-related reactions occurred in 12% (37/300) of patients.

    In separate Phase 3 trials of YERVOY 3 mg/kg and 10 mg/kg monotherapy, infusion-related reactions occurred in 2.9% (28/982) of patients.

    Complications of Allogeneic Hematopoietic Stem Cell Transplantation

    Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with OPDIVO or YERVOY. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between OPDIVO or YERVOY and allogeneic HSCT.

    Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO and YERVOY prior to or after an allogeneic HSCT.

    Embryo-Fetal Toxicity

    Based on its mechanism of action and findings from animal studies, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and YERVOY and for at least 5 months after the last dose.

    Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone

    In randomized clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

    Lactation

    There are no data on the presence of OPDIVO or YERVOY in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 5 months after the last dose.

    Serious Adverse Reactions

    In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (74% and 44%), adverse reactions leading to permanent discontinuation (47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4 adverse reactions (72% and 51%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.2%), colitis (10% and 1.9%), and pyrexia (10% and 1.0%). In Checkmate 227, serious adverse reactions occurred in 58% of patients (n=576). The most frequent (≥2%) serious adverse reactions were pneumonia, diarrhea/colitis, pneumonitis, hepatitis, pulmonary embolism, adrenal insufficiency, and hypophysitis. Fatal adverse reactions occurred in 1.7% of patients; these included events of pneumonitis (4 patients), myocarditis, acute kidney injury, shock, hyperglycemia, multi-system organ failure, and renal failure. In Checkmate 9LA, serious adverse reactions occurred in 57% of patients (n=358). The most frequent (>2%) serious adverse reactions were pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, musculoskeletal pain, dyspnea, pneumonitis, and respiratory failure. Fatal adverse reactions occurred in 7 (2%) patients, and included hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia, and massive hemoptysis in the setting of thrombocytopenia. In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 057, fatal adverse reactions occurred; these included events of infection (7 patients, including one case of Pneumocystis jirovecii pneumonia), pulmonary embolism (4 patients), and limbic encephalitis (1 patient). In Checkmate 743, serious adverse reactions occurred in 54% of patients receiving OPDIVO plus YERVOY. The most frequent serious adverse reactions reported in ≥2% of patients were pneumonia, pyrexia, diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney injury, infusion-related reaction, musculoskeletal pain, and pulmonary embolism. Fatal adverse reactions occurred in 4 (1.3%) patients and included pneumonitis, acute heart failure, sepsis, and encephalitis. In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY (n=547). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis. In Checkmate 9ER, serious adverse reactions occurred in 48% of patients receiving OPDIVO and cabozantinib (n=320). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pneumonia, pneumonitis, pulmonary embolism, urinary tract infection, and hyponatremia. Fatal intestinal perforations occurred in 3 (0.9%) patients. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, adverse reactions leading to discontinuation occurred in 7% and dose delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in ≥1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural effusion, pneumonitis, and rash. Eleven patients died from causes other than disease progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection 8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=236). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO with YERVOY (n=119), serious adverse reactions occurred in 47% of patients. The most frequent serious adverse reactions reported in ≥2% of patients were colitis/diarrhea, hepatic events, abdominal pain, acute kidney injury, pyrexia, and dehydration. In Checkmate 040, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=154). The most frequent serious adverse reactions reported in ≥2% of patients were pyrexia, ascites, back pain, general physical health deterioration, abdominal pain, pneumonia, and anemia. In Checkmate 040, serious adverse reactions occurred in 59% of patients receiving OPDIVO with YERVOY (n=49). Serious adverse reactions reported in ≥4% of patients were pyrexia, diarrhea, anemia, increased AST, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin, and pneumonitis. In Checkmate 238, serious adverse reactions occurred in 18% of patients receiving OPDIVO (n=452). Grade 3 or 4 adverse reactions occurred in 25% of OPDIVO-treated patients (n=452). The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of OPDIVO-treated patients were diarrhea and increased lipase and amylase. In Attraction-3, serious adverse reactions occurred in 38% of patients receiving OPDIVO (n=209). Serious adverse reactions reported in ≥2% of patients who received OPDIVO were pneumonia, esophageal fistula, interstitial lung disease, and pyrexia. The following fatal adverse reactions occurred in patients who received OPDIVO: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).

    Common Adverse Reactions

    In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%). In Checkmate 227, the most common (≥20%) adverse reactions were fatigue (44%), rash (34%), decreased appetite (31%), musculoskeletal pain (27%), diarrhea/colitis (26%), dyspnea (26%), cough (23%), hepatitis (21%), nausea (21%), and pruritus (21%). In Checkmate 9LA, the most common (>20%) adverse reactions were fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea (31%), rash (30%), decreased appetite (28%), constipation (21%), and pruritus (21%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 743, the most common adverse reactions (≥20%) in patients receiving OPDIVO plus YERVOY were fatigue (43%), musculoskeletal pain (38%), rash (34%), diarrhea (32%), dyspnea (27%), nausea (24%), decreased appetite (24%), cough (23%), and pruritus (21%). In Checkmate 214, the most common adverse reactions (≥20%) reported in patients treated with OPDIVO plus YERVOY (n=547) were fatigue (58%), rash (39%), diarrhea (38%), musculoskeletal pain (37%), pruritus (33%), nausea (30%), cough (28%), pyrexia (25%), arthralgia (23%), decreased appetite (21%), dyspnea (20%), and vomiting (20%). In Checkmate 9ER, the most common adverse reactions (≥20%) in patients receiving OPDIVO and cabozantinib (n=320) were diarrhea (64%), fatigue (51%), hepatotoxicity (44%), palmar-plantar erythrodysaesthesia syndrome (40%), stomatitis (37%), rash (36%), hypertension (36%), hypothyroidism (34%), musculoskeletal pain (33%), decreased appetite (28%), nausea (27%), dysgeusia (24%), abdominal pain (22%), cough (20%) and upper respiratory tract infection (20%). In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were fatigue (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=266) were upper respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%) and pruritus (20%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO (n=236) were cough (14%) and dyspnea (14%) at a higher incidence than investigator's choice. In Checkmate 275, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO as a single agent, the most common adverse reactions (≥20%) were fatigue (54%), diarrhea (43%), abdominal pain (34%), nausea (34%), vomiting (28%), musculoskeletal pain (28%), cough (26%), pyrexia (24%), rash (23%), constipation (20%), and upper respiratory tract infection (20%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO with YERVOY (n=119), the most common adverse reactions (≥20%) were fatigue (49%), diarrhea (45%), pyrexia (36%), musculoskeletal pain (36%), abdominal pain (30%), pruritus (28%), nausea (26%), rash (25%), decreased appetite (20%), and vomiting (20%). In Checkmate 040, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=154) were fatigue (38%), musculoskeletal pain (36%), abdominal pain (34%), pruritus (27%), diarrhea (27%), rash (26%), cough (23%), and decreased appetite (22%). In Checkmate 040, the most common adverse reactions (≥20%) in patients receiving OPDIVO with YERVOY (n=49), were rash (53%), pruritus (53%), musculoskeletal pain (41%), diarrhea (39%), cough (37%), decreased appetite (35%), fatigue (27%), pyrexia (27%), abdominal pain (22%), headache (22%), nausea (20%), dizziness (20%), hypothyroidism (20%), and weight decreased (20%). In Checkmate 238, the most common adverse reactions (≥20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%). The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%). In Attraction-3, the most common adverse reactions (≥20%) in OPDIVO-treated patients (n=209) were rash (22%) and decreased appetite (21%).

    In a separate Phase 3 trial of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

    Please see US Full Prescribing Information for OPDIVO and YERVOY.

    Clinical Trials and Patient Populations

    Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 227–previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 025–previously treated renal cell carcinoma; Checkmate 205/039–classical Hodgkin lymphoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 275–urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 040–hepatocellular carcinoma, as a single agent or in combination with YERVOY; Checkmate 238–adjuvant treatment of melanoma; Attraction-3–esophageal squamous cell carcinoma

    CABOMETYX® INDICATIONS

    CABOMETYX®(cabozantinib) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC).

    CABOMETYX®(cabozantinib) is indicated for the treatment of patients with advanced RCC, as a first-line treatment in combination with nivolumab.

    CABOMETYX®(cabozantinib) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.

    CABOMETYX® IMPORTANT SAFETY INFORMATION

    WARNINGS AND PRECAUTIONS

    Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

    Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

    Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

    Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

    Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

    Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

    Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.

    Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

    With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab.

    Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab depending on severity.

    Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.

    Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

    Proteinuria: Proteinuria was observed in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

    Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

    Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

    Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

    Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

    ADVERSE REACTIONS

    The most common (≥20%) adverse reactions are:

    CABOMETYX as a single agent: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation, and dysphonia.

    CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

    DRUG INTERACTIONS

    Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

    Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John's wort.

    USE IN SPECIFIC POPULATIONS

    Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

    Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

    Please see accompanying full Prescribing Information https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.

    You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www. FDA.gov/medwatch or call 1-800-FDA-1088.

    About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration

    In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies' strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

    About Bristol Myers Squibb

    Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

    Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery - all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Bristol Myers Squibb Cautionary Statement Regarding Forward-Looking Statements

    This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on historical performance and current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results will be consistent with the results to date and whether OPDIVO in combination with CABOMETYX for the indications described in this release will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb's business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2019, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.

    Exelixis Forward-Looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: the presentation of data from the CheckMate -9ER study at the virtual ASCO 2021 Genitourinary Cancers Symposium; the potential for the combination of CABOMETYX and Opdivo to help patients with RCC and to play an important role alongside other first-line treatment options; the potential for CABOMETYX in combination with immunotherapies to help more patients with difficult-to-treat tumor types; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the availability of data at the referenced times; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis' and BMS' continuing compliance with applicable legal and regulatory requirements; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating the combination of CABOMETYX and Opdivo; the continuing COVID-19 pandemic and its impact on Exelixis' product development and commercial activities; Exelixis' dependence on its relationships with its collaboration partners, including their pursuit of regulatory approvals for partnered compounds in new indications and their adherence to their obligations under relevant collaboration agreements; Exelixis' dependence on third-party vendors for the development, manufacture and supply of cabozantinib; Exelixis' ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions; and other factors discussed under the caption "Risk Factors" in Exelixis' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 5, 2020, and in Exelixis' future filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a Japanese trademark.

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  10. - Presentation to be webcast on www.exelixis.com -

    Exelixis, Inc. (NASDAQ:EXEL) today announced that Michael M. Morrissey, Ph.D., the company's President and Chief Executive Officer will participate in a fireside chat as part of the Guggenheim Healthcare Talks Oncology Day on Thursday, February 11, 2021 at 11:30 AM EST / 8:30 AM PST. Due to the ongoing COVID-19 pandemic, the conference will be held as a virtual event.

    To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast…

    - Presentation to be webcast on www.exelixis.com -

    Exelixis, Inc. (NASDAQ:EXEL) today announced that Michael M. Morrissey, Ph.D., the company's President and Chief Executive Officer will participate in a fireside chat as part of the Guggenheim Healthcare Talks Oncology Day on Thursday, February 11, 2021 at 11:30 AM EST / 8:30 AM PST. Due to the ongoing COVID-19 pandemic, the conference will be held as a virtual event.

    To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast. A replay will also be available at the same location for 14 days.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a registered Japanese trademark.

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  11. - Exelixis will utilize Adagene's proprietary SAFEbody technology to develop novel masked antibody-drug conjugates (ADCs) with potential for improved therapeutic index -

    Exelixis, Inc. (NASDAQ:EXEL) and Adagene today announced a collaboration and license agreement under which Exelixis will utilize Adagene's SAFEbody™ technology platform to generate masked versions of monoclonal antibodies from Exelixis' growing preclinical pipeline for the development of ADCs or other innovative biologics against Exelixis-nominated targets. Under the terms of the agreement, Exelixis will make an upfront payment of $11 million to Adagene and will have the ability to nominate two targets during the collaboration term. Adagene will be eligible for development…

    - Exelixis will utilize Adagene's proprietary SAFEbody technology to develop novel masked antibody-drug conjugates (ADCs) with potential for improved therapeutic index -

    Exelixis, Inc. (NASDAQ:EXEL) and Adagene today announced a collaboration and license agreement under which Exelixis will utilize Adagene's SAFEbody™ technology platform to generate masked versions of monoclonal antibodies from Exelixis' growing preclinical pipeline for the development of ADCs or other innovative biologics against Exelixis-nominated targets. Under the terms of the agreement, Exelixis will make an upfront payment of $11 million to Adagene and will have the ability to nominate two targets during the collaboration term. Adagene will be eligible for development and commercialization milestones, as well as royalties on net sales of products developed around each of these targets.

    This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210201005459/en/

    "SAFEbody provides a solution to on-target off-tumor toxicity, which is a long-lasting challenge associated with many approved antibody therapeutics," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer, and Chairman of Adagene. "This partnership with Exelixis strengthens our growing roster of collaborations with global biopharmaceutical companies. We are very pleased to collaborate with Exelixis and look forward to the company's development of ADCs that leverage our SAFEbody technology."

    Biologic therapies, including therapeutic antibodies such as ADCs, are designed to bind to their targets with high efficiency. However, while the targets for biologic cancer therapies are expressed at high levels in cancer cells, many are also expressed at lower levels on healthy cells. Binding of these therapies to healthy cells may lead to unwanted safety or tolerability issues. Adagene's SAFEbody platform is designed to overcome this challenge by incorporating a masking peptide that covers the binding domain of the biologic therapy. Specific conditions within the tumor environment allow the biologic therapy to preferentially bind to its target in tumor cells. This allows for improved tumor-specific targeting of antibodies while minimizing on-target toxicity in healthy tissues. Adagene's most advanced SAFEbody candidate has been approved to start a clinical trial in Australia and the United States.

    "As we expand our pipeline beyond small molecule therapies, we are committed to developing novel biotherapeutics that are optimized for safety and efficacy," said Peter Lamb, Ph.D., Executive Vice President, Scientific Strategy and Chief Scientific Officer of Exelixis. "We believe the SAFEbody platform has the potential to significantly improve the safety profile of ADCs, and we will initially focus on incorporating this innovative technology into novel ADCs that also utilize next-generation linkers and payloads. The combination of these cutting-edge technologies is expected to yield ADC product candidates with differentiated target profiles and/or improved therapeutic indices. We are committed to expanding our development pipeline into additional therapeutic classes even as we drive additional momentum toward broadening the label for cabozantinib into additional cancer indications."

    About Adagene

    Adagene Inc. is a platform-driven, clinical-stage biopharmaceutical company committed to transforming the discovery and development of novel antibody-based cancer immunotherapies. Adagene combines computational biology and artificial intelligence to design novel antibodies that address unmet patient needs. Its proprietary pipeline is comprised of novel immunotherapy programs. Adagene has forged strategic collaborations with reputable global partners that leverage its technology in multiple approaches at the vanguard of science.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery — all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Exelixis Forward-Looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: Exelixis' strategy to build a growing preclinical pipeline for the development of ADCs and the therapeutic potential of such ADC product candidates; Exelixis' immediate and potential future financial and other obligations under the collaboration and license agreement with Adagene; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the continuing COVID-19 pandemic and its impact on Exelixis' research and development operations; the level of costs associated with Exelixis' commercialization, research and development, in-licensing or acquisition of product candidates, and other activities; uncertainties inherent in the drug discovery and product development process; Exelixis' dependence on its relationship with Adagene, including Adagene's adherence to its obligations under the collaboration and license agreement and the level of Adagene's assistance to Exelixis in completing clinical trials, pursuing regulatory approvals or successfully commercializing partnered compounds in the territories where they may be approved; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis' and Adagene's continuing compliance with applicable legal and regulatory requirements; Exelixis' and Adagene's ability to protect their respective intellectual property rights; market competition; changes in economic and business conditions; and other factors affecting Exelixis and its product pipeline discussed under the caption "Risk Factors" in Exelixis' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 5, 2020, and in Exelixis' future filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    Adagene Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of federal securities laws, including statements regarding the potential benefits and collaborations under the collaboration and license agreement with Exelixis, which involve risks and uncertainties that could cause the actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are made under the "safe harbor" provisions of the U.S. Private Securities Litigation Reform Act of 1995. Statements that are not historical facts, including statements about the Company's beliefs and expectations, are forward-looking statements. Forward-looking statements involve inherent risks and uncertainties, and a number of factors could cause actual results to differ materially from those contained in any forward-looking statement. In some cases, forward-looking statements can be identified by words or phrases such as "may", "will," "expect," "anticipate," "target," "aim," "estimate," "intend," "plan," "believe," "potential," "continue," "is/are likely to" or other similar expressions. Further information regarding these and other risks, uncertainties or factors is included in the Company's filings with the SEC. All information provided in this press release is as of the date of this press release, and the Company does not undertake any duty to update such information, except as required under applicable law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a registered Japanese trademark.

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  12. Conference Call and Webcast to Follow at 5:00 p.m. EST / 2:00 p.m. PST –

    Exelixis, Inc. (NASDAQ:EXEL) announced today that its fourth quarter and full year 2020 financial results will be released on Wednesday, February 10, 2021 after the markets close. At 5:00 p.m. EST / 2:00 p.m. PST, Exelixis management will host a conference call and webcast to discuss the results and provide a general business update. Access to the event is available via the Internet from the company's website.

    To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the conference call to ensure adequate time…

    Conference Call and Webcast to Follow at 5:00 p.m. EST / 2:00 p.m. PST –

    Exelixis, Inc. (NASDAQ:EXEL) announced today that its fourth quarter and full year 2020 financial results will be released on Wednesday, February 10, 2021 after the markets close. At 5:00 p.m. EST / 2:00 p.m. PST, Exelixis management will host a conference call and webcast to discuss the results and provide a general business update. Access to the event is available via the Internet from the company's website.

    To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the conference call to ensure adequate time for any software download that may be required to listen to the webcast. Alternatively, please call 855-793-2457 (domestic) or 631-485-4921 (international) and provide the conference call passcode 5481036 to join by phone.

    A telephone replay will be available until 8:00 p.m. EST on February 12, 2021. Access numbers for the telephone replay are: 855-859-2056 (domestic) and 404-537-3406 (international); the passcode is 5481036. A webcast replay will also be archived on www.exelixis.com for one year.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a registered Japanese trademark.

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  13. – Encouraging preclinical data presented in 2020 support advancement to clinical evaluation for XL102, Exelixis' novel oral CDK7 inhibitor –

    – Expansion phase of the trial will include cohorts for ovarian, breast and prostate cancers –

    Exelixis, Inc. (NASDAQ:EXEL) today announced initiation of the first-in-human phase 1 trial evaluating the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of XL102 alone or in combination with other anti-cancer agents in patients with inoperable locally advanced or metastatic solid tumors. XL102 is a potent, selective and orally bioavailable inhibitor of cyclin-dependent kinase 7 (CDK7), an important regulator of the cell cycle that has been implicated in cancer.

    "The initiation…

    – Encouraging preclinical data presented in 2020 support advancement to clinical evaluation for XL102, Exelixis' novel oral CDK7 inhibitor –

    – Expansion phase of the trial will include cohorts for ovarian, breast and prostate cancers –

    Exelixis, Inc. (NASDAQ:EXEL) today announced initiation of the first-in-human phase 1 trial evaluating the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of XL102 alone or in combination with other anti-cancer agents in patients with inoperable locally advanced or metastatic solid tumors. XL102 is a potent, selective and orally bioavailable inhibitor of cyclin-dependent kinase 7 (CDK7), an important regulator of the cell cycle that has been implicated in cancer.

    "The initiation of our first-in-human phase 1 trial of XL102 is an important step in our commitment to developing novel medicines that can help patients with cancer," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "The potential of this novel CDK7 inhibitor has been shown in preclinical studies demonstrating anti-proliferative activity and an ability to induce cell death in multiple cancer cell lines. We are excited to begin this trial and look forward to the possibility of helping more patients with advanced or metastatic solid tumors."

    The XL102-101 trial is a phase 1, open-label dose-escalation and cohort-expansion study evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity and effect on biomarkers of XL102 administered orally alone and in multiple combination regimens in up to 298 patients with advanced solid tumors. The study will include patients with advanced solid tumors for whom either life-prolonging therapies do not exist or available therapies are intolerable or no longer effective. It will begin with a dose-escalation stage to determine the maximum tolerated dose or recommended dose of XL102 as a single agent and in combination therapy. In the subsequent cohort-expansion stage, XL102 will be evaluated in patients with certain types of ovarian, breast and prostate cancers. The goal of the cohort-expansion stage is to evaluate the anti-tumor activity of XL102, as assessed per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as well as its safety, tolerability and pharmacokinetic profile.

    About XL102

    XL102 is a potent, selective and orally bioavailable covalent inhibitor of CDK7, which is an important regulator of the cellular transcriptional and cell cycle machinery. CDK7 helps regulate cell cycle progression, with overexpression observed in multiple cancers, such as breast and gastric. In preclinical studies, XL102 revealed potent anti-proliferative activity, induced cell death in a large panel of cancer cell lines and caused tumor growth inhibition and regression in xenograft models, demonstrating its potential as a targeted antitumor agent.

    XL102 (previously known as AUR102) was in-licensed by Exelixis from Aurigene in 2020. Exelixis has assumed responsibility for the future clinical development, commercialization and global manufacturing of XL102.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Forward-looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: the clinical and therapeutic potential of XL102 for patients with advanced or metastatic solid tumors; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis' continuing compliance with applicable legal and regulatory requirements; the potential failure of XL102 or the combination of XL102 and other anticancer agents to demonstrate safety and/or efficacy in XL102-101 and in future trials; uncertainties inherent in the product development process; the continuing COVID-19 pandemic and its impact on Exelixis' research and development operations, including Exelixis' ability to initiate new clinical trials and clinical trial sites, enroll clinical trial patients, conduct trials per protocol, and conduct drug research and discovery operations and related activities; the costs of conducting clinical trials, including the ability or willingness of Exelixis' collaboration partners to invest in the resources necessary to complete the trials; Exelixis' dependence on third-party vendors for the development, manufacture and supply of XL102; Exelixis' ability to protect its intellectual property rights; market competition; changes in economic and business conditions; and other factors affecting Exelixis and its development programs discussed under the caption "Risk Factors" in Exelixis' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 5, 2020, and in Exelixis' future filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a Japanese trademark.

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  14. – FDA approval based on CheckMate -9ER trial, in which the combination of CABOMETYX and OPDIVO significantly improved overall survival while doubling progression-free survival and objective response rate versus sunitinib as a first-line treatment for patients with advanced RCC –

    – Exelixis prepared to fully support expanded indication immediately –

    – Application approved prior to Prescription Drug User Fee Act action date of February 20, 2021 and reviewed under the Real-Time Oncology Review pilot program –

    Exelixis, Inc. (NASDAQ:EXEL) today announced that the U.S. Food and Drug Administration (FDA) approved CABOMETYX® (cabozantinib) for patients with advanced renal cell carcinoma (RCC) as a first-line treatment in combination with OPDIVO…

    – FDA approval based on CheckMate -9ER trial, in which the combination of CABOMETYX and OPDIVO significantly improved overall survival while doubling progression-free survival and objective response rate versus sunitinib as a first-line treatment for patients with advanced RCC –

    – Exelixis prepared to fully support expanded indication immediately –

    – Application approved prior to Prescription Drug User Fee Act action date of February 20, 2021 and reviewed under the Real-Time Oncology Review pilot program –

    Exelixis, Inc. (NASDAQ:EXEL) today announced that the U.S. Food and Drug Administration (FDA) approved CABOMETYX® (cabozantinib) for patients with advanced renal cell carcinoma (RCC) as a first-line treatment in combination with OPDIVO® (nivolumab). RCC is the most common form of kidney cancer, which is among the 10 most frequently diagnosed cancers in the U.S. annually.1

    "This combination of cabozantinib and nivolumab significantly improved key efficacy measures compared to sunitinib – progression-free survival, overall survival and objective response rate – while showing a low rate of treatment discontinuations due to side effects. The therapeutic benefit demonstrated in CheckMate -9ER and quality of life measures explored emphasize the role of this combination for patients with advanced kidney cancer," said Dr. Toni Choueiri, Director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and the Jerome and Nancy Kohlberg Professor of Medicine at Harvard Medical School. "With this important FDA approval, the combination is poised to become a standard in newly diagnosed metastatic kidney cancer."

    The approval is based on results from CheckMate -9ER, a phase 3 pivotal trial evaluating the combination of CABOMETYX and OPDIVO compared with sunitinib in previously untreated advanced or metastatic RCC. These results were presented during the European Society of Medical Oncology Virtual Congress 2020 in September. The FDA reviewed the application for CABOMETYX and OPDIVO under the Real-Time Oncology Review (RTOR) pilot program and Fast Track designation. The RTOR pilot program, which allows an applicant to pre-submit components of the application to allow the FDA to review clinical trial data before the complete filing is submitted, aims to explore a more efficient review process to ensure safe and effective treatments are available to patients sooner.

    "As the only combination treatment regimen to double median progression-free survival and objective response rate compared with sunitinib while also significantly improving overall survival, we are excited that CABOMETYX in combination with OPDIVO is now available for the first-line treatment of patients with advanced kidney cancer," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "This approval is a meaningful milestone for this patient community and speaks to the broad potential of CABOMETYX as we continue to generate important clinical trial results supporting its use in combination with immune checkpoint inhibitors to benefit patients with other difficult-to-treat cancers. We would like to thank the clinical trial participants, the physicians and their staff who participated in the CheckMate -9ER trial and to acknowledge the team at the FDA for their collaboration during the review of our application."

    In CheckMate -9ER, the combination regimen significantly improved overall survival (OS) compared with sunitinib (HR= 0.60, 98.89% CI 0.40-0.89; p=0.001). Median OS has not yet been reached in either treatment arm. Median progression-free survival (PFS) was doubled at 16.6 months for CABOMETYX in combination with OPDIVO compared with 8.3 months for sunitinib (HR 0.51, 95% CI 0.41-0.64; p<0.0001). Objective response rate (ORR) was also doubled: 56% with CABOMETYX in combination with OPDIVO and 27% with sunitinib (p<0.0001). Consistent results for PFS were observed across subgroups of International Metastatic RCC Database Consortium risk status and PD-L1 tumor expression with CABOMETYX in combination with OPDIVO.

    CABOMETYX in combination with OPDIVO was generally well tolerated and reflected the known safety profiles of the tyrosine kinase inhibitor and immunotherapy components in previously untreated advanced RCC. The most common adverse reactions reported in at least 20% of patients treated with CABOMETYX in combination with OPDIVO were diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough and upper respiratory tract infection. The discontinuation rate due to all causality adverse events in the CABOMETYX in combination with OPDIVO arm was 20% for either CABOMETYX or OPDIVO (8% for CABOMETYX only, 7% for OPDIVO only and 6% for both CABOMETYX and OPDIVO due to the same adverse event at the same time).

    "While significant progress has been made in the treatment landscape for advanced kidney cancer over the last several years, patients still need more therapeutic options to treat this disease as we search for a possible cure," said Bryan Lewis, President and Co-founder of KidneyCAN. "As patients are living longer with advanced kidney cancer, focusing on the safety and effectiveness of new treatments has become even more important. The findings for the combination of CABOMETYX and OPDIVO in the CheckMate -9ER trial make the FDA approval of this combination a notable development for the patient community."

    Exelixis' partner Ipsen Pharma SAS (Ipsen), which has exclusive rights to commercialize and develop CABOMETYX outside of the U.S. and Japan, and Bristol-Myers Squibb Company (BMS) each submitted type II variation applications for CABOMETYX in combination with OPDIVO to the European Medicines Agency (EMA). On September 12, 2020, the EMA validated the type II variations, confirming the submissions are complete and beginning the EMA's centralized review process. On October 27, 2020 Takeda Pharmaceutical Company Limited (Takeda), Exelixis' partner responsible for the clinical development and commercialization of CABOMETYX in Japan, and Ono Pharmaceuticals Co., Ltd., BMS' development and commercialization partner in Japan, submitted a supplemental application to the Japanese Ministry of Health, Labour and Welfare for manufacturing and marketing approval of CABOMETYX in combination with OPDIVO for the treatment of patients with unresectable, advanced or metastatic RCC.

    About CheckMate -9ER

    CheckMate -9ER is an open-label, randomized (1:1), multi-national phase 3 trial evaluating patients with previously untreated advanced or metastatic renal cell carcinoma with a clear cell component. A total of 651 patients (22% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 ≥1%) were randomized to CABOMETYX at a dose of 40 mg QD and OPDIVO (n = 323) versus sunitinib (n = 328). The primary endpoint is PFS. Secondary endpoints include OS and ORR. The primary efficacy analysis compares the doublet combination regimen of CABOMETYX and OPDIVO versus sunitinib in all randomized patients. The trial is sponsored by BMS and Ono Pharmaceutical Co. and co-funded by Exelixis, Ipsen and Takeda.

    About RCC

    The American Cancer Society's 2021 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common type of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 13%.1 Approximately 32,000 patients in the U.S. and 71,000 worldwide will require systemic treatment for advanced kidney cancer in 2021.3

    About 70% of RCC cases are known as "clear cell" carcinomas, based on histology.4 The majority of clear cell RCC tumors have below-normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.5,6 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.7,8,9,10 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.6,7

    About CABOMETYX® (cabozantinib)

    In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC; for the treatment of patients with HCC who have been previously treated with sorafenib; and for patients with advanced RCC as a first-line treatment in combination with OPDIVO (nivolumab). CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

    Important Safety Information

    Warnings and Precautions

    Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

    Perforations and Fistulas: Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

    Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events that require medical intervention.

    Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

    Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

    Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

    Hepatotoxicity: CABOMETYX in combination with nivolumab can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone.

    Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes than when the drugs are administered as single agents. For elevated liver enzymes, interrupt CABOMETYX and nivolumab and consider administering corticosteroids.

    With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. ALT or AST >3 times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%) received systemic corticosteroids; ALT or AST resolved to Grades 0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT or AST who were rechallenged with either CABOMETYX (n=9) or nivolumab (n=11) as a single agent or with both (n=24), recurrence of Grade ≥2 increased ALT or AST was observed in 2 patients receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients receiving both CABOMETYX and nivolumab.

    Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold CABOMETYX and/or nivolumab depending on severity.

    Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of CABOMETYX and nivolumab in 0.9% and withholding of CABOMETYX and nivolumab in 2.8% of patients with RCC.

    Approximately 80% (12/15) of patients with adrenal insufficiency received hormone replacement therapy, including systemic corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the 15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was withheld for adrenal insufficiency, 6 reinstated treatment after symptom improvement; of these, all (n=6) received hormone replacement therapy and 2 had recurrence of adrenal insufficiency.

    Proteinuria: Proteinuria was observed in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

    Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

    Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

    Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

    Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

    ADVERSE REACTIONS

    The most common (≥20%) adverse reactions are:

    CABOMETYX as a single agent: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, vomiting, weight decreased, constipation, and dysphonia.

    CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

    DRUG INTERACTIONS

    Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

    Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John's wort.

    USE IN SPECIFIC POPULATIONS

    Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

    Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

    Please see accompanying full Prescribing Information https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.

    You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery — all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Forward-Looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: the potential for the combination of CABOMETYX and OPDIVO to become a standard of care in newly diagnosed metastatic kidney cancer; the broad therapeutic potential of CABOMETYX in combination with immune checkpoint inhibitors to benefit patients with other difficult-to-treat cancers; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the degree of market acceptance that the combination of CABOMETYX and OPDIVO may achieve in any territories where it may be approved, and Exelixis' ability to obtain or maintain coverage and reimbursement for CABOMETYX; Exelixis' ability to maintain and scale adequate sales, marketing, market access and product distribution capabilities for its products or to enter into and maintain agreements with third parties to do so; Exelixis' continuing compliance with applicable legal and regulatory requirements; the continuing COVID-19 pandemic and its impact on Exelixis' commercial activities; Exelixis' ability to protect its intellectual property rights; Exelixis' dependence on third-party vendors for the development, manufacture and supply of cabozantinib; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions; and other factors affecting Exelixis and its commercial programs and partnerships discussed under the caption "Risk Factors" in Exelixis' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 5, 2020, and in Exelixis' future filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a Japanese trademark.

    OPDIVO® is a registered trademark of Bristol-Myers Squibb Company.


    1 American Cancer Society: Cancer Facts & Figures 2021. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf. Accessed January 2021.

    2Jonasch, E., Gao, J., Rathmell, W., Renal cell carcinoma. BMJ. 2014; 349:g4797.

    3Decision Resources Report: Renal Cell Carcinoma. October 2014 (internal data on file).

    4American Cancer Society: What is Kidney Cancer? Available at: https://www.cancer.org/cancer/kidney-cancer/about/what-is-kidney-cancer.html. Accessed January 2021.

    5Harshman, L., and Choueiri, T. Targeting the hepatocyte growth factor/c-Met signaling pathway in renal cell carcinoma. Cancer J. 2013; 19:316-323.

    6Rankin, et al. Direct regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET. Proc Natl Acad Sci USA. 2014; 111:13373-13378.

    7Zhou, L., Liu, X-D., Sun, M., et al. Targeting MET and AXL overcomes resistance to sunitinib therapy in renal cell carcinoma. Oncogene. 2016; 35:2687-2697.

    8Koochekpour, et al. The von Hippel-Lindau tumor suppressor gene inhibits hepatocyte growth factor/scatter factor-induced invasion and branching morphogenesis in renal carcinoma cells. Mol Cell Biol. 1999; 19:5902–5912.

    9Takahashi, A., Sasaki, H., Kim, S., et al. Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. Cancer Res. 1994; 54:4233-4237.

    10Nakagawa, M., Emoto, A., Hanada, T., Nasu, N., Nomura, Y. Tubulogenesis by microvascular endothelial cells is mediated by vascular endothelial growth factor (VEGF) in renal cell carcinoma. Br J Urol. 1997; 79:681-687.

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  15. Cabozantinib Franchise Preliminary Net Product Revenue of $200 million for the Fourth Quarter 2020, and $741 million for the Full Year 2020 –

    Full Year 2021 Net Product Revenue Guidance of $950 million to $1,050 million –

    – Corporate priorities for 2021 include potentially filing supplemental New Drug Applications for cabozantinib in three additional indications –

    – Presentation and webcast at 2021 J.P. Morgan Healthcare Conference on Monday, January 11th at 5:20 PM EST / 2:20 PM PST –

    Exelixis, Inc. (NASDAQ:EXEL) today announced its preliminary unaudited financial results for the fourth quarter and full year 2020, provided financial guidance for full year 2021, and delivered an update on its business. This 2021 financial guidance takes…

    Cabozantinib Franchise Preliminary Net Product Revenue of $200 million for the Fourth Quarter 2020, and $741 million for the Full Year 2020 –

    Full Year 2021 Net Product Revenue Guidance of $950 million to $1,050 million –

    – Corporate priorities for 2021 include potentially filing supplemental New Drug Applications for cabozantinib in three additional indications –

    – Presentation and webcast at 2021 J.P. Morgan Healthcare Conference on Monday, January 11th at 5:20 PM EST / 2:20 PM PST –

    Exelixis, Inc. (NASDAQ:EXEL) today announced its preliminary unaudited financial results for the fourth quarter and full year 2020, provided financial guidance for full year 2021, and delivered an update on its business. This 2021 financial guidance takes into consideration the anticipated U.S. Food and Drug Administration (FDA) approval and commercial launch of CABOMETYX® (cabozantinib) in combination with OPDIVO® (nivolumab) as a first-line treatment for patients with advanced renal cell carcinoma (RCC), which has a Prescription Drug Use Fee Act (PDUFA) target action date of February 20, 2021.

    Preliminary Fourth Quarter and Full Year 2020 Financial Results & 2021 Financial Guidance

    Exelixis is providing the following preliminary unaudited 2020 financial results and financial guidance for 2021:

     

    Fourth Quarter 2020

    Full Year 2020

    Full Year 2021 Guidance

    Total revenues

    $270 million

    $988 million

    $1,150 million - $1,250 million

    Net product revenues

    $200 million

    $741 million

    $950 million - $1,050 million

    Cost of goods sold

    4.5%

    4.9%

    ~ 5-6% of net product revenues

    Research and development expenses

    $155 million(1)

    $549 million(2)

    $600 million - $650 million(3)

    Selling, general and administrative expenses

    $83 million(4)

    $295 million(5)

    $375 million - $425 million(6)

    Effective tax rate

    n/a(7)

    n/a(7)

    20% - 22%

    Cash and investments at year-end(8)

    ~ $1.5 billion

    $1.6 billion - $1.7 billion

    (1)

    Includes $7.1 million of non-cash stock-based compensation expense.

    (2)

    Includes $37.2 million of non-cash stock-based compensation expense.

    (3)

    Includes $45.0 million of non-cash stock-based compensation expense.

    (4)

    Includes $12.2 million of non-cash stock-based compensation expense.

    (5)

    Includes $67.9 million of non-cash stock-based compensation expense.

    (6)

    Includes $60.0 million of non-cash stock-based compensation expense.

    (7)

    Preliminary results not yet available.

    (8)

    This cash and investments guidance does not include any potential new business development activity.

    The preliminary 2020 financial information presented in this press release has not been audited and is subject to change. The complete Exelixis Fourth Quarter and Full Year 2020 Financial Results are planned for release after market on Wednesday, February 10, 2021.

    "2020 was a year of focused execution for Exelixis as we strengthened our foundation to potentially accelerate top-line revenue growth in 2021 and beyond. Throughout the year, the team advanced all of the components of our business and navigated the challenging COVID-19 pandemic environment to report data from late-stage trials, start new pivotal studies, ready next-generation Exelixis compounds for the clinic, and bring new assets and technologies into our pipeline," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "We start 2021 with significant momentum as we prepare for the anticipated FDA approval of CABOMETYX in combination with OPDIVO based on the CheckMate -9ER trial. With the preliminary 2020 financial results announced today along with our 2021 guidance, we believe we are well positioned to deliver significant revenue growth throughout the new year and beyond as we capitalize on CABOMETYX's future potential indications."

    Dr. Morrissey continued: "In 2021 and beyond, we intend to pursue additional cabozantinib regulatory approvals and clinical development activities that unlock new treatment regimens, benefit a substantially greater number of patients and create the potential for a multi-billion-dollar franchise. CABOMETYX revenue directly supports our emerging pipeline of compounds with the potential to generate significant clinical and commercial value, including XL092, our improved next-generation oral, multi-targeted tyrosine kinase inhibitor that builds on our experience with cabozantinib. We expect to advance XL092 into pivotal trials in 2021 and believe it may ultimately become a source of long-term revenue for Exelixis. Additional programs are advancing alongside XL092, including XL102, our small molecule CDK7 inhibitor; XB002, our first antibody-drug conjugate; and multiple other programs. Overall, between our commercial, clinical, and pipeline activities, we are well on our way to becoming a multi-product oncology company that delivers on our mission to help cancer patients recover stronger and live longer."

    Ahead of the company's presentation at the J.P. Morgan Healthcare Conference tomorrow, Exelixis is also announcing its corporate priorities and anticipated key milestones for 2021, including potential supplemental New Drug Applications (sNDAs) for CABOMETYX, expanded clinical development activities for XL092, and multiple Investigational New Drug applications (INDs) for preclinical assets.

    CABOMETYX and OPDIVO Combination for First-line Advanced RCC Represents Large and Growing Commercial Opportunity

    • In August 2020, Exelixis announced the submission of an sNDA to the FDA for CABOMETYX in combination with Bristol Myers Squibb's (BMS) OPDIVO for patients with advanced RCC. In October 2020, Exelixis and BMS announced that the FDA had accepted each company's regulatory application, granted Priority Review, and assigned a PDUFA goal date, or target action date, of February 20, 2021. Exelixis is ready to commercially launch this combination regimen in the United States, where an estimated 15,000 patients with advanced RCC are eligible for first-line treatment every year and with immune checkpoint inhibitor (ICI) combination therapy consisting of approximately 80% of that market. Based on the efficacy, safety and longer duration of therapy as observed in the CheckMate -9ER trial, Exelixis estimates that a doubling of CABOMETYX revenues in RCC alone may be achievable, with a potential $1.5 billion annualized run rate exiting 2022.

    Potential sNDA Submissions for Cabozantinib in 2021

    • Relapsed radioiodine-refractory differentiated thyroid cancer (DTC): Exelixis expects to file an sNDA for the approval of cabozantinib monotherapy in patients with radioactive iodine-refractory DTC previously treated with a vascular endothelial growth factor receptor-targeted therapy. The sNDA will be based on the positive results from the phase 3 pivotal COSMIC-311 trial, which met its co-primary endpoint of progression-free survival (PFS) in December 2020.
    • Advanced hepatocellular carcinoma (HCC): Exelixis expects to report top-line data from COSMIC-312, a global phase 3 pivotal trial evaluating cabozantinib in combination with atezolizumab (TECENTRIQ®), F. Hoffmann-La Roche Ltd.'s (Roche) anti-PD-L1 ICI, versus sorafenib in previously untreated advanced HCC, for the co-primary endpoints of PFS and overall survival (OS) in the first half of 2021. If the data are supportive, the company anticipates filing an sNDA in 2021, and its partner Ipsen Pharma SAS would also seek to file marketing applications with regulatory agencies in its respective territories based on the results. Exelixis completed enrollment in August 2020 for this global phase 3 pivotal trial. Separately, patient enrollment remains open in China in order to enroll a sufficient number of patients to potentially enable local registration.
    • Metastatic castration-resistant prostate cancer (CRPC): Should the data continue to be supportive, Exelixis anticipates filing an sNDA in 2021 seeking accelerated approval of cabozantinib in combination with atezolizumab, for the treatment of metastatic CRPC. A confirmatory phase 3 pivotal trial of this regimen in this patient population (CONTACT-02) was initiated in June 2020 under the clinical trial collaboration between Exelixis and Roche.

    Additional Cabozantinib Clinical Updates

    • COSMIC-313: Exelixis expanded the enrollment target to 840 patients to provide additional power to assess the secondary endpoint of OS for COSMIC-313, the phase 3 pivotal trial evaluating the triplet combination of cabozantinib, nivolumab and ipilimumab (YERVOY®) versus the combination of nivolumab and ipilimumab in patients with previously untreated advanced intermediate- or poor-risk RCC and expects to complete the expanded enrollment in early 2021. Top-line results of the event-driven analyses from the study are expected in 2022. If the data are supportive, the company would seek to file an sNDA with the FDA.
    • CONTACT trials: In 2020, as part of a clinical trial collaboration between Exelixis and Roche, three phase 3 global pivotal trials were initiated evaluating the combination of cabozantinib and atezolizumab: CONTACT-01 in patients with metastatic non-small cell lung cancer who have been previously treated with an ICI and platinum-containing chemotherapy; CONTACT-02 in patients with metastatic CRPC who have been previously treated with one novel hormonal therapy; and CONTACT-03, in patients with inoperable, locally advanced or metastatic RCC who progressed during or following treatment with an ICI.

    Anticipated Progress for XL092 and Other Compounds Beginning Clinical Development in 2021

    • XL092: Exelixis is currently enrolling patients into the dose escalation cohorts of the phase 1b clinical trial of XL092 in combination with atezolizumab, and expects to initiate enrollment in the clear cell and non-clear cell RCC, hormone-receptor positive breast cancer and metastatic CRPC expansion cohorts shortly. The company also plans to initiate additional expansion cohorts in other tumor types, as well as potential additional studies, evaluating XL092 in combination with other oncology therapies, including ICIs. As data from these cohorts mature and are supportive, XL092 could enter pivotal trials over the course of 2021.
    • XL102: Following the FDA's acceptance of its IND, Exelixis expects to initiate a phase 1 trial of XL102 (formerly known as AUR102), alone or in combination therapy for the treatment of inoperable, locally advanced or metastatic solid tumors. Exelixis in-licensed XL102 from Aurigene Discovery Technologies Limited in December 2020.
    • XB002: Exelixis anticipates beginning a phase 1 trial of XB002 (formerly known as ICON-2), in patients with inoperable, locally advanced or metastatic solid tumors. Exelixis in-licensed XB002 from Iconic Therapeutics, Inc. in December 2020 and plans to file an IND once the drug product release assays are finalized.
    • Additional INDs planned: Subject to preclinical data, Exelixis has the potential to file up to two additional INDs.

    Presentation and Webcast

    Exelixis President and Chief Executive Officer Michael M. Morrissey, Ph.D., will provide a corporate overview and discuss the company's preliminary fourth quarter and full year 2020 financial results, 2021 financial guidance, and key priorities and milestones for 2021 during the company's presentation at the J.P. Morgan Healthcare Conference beginning at 5:20 p.m. EST / 2:20 p.m. PST on Monday, January 11, 2021.

    To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast. A replay will also be available at the same location for 90 days.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Forward-Looking Statements and Preliminary Financial Results

    This press release contains forward-looking statements, including, without limitation, statements related to: Exelixis' anticipation of the FDA's approval and commercial launch of CABOMETYX for patients with advanced RCC as a first-line treatment in combination with Opdivo; Exelixis' 2021 financial guidance; the therapeutic and commercial potential of CABOMETYX and Exelixis' belief that it is well-positioned to deliver significant revenue growth throughout 2021 and beyond; Exelixis' intention to pursue additional regulatory approvals and clinical development activities that create the potential for a multi-billion dollar franchise; Exelixis' clinical development plans for XL092 and belief that it may ultimately become a source of long-term revenue; Exelixis' belief that it is well on its way to becoming a multi-product oncology company; Exelixis' corporate priorities and anticipated key milestones for 2021, including the potential filing of sNDAs for CABOMETYX in three additional indications, expanded clinical development activities for XL092, and multiple INDs for preclinical assets; Exelixis' estimate for CABOMETYX revenues in RCC exiting 2022; Exelixis' expectations for, and the related anticipated timelines for, completing enrollment in, conducting analyses of and obtaining top-line results from its ongoing potential label-enabling clinical studies evaluating cabozantinib, and if supported by the data, pursuing potential regulatory approvals; Exelixis' clinical development plans for XL102 and XB002; Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery; and other statements that are not historical facts. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with: the continuing COVID-19 pandemic and its impact on Exelixis' clinical trial, drug discovery and commercial activities; the degree of market acceptance of CABOMETYX and other Exelixis products in the indications for which they are approved and in the territories where they are approved, and Exelixis' and its partners' ability to obtain or maintain coverage and reimbursement for these products; the effectiveness of CABOMETYX and other Exelixis products in comparison to competing products; the level of costs associated with Exelixis' commercialization, research and development, in-licensing or acquisition of product candidates, and other activities; Exelixis' ability to maintain and scale adequate sales, marketing, market access and product distribution capabilities for its products or to enter into and maintain agreements with third parties to do so; the availability of data at the referenced times; the potential failure of cabozantinib and other Exelixis product candidates, both alone and in combination with other therapies, to demonstrate safety and/or efficacy in clinical testing; uncertainties inherent in the drug discovery and product development process, including evolving regulatory requirements, slower than anticipated patient enrollment or inability to identify a sufficient number of clinical trial sites; Exelixis' dependence on its relationships with its collaboration partners, including their pursuit of regulatory approvals for partnered compounds in new indications, their adherence to their obligations under relevant collaboration agreements and the level of their investment in the resources necessary to complete clinical trials or successfully commercialize partnered compounds in the territories where they are approved; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere, including the risk that regulatory authorities may not approve Exelixis' products as treatments for the indications in which approval has been sought, if at all, as well as the related risk that regulatory authorities may not approve the labeling claims that are necessary or desirable for the successful commercialization of CABOMETYX in any additional indications or of any newly-approved product; Exelixis' continuing compliance with applicable legal and regulatory requirements; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating cabozantinib and other Exelixis products; Exelixis' dependence on third-party vendors for the development, manufacture and supply of its products and product candidates; Exelixis' ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of Exelixis' marketed products; changes in economic and business conditions; and other factors discussed under the caption "Risk Factors" in Exelixis' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 5, 2020, and in Exelixis' future filings with the SEC, including, without limitation, Exelixis' Annual Report on Form 10-K expected to be filed with the SEC on February 10, 2021. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    In addition, this press release includes Exelixis' preliminary financial results for the quarter and fiscal year ended January 1, 2021. Exelixis is currently in the process of finalizing its full financial results for the quarter and fiscal year ended January 1, 2021, and the preliminary financial results presented in this press release are based only upon preliminary information available to Exelixis as of January 10, 2021. Exelixis' preliminary financial results should not be viewed as a substitute for full audited financial statements prepared in accordance with U.S. GAAP, and undue reliance should not be placed on Exelixis' preliminary financial results. Exelixis' independent registered public accounting firm has not audited or reviewed the preliminary financial results included in this press release or expressed any opinion or other form of assurance on such preliminary financial results. In addition, items or events may be identified or occur after the date of this press release due to the completion of operational and financial closing procedures, final audit adjustments and other developments may arise that would require Exelixis to make material adjustments to the preliminary financial results included in this press release. Therefore, the preliminary financial results included in this press release may differ, perhaps materially, from the financial results that will be reflected in Exelixis' audited consolidated financial statements for the fiscal year ended January 1, 2021.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks.

    MINNEBRO is a Japanese trademark.

    OPDIVO® and YERVOY® are registered trademarks of Bristol-Myers Squibb Company.

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  16. Presentation to be webcast on www.exelixis.com

    Exelixis, Inc. (NASDAQ:EXEL) today announced that Michael M. Morrissey, Ph.D., the company's President and Chief Executive Officer, will provide a corporate overview at the virtual 39th Annual J.P. Morgan Healthcare Conference on Monday, January 11, 2021 at 5:20 p.m. EST / 2:20 p.m. PST.

    To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast. A replay will also be available at the same location for 14 days.

    About Exelixis

    Presentation to be webcast on www.exelixis.com

    Exelixis, Inc. (NASDAQ:EXEL) today announced that Michael M. Morrissey, Ph.D., the company's President and Chief Executive Officer, will provide a corporate overview at the virtual 39th Annual J.P. Morgan Healthcare Conference on Monday, January 11, 2021 at 5:20 p.m. EST / 2:20 p.m. PST.

    To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast. A replay will also be available at the same location for 14 days.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery - all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a registered Japanese trademark.

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  17. Cabozantinib reduced the risk of disease progression or death by 78%;

    Exelixis will discuss the trial results and regulatory filing plans with the U.S. Food and Drug Administration (FDA) –

    Exelixis, Inc. (NASDAQ:EXEL) today announced that COSMIC-311, the phase 3 pivotal trial evaluating cabozantinib (CABOMETYX®) versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after up to two prior vascular endothelial growth factor receptor (VEGFR)-targeted therapies, met the co-primary endpoint of demonstrating significant improvement in progression-free survival. Cabozantinib reduced the risk of disease progression or death by 78% with a hazard…

    Cabozantinib reduced the risk of disease progression or death by 78%; hazard ratio = 0.22, (p<0.0001) compared to placebo –

    Exelixis will discuss the trial results and regulatory filing plans with the U.S. Food and Drug Administration (FDA) –

    Exelixis, Inc. (NASDAQ:EXEL) today announced that COSMIC-311, the phase 3 pivotal trial evaluating cabozantinib (CABOMETYX®) versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after up to two prior vascular endothelial growth factor receptor (VEGFR)-targeted therapies, met the co-primary endpoint of demonstrating significant improvement in progression-free survival. Cabozantinib reduced the risk of disease progression or death by 78% with a hazard ratio of 0.22 (96% CI 0.13 – 0.36; p<0.0001) at this planned interim analysis. The safety profile was consistent with that previously observed for cabozantinib.

    "Considering the poor prognosis and lack of progress in the treatment of differentiated thyroid cancer following anti-VEGFR therapy, a significant improvement in progression-free survival is a long-awaited clinical advance," said Marcia S. Brose, M.D., Ph.D., Full Professor of Otorhinolaryngology: Head and Neck Surgery and Director of the Center for Rare Cancers and Personalized Therapy at the Abramson Cancer Center of the University of Pennsylvania, and principal investigator of the trial. "These encouraging results from COSMIC-311 suggest cabozantinib has the potential to become an important new option for these patients. We look forward to sharing the detailed data from the trial at an upcoming medical meeting."

    Given these results, the independent data monitoring committee for the study recommended to stop enrollment and unblind sites and patients. Exelixis intends to discuss the study results, proposed changes to the study conduct, as well as plans for a regulatory filing with the U.S. FDA in the near term.

    "We are very pleased that at this early interim analysis of COSMIC-311, cabozantinib has demonstrated a clinically meaningful and statistically significant improvement in progression-free survival for patients with differentiated thyroid cancer who are in need of additional treatment options after prior therapy," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "We are thankful to the patients, physicians and site staff who are participating in this trial during the COVID-19 pandemic. We intend to discuss the findings with regulatory authorities and look forward to sharing the detailed final COSMIC-311 results when they become available."

    COSMIC-311 is a multicenter, randomized, double-blind, placebo-controlled phase 3 pivotal trial that aimed to enroll approximately 300 patients at 150 sites globally. Patients were randomized in a 2:1 ratio to receive either cabozantinib 60 mg or placebo once daily. Detailed results will be submitted for presentation at a future medical conference. More information about this trial is available at ClinicalTrials.gov.

    About Differentiated Thyroid Cancer

    Approximately 53,000 new cases of thyroid cancer will be diagnosed in the U.S. in 2020.1 Nearly three out of four of these cases will be in women, and the disease is more commonly diagnosed at a younger age compared to most other adult cancers.1 While cancerous thyroid tumors include differentiated, medullary and anaplastic forms, differentiated thyroid tumors make up about 90 percent of cases.1 These include papillary, follicular and Hürthle cell cancer.1 Differentiated thyroid cancer is typically treated with surgery followed by ablation of the remaining thyroid tissue with radioiodine, but approximately 5% to 15% of cases are resistant to radioiodine treatment. 2,3 For these patients, life expectancy is only three to six years from the time metastatic lesions are detected.4,5,6

    About CABOMETYX® (cabozantinib)

    In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with HCC who have been previously treated with sorafenib. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

    CABOMETYX is not indicated for radioiodine-refractory differentiated thyroid cancer.

    Important Safety Information

    Warnings and Precautions

    Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

    Perforations and Fistulas: Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

    Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic event requiring medical intervention.

    Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension occurred in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

    Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

    Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

    Proteinuria: Proteinuria occurred in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

    Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

    Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

    Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

    Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

    Adverse Reactions

    The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, and vomiting.

    Drug Interactions

    Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

    Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John's wort.

    USE IN SPECIFIC POPULATIONS

    Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

    Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

    Please see accompanying full Prescribing Information: https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery — all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Forward-Looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: the potential for cabozantinib to become an important new option for patients with differentiated thyroid cancer following anti-VEGFR therapy; Exelixis' plans to discuss the study results, proposed changes to the study conduct, as well as plans for a regulatory filing with the U.S. FDA in the near term; Exelixis' plans to present detailed final COSMIC-311 results, when they become available, at a future medical conference; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the availability of data at the referenced times; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis' continuing compliance with applicable legal and regulatory requirements; the potential failure of cabozantinib to demonstrate continued safety and efficacy in clinical testing; uncertainties inherent in the product development process; the continuing COVID-19 pandemic and its impact on Exelixis' research and development operations; the costs of conducting clinical trials; Exelixis' dependence on third-party vendors for the development, manufacture and supply of cabozantinib; Exelixis' ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions; and other factors affecting Exelixis and its development programs discussed under the caption "Risk Factors" in Exelixis' quarterly report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 5, 2020, and in Exelixis' future filings with the SEC. The forward-looking statements made in this press release speak only as of the date of this press release. Exelixis expressly disclaims any duty, obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Exelixis' expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based, except as required by law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a Japanese trademark.


    1 American Cancer Society. About Thyroid Cancer. Available at: https://www.cancer.org/cancer/thyroid-cancer/about.html. Accessed December 2020.

    2 Cooper DS, et al. 2009. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 19:1167–1214.

    3 Worden F. 2014. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer. Ther Adv Med Oncol. 6:267–279.

    4 Xing M, Haugen BR, Schlumberger M. 2013. Progress in molecular-based management of differentiated thyroid cancer. Lancet. 381:1058–1069.

    5 Pacini F, et al. 2012. Radioactive iodine-refractory differentiated thyroid cancer: unmet needs and future directions. Expert Rev Endocrinol Metab. 7:541–554.

    6 Durante C, et al. 2006. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 91:2892–2899.

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  18. REDWOOD CITY, Calif. and WUHAN, China, Dec. 16, 2020 (GLOBE NEWSWIRE) -- XWPharma Ltd. today announced that Michael M. Morrissey, Ph.D. has been appointed to the company's Board of Directors. Dr. Morrissey brings extensive experience as a scientist, leader of highly productive Research and Development organizations, and chief executive officer of a fully-integrated, widely respected biopharma company.

    "We are very excited to welcome Mike to our Board," said Leonard Blum, XWPharma President and CEO. "As a seasoned R&D and company leader, his perspective will be invaluable as we prioritize the multiple high potential opportunities our research unit has identified and navigate the evolving landscape of creating first of their kind therapeutics…

    REDWOOD CITY, Calif. and WUHAN, China, Dec. 16, 2020 (GLOBE NEWSWIRE) -- XWPharma Ltd. today announced that Michael M. Morrissey, Ph.D. has been appointed to the company's Board of Directors. Dr. Morrissey brings extensive experience as a scientist, leader of highly productive Research and Development organizations, and chief executive officer of a fully-integrated, widely respected biopharma company.

    "We are very excited to welcome Mike to our Board," said Leonard Blum, XWPharma President and CEO. "As a seasoned R&D and company leader, his perspective will be invaluable as we prioritize the multiple high potential opportunities our research unit has identified and navigate the evolving landscape of creating first of their kind therapeutics for patients suffering from CNS disorders with compelling unmet needs."

    "Joining XWPharma at this stage and playing a part in its future growth is very exciting for me," added Dr. Morrissey. "The company has assembled an organization with broad experience, a special energy, and a shared commitment to bring forward truly original medicines for treating sleep disorders, major depression, chronic pain and other disease states that continue to present huge and underserved challenges for patients, health care systems, and societies around the world. Its trans-Pacific heritage and operations present intriguing opportunities that may deliver important scientific and medical advances."

    Dr. Morrissey has served as a director and as President and Chief Executive Officer of Exelixis, Inc. (NASDAQ:EXEL) since July 2010. During his tenure, the company has grown its flagship medicine, CABOMETYX® (cabozantinib), into a global oncology franchise for the treatment of multiple forms of cancer. At the same time, Exelixis has begun building a differentiated pipeline behind its lead product through internal drug discovery activities at its growing Alameda campus and targeted business development. Prior to becoming Exelixis' CEO, Dr. Morrissey held positions of increasing responsibility at the company, including serving as its President of Research and Development from January 2007 until July 2010. From 1991 to 2000, Dr. Morrissey held several positions at Berlex Biosciences, last holding the position of Vice President, Discovery Research. Earlier in his career, Dr. Morrissey served as a Senior Scientist and Project Team Leader in Medicinal Chemistry at CIBA-Geigy Corporation. He is the author of numerous scientific publications in medicinal chemistry and drug discovery and an inventor on 70 issued U.S. patents and 25 additional published U.S. patent applications. Dr. Morrissey holds a B.S. (Honors) in Chemistry from the University of Wisconsin and a Ph.D. in Chemistry from Harvard University.

    About XWPharma

    XWPharma (formerly XW Laboratories) is a biopharmaceutical company dedicated to the discovery and development of therapeutics that apply novel platform chemistry to time-regulated neurobiology. XWPharma's expertise in drug design is focused on providing potential first- and best-in-class medicines with differentiated features to address the unmet medical needs of patients suffering from debilitating neurological diseases. XW10172 is a clinical-stage, GABAB agonist in development as an investigational once-nightly therapy intended to regulate the patient's sleep cycle in order to alleviate excessive daytime sleepiness and other consequences of sleep dysfunction associated with neurodegenerative diseases, including Parkinson's disease, and narcolepsy. XW10508 is a glutamatergic NMDA antagonist and AMPA activator in development as an oral, once-daily therapy with potential abuse deterrent properties designed for the treatment of major depressive disorder and chronic pain.   

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  19. – Phase 1 clinical trial expected to begin in Q1 2021 –

    – Under the terms of the companies' agreement, Exelixis will make an option exercise payment of $12 million to Aurigene –

    – Promising preclinical data support further advancement of XL102 (formerly AUR102) alone or in combination with chemotherapy –

    Exelixis, Inc. (NASDAQ:EXEL) and Aurigene today announced that Exelixis has exercised its exclusive option for Aurigene's novel CDK7 inhibitor under the companies' July 2019 agreement. Exelixis has now assumed responsibility for the future clinical development, commercialization, and global manufacturing of the compound now known as XL102 (formerly AUR102). Exelixis also announced that it has submitted an Investigational New Drug Application…

    – Phase 1 clinical trial expected to begin in Q1 2021 –

    – Under the terms of the companies' agreement, Exelixis will make an option exercise payment of $12 million to Aurigene –

    – Promising preclinical data support further advancement of XL102 (formerly AUR102) alone or in combination with chemotherapy –

    Exelixis, Inc. (NASDAQ:EXEL) and Aurigene today announced that Exelixis has exercised its exclusive option for Aurigene's novel CDK7 inhibitor under the companies' July 2019 agreement. Exelixis has now assumed responsibility for the future clinical development, commercialization, and global manufacturing of the compound now known as XL102 (formerly AUR102). Exelixis also announced that it has submitted an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) to evaluate XL102 alone or in combination therapy for the treatment of inoperable locally advanced or metastatic solid tumors. XL102 is a potent, selective, and orally bioavailable covalent inhibitor of cyclin-dependent kinase 7 (CDK7), which is an important regulator of the cellular transcriptional and cell cycle machinery. Aurigene presented positive preclinical data demonstrating that XL102 has potent anti-proliferative activity and induces cell death in a large panel of cancer cell lines at the 32nd EORTC-NCI-AACR (ENA) Symposium (Abstract 170) in October 2020.

    This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20201207005499/en/

    "With single-agent and combination potential across a variety of forms of cancer, XL102 is an important addition to the growing Exelixis pipeline," said Peter Lamb, Ph.D., Executive Vice President and Chief Scientific Officer of Exelixis. "Aurigene has done an excellent job advancing the program and maintaining development timelines during a year in which global biopharmaceutical research came under pressure from COVID-19. We are excited to begin clinical development for XL102 following the FDA's recent acceptance of our IND. As we maximize the opportunity for cabozantinib, our lead medicine, we are committed to building a diversified high-value pipeline with the potential to become novel medicines that could one day help patients with cancer recover stronger and live longer."

    "Exelixis' decision to in-license XL102 and file its IND with the FDA provides important validation of Aurigene's discovery and preclinical development capabilities and the value of our partnership with Exelixis overall," said Murali Ramachandra, Ph.D., Chief Executive Officer of Aurigene. "The preclinical data generated to date for XL102 demonstrate that this novel CDK7 inhibitor is orally available and has significant potential to improve care and outcomes for patients with diverse cancer indications, including breast cancer, prostate cancer, leukemia, and lymphoma. We continue to generate additional data from the other programs that are part of our partnership with Exelixis and believe that these programs will provide additional value-creating opportunities for both companies."

    Under the terms of the July 2019 agreement, Exelixis made an upfront payment of $10 million for exclusive options to license three preexisting programs, including the compound now known as XL102, from Aurigene. In addition, Exelixis and Aurigene initiated three Aurigene-led drug discovery programs on mutually agreed upon targets, in exchange for additional upfront option payments of $2.5 million per program. Exelixis is also contributing research funding to Aurigene to facilitate discovery and preclinical development work on all six programs. As the programs mature, Exelixis will have the opportunity to exercise an exclusive option for each program up until the time of IND filing acceptance. If Exelixis decides to exercise an option, it will make an option exercise payment to Aurigene and assume responsibility for that program's future clinical development and commercialization including global manufacturing. To exercise its option for XL102, Exelixis will make an option exercise payment of $12 million. Once Exelixis in-licenses a program, Aurigene will be eligible for clinical development, regulatory, and sales milestones, as well as royalties on sales. Under the terms of the agreement, Aurigene retains limited development and commercial rights for India and Russia.

    About Aurigene

    Aurigene Discovery Technologies Limited is a development stage biotech company engaged in discovery and clinical development of novel and best-in-class therapies to treat cancer and inflammatory diseases and a wholly owned subsidiary of Dr. Reddy's Laboratories Ltd. ((BSE: 500124, NSE: DRREDDY, NYSE:RDY). Aurigene is focused on precision-oncology, oral immune checkpoint inhibitors, and the Th-17 pathway. Aurigene's programs currently in clinical development include an oral ROR-gamma inhibitor AUR101 for moderate to severe psoriasis in phase 2 under a U.S. FDA IND and a PD-L1/VISTA antagonist CA-170 for non-squamous non-small cell lung cancer in phase 2b/3 in India. Additionally, Aurigene has multiple compounds at different stages of pre-clinical development. Aurigene has also partnered with several large and mid-pharma companies in the United States and Europe and has multiple programs in clinical development. For more information, please visit Aurigene's website at www.aurigene.com.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery – all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Exelixis Forward-Looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: Exelixis' plans to initiate a phase 1 clinical trial of XL102 in the first quarter of 2021; the therapeutic potential of XL102 to improve care and outcomes for patients with diverse cancer indications; the potential for Exelixis' and Aurigene's partnership to provide additional value-creating opportunities for both companies; Exelixis' potential future financial and other obligations under the exclusive collaboration, option and license agreement with Aurigene; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the continuing COVID-19 pandemic and its impact on Exelixis' research and development operations; the level of costs associated with Exelixis' commercialization, research and development, in-licensing or acquisition of product candidates, and other activities; uncertainties inherent in the drug discovery and product development process; Exelixis' dependence on its relationship with Aurigene, including Aurigene's adherence to its obligations under the exclusive collaboration, option and license agreement and the level of Aurigene's assistance to Exelixis in completing clinical trials, pursuing regulatory approvals or successfully commercializing partnered compounds in the territories where they may be approved; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis' and Aurigene's continuing compliance with applicable legal and regulatory requirements; Exelixis' and Aurigene's ability to protect their respective intellectual property rights; market competition; changes in economic and business conditions; and other factors affecting Exelixis and its product pipeline discussed under the caption "Risk Factors" in Exelixis' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 5, 2020, and in Exelixis' future filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a registered Japanese trademark.

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  20. Phase 1 clinical trial planned for early 2021, pending the FDA's acceptance of Exelixis' planned IND filing –

    – Under the terms of the companies' agreement, Exelixis has made an option exercise payment of $20 million to Iconic Therapeutics –

    – Preclinical data underscore best-in-class potential for XB002 (formerly ICON-2) in treatment of solid tumors –

    Exelixis, Inc. (NASDAQ:EXEL), Iconic Therapeutics, Inc. (Iconic) and Zymeworks Inc. (NYSE:ZYME) today announced that Exelixis has exercised its exclusive option for Iconic's lead oncology antibody-drug conjugate (ADC) program under the companies' May 2019 agreement. As a result, Exelixis now has responsibility for the future clinical development, commercialization, and manufacturing of the…

    Phase 1 clinical trial planned for early 2021, pending the FDA's acceptance of Exelixis' planned IND filing –

    – Under the terms of the companies' agreement, Exelixis has made an option exercise payment of $20 million to Iconic Therapeutics –

    – Preclinical data underscore best-in-class potential for XB002 (formerly ICON-2) in treatment of solid tumors –

    Exelixis, Inc. (NASDAQ:EXEL), Iconic Therapeutics, Inc. (Iconic) and Zymeworks Inc. (NYSE:ZYME) today announced that Exelixis has exercised its exclusive option for Iconic's lead oncology antibody-drug conjugate (ADC) program under the companies' May 2019 agreement. As a result, Exelixis now has responsibility for the future clinical development, commercialization, and manufacturing of the Tissue Factor (TF)-targeting ADC now known as XB002 (formerly ICON-2). A rationally designed next-generation ADC, XB002 comprises a Tissue Factor-targeting antibody with Zymeworks' proprietary ZymeLink™ linker-payload, creating the potential for an improved therapeutic index and favorable safety profile as compared to earlier-generation, TF-targeting ADCs. Exelixis plans to file an Investigational New Drug application (IND) with the U.S. Food and Drug Administration (FDA) for XB002 in the near-term and, pending the FDA's acceptance of the IND, initiate a phase 1 clinical trial of XB002 in early 2021.

    This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20201202005375/en/

    "XB002 is an important addition to the Exelixis pipeline given its potential differentiation from other Tissue Factor-targeting antibody-drug conjugates and its status as the first program in our growing biologics portfolio to reach IND filing stage," said Peter Lamb, Ph.D., Executive Vice President and Chief Scientific Officer of Exelixis. "Iconic designed a highly promising molecule and advanced it through a rigorous preclinical evaluation, setting the stage for Exelixis to complete our planned IND filing in the coming weeks. We are grateful for Iconic's partnership over the past 18 months and look forward to fully evaluating the potential of XB002 to help patients with cancer."

    Under the terms of the May 2019 agreement between Exelixis and Iconic, Exelixis gained an exclusive option to license XB002 (then ICON-2) in exchange for an upfront payment to Iconic of $7.5 million and a commitment of preclinical development funding. In exercising its exclusive option, Exelixis has made an additional option exercise payment of $20 million to Iconic. Iconic is now also eligible for future development, regulatory and commercialization milestone payments, as well as royalties on potential sales. The ZymeLink ADC technology in XB002 was originally licensed to Iconic from Zymeworks. Under the terms of their 2019 agreement, Zymeworks will receive a share of the $20 million option fee and is eligible to receive a share of all future revenue received by Iconic, as well as tiered royalties on worldwide sales.

    "Exelixis' decision to in-license our lead oncology program provides important validation of Iconic's discovery and development capabilities, our platform of proprietary anti-Tissue Factor molecules designed to efficiently but safely bind Tissue Factor, and the potential of Tissue Factor as an oncology antibody-drug conjugate target," said William L. Greene, M.D., Chief Executive Officer of Iconic Therapeutics. "Preclinical data presented earlier this year demonstrate that XB002 binds Tissue Factor without affecting the coagulation cascade, which has hindered prior development of Tissue Factor-targeting molecules, has activity in multiple solid tumor cancer models and has improved tolerability compared to other Tissue Factor-targeting ADCs. We are excited to see XB002 make further progress as part of Exelixis' highly-regarded clinical development organization."

    "We are excited to see this promising molecule take an important step towards clinical trials backed by the experienced clinical team at Exelixis," said Tony Polverino, Ph.D., Executive Vice President, Early Development and Chief Scientific Officer of Zymeworks. "This would mark the second ZymeLink-based therapeutic to enter the clinic in addition to our bispecific HER2 antibody-drug conjugate, ZW49, further highlighting the differentiative potential of our novel antibody-drug conjugate platform."

    Pending the completion of Exelixis' planned IND and the FDA's acceptance of the filing, Exelixis intends to initiate a phase 1 dose escalation and expansion study of XB002 in subjects with inoperable locally advanced or metastatic solid tumors early in 2021.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery - all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    About Iconic Therapeutics

    Iconic Therapeutics, Inc. is a biopharmaceutical company dedicated to leveraging its deep insight into tissue factor biology and TF's role in inflammation, tumor growth, and angiogenesis to develop new therapeutics for serious diseases including retinal disease and cancer. The Company has developed a portfolio of proprietary molecules which bind to and antagonize TF expressed in several disease states. In May, 2019, Iconic Therapeutics entered into a licensing agreement with Zymeworks that granted to Iconic non-exclusive rights to Zymeworks' proprietary ZymeLink™ antibody-drug conjugate (ADC) platform. Please visit www.iconictherapeutics.com for additional information.

    About Zymeworks

    Zymeworks is a clinical-stage biopharmaceutical company dedicated to the development of next-generation multifunctional biotherapeutics. Zymeworks' suite of therapeutic platforms and its fully integrated drug development engine enable precise engineering of highly differentiated product candidates. Zymeworks' lead clinical candidate, zanidatamab (ZW25), is a novel Azymetric™ bispecific antibody which has been granted Breakthrough Therapy designation by the FDA and is currently enrolling in a registration-enabling clinical trial for refractory HER2+ biliary tract cancer as well as several Phase 2 clinical trials for HER2+ gastroesophageal and breast cancers. Zymeworks' second clinical candidate, ZW49, is a bispecific antibody-drug conjugate currently in Phase 1 clinical development and combines the unique design and antibody framework of zanidatamab with Zymeworks' proprietary ZymeLink™ linker-cytotoxin. Zymeworks is also advancing a deep preclinical pipeline in oncology (including immuno-oncology agents) and other therapeutic areas. In addition, its therapeutic platforms are being leveraged through strategic partnerships with nine biopharmaceutical companies. For additional information about Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on Twitter.

    Exelixis Forward-Looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: Exelixis' plans to file an IND with the FDA for XB002 in the near-term and, pending the FDA's acceptance of the IND, initiate a phase 1 clinical trial of XB002 in early 2021; the therapeutic potential of XB002 for cancer patients and favorable safety profile of the molecule as compared to earlier-generation, TF-targeting ADCs; Exelixis' potential future financial and other obligations under the exclusive option and license agreement with Iconic; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the level of costs associated with Exelixis' commercialization, research and development, in-licensing or acquisition of product candidates, and other activities; uncertainties inherent in the drug discovery and product development process; Exelixis' dependence on its relationship with Iconic, including Iconic's adherence to its obligations under the exclusive option and license agreement and the level of Iconic's assistance to Exelixis in completing clinical trials, pursuing regulatory approvals or successfully commercializing partnered compounds in the territories where they may be approved; the continuing COVID-19 pandemic and its impact on Exelixis' research and development operations; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis' and Iconic's continuing compliance with applicable legal and regulatory requirements; Exelixis', Iconic's and Zymeworks' ability to protect their respective intellectual property rights; market competition; changes in economic and business conditions; and other factors affecting Exelixis and its product pipeline discussed under the caption "Risk Factors" in Exelixis' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 5, 2020, and in Exelixis' future filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    Zymeworks Forward-Looking Statement

    This press release includes "forward-looking statements" within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and "forward-looking information" within the meaning of Canadian securities laws, or collectively, forward-looking statements. Forward-looking statements in this press release include, but are not limited to, statements that relate to the payment to Zymeworks of a share of the $20 million option fee received by Iconic, Zymeworks' eligibility to receive a share of future revenue received by Iconic as well as tiered royalties on worldwide sales, Zymeworks' clinical and preclinical development of its product candidates, and other information that is not historical information. When used herein, words such as "will", "plan", "intend", and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon Zymeworks' current expectations and various assumptions. Zymeworks believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. Zymeworks may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various factors, including, without limitation, market conditions and the factors described under "Risk Factors" in Zymeworks' Quarterly Report on Form 10-Q for its quarter ended September 30, 2020 (a copy of which may be obtained at www.sec.gov and www.sedar.com). Consequently, forward-looking statements should be regarded solely as Zymeworks' current plans, estimates and beliefs. Investors should not place undue reliance on forward-looking statements. Zymeworks cannot guarantee future results, events, levels of activity, performance, or achievements. Zymeworks does not undertake and specifically declines any obligation to update, republish, or revise any forward-looking statements to reflect new information, future events or circumstances or to reflect the occurrences of unanticipated events, except as may be required by law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a registered Japanese trademark.

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  21. Approval based on results of two clinical trials in patients with advanced hepatocellular carcinoma who had received prior systemic therapy

    Exelixis, Inc. (NASDAQ:EXEL) today announced that Takeda Pharmaceutical Company Limited (Takeda), its partner responsible for the clinical development and commercialization of CABOMETYX® (cabozantinib) in Japan, received approval from the Japanese Ministry of Health, Labor and Welfare to manufacture and market CABOMETYX as a treatment for patients with unresectable hepatocellular carcinoma (HCC) that has progressed after prior systemic therapy.

    Takeda's application is based on the results of two clinical trials in patients with advanced HCC who had received prior systemic therapy: CELESTIAL (XL184-309…

    Approval based on results of two clinical trials in patients with advanced hepatocellular carcinoma who had received prior systemic therapy

    Exelixis, Inc. (NASDAQ:EXEL) today announced that Takeda Pharmaceutical Company Limited (Takeda), its partner responsible for the clinical development and commercialization of CABOMETYX® (cabozantinib) in Japan, received approval from the Japanese Ministry of Health, Labor and Welfare to manufacture and market CABOMETYX as a treatment for patients with unresectable hepatocellular carcinoma (HCC) that has progressed after prior systemic therapy.

    Takeda's application is based on the results of two clinical trials in patients with advanced HCC who had received prior systemic therapy: CELESTIAL (XL184-309), a global, randomized, placebo-controlled, double-blind phase 3 clinical trial, and Cabozantinib-2003, a phase 2 clinical trial conducted in Japan. The CELESTIAL trial was the basis for the CABOMETYX approvals in the U.S. and the EU for the treatment of patients with HCC who have been previously treated with sorafenib.

    "Hepatocellular carcinoma causes approximately 30,000 deaths in Japan each year and is a leading cause of cancer-related death worldwide," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "The approval of CABOMETYX in Japan is an exciting next step toward bringing this treatment to liver cancer patients who otherwise have limited treatment options following prior systemic therapy. We're proud to collaborate with Takeda as we work to bring this treatment to patients in Japan."

    Per the terms of Exelixis and Takeda's collaboration and license agreement, Exelixis is eligible to receive a $15 million milestone payment from Takeda upon the first commercial sale of CABOMETYX for unresectable HCC, which is expected to occur in the fourth quarter of 2020. In January 2020, Takeda's application for approval to manufacture and sell CABOMETYX as a treatment for patients with unresectable HCC that had progressed after prior systemic therapy in Japan triggered a $10 million milestone payment. Exelixis continues to be eligible to receive additional development, regulatory and first-sale milestones for potential future cabozantinib indications and is also eligible for sales revenue milestones and royalties on net sales of cabozantinib in Japan.

    Takeda fully funds cabozantinib development activities that are exclusively for the benefit of Japan and has the opportunity to share the costs associated with global cabozantinib clinical trials, providing the company opts into those trials.

    About HCC

    Liver cancer is a leading cause of cancer death worldwide, accounting for more than 700,000 deaths and 800,000 new cases each year.1 In the U.S., the incidence of liver cancer has more than tripled since 1980.2 HCC is the most common form of liver cancer, making up about three-fourths of the estimated 43,000 new cases in the U.S. in 2020.2 HCC is the fastest-rising cause of cancer-related death in the U.S.3 Without treatment, patients with advanced HCC usually survive less than 6 months.4

    About CABOMETYX® (cabozantinib)

    In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with HCC who have been previously treated with sorafenib. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the United States.

    U.S. Important Safety Information

    Warnings and Precautions

    Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

    Perforations and Fistulas: Gastrointestinal (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a Grade 4 fistula or a GI perforation.

    Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic event requiring medical intervention.

    Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension occurred in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.

    Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.

    Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

    Proteinuria: Proteinuria occurred in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

    Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible. Withhold CABOMETYX for development of ONJ until complete resolution.

    Impaired Wound Healing: Wound complications occurred with CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer CABOMETYX for at least 2 weeks after major surgery and until adequate wound healing is observed. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

    Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic findings on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

    Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.

    Adverse Reactions

    The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, and vomiting.

    Drug Interactions

    Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

    Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John's wort.

    USE IN SPECIFIC POPULATIONS

    Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

    Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

    Please see accompanying full Prescribing Information https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery — all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Forward-Looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: the therapeutic potential of CABOMETYX for patients with liver cancer and Exelixis' and Takeda's collaboration to bring CABOMETYX to HCC patients in Japan; Exelixis' eligibility to receive a $15 million milestone payment from Takeda upon Takeda's first commercial sale of CABOMETYX for unresectable HCC, which is expected to occur in the fourth quarter of 2020; Exelixis' eligibility for future development, regulatory and first-sale milestones, plus sales revenue milestones and royalties on net sales under its collaboration with Takeda; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the degree of market acceptance of CABOMETYX in Japan; Exelixis' dependence on its relationship with Takeda, including Takeda's investment in the resources necessary to successfully commercialize CABOMETYX in Japan; Exelixis' and Takeda's ability to maintain and scale adequate sales, marketing, market access and product distribution capabilities for their products or to enter into and maintain agreements with third parties to do so; Exelixis' and Takeda's continuing compliance with applicable legal and regulatory requirements; the continuing COVID-19 pandemic and its impact on Exelixis' and Takeda's commercial activities; Exelixis' ability to protect its intellectual property rights; Exelixis' dependence on third-party vendors for the development, manufacture and supply of cabozantinib; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions; and other factors affecting Exelixis and its commercial programs and partnerships discussed under the caption "Risk Factors" in Exelixis' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 5, 2020, and in Exelixis' future filings with the SEC. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a Japanese trademark.

    1 International Agency for Research on Cancer. GLOBOCAN 2018. Liver Fact Sheet. Available at: http://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf. Accessed November 2020.

    2 American Cancer Society: Cancer Facts & Figures 2020. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf. Accessed November 2020.

    3 Siegel R, Miller K, Jemal A: Cancer Statistics, 2020. CA: A Cancer Journal for Clinicians. Volume 70, Issue 1: 7-30. Available at: https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21590. Accessed November 2020.

    4 Weledji E, Orock G, Ngowe M, NsaghaD. How grim is hepatocellular carcinoma? Ann Med Surg. 2014. 3:71-76.

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  22. – Presentations to be webcast on www.exelixis.com

    Exelixis, Inc. (NASDAQ:EXEL) today announced that members of the company's management team will participate in fireside chats at the following virtual investor conferences in December:

    • Piper Sandler 32nd Annual Virtual Healthcare Conference: Due to the virtual nature of this year's conference, presentation sessions were pre-recorded and available on-demand. Exelixis' fireside chat session is now available to stream on the company's website.
    • Evercore ISI 3rd Annual HealthCONx: Exelixis is scheduled to present at 3:05pm EST / 12:05pm PST on Tuesday, December 1, 2020.

    To access the webcast links, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the…

    – Presentations to be webcast on www.exelixis.com

    Exelixis, Inc. (NASDAQ:EXEL) today announced that members of the company's management team will participate in fireside chats at the following virtual investor conferences in December:

    • Piper Sandler 32nd Annual Virtual Healthcare Conference: Due to the virtual nature of this year's conference, presentation sessions were pre-recorded and available on-demand. Exelixis' fireside chat session is now available to stream on the company's website.
    • Evercore ISI 3rd Annual HealthCONx: Exelixis is scheduled to present at 3:05pm EST / 12:05pm PST on Tuesday, December 1, 2020.

    To access the webcast links, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the presentations to ensure adequate time for any software download that may be required to listen to the webcasts. Replays will also be available at the same location for 14 days.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery - all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks.

    MINNEBRO is a registered Japanese trademark.

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  23. - Total Revenues of $231.1 Million, Cabozantinib Franchise Revenues of $168.6 Million -

    - GAAP Diluted EPS of $(0.10), Non-GAAP Diluted EPS of $0.04 -

    - Conference Call and Webcast Today at 5:00 PM Eastern Time -

    Exelixis, Inc. (NASDAQ:EXEL) today reported financial results for the third quarter of 2020 and provided an update on progress toward fulfilling its key corporate objectives, as well as commercial and clinical development milestones.

    "In the third quarter of 2020, the Exelixis team built the foundation to accelerate revenue growth with CABOMETYX® (cabozantinib) in 2021," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "Based on the positive results from the CheckMate -9ER phase 3 pivotal trial…

    - Total Revenues of $231.1 Million, Cabozantinib Franchise Revenues of $168.6 Million -

    - GAAP Diluted EPS of $(0.10), Non-GAAP Diluted EPS of $0.04 -

    - Conference Call and Webcast Today at 5:00 PM Eastern Time -

    Exelixis, Inc. (NASDAQ:EXEL) today reported financial results for the third quarter of 2020 and provided an update on progress toward fulfilling its key corporate objectives, as well as commercial and clinical development milestones.

    "In the third quarter of 2020, the Exelixis team built the foundation to accelerate revenue growth with CABOMETYX® (cabozantinib) in 2021," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "Based on the positive results from the CheckMate -9ER phase 3 pivotal trial evaluating cabozantinib in combination with nivolumab in previously untreated patients with advanced renal cell carcinoma, we and Bristol Myers Squibb completed our respective regulatory filings for the combination in August. In September, the first detailed results from the trial were presented during a Presidential Symposium of the ESMO Virtual Congress 2020. And then just last month, we announced the FDA accepted the filings, granted Priority Review designation and assigned an action date of February 20th of next year. Exelixis is launch-ready and prepared to immediately support this important new combination regimen, pending FDA approval."

    Dr. Morrissey continued: "As we continue working to maximize the clinical and commercial potential for CABOMETYX, we're moving quickly in parallel to build a diversified pipeline behind it. In October, we presented the preclinical profile and initial clinical pharmacokinetic data for XL092, our next-generation oral tyrosine kinase inhibitor that builds on the experience and target profile of cabozantinib with improved characteristics, including a shorter pharmacokinetic half-life. Encouraged by the data we've seen to date, we expanded the phase 1 study to evaluate XL092 in combination with atezolizumab in multiple solid tumors, with enrollment now underway. The XL092 program is an important component of our growing pipeline, as well as an opportunity to drive growth into new and potentially larger indications with unmet medical need. We further strengthened our pipeline during the quarter through business development activities, with two additional collaboration and license agreements focused on the discovery and development of novel antibody-drug conjugates. Our continued efforts to expand the breadth and depth of our discovery pipeline beyond small molecules, along with a focused investment in the development of cabozantinib and XL092, have the potential to drive top-line growth significantly for Exelixis, and provide new treatment options for the patients we serve."

    Third Quarter 2020 Financial Results

    Total revenues for the quarter ended September 30, 2020 were $231.1 million, compared to $271.7 million for the comparable period in 2019.

    Total revenues for the quarter ended September 30, 2020 included net product revenues of $168.6 million, compared to $191.8 million for the comparable period in 2019. The decrease in net product revenues was due to a decrease in sales volumes driven by decreases in prescriptions, which were in line with market trends, and lower customer inventory.

    Collaboration revenues, composed of license revenues and collaboration services revenues, were $62.5 million for the quarter ended September 30, 2020, compared to $79.9 million for the comparable period in 2019. The decrease in collaboration revenues was primarily related to a decrease in the recognition of milestone related revenues, which was partially offset by increases in development cost reimbursements earned, and higher royalty revenues for the sales of cabozantinib outside of the U.S. generated by Exelixis' collaboration partners, Ipsen Pharma SAS (Ipsen) and Takeda Pharmaceutical Company Limited (Takeda).

    Research and development expenses for the quarter ended September 30, 2020 were $176.8 million, compared to $97.3 million for the comparable period in 2019. The increase in research and development expenses was primarily related to increases in clinical trial costs, license and other collaboration costs and personnel expenses. The increase in clinical trial costs was primarily due to costs associated with expanding clinical trial programs for cabozantinib, which includes CONTACT-02, COSMIC-313, COSMIC-312 and COSMIC-021. The increase in license and other collaboration costs was primarily due to an increase in upfront license fee payments from recent business development activities with two additional collaboration and license agreements focused on the discovery and development of novel antibody-drug conjugates (ADCs). The increase in personnel expenses was primarily due to an increase in stock-based compensation expense attributable to the performance-based restricted stock units (PSUs) granted in 2019 that became probable of achievement during the third quarter of 2020 and an increase in headcount to support Exelixis' expanding discovery and development efforts.

    Selling, general and administrative expenses for the quarter ended September 30, 2020 were $88.2 million, compared to $51.3 million for the comparable period in 2019. The increase in selling, general and administrative expenses was primarily related to increases in personnel expenses and marketing costs. The increase in personnel expenses was primarily due to an increase in stock-based compensation expense attributable to the PSUs granted in 2019 that became probable of achievement during the third quarter of 2020 and an increase in administrative headcount to support Exelixis' commercial and research and development organizations.

    Provision for (benefit from) income taxes for the quarter ended September 30, 2020 was $(6.0) million, compared to $25.2 million for the comparable period in 2019, primarily due to the change in pre-tax income (loss).

    GAAP net income (loss) for the quarter ended September 30, 2020 was $(32.0) million, or $(0.10) per share, basic and diluted, compared to GAAP net income of $97.5 million, or $0.32 per share, basic and $0.31 per share, diluted, for the comparable period in 2019. The change in GAAP net income was primarily related to an increase in operating expenses and a decrease in total revenues.

    Non-GAAP net income for the quarter ended September 30, 2020 was $11.2 million, or $0.04 per share, basic and diluted, compared to non-GAAP net income of $107.6 million, or $0.35 per share, basic and $0.34 per share, diluted, for the comparable period in 2019. Non-GAAP net income excludes stock-based compensation, adjusted for the related income tax effect.

    Cash and investments were $1.5 billion at September 30, 2020, compared to $1.4 billion at December 31, 2019.

    Non-GAAP Financial Measures

    To supplement Exelixis' financial results presented in accordance with U.S. Generally Accepted Accounting Principles (GAAP), Exelixis presents non-GAAP net income (and the related per share measures), which excludes from GAAP net income (loss) (and the related per share measures) stock-based compensation expense, adjusted for the related income tax effect for all periods presented.

    Exelixis believes that the presentation of these non-GAAP financial measures provides useful supplementary information to, and facilitates additional analysis by, investors. In particular, Exelixis believes that these non-GAAP financial measures, when considered together with its financial information prepared in accordance with GAAP, can enhance investors' and analysts' ability to meaningfully compare Exelixis' results from period to period, and to identify operating trends in Exelixis' business. Exelixis has excluded stock-based compensation expense, adjusted for the related income tax effect, because it is a non-cash item that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. Exelixis also regularly uses these non-GAAP financial measures internally to understand, manage and evaluate its business and to make operating decisions.

    These non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. Exelixis encourages investors to carefully consider its results under GAAP, as well as its supplemental non-GAAP financial information and the reconciliation between these presentations, to more fully understand Exelixis' business. Reconciliations between GAAP and non-GAAP results are presented in the tables of this release.

    2020 Financial Guidance

    Exelixis is providing the following updated financial guidance for fiscal year 2020:

    Total revenues

     

    $900 million - $950 million

    Net product revenues (1)

     

    $700 million - $725 million

    Cost of goods sold (1)

     

    Approximately 5% of net product revenues

    Research and development expenses (1)(2)

     

    $550 million - $575 million

    Selling, general and administrative expenses (1)(3)

     

    $290 million - $300 million

    Effective tax rate (1)

     

    14% - 16%

    Cash and investments (4)

     

    $1.5 billion - $1.6 billion

    (1)

    Guidance updated on November 5, 2020 from previously provided guidance on August 6, 2020.

    (2)

    Includes $40 million of non-cash stock-based compensation expense.

    (3)

    Includes $70 million of non-cash stock-based compensation expense.

    (4)

    This cash and investments guidance does not include any potential new business development activity, which remains a key priority for Exelixis as it continues to build toward becoming a multi-product oncology company.

    Cabozantinib Highlights

    Cabozantinib Franchise Net Product Revenues and Royalties. Net product revenues generated by the cabozantinib franchise in the U.S. were $168.6 million during the third quarter of 2020, with net product revenues of $159.6 million from CABOMETYX® and $9.0 million from COMETRIQ® (cabozantinib). Based upon cabozantinib-related revenues generated by Exelixis' collaboration partner Ipsen in the third quarter of 2020, Exelixis earned $19.9 million in royalty revenues.

    Initiation of CONTACT-03 Phase 3 Pivotal Trial of Cabozantinib in Combination with Atezolizumab in Previously Treated Metastatic Renal Cell Carcinoma (RCC). In July 2020, Exelixis announced the initiation of CONTACT-03, a global phase 3 pivotal trial of cabozantinib in combination with atezolizumab in patients with inoperable, locally advanced or metastatic RCC who progressed during or following treatment with an immune checkpoint inhibitor as the immediate preceding therapy. CONTACT-03 is part of a clinical trial collaboration between Exelixis and F. Hoffmann-La Roche Ltd. that includes two additional ongoing phase 3 pivotal trials – CONTACT-01 in patients with metastatic non-small cell lung cancer who have been previously treated with an immune checkpoint inhibitor and platinum-containing chemotherapy and CONTACT-02 in patients with metastatic castration-resistant prostate cancer (mCRPC) who have been previously treated with one novel hormonal therapy.

    Completion of Patient Enrollment for EXAMINER Phase 4 Trial of Cabozantinib in Metastatic Medullary Thyroid Cancer. In July 2020, Exelixis announced the completion of patient enrollment in EXAMINER, the phase 4 trial evaluating the safety and efficacy of the 60 mg tablet formulation of cabozantinib compared with the 140 mg capsule formulation, which is marketed as COMETRIQ, for the treatment of patients with progressive, metastatic medullary thyroid cancer. EXAMINER is a post-marketing requirement from the U.S. Food and Drug Administration (FDA) and the European Commission. The trial was designed to enroll up to 250 patients, and top-line results from the trial are anticipated later this year.

    Submission of Supplemental New Drug Application (sNDA) to and Acceptance by the FDA for Cabozantinib in Combination with Nivolumab for Advanced Renal Cell Carcinoma. In August 2020, Exelixis announced the submission of an sNDA to the FDA for cabozantinib in combination with Bristol-Myers Squibb Company's (BMS) nivolumab for patients with advanced RCC. The sNDA submission was based on the positive results of the CheckMate -9ER phase 3 pivotal trial, which met its primary endpoint of significantly improving progression-free survival (PFS) and secondary endpoints of overall survival (OS) and objective response rate. In October 2020, Exelixis and BMS announced that the FDA had accepted Exelixis' sNDA and BMS' supplemental Biologics License Application (sBLA), granted Priority Review to both applications and assigned a Prescription Drug User Fee Act goal date, or target action date, of February 20, 2021.

    Completion of Patient Enrollment for the COSMIC-312 Phase 3 Pivotal Trial in Previously Untreated Hepatocellular Carcinoma (HCC). In August 2020, Exelixis announced the completion of patient enrollment in COSMIC-312, a global phase 3 pivotal trial evaluating cabozantinib in combination with atezolizumab versus sorafenib as a treatment for patients with previously untreated advanced HCC, providing the patient population for the event-driven analyses of the study's endpoints. Separately, patient enrollment remains open in China in order to enroll a sufficient number of patients to enable local registration, if supported by the clinical data. The co-primary endpoints of the trial are PFS and OS for the combination of cabozantinib and atezolizumab versus sorafenib. Based on current event rates, Exelixis anticipates announcing top-line results in the first half of 2021.

    Presentation of Positive Results from CheckMate -9ER Phase 3 Pivotal Trial during Presidential Symposium I at the European Society for Medical Oncology Virtual Congress 2020 (ESMO 2020). In September 2020, Exelixis and BMS announced the first presentation of results from the CheckMate -9ER phase 3 pivotal trial as part of Presidential Symposium I at ESMO 2020, in which cabozantinib in combination with nivolumab demonstrated significant improvements across all efficacy endpoints, including OS, in previously untreated advanced RCC, with a favorable tolerability profile versus sunitinib.

    Validation of Regulatory Filings for Cabozantinib plus Nivolumab in the European Union (EU). In September 2020, Exelixis, BMS, and Ipsen announced that the European Medicines Agency (EMA) had validated BMS' and Ipsen's type II variation applications for cabozantinib plus nivolumab, which confirmed the submissions were complete and began the EMA's centralized review process. Like BMS' and Exelixis' own regulatory filings in the United States, BMS' and Ipsen's EU filings were based on positive data from the CheckMate -9ER phase 3 pivotal trial.

    Presentation of Positive Results from Two RCC Cohorts of the COSMIC-021 Trial of Cabozantinib in Combination with Atezolizumab at ESMO 2020. In September 2020, Exelixis presented positive phase 1b clinical trial results for the combination of cabozantinib and atezolizumab in patients with locally advanced or metastatic solid tumors at ESMO 2020. Data from the clear cell RCC and non-clear cell RCC expansion cohorts of the COSMIC-021 trial were presented as part of the GU Proffered Paper Session and as part of a poster presentation, respectively, and showed that cabozantinib in combination with atezolizumab demonstrated promising preliminary efficacy and a favorable safety profile.

    Announcement of Submission of Supplemental Application for Cabozantinib in Combination with Nivolumab in Japan for the Treatment of Unresectable, Advanced or Metastatic RCC. In October 2020, Exelixis announced that its collaboration partner Takeda, and Ono Pharmaceuticals Co., Ltd. (Ono), submitted a supplemental application to the Japanese Ministry of Health, Labour and Welfare for Manufacturing and Marketing Approval of cabozantinib in combination with nivolumab for the treatment of patients with unresectable, advanced or metastatic RCC. The application is also based on the results from the CheckMate -9ER study. Takeda has licensed the exclusive rights to cabozantinib from Exelixis for development and commercialization in Japan, while Ono jointly develops and commercializes nivolumab, in collaboration with BMS, in Japan, South Korea and Taiwan. Takeda previously received approval in March 2020 to market single-agent cabozantinib for the treatment of patients with curatively unresectable or metastatic RCC in Japan.

    Pipeline Highlights

    Presentations of Data for XL092 and AUR102 at the 32nd EORTC-NCI-AACR (ENA) Symposium on Molecular Targets and Cancer Therapeutics. In October 2020, Exelixis presented the preclinical profile and initial clinical pharmacokinetics (PK) for XL092 at the ENA Symposium. The poster discussion presentation included preclinical results demonstrating robust target and tumor growth inhibition, as well as increased efficacy for XL092 when combined with an immune checkpoint inhibitor. PK data from the ongoing phase 1 trial suggested a significantly shorter PK half-life for XL092 as compared to cabozantinib. Also at the ENA Symposium, Aurigene presented promising preclinical data for AUR102, its novel inhibitor of cyclin-dependent kinase 7, including potent anti-tumor activity in a large panel of cancer cell lines. Exelixis has an exclusive option for AUR102 under its July 2019 exclusive collaboration, option and license agreement with Aurigene. Exelixis' option window extends up until the time of Investigational New Drug application (IND) acceptance; AUR102 could be the subject of an IND later this year.

    Enrollment of First Patient in Phase 1 Trial Cohort Evaluating XL092 in Combination with Atezolizumab in Patients with Advanced Solid Tumors. In October 2020, Exelixis announced enrollment of the first patient into the dose-escalation cohort of the combination arm of the phase 1 trial evaluating the safety, tolerability, PK and preliminary anti-tumor activity of XL092 alone and in combination with atezolizumab in patients with advanced solid tumors. Initiated in February 2019, the dose-escalation evaluation of the XL092 monotherapy arm of the phase 1 trial is ongoing. Once the recommended doses of both single-agent XL092 and XL092 in combination with atezolizumab are established, the trial will begin to enroll expansion cohorts for patients with clear cell and non-clear cell RCC, hormone-receptor positive breast cancer and mCRPC.

    Corporate Updates

    FDA Approves TECENTRIQ® (Atezolizumab) Plus COTELLIC® (Cobimetinib) and ZELBORAF® (Vemurafenib) for Previously Untreated BRAF V600 Mutation-Positive Advanced Melanoma. In July 2020, the FDA approved the sBLA submitted by Genentech, Inc. (a member of the Roche Group) (Genentech), for TECENTRIQ plus COTELLIC and ZELBORAF for the treatment of BRAF V600 mutation-positive advanced melanoma in previously untreated patients. The approval is based on positive results from the phase 3 IMspire150 study, which demonstrated that adding TECENTRIQ to COTELLIC and ZELBORAF helped to reduce the risk of disease worsening or death, compared to placebo plus COTELLIC and ZELBORAF. This was the second FDA approval for a regimen including COTELLIC, which was discovered by Exelixis and is being developed and commercialized by Genentech as part of a worldwide collaboration agreement between the two companies.

    Exelixis and Catalent, Inc. (Catalent) Enter into Exclusive Collaboration and License Agreement to Develop ADCs Leveraging SMARTag® Bioconjugation Technology. In September 2020, Exelixis and Catalent announced a partnership under which Catalent's Redwood Bioscience subsidiary will develop multiple ADCs for Exelixis using Catalent's proprietary SMARTag® site-specific bioconjugation technology. Under the terms of the agreement, Exelixis made an upfront payment of $10.0 million to Catalent in exchange for the ability to nominate and have the exclusive option to license target programs.

    Exelixis and NBE-Therapeutics AG (NBE) Enter into Exclusive Collaboration and License Agreement to Discover and Develop Novel ADCs for the Treatment of Cancer. In September 2020, Exelixis and NBE announced a partnership to discover and develop multiple ADCs for oncology applications by leveraging NBE's unique expertise and proprietary platforms in ADC discovery, including NBE's SMAC-Technology™ (a site-specific conjugation technology) and novel payloads. Under the terms of the agreement, Exelixis made an upfront payment of $25.0 million to NBE in exchange for the ability to nominate and have the exclusive option to license target programs.

    Exelixis and Iconic Therapeutics, Inc. (Iconic) Announce Promising Preclinical Data for ICON-2 in Treatment of Solid Tumors at the World ADC Digital Conference. In September 2020, Exelixis and Iconic announced new preclinical data that support the continued development of ICON-2, an ADC comprised of an anti-Tissue Factor antibody and a proprietary linker-payload developed by Zymeworks Inc., for the treatment of diverse solid tumors. Exelixis has an exclusive option to license ICON-2 in oncology indications under its May 2019 option and license agreement with Iconic.

    Inclusion in Fortune's 100 Fastest-Growing Companies List. In November 2020, Exelixis was named to Fortune's 100 Fastest-Growing Companies list, which ranks companies that are traded on a major U.S. stock exchange by their revenue growth rate, EPS growth rate and three-year annualized total return for the period ended June 30, 2020. In its first year on the list, Exelixis ranked 17th overall and was the third-highest biopharmaceutical company.

    Basis of Presentation

    Exelixis has adopted a 52- or 53-week fiscal year that generally ends on the Friday closest to December 31st. For convenience, references in this press release as of and for the fiscal periods ended October 2, 2020, January 3, 2020 and September 27, 2019 are indicated as being as of and for the periods ended September 30, 2020, December 31, 2019 and September 30, 2019, respectively.

    Conference Call and Webcast

    Exelixis management will discuss the company's financial results for the third quarter of 2020 and provide a general business update during a conference call beginning at 5:00 p.m. EST / 2:00 p.m. PST today, Thursday, November 5, 2020.

    To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company's website at least 15 minutes prior to the conference call to ensure adequate time for any software download that may be required to listen to the webcast. Alternatively, please call 855-793-2457 (domestic) or 631-485-4921 (international) and provide the conference call passcode 6945239 to join by phone.

    A telephone replay will be available until 8:00 p.m. EST on November 7, 2020. Access numbers for the telephone replay are: 855-859-2056 (domestic) and 404-537-3406 (international); the passcode is 6945239. A webcast replay will also be archived on www.exelixis.com for one year.

    About Exelixis

    Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially successful, oncology-focused biotechnology company that strives to accelerate the discovery, development and commercialization of new medicines for difficult-to-treat cancers. Following early work in model system genetics, we established a broad drug discovery and development platform that has served as the foundation for our continued efforts to bring new cancer therapies to patients in need. Our discovery efforts have resulted in four commercially available products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have entered into partnerships with leading pharmaceutical companies to bring these important medicines to patients worldwide. Supported by revenues from our marketed products and collaborations, we are committed to prudently reinvesting in our business to maximize the potential of our pipeline. We are supplementing our existing therapeutic assets with targeted business development activities and internal drug discovery - all to deliver the next generation of Exelixis medicines and help patients recover stronger and live longer. Exelixis is a member of the Standard & Poor's (S&P) MidCap 400 index, which measures the performance of profitable mid-sized companies. In November 2020, the company was named to Fortune's 100 Fastest-Growing Companies list for the first time, ranking 17th overall and the third-highest biopharmaceutical company. For more information about Exelixis, please visit www.exelixis.com, follow @ExelixisInc on Twitter or like Exelixis, Inc. on Facebook.

    Forward-Looking Statements

    This press release contains forward-looking statements, including, without limitation, statements related to: Exelixis' belief that recent activities, specifically positive results from CheckMate -9ER and related data presentations and regulatory filings, are a foundation to accelerate revenue growth with CABOMETYX in 2021; Exelixis' belief that the XL092 program is an opportunity to drive growth into new and potentially larger indications with unmet medical need; the potential for Exelixis' ongoing efforts to expand the pipeline and drive top-line growth significantly for Exelixis, and provide new treatment options for patients; Exelixis' updated 2020 financial guidance; Exelixis' anticipated timelines for top-line results from COSMIC-312 and EXAMINER; Exelixis' plans to file an IND for AUR102 later in 2020; and Exelixis' plans to reinvest in its business to maximize the potential of the company's pipeline, including through targeted business development activities and internal drug discovery. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis' current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the continuing COVID-19 pandemic and its impact on Exelixis' clinical trial, drug discovery and commercial activities; the degree of market acceptance of CABOMETYX and other Exelixis products in the indications for which they are approved and in the territories where they are approved, and Exelixis' and its partners' ability to obtain or maintain coverage and reimbursement for these products; the effectiveness of CABOMETYX and other Exelixis products in comparison to competing products; the level of costs associated with Exelixis' commercialization, research and development, in-licensing or acquisition of product candidates, and other activities; Exelixis' ability to maintain and scale adequate sales, marketing, market access and product distribution capabilities for its products or to enter into and maintain agreements with third parties to do so; the availability of data at the referenced times; the potential failure of cabozantinib and other Exelixis product candidates, both alone and in combination with other therapies, to demonstrate safety and/or efficacy in clinical testing; uncertainties inherent in the drug discovery and product development process; Exelixis' dependence on its relationships with its collaboration partners, including their pursuit of regulatory approvals for partnered compounds in new indications, their adherence to their obligations under relevant collaboration agreements and the level of their investment in the resources necessary to complete clinical trials or successfully commercialize partnered compounds in the territories where they are approved; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis' continuing compliance with applicable legal and regulatory requirements; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating cabozantinib, cobimetinib or esaxerenone; Exelixis' dependence on third-party vendors for the development, manufacture and supply of its products and product candidates; Exelixis' ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of Exelixis' marketed products; changes in economic and business conditions; and other factors discussed under the caption "Risk Factors" in Exelixis' Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on August 6, 2020, and in Exelixis' future filings with the SEC, including, without limitation, Exelixis' Quarterly Report on Form 10-Q expected to be filed with the SEC on November 5, 2020. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

    Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are registered U.S. trademarks.

    MINNEBRO is a registered Japanese trademark.

    -see attached financial tables-

    EXELIXIS, INC.

    CONDENSED CONSOLIDATED STATEMENTS OF INCOME

    (in thousands, except per share amounts)

    (unaudited)

     

    Three Months Ended September 30,

     

    Nine Months Ended September 30,

     

    2020

     

    2019

     

    2020

     

    2019

    Revenues:

     

     

     

     

     

     

     

    Net product revenues

    $

    168,587

     

     

    $

    191,768

     

     

    $

    541,197

     

     

    $

    565,024

     

    License revenues

    33,205

     

     

    69,137

     

     

    113,318

     

     

    132,443

     

    Collaboration services revenues

    29,300

     

     

    10,798

     

     

    62,971

     

     

    29,998

     

    Total revenues

    231,092

     

     

    271,703

     

     

    717,486

     

     

    727,465

     

    Operating expenses:

     

     

     

     

     

     

     

    Cost of goods sold

    8,725

     

     

    7,537

     

     

    27,235

     

     

    22,577

     

    Research and development

    176,762

     

     

    97,295

     

     

    393,572

     

     

    242,516

     

    Selling, general and administrative

    88,185

     

     

    51,265

     

     

    210,916

     

     

    170,218

     

    Total operating expenses

    273,672

     

     

    156,097

     

     

    631,723

     

     

    435,311

     

    Income (loss) from operations

    (42,580

    )

     

    115,606

     

     

    85,763

     

     

    292,154

     

    Interest income

    3,994

     

     

    7,191

     

     

    16,376

     

     

    20,253

     

    Other income (expense), net

    565

     

     

    (140

    )

     

    571

     

     

    688

     

    Income (loss) before income taxes

    (38,021

    )

     

    122,657

     

     

    102,710

     

     

    313,095

     

    Provision for (benefit from) income taxes

    (5,981

    )

     

    25,205

     

     

    19,317

     

     

    60,826

     

    Net income (loss)

    $

    (32,040

    )

     

    $

    97,452

     

     

    $

    83,393

     

     

    $

    252,269

     

    Net income (loss) per share:

     

     

     

     

     

     

     

    Basic

    $

    (0.10

    )

     

    $

    0.32

     

     

    $

    0.27

     

     

    $

    0.84

     

    Diluted

    $

    (0.10

    )

     

    $

    0.31

     

     

    $

    0.26

     

     

    $

    0.80

     

    Weighted-average common shares outstanding:

     

     

     

     

     

     

     

    Basic

    309,116

     

     

    303,268

     

     

    307,437

     

     

    301,999

     

    Diluted

    309,116

     

     

    315,453

     

     

    317,495

     

     

    315,046

     

     

    EXELIXIS, INC.

    CONDENSED CONSOLIDATED BALANCE SHEET DATA

    (in thousands)

    (unaudited)

     

    September 30, 2020

     

    December 31, 2019

    Cash and investments

    $

    1,545,960

     

     

    $

    1,388,628

     

    Working capital

    $

    1,206,465

     

     

    $

    868,444

     

    Total assets

    $

    2,111,043

     

     

    $

    1,885,670

     

    Total stockholders' equity

    $

    1,852,031

     

     

    $

    1,685,970

     

     

    EXELIXIS, INC.

    RECONCILIATION OF GAAP NET INCOME TO NON-GAAP NET INCOME

    (in thousands, except per share amounts)

    (unaudited)

     

    Three Months Ended September 30,

     

    Nine Months Ended September 30,

     

    2020

     

    2019

     

    2020

     

    2019

    GAAP net income (loss)

    $

    (32,040

    )

     

    $

    97,452

     

     

    $

    83,393

     

     

    $

    252,269

     

    Adjustments:

     

     

     

     

     

     

     

    Stock-based compensation - research and development expenses (1)

    18,936

     

     

    4,301

     

     

    30,134

     

     

    13,745

     

    Stock-based compensation - selling, general and administrative expenses (1)

    36,719

     

     

    8,838

     

     

    55,657

     

     

    27,002

     

    Income tax effect of the above adjustments

    (12,406

    )

     

    (2,954

    )

     

    (19,195

    )

     

    (9,148

    )

    Non-GAAP net income

    $

    11,209

     

     

    $

    107,637

     

     

    $

    149,989

     

     

    $

    283,868

     

    GAAP net income (loss) per share:

     

     

     

     

     

     

     

    Basic

    $

    (0.10

    )

     

    $

    0.32

     

     

    $

    0.27

     

     

    $

    0.84

     

    Diluted (2)

    $

    (0.10

    )

     

    $

    0.31

     

     

    $

    0.26

     

     

    $

    0.80

     

    Non-GAAP net income per share:

     

     

     

     

     

     

     

    Basic

    $

    0.04

     

     

    $

    0.35

     

     

    $

    0.49

     

     

    $

    0.94

     

    Diluted

    $

    0.04

     

     

    $

    0.34

     

     

    $

    0.47

     

     

    $

    0.90

     

    Weighted-average common shares outstanding:

     

     

     

     

     

     

     

    Basic

    309,116

     

     

    303,268

     

     

    307,437

     

     

    301,999

     

    Diluted (2)

    318,501

     

     

    315,453

     

     

    317,495

     

     

    315,046

     

    ____________________

    (1)

    Non-cash stock-based compensation expense used for GAAP reporting in accordance with Accounting Standards Codification Topic 718, Compensation—Stock Compensation.

    (2)

    The dilutive effect of shares related to employee stock plans are not included in the calculation of GAAP diluted loss per share in the third quarter of 2020 as the effect would be anti-dilutive.

     

    View Full Article Hide Full Article
    • Reports Third Quarter Revenues of $10.5 Billion
    • Posts GAAP EPS of $0.82 and Non-GAAP EPS of $1.63
    • Extends and Strengthens Leading Cardiovascular Franchise with Planned MyoKardia Acquisition
    • Delivers Significant Pipeline and Regulatory Milestones
    • Achieves Positive Results from POETYK-PSO-1 Evaluating Deucravacitinib (TYK2 inhibitor) for the Treatment of Moderate to Severe Plaque Psoriasis
    • Raises 2020 GAAP and Non-GAAP EPS Guidance; Reaffirms 2021 Non-GAAP EPS Guidance

    Bristol Myers Squibb (NYSE:BMY) today reports results for the third quarter of 2020, which reflect strong product sales, continued pipeline advancement and robust operating performance.

    "I am proud of the significant achievements of our new company over the past year…

    • Reports Third Quarter Revenues of $10.5 Billion
    • Posts GAAP EPS of $0.82 and Non-GAAP EPS of $1.63
    • Extends and Strengthens Leading Cardiovascular Franchise with Planned MyoKardia Acquisition
    • Delivers Significant Pipeline and Regulatory Milestones
    • Achieves Positive Results from POETYK-PSO-1 Evaluating Deucravacitinib (TYK2 inhibitor) for the Treatment of Moderate to Severe Plaque Psoriasis
    • Raises 2020 GAAP and Non-GAAP EPS Guidance; Reaffirms 2021 Non-GAAP EPS Guidance

    Bristol Myers Squibb (NYSE:BMY) today reports results for the third quarter of 2020, which reflect strong product sales, continued pipeline advancement and robust operating performance.

    "I am proud of the significant achievements of our new company over the past year, and the strong foundation we have created for near- and long-term growth" said Giovanni Caforio, M.D., board chair and chief executive officer, Bristol Myers Squibb. "Our financial strength and flexibility combined with our robust inline businesses, multiple launches and progress in our deep pipeline, including the promising results from the deucravacitinib trial, strongly position the company to deliver our mission and help more patients. The strength of our third quarter performance is a testament to the commitment of our people who continue to innovate and deliver novel medicines for patients with serious disease."

    Third Quarter

    $ amounts in millions, except per share amounts

     

     

     

     

    2020

    2019

    Change

    Total Revenues

    $10,540

    $6,007

    75%

    GAAP Diluted EPS

    0.82

    0.83

    (1)%

    Non-GAAP Diluted EPS

    1.63

    1.17

    39%

    Total Pro Forma Revenues*

    10,540

    9,962

    6%

     

     

     

     

    *The pro forma revenues assume the company's acquisition of Celgene (Celgene Acquisition) and its divestiture of Otezla® to Amgen Inc. (Otezla® Divestiture) occurred on January 1, 2019 and exclude foreign currency hedge gains and losses. Management believes that measuring revenue rates on a comparable pro forma basis is an appropriate way for investors to best understand the underlying performance of the business. The pro forma revenue is presented for informational purposes only and does not purport to represent what the company's results of operations or financial position would have been if the company's planned acquisition of MyoKardia, Inc. (MyoKardia) occurred on January 1, 2019 nor does it purport to project the results of operations or financial position for any future period or as of any future date. See "Worldwide Pro Forma Revenue" in Quarterly Package of Financial Information for this quarter, which is available on bms.com/investors/financial-reporting/quarterly-results, for information on the revenue of the company and Celgene on a stand-alone basis for the prior-year period. Otezla® is a trademark of Amgen Inc.

    THIRD QUARTER FINANCIAL RESULTS

    All comparisons are made versus the same period in 2019 unless otherwise stated.

    • Bristol Myers Squibb posted third quarter revenues of $10.5 billion, an increase of 75% on a reported basis and 6% on a pro forma basis. The increase was driven primarily by the impact of the Celgene Acquisition, which was completed on November 20, 2019.
    • U.S. revenues increased 88% to $6.5 billion in the quarter. International revenues increased 58% to $4.0 billion in the quarter. When adjusted for foreign exchange impact, international revenues increased 57%.
    • Gross margin as a percentage of revenue increased from 70.2% to 76.3% in the quarter primarily due to product mix, partially offset by the unwinding of inventory purchase price accounting adjustments.
    • Marketing, selling and administrative expenses increased 62% to $1.7 billion in the quarter primarily due to $500 million of costs associated with the broader portfolio resulting from the Celgene Acquisition.
    • Research and development expenses increased 81% to $2.5 billion in the quarter primarily due to $900 million of costs associated with the broader portfolio resulting from the Celgene Acquisition.
    • Amortization of acquired intangible assets was $2.5 billion in the quarter primarily due to the Celgene Acquisition.
    • The effective tax rate was 16.8% in the quarter. The effective tax benefit rate was 1.3% in the same period a year ago due to jurisdictional tax rates and other tax impacts attributed to pension settlement charges and the UPSA business divestiture gain.
    • The company reported net earnings attributable to Bristol Myers Squibb of $1.9 billion, or $0.82 per share, in the third quarter, compared to net earnings of $1.4 billion, or $0.83 per share, for the same period a year ago. The results in the current quarter include costs and expenses resulting from purchase price accounting, contingent value rights fair value adjustments, equity investment gains and other acquisition and integration expenses.
    • The company reported non-GAAP net earnings attributable to Bristol Myers Squibb of $3.7 billion, or $1.63 per share, in the third quarter, compared to non-GAAP net earnings of $1.9 billion, or $1.17 per share, for the same period a year ago. A discussion of the non-GAAP financial measures is included under the "Use of Non-GAAP Financial Information" section.

    THIRD QUARTER PRODUCT REVENUE HIGHLIGHTS

    $ amounts in millions

    Product

    Quarter Ended

    September 30, 2020 on

    Reported Basis

    % Change from Quarter

    Ended September 30,

    2019 on Reported Basis

    % Change from Quarter

    Ended September 30,

    2019 on Pro Forma Basis**

    Revlimid

    $3,027

    N/A*

    10%

    Eliquis

    $2,095

    9%

    9%

    Opdivo

    $1,780

    (2)%

    (2)%

    Orencia

    $826

    8%

    8%

    Pomalyst/Imnovid

    $777

    N/A*

    17%

    Sprycel

    $544

    (3)%

    (3)%

    Yervoy

    $446

    26%

    26%

    Abraxane

    $342

    N/A*

    8%

    Empliciti

    $96

    8%

    8%

    Reblozyl

    $96

    N/A*

    N/A

    Inrebic

    $13

    N/A*

    N/A

    Zeposia

    $2

    N/A*

    N/A

    Onureg

    $3

    N/A*

    N/A

    *Prod