1. Heart failure and asthma studies will pilot a new digital health platform to help improve outcomes for patients with chronic diseases

    AstraZeneca has entered into a collaboration agreement with Massachusetts General Hospital (MGH), leveraging robust data and clinical best practices to create digital health solutions that address today's most urgent healthcare challenges. Catalyzed by the COVID-19 pandemic and a shared mission to improve care for patients with chronic illness, this novel partnership is focused on creating and clinically validating patient-centric digital health solutions and establishing a new standard of care for chronic illness management outside of a clinical setting.

    This collaboration is being led by the MGH Center for…

    Heart failure and asthma studies will pilot a new digital health platform to help improve outcomes for patients with chronic diseases

    AstraZeneca has entered into a collaboration agreement with Massachusetts General Hospital (MGH), leveraging robust data and clinical best practices to create digital health solutions that address today's most urgent healthcare challenges. Catalyzed by the COVID-19 pandemic and a shared mission to improve care for patients with chronic illness, this novel partnership is focused on creating and clinically validating patient-centric digital health solutions and establishing a new standard of care for chronic illness management outside of a clinical setting.

    This collaboration is being led by the MGH Center for Innovation in Digital Healthcare (CIDH) and will utilize AstraZeneca's new AMAZE disease management platform in studies for heart failure and asthma management. These first two studies will pilot AMAZE in a real-world setting with the goals of improving patient engagement, care-team communication and clinical outcomes while reducing healthcare costs.

    Through remote monitoring, AMAZE identifies at-risk patients and delivers insights to the clinical care team at the point of care to improve the management of complex patient populations. The digital platform, including a patient app and clinician dashboard, is intended to speed up evidence-based clinical practice with the aim of continuously improving the standard of patient care and healthcare efficiency.

    Ruud Dobber, Ph.D, Executive Vice President and President, BioPharmaceuticals Business Unit, said: "We believe the AMAZE disease management platform has the potential to transform the current healthcare delivery paradigm for patients around the world living with chronic diseases. We are incredibly proud to be working closely with Massachusetts General Hospital to utilize this digital platform to close gaps in patient care, ultimately leading to better outcomes."

    "This extraordinary level of collaboration between an academic medical center and a pharmaceutical company, opens a pathway to innovative digital health solutions that place the patient at the center of care," said Peter L. Slavin, MD, President, Massachusetts General Hospital. "By embracing the tension of different perspectives and expertise, we can move faster and more efficiently while maintaining the highest levels of scientific rigor and clinical excellence. While there is no precedent for this type of deep relationship, we hope this alliance will serve as a model for future collaboration between pharma and healthcare providers."

    Following the successful conclusion of the heart failure and asthma studies, AstraZeneca and Massachusetts General Hospital plan to expand the use of AMAZE across multiple chronic disease areas, reaching patients throughout the Mass General Brigham system, and beyond.

    About AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

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  2. 76% vaccine efficacy against symptomatic COVID-19

    100% efficacy against severe or critical disease and hospitalization

    85% efficacy against symptomatic COVID-19 in participants aged 65 years and over

    Positive high-level results from the primary analysis of the Phase III trial of AZD1222 in the US have confirmed vaccine efficacy consistent with the pre-specified interim analysis announced on Monday, March 22, 2021.

    These results have been presented to the independent Data Safety Monitoring Board. The primary analysis is pre-specified in the protocol and will be the basis for a regulatory submission for Emergency Use Authorization to the US Food and Drug Administration in the coming weeks.

    This primary efficacy analysis included the accrual…

    76% vaccine efficacy against symptomatic COVID-19

    100% efficacy against severe or critical disease and hospitalization

    85% efficacy against symptomatic COVID-19 in participants aged 65 years and over

    Positive high-level results from the primary analysis of the Phase III trial of AZD1222 in the US have confirmed vaccine efficacy consistent with the pre-specified interim analysis announced on Monday, March 22, 2021.

    These results have been presented to the independent Data Safety Monitoring Board. The primary analysis is pre-specified in the protocol and will be the basis for a regulatory submission for Emergency Use Authorization to the US Food and Drug Administration in the coming weeks.

    This primary efficacy analysis included the accrual of 190 symptomatic cases of COVID-19 from the 32,449 trial participants, an additional 49 cases to the previously announced interim analysis. Participants were randomized on a 2:1 ratio between the vaccine and placebo group.

    The primary endpoint, vaccine efficacy at preventing symptomatic COVID-19 was 76% (confidence interval (CI): 68% to 82%) occurring 15 days or more after receiving two doses given four weeks apart. In addition, results were comparable across age groups, with vaccine efficacy of 85% (CI: 58% to 95%) in adults 65 years and older. A key secondary endpoint, preventing severe or critical disease and hospitalization, demonstrated 100% efficacy. There were eight cases of severe COVID-19 observed in the primary analysis with all of those cases in the placebo group.

    The vaccine was well tolerated, and no safety concerns related to the vaccine were identified.

    Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: "The primary analysis is consistent with our previously released interim analysis, and confirms that our COVID-19 vaccine is highly effective in adults, including those aged 65 years and over. We look forward to filing our regulatory submission for Emergency Use Authorization in the US and preparing for the rollout of millions of doses across America."

    There were 190 cases in the primary analysis. There are 14 additional possible or probable cases to be adjudicated so the total number of cases and the point estimate may fluctuate slightly.

    AstraZeneca will also submit the primary analysis for peer-reviewed publication in the coming weeks.

    D8110C00001

    The US Phase III trial, called D8110C00001, was led by AstraZeneca and funded by the Biomedical Advanced Research and Development Authority (BARDA), part of the office of the Assistant Secretary for Preparedness and Response (ASPR) at the US Department of Health and Human Services (HHS) in collaboration with the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) and the Army Contracting Command, and the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health. The NIAID-supported COVID-19 Prevention Network (CoVPN) participated in the trial.

    D8110C00001 is a randomized, double-blind, placebo-controlled multicenter Phase III trial assessing the safety, efficacy, and immunogenicity of AZD1222 compared to placebo for the prevention of COVID-19, in 32,449 participants across 88 trial centers in the US, Peru and Chile. Trial participants aged 18 years or over who are healthy or have medically stable chronic diseases and are at increased risk for being exposed to the SARS-CoV-2 virus and COVID-19 were randomized in a 2:1 ratio to receive two intramuscular doses of either 5 x1010 viral particles of AZD1222 or saline placebo four weeks apart.

    The pre-specified statistical analysis plan required at least 75 adjudicated cases at interim analysis, and at least 150 adjudicated cases at primary analysis.

    AZD1222

    AZD1222 was co-invented by the University of Oxford and its spin-out company, Vaccitech. It uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body.

    In May 2020, AstraZeneca received support of more than $1bn from BARDA for the development, production and delivery of the vaccine under an agreement with the US Department of Defense's Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense. The Phase III D8110C00001 trial is part of this funding agreement.

    The vaccine has been granted a conditional marketing authorization or emergency use in more than 70 countries across six continents, and with the Emergency Use Listing granted by the World Health Organization this accelerates the pathway to access in up to 142 countries through the COVAX Facility.

    BARDA, ASPR, HHS

    HHS works to enhance and protect the health and well-being of all Americans, providing for effective health and human services and fostering advances in medicine, public health, and social services. The mission of ASPR is to save lives and protect Americans from 21st century health security threats. Within ASPR, BARDA invests in the innovation, advanced research and development, acquisition, and manufacturing of medical countermeasures – vaccines, drugs, therapeutics, diagnostic tools, and non-pharmaceutical products needed to combat health security threats. The AstraZeneca vaccine candidate is one of six BARDA is supporting in development and manufacturing, and the third BARDA-supported SARS-COVD-2 vaccine supported to successfully complete a large Phase III trial. To learn more about BARDA's support for the COVID-19 pandemic response, visit medicalcountermeasures.gov.

    JPEO-CBRND

    As part of the Department of Defense, JPEO-CBRND protects the Joint Force by providing medical countermeasures and defense equipment against chemical, biological, radiological and nuclear (CBRN) threats. JPEO-CBRND's goal is to enable the Joint Force to fight and win unencumbered by a CBRN environment. JPEO-CBRND facilitates the rapid response, advanced development, manufacturing and acquisition of medical solutions, such as vaccines, therapeutics, and diagnostics, to combat CBRN and emerging threats such as COVID-19. To learn more about JPEO-CBRND's COVID-19 response, visit https://www.jpeocbrnd.osd.mil/coronavirus.

    NIAID and the CoVPN

    The CoVPN was formed by the NIAID at the US National Institutes of Health, part of the US Department of Health and Human Services, to respond to the global pandemic. Through the CoVPN, NIAID is leveraging the infectious disease and community engagement expertise of its existing research networks and global partners to address the pressing need for vaccines and antibodies against the SARS-CoV-2 virus. CoVPN will work to develop and conduct studies to ensure rapid and thorough evaluation of vaccines and antibodies for the prevention of COVID-19.

    About AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

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  3. 79% vaccine efficacy at preventing symptomatic COVID-19

    100% efficacy against severe or critical disease and hospitalization

    Comparable efficacy result across ethnicity and age, with 80% efficacy in participants aged 65 years and over

    Favorable reactogenicity and overall safety profile

    The AstraZeneca US Phase III trial of AZD1222 demonstrated statistically significant vaccine efficacy of 79% at preventing symptomatic COVID-19 and 100% efficacy at preventing severe disease and hospitalization.

    This interim safety and efficacy analysis was based on 32,449 participants accruing 141 symptomatic cases of COVID-19. The trial had a 2:1 randomization of vaccine to placebo.

    Vaccine efficacy was consistent across ethnicity and age. Notably, in…

    79% vaccine efficacy at preventing symptomatic COVID-19

    100% efficacy against severe or critical disease and hospitalization

    Comparable efficacy result across ethnicity and age, with 80% efficacy in participants aged 65 years and over

    Favorable reactogenicity and overall safety profile

    The AstraZeneca US Phase III trial of AZD1222 demonstrated statistically significant vaccine efficacy of 79% at preventing symptomatic COVID-19 and 100% efficacy at preventing severe disease and hospitalization.

    This interim safety and efficacy analysis was based on 32,449 participants accruing 141 symptomatic cases of COVID-19. The trial had a 2:1 randomization of vaccine to placebo.

    Vaccine efficacy was consistent across ethnicity and age. Notably, in participants aged 65 years and over, vaccine efficacy was 80%.

    The vaccine was well tolerated, and the data safety monitoring board (DSMB) identified no safety concerns related to the vaccine. The DSMB conducted a specific review of thrombotic events, as well as cerebral venous sinus thrombosis (CVST) with the assistance of an independent neurologist. The DSMB found no increased risk of thrombosis or events characterized by thrombosis among the 21,583 participants receiving at least one dose of the vaccine. The specific search for CVST found no events in this trial.

    Ann Falsey, Professor of Medicine, University of Rochester School of Medicine, US, and co-lead Principal Investigator for the trial, said: "These findings reconfirm previous results observed in AZD1222 trials across all adult populations but it's exciting to see similar efficacy results in people over 65 for the first time. This analysis validates the AstraZeneca COVID-19 vaccine as a much-needed additional vaccination option, offering confidence that adults of all ages can benefit from protection against the virus."

    Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: "These results add to the growing body of evidence that shows this vaccine is well tolerated and highly effective against all severities of COVID-19 and across all age groups. We are confident this vaccine can play an important role in protecting millions of people worldwide against this lethal virus. We are preparing to submit these findings to the FDA and for the rollout of millions of doses across America should the vaccine be granted emergency use authorization."

    AstraZeneca will continue to analyze the data and prepare for the primary analysis to be submitted to the US Food and Drug Administration (FDA) for Emergency Use Authorization (EUA) in the coming weeks. In parallel, the primary analysis will be submitted for publication in a peer-reviewed journal.

    Amongst participants in the interim analysis, approximately 79% were white/Caucasian, 8% black/African American, 4% Native American and 4% Asian, and 22% of participants were Hispanic.

    Approximately 20% of participants were 65 years and over, and approximately 60% had co-morbidities associated with an increased risk for progression of severe COVID-19, such as diabetes, severe obesity or cardiac disease.

    This AstraZeneca led US Phase III trial included two doses administered at a four week interval. Previous studies have shown that an extended interval of up to 12 weeks demonstrated greater efficacy, which was also supported by immunogenicity data. This evidence suggests administration of the second dose with an interval longer than four weeks could further increase efficacy, and accelerates the number of people who can receive their first dose.

    The vaccine can be stored, transported and handled at normal refrigerated conditions (2-8 degrees Celsius/ 36-46 degrees Fahrenheit) for at least six months and administered without the need for preparation within existing healthcare settings.

    AstraZeneca continues to engage with governments, multilateral organizations and collaborators around the world to ensure broad and equitable access to the vaccine at no profit for the duration of the pandemic.

    D8110C00001

    The US Phase III trial, called D8110C00001, was led by AstraZeneca and funded by the Biomedical Advanced Development Authority (BARDA), part of the office of the Assistant Secretary for Preparedness and Response (ASPR) at the US Department of Health and Human Services (HHS) and the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health. The NIAID-supported COVID-19 Prevention Network (CoVPN) participated in the trial.

    D8110C00001 is a Phase III randomized, double-blind, placebo-controlled multicenter study assessing the safety, efficacy, and immunogenicity of AZD1222 compared to placebo for the prevention of COVID-19, in 32,449 participants across 88 trial centers in the US, Peru and Chile. Trial participants aged 18 years or over who are healthy or have medically stable chronic diseases and are at increased risk for being exposed to the SARS-CoV-2 virus and COVID-19 were randomized in a 2:1 ratio to receive two intramuscular doses of either 5 x1010 viral particles of AZD1222 or saline placebo four weeks apart.

    COVID-19 Vaccine AstraZeneca, formerly AZD1222

    COVID-19 Vaccine AstraZeneca was co-invented by the University of Oxford and its spin-out company, Vaccitech. It uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body.

    In May 2020, AstraZeneca received support of more than $1bn from BARDA for the development, production and delivery of the vaccine. The Phase III D8110C00001 trial is part of this funding agreement.

    The vaccine has been granted a conditional marketing authorization or emergency use in more than 70 countries across six continents, and with the Emergency Use Listing granted by the World Health Organization this accelerates the pathway to access in up to 142 countries through the COVAX Facility.

    BARDA, ASPR, HHS

    HHS works to enhance and protect the health and well-being of all Americans, providing for effective health and human services and fostering advances in medicine, public health, and social services. The mission of ASPR is to save lives and protect Americans from 21st century health security threats. Within ASPR, BARDA invests in the innovation, advanced research and development, acquisition, and manufacturing of medical countermeasures – vaccines, drugs, therapeutics, diagnostic tools, and non-pharmaceutical products needed to combat health security threats. To learn more about federal support for the nationwide COVID-19 response, visit coronavirus.gov.

    NIAID and the CoVPN

    The CoVPN was formed by the NIAID at the US National Institutes of Health to respond to the global pandemic. Through the CoVPN, NIAID is leveraging the infectious disease and community engagement expertise of its existing research networks and global partners to address the pressing need for vaccines and antibodies against the SARS-CoV-2 virus. CoVPN will work to develop and conduct studies to ensure rapid and thorough evaluation of vaccines and antibodies for the prevention of COVID-19.

    About AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

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    • Lacutamab received PRIME designation from the European Medicines Agency in Sezary Syndrome; clinical development program advances in mycosis fungoides and peripheral T-cell lymphoma
    • Company's first NK cell engager selected by Sanofi as drug candidate for development
    • Monalizumab advanced to a Phase 3 clinical trial in combination with cetuximab in IO-pretreated head and neck cancer patients; triggered $50 million milestone payment from AstraZeneca
    • US and EU Lumoxiti commercialization rights returning to AstraZeneca
    • Cash position of €190.6 million2 as of December 31, 2020

    MARSEILLE, France, March 18, 2021 (GLOBE NEWSWIRE) -- Innate Pharma SA (OTC:IPHYF, NASDAQ:IPHA) ("Innate" or the "Company") today reported its consolidated financial results for…

    • Lacutamab received PRIME designation from the European Medicines Agency in Sezary Syndrome; clinical development program advances in mycosis fungoides and peripheral T-cell lymphoma
    • Company's first NK cell engager selected by Sanofi as drug candidate for development
    • Monalizumab advanced to a Phase 3 clinical trial in combination with cetuximab in IO-pretreated head and neck cancer patients; triggered $50 million milestone payment from AstraZeneca
    • US and EU Lumoxiti commercialization rights returning to AstraZeneca
    • Cash position of €190.6 million2 as of December 31, 2020

    MARSEILLE, France, March 18, 2021 (GLOBE NEWSWIRE) -- Innate Pharma SA (OTC:IPHYF, NASDAQ:IPHA) ("Innate" or the "Company") today reported its consolidated financial results for the year ending December 31, 2020. The consolidated financial statements are attached to this press release.

    "In 2020, we made the strategic decision to re-prioritize our investments in our R&D portfolio, enabling us to concentrate our resources and further strengthen our clinical pipeline," commented Mondher Mahjoubi, Chief Executive Officer of Innate Pharma. "Our priority going forward is to advance the clinical development of our lead proprietary candidate, lacutamab, as well as leverage our multispecific NKCE antibody platform, to create potential innovative therapeutics for patients and provide long-term value to our shareholders."



    Webcast and conference call will be held today at 2:00pm CET (9:00am EST)

    Access to live webcast: https://edge.media-server.com/mmc/p/ua5uuvep



    Participants may also join via telephone to ask questions by registering in advance of the event at http://emea.directeventreg.com/registration/2673359.



    Upon registration, participants will be provided with dial-in numbers, a direct event passcode and

    a unique registrant ID that they may use 10 minutes prior to the event start to access the call.



    This information can also be found on the Investors section of the Innate Pharma website, www.innate-pharma.com.

    A replay of the webcast will be available on the Company website for 90 days following the event.



    Pipeline highlights:

    Lacutamab (IPH4102, anti-KIR3DL2 antibody):

    • The TELLOMAK Phase 2 clinical trial, which is evaluating the efficacy and safety of lacutamab in patients with advanced cutaneous T-cell lymphomas, is now fully open to enrollment in countries that had a partial regulatory hold following the successful resolution of Good Manufacturing Practice issues.
    • In November, the Company announced that the European Medicines Agency (EMA) granted PRIME designation to lacutamab for the treatment of patients with relapsed or refractory Sézary syndrome (SS) who have received at least two prior systemic therapies. This is the first time PRIME designation has been granted for a potential treatment of any sub-type of T-cell lymphoma. This follows the Fast Track designation that was awarded to lacutamab by the U.S. Food and Drug Administration in 2019.
    • In February 2021, the Company announced lacutamab demonstrated a positive early signal in cohort 2 of KIR3DL2-expressing mycosis fungoides patients in the TELLOMAK clinical trial earlier than anticipated. This cohort reached the pre-determined number of responses needed to advance to stage 2. The Company plans to present this preliminary data at a scientific meeting in 2021.
    • The Company will initiate two parallel clinical trials to study lacutamab in KIR3DL2-expressing patients with relapsed/refractory peripheral t-cell lymphoma (PTCL):
      • Phase 1b trial: a Company-sponsored Phase 1b clinical trial to evaluate lacutamab as a monotherapy in KIR3DL2-expressing patients with relapsed PTCL.
      • Phase 2 KILT (anti-KIR in T Cell Lymphoma) trial: The Lymphoma Study Association (LYSA) will launch an investigator-sponsored, randomized trial to evaluate lacutamab in combination with chemotherapy GEMOX (gemcitabine in combination with oxaliplatin) versus GEMOX alone in KIR3DL2-expressing relapsed/refractory patients.

    IPH6101 (NKp46-based NK cell engager), partnered with Sanofi:

    • Progress was made in the NKCE collaboration with Sanofi, resulting in the decision announced in January 2021 that Sanofi will transition IPH6101/SAR443579 into investigational new drug (IND)-enabling studies. IPH6101 is a NKp46-based NK cell engager (NKCE) using Innate's proprietary multispecific antibody format (Gauthier et al. Cell 2019). The decision triggered a €7 million milestone payment from Sanofi to Innate.
    • In January 2021, a GLP-tox study was initiated for the IPH6101/SAR443579 program.

    Monalizumab (anti-NKG2A antibody), partnered with AstraZeneca:

    • In October 2020, AstraZeneca (NASDAQ:AZN) dosed the first patient in its randomized Phase 3 clinical trial, INTERLINK-1, evaluating monalizumab in combination with cetuximab vs. placebo and cetuximab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) who have been previously treated with platinum-based chemotherapy and PD-(L)1 inhibitors. Dosing of the first patient in this trial triggered a $50 million milestone payment from AstraZeneca to Innate. Innate is eligible to receive an additional $50 million milestone payment after the interim analysis demonstrates the combination meets a pre-defined threshold of clinical activity. To date, the Company has received a total of $400 million from the AstraZeneca partnership for monalizumab.
    • The Company presented efficacy data on the Phase 2 expansion cohort investigating the combination of monalizumab and cetuximab in patients with recurrent or metastatic head and neck squamous cell cancer (R/M SCCHN) who have been previously treated with platinum-based chemotherapy and PD-(L)1 inhibitors at ASCO20 Virtual Scientific Conference held in May 2020. This data showed an overall response rate in line with previously reported data and a manageable safety profile. The Company presented updated results at the ESMO Immuno-oncology Virtual Congress in December 2020.
    • In 2020, the Company expanded a Phase 2 expansion cohort ("cohort 3"), exploring the combination of monalizumab, cetuximab and durvalumab in first-line IO naïve patients with R/M SCCHN, from 20 to 40 patients. Recruitment for cohort 3 is complete, and the Company expects to publish data in 2021.

    Avdoralimab in Inflammation (anti-C5aR1 antibody):

    • In November 2020, the first patient was dosed in the investigator-sponsored Phase 2 clinical trial in bullous pemphigoid (BP) where the C5aR1 pathway has been shown to be involved in the physiopathology of the disease. The trial is investigating the clinical efficacy of avdoralimab in addition to topical steroids compared to topical steroids alone in BP patients.

    Avdoralimab in COVID-19:

    • The investigator-sponsored Phase 2 clinical trial, FORCE (FOR COVID-19 Elimination), has completed enrollment and is ongoing for patient follow-up and data analysis. More information on this study can be found at clinical trials.gov.
      • Results from the exploratory translational EXPLORE study supporting this trial were published online in Nature on July 29, 2020.
    • The investigator-sponsored Phase 2 clinical trial, ImmunONCOVID-20, has resumed, and is currently recruiting. This study is exploring the potential efficacy of monalizumab and avdoralimab amongst other treatment arms, against COVID-19 in cancer patients with mild symptoms and pneumonia respectively.
    • In August 2020, the Company announced it obtained €6.8 million in public funding from the French government for its COVID-19 R&D activities. This funding is part of the government's PSPC COVID call for COVID-19 related projects and will enable the Company to cover the development of its current COVID-19 activities, which began in March 2020, including the EXPLORE COVID-19 translational research study and its two Phase 2 clinical trials, FORCE and ImmunONCOVID-20.

    Avdoralimab in Oncology:

    • In September 2020, the Company announced the decision to stop enrollment in STELLAR-001, a Phase 1 dose escalation and expansion study in combination with durvalumab in three expansion cohorts: 1) NSCLC patients with secondary resistance to prior immuno-oncology (IO) treatment; 2) IO-naïve HCC patients; and 3) IO-pretreated HCC patients. The decision was made based on the data from the Company's cohort expansions in NSCLC and IO-naïve HCC.

    IPH5201 (anti-CD39 antibody), partnered with AstraZeneca:

    • In February 2020, the AstraZeneca sponsored, multicenter, open-label, dose-escalation Phase I trial evaluating IPH5201 as monotherapy or in combination with durvalumab (anti-PD-L1) with or without oleclumab (anti-CD73) in advanced solid tumors started. Following the dosing of the first patient in the trial on March 9, 2020, AstraZeneca made a $5 million milestone payment to Innate under the companies' October 2018 multi-product oncology development collaboration. Innate made a €2.7 million milestone payment to Orega Biotech SAS pursuant to Innate's exclusive licensing agreement.

    Lumoxiti (CD22-directed immunotoxin):

    • In December 2020, the Company announced that it will return the US and EU commercialization rights of Lumoxiti (moxetumomab pasudotox-tdfk) to AstraZeneca3. Innate licensed the US and EU rights to AstraZeneca's FDA-approved Lumoxiti for certain patients with relapsed or refractory hairy cell leukemia in October 2018.
    • Innate and AstraZeneca are currently in discussions regarding the transition plan for the transfer of the US marketing authorization and distribution of Lumoxiti to AstraZeneca, including timing and costs (see Contingent liabilities).

    Corporate Update:

    • In July 2020, Dr. Joyson Karakunnel was appointed as Executive Vice President and Chief Medical Officer (CMO). Dr. Pierre Dodion, CMO since 2014, retired from this position. Dr. Karakunnel comes to the Company with deep experience in immuno-oncology, and a proven track record in drug development. Most recently, Dr. Karakunnel served as CMO and Senior Vice President at Tizona Therapeutics, where he led the development of the company's biotherapeutics pipeline.
    • Laure-Helene Mercier, Executive Vice President, Chief Financial Officer and member of the Executive Board, has decided to step down from her position, after leading the Company through more than 14 years of growth, including an initial public offering in the US. Frederic Lombard will join the company as CFO on April 1, 2021. Mr. Lombard will be joining Innate with more than 20 years of financial experience in the pharmaceutical industry, holding senior finance roles at Ipsen, AstraZeneca and Novartis. Ms. Mercier will remain at the Company until the end of the year to ensure a smooth transition of responsibilities.

    Financial highlights for 2020:

    The key elements of Innate's financial position and financial results as of and for the year ended December 31, 2020 are as follows:

    • Cash, cash equivalents, short-term investments and financial assets amounting to €190.6 million (€m) as of December 31, 2020 (€255.9m as of December 31, 2019), including non-current financial instruments amounting to €38.9m (€37.0m as of December 31, 2019).
      • Cash and cash equivalents include the milestone payment of $50.0m (€41.2m) following the inclusion by AstraZeneca of the first patient in its Phase 3 randomized clinical trial evaluating monalizumab, INTERLINK-1. It doesn't include the milestone payment of €7.0m from Sanofi relating to the progress of IPH6101/SAR443579 into new drug (IND)-enabling studies, received in February 2021.
    • As of December 31, 2020, financial liabilities amount to €19.1m (€18.7m as of December 31, 2019). This change is partly linked to the receipt, in August 2020, of €1.4m in repayable advance in connection with the financing contract signed with BPI Financement (COVID-19).
    • Revenue and other income amounted to €70.5m in 2020 (2019: €85.8m, -17.9%). It mainly comprises revenue from collaboration and licensing agreements (€56.2m in 2020 vs €69.0m in 2019, -18.6%), and research tax credit (€13.1m in 2020 vs €16.7m in 2019, -21.8%):
      • Revenue from collaboration and licensing agreement with AstraZeneca amounted to €49.0m in 2020 (€69.0m in 2019, -29.0%) and mainly resulted from (i) the spreading of the upfront and opt-in payments received from AstraZeneca and (ii) the invoicing to AstraZeneca of certain fees for the work performed by Innate for the partnered programs. The variation between the two periods is notably explained by the completion of (i) the recruitment of the Cohort 2 in the monalizumab Phase 2 trials performed by Innate in 2019, and (ii) the preclinical work related to the Phase 1 program of IPH5201, which started in 2020.
      • Revenue of €7.0m from Sanofi for the progress of IPH6101/SAR443579 into investigational new drug (IND)-enabling studies.
      • The variation in the research tax credit mainly results from a decrease in the amortization for the intangible assets related to acquired licenses (monalizumab, IPH5201).
    • Operating expenses of €89.9m in 2020 (2019: €104.6m, -14.1%):
      • Selling, general and administrative (SG&A) expenses amounted to €31.2m in 2020 (2019: €25.8m, +21.1%). This increase mainly results from the full-year effect of personnel costs related to our US subsidiary, including personnel assigned to Lumoxiti commercial activities.
      • R&D expenses amounted to €58.6m in 2020 (2019: €78.8m, -25.7%). This variation mainly results from a decrease in direct R&D expenses (mainly related to Lumoxiti, IPH5201 and IPH5301) and in depreciation and amortization of intangible assets acquired by the Company (IPH5201 and monalizumab).
    • Lumoxiti intangible asset full impairment of €43.5m, following the Company's decision to return the US and EU commercialization rights of Lumoxiti to AstraZeneca.
    • The Lumoxiti distribution agreement generated a net income of €0.9m in the first three quarters of 2020 (a net loss of €8.2m in 2019). During the 2020 fourth quarter, the Company recognized net sales from Lumoxiti of €0.7m.
    • A net loss of €64.0m in 2020 (2019: net loss of €20.8m).

    The table below summarizes the IFRS consolidated financial statements4 as of and for the year ended December 31, 2020, including 2019 comparative information.

    In thousands of euros, except for data per shareDecember 31, 2020December 31, 2019
    Revenue and other income70,45185,814
    Research and development(58,613)(78,844)
    Selling, general and administrative(31,246)(25,803)
    Total operating expenses(89,859)(104,647)
    Net income (loss) from distribution agreements861(8,219)
    Operating income (loss) before impairment(18,547)(27,052)
    Impairment of intangible assets(43,529)
    Operating income (loss) after impairment(62,076)(27,052)
    Net financial income (loss)(1,908)6,293
    Income tax expense
    Net income (loss)(63,984)(20,759)
    Weighted average number of shares outstanding (in thousands)78,93566,908
    Basic income (loss) per share(0.81)(0.31)
    Diluted income (loss) per share(0.81)(0.31)
     
     December 31, 2020December 31, 2019
    Cash, cash equivalents and financial asset190,571255,869
    Total assets307,423401,361
    Shareholders' equity155,975217,416
    Total financial debt19,08718,723

    About Innate Pharma:

    Innate Pharma S.A. is a global, clinical-stage oncology-focused biotech company dedicated to improving treatment and clinical outcomes for patients through therapeutic antibodies that harness the immune system to fight cancer.

    Innate Pharma's broad pipeline of antibodies includes several potentially first-in-class clinical and preclinical candidates in cancers with high unmet medical need.

    Innate has been a pioneer in the understanding of natural killer cell biology and has expanded its expertise in the tumor microenvironment and tumor-antigens, as well as antibody engineering. This innovative approach has resulted in a diversified proprietary portfolio and major alliances with leaders in the biopharmaceutical industry including Bristol-Myers Squibb, Novo Nordisk A/S, Sanofi, and a multi-products collaboration with AstraZeneca.

    Headquartered in Marseille, France with a US office in Rockville, MD, Innate Pharma is listed on Euronext Paris and Nasdaq in the US.

    Learn more about Innate Pharma at www.innate-pharma.com

    Information about Innate Pharma shares:

    ISIN code

    Ticker code

    LEI
    FR0010331421

    Euronext: IPH Nasdaq: IPHA

    9695002Y8420ZB8HJE29

    Disclaimer on forward-looking information and risk factors:

    This press release contains certain forward-looking statements, including those within the meaning of the Private Securities Litigation Reform Act of 1995.The use of certain words, including "believe," "potential," "expect" and "will" and similar expressions, is intended to identify forward-looking statements. Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. These risks and uncertainties include, among other things, the uncertainties inherent in research and development, including related to safety, progression of and results from its ongoing and planned clinical trials and preclinical studies, review and approvals by regulatory authorities of its product candidates, the Company's commercialization efforts, the Company's continued ability to raise capital to fund its development and the overall impact of the COVID-19 outbreak on the global healthcare system as well as the Company's business, financial condition and results of operations. For an additional discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors ("Facteurs de Risque") section of the Universal Registration Document filed with the French Financial Markets Authority ("AMF"), which is available on the AMF website http://www.amf-france.org or on Innate Pharma's website, and public filings and reports filed with the U.S. Securities and Exchange Commission ("SEC"), including the Company's Annual Report on Form 20-F for the year ended December 31, 2019, and subsequent filings and reports filed with the AMF or SEC, or otherwise made public, by the Company.

    This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country.

    For additional information, please contact:
    Investors



    Innate Pharma

    Tel.: +33 (0)4 30 30 30 30

     Media



    Innate Pharma

    Tracy Rossin (Global/US)

    Tel.: +1 240 801 0076





    ATCG Press

    Marie Puvieux (France)

    Tel.: +33 (0)9 81 87 46 72

    innate-pha



    Summary of Consolidated Financial5 Statements and Notes

    as of December 31, 2020



    Consolidated Statements of Financial Position
    (in thousand euros)



     December 31, 2020December 31, 2019
       
    Assets  
       
    Cash and cash equivalents136,792202,887
    Short-term investments14,84515,978
    Trade receivables and others - current21,69518,740
    Total current assets173,332237,605
       
    Intangible assets46,28996,968
    Property and equipment11,69411,672
    Non-current financial assets38,93437,005
    Other non-current assets14789
    Deferred tax assets7,0871,286
    Trade receivables and others – non-current29,94016,737
    Total non-current assets134,091163,756
       
    Total assets307,423401,361
       
    Liabilities  
    Trade payables and others29,53949,504
    Collaboration liabilities – Current portion1,83221,304
    Financial liabilities – Current portion2,1422,130
    Deferred revenue – Current portion12,50548,770
    Provisions – Current portion676114
    Total current liabilities46,694121,822
       
    Collaboration liabilities – Non current portion44,854
    Financial liabilities – Non-current portion16,94516,593
    Defined benefit obligations4,1773,760
    Deferred revenue – Non-current portion31,46940,342
    Provisions – Current portion221142
    Deferred tax liabilities7,0871,286
    Total non-current liabilities104,75362,123
       
    Share capital3,9503,941
    Share premium372,130369,617
    Retained earnings(156,476)(134,912)
    Other reserves355(472)
    Net income (loss)(63,984)(20,759)
    Total shareholders' equity155,975217,416
       
    Total liabilities and shareholders' equity307,423401,361





    Consolidated Statements of Income (loss)
    (in thousand euros)



     December 31, 2020December 31, 2019
       
       
    Revenue from collaboration and licensing agreements56,15568,974
    Government financing for research expenditures13,61816,840
    Sales678 
       
    Revenue and other income70,45185,814
       
    Research and development expenses(58,613)(78,844)
    Selling, general and administrative expenses(31,246)(25,803)
       
    Operating expenses(89,859)(104,647)
       
    Net income (loss) from distribution agreements861(8,219)
       
    Operating income (loss) before impairment of intangible assets(18,547)(27,052)
       
    Impairment of intangible assets(43,529)
       
    Operating income (loss) after impairment of intangible assets(62,076)(27,052)
       
    Financial income4,85511,269
    Financial expenses(6,763)(4,976)
       
    Net financial income (loss)(1,908)6,293
       
    Net income (loss) before tax(63,984)(20,759)
       
    Income tax expense
       
    Net income (loss)(63,984)(20,759)
       
    Net income (loss) per share:  
    (in € per share)  
    - basic income (loss) per share(0.81)(0.31)
    - diluted income (loss) per share(0.81)(0.31)





    Consolidated Statements of Cash Flows
    (in thousand euros)



     December 31, 2020December 31, 2019
    Net income (loss)(63,984)(20,759)
    Depreciation and amortization56,79716,529
    Employee benefits costs216685
    Provisions for charges604(484)
    Share-based compensation expense2,4753,826
    Change in valuation allowance on financial assets577(4,065)
    Gains (losses) on financial assets1,256(280)
    Change in valuation allowance on financial assets372(237)
    Gains (losses) on assets and other financial assets(962)(1,290)
    Interest paid341204
    Other profit or loss items with no cash effect(296)550
    Operating cash flow before change in working capital(2,604)(5,321)
    Change in working capital(49,204)40,245
    Net cash generated from / (used in) operating activities:(51,807)34,924
    Acquisition of intangible assets, net(10,375)(64,130)
    Acquisition of property and equipment, net(907)(1,271)
    Acquisition of non-current financial assets(3,000)-
    Disposal of property and equipment9-
    Disposal of other assets(59)(10)
    Disposal of non-current financial instruments-2,000
    Interest received on financial assets9621,290
    Net cash generated from / (used in) investing activities:(13,370)(62,121)
    Proceeds from the exercise / subscription of equity instruments4844
    Increase in capital, net-66,006
    Proceeds from borrowings1,36013,900
    Repayment of borrowings(2,204)(1,982)
    Net interest paid(341)(204)
    Net cash generated from financing activities:(1,136)77,765
    Effect of the exchange rate changes2195
    Net increase / (decrease) in cash and cash equivalents:(66,095)50,572
    Cash and cash equivalents at the beginning of the year:202,887152,314
    Cash and cash equivalents at the end of the year :136,792202,887



    Revenue and other income

    The following table summarizes operating revenue for the periods under review:

    In thousands of euroDecember 31, 2020December 31, 2019
    Revenue from collaboration and licensing agreements56,15568,974
    Government financing for research expenditures13,61816,840
    Sales678
    Revenue and other income70,45185,814

    Revenue from collaboration and licensing agreements

    Revenue from collaboration and licensing agreements decreased by €12.8 million, or 18.6%, to €56.2 million for the year ended December 31, 2020, as compared to €69.0 million for the year ended December 31, 2019. Revenue from collaboration and licensing agreements mainly results from the spreading of the initial payments and the exercise of options related to the agreements signed with AstraZeneca in April 2015 and October 2018, on the basis of the completion of work that the Company is committed to carry out. The evolution in 2020 is mainly due to:

    • A €8.9 million decrease in revenue related to monalizumab to €33.6 million for the year ended December 31, 2020, as compared to €42.5 million for the year ended December 31, 2019. This decrease is mainly explained by the decrease in direct monalizumab research and development costs over the period in connection with the end of the recruitment of Phase 2 Cohort 2 during 2019. As of December 31, 2020, the deferred revenue related to monalizumab amounts to €26.6 million (€11.3 million as "Deferred revenue—Current portion" and €15.3 million as "Deferred revenue—Non-current portion").
    • A €5.4 million decrease in revenue related to IPH5201 to €13.4 million for the year ended December 31, 2020, as compared to €18.8 million for the year ended December 31, 2019. As of December 31, 2020, the Company having fulfilled all of its commitments on preclinical work related to the start of Phase 1 of the IPH5201 program, the initial payment of $50.0 million and the milestone payment of $5.0 million were fully recognized in revenue.
    • A €4.4 million decrease in revenue from invoicing of research and development costs to €2.5 million for the year ended December 31, 2020, as compared to €6.9 million for the year ended December 31, 2019. Pursuant to our agreements with AstraZeneca, research and development costs related to avdoralimab in oncology are equally shared between us and AstraZeneca and research and development costs related to IPH5201 are fully borne by AstraZeneca. The decrease between the two periods is mainly explained by the decrease in research and development costs relating to IPH5201 re-invoiced to AstraZeneca following the transition of the program in Phase 1 clinical trial, supported AstraZeneca.
    • On January 8, 2016, the Company announced the signing of a collaboration and research license agreement with Sanofi. As part of this agreement, and on December 8, 2020, Sanofi informed the Company of its intention to advance IPH6101/SAR443579 into investigational new drug (IND)-enabling studies. This decision triggered a milestone payment of €7.0 million from Sanofi to the Company, fully recognized in revenue as of December 31, 2020.

    Government funding for research expenditures

    Government funding for research expenditures decreased by €3.2 million, or 19.1%, to €13.6 million for the year ended December 31, 2020, as compared to €16.8 million for the year ended December 31, 2019. This change is primarily a result of a decrease in the research tax credit of €3.7 million, which is mainly due to a decrease in the amortization expense relating to the intangible assets related to the acquired licenses (see R&D expenses).

    The research tax credit is calculated as 30% of the amount of research and development expenses, net of grants received, eligible for the research tax credit for the fiscal year. Following the loss of the SME status under European Union criteria as of December 31, 2019, the CIR for the tax year 2020 will be imputable on the tax expense of the following three tax years, or refunded if necessary at the end of such period, in 2023 (see Balance sheet items - Non-current receivables).

    Sales

    As of December 31, 2020, following the end of the transition period relating to the commercialization of Lumoxiti in the United States on September 30, 2020, the Company recognized net sales of Lumoxiti for the fourth quarter for an amount of €0.7 million.

    Operating expenses

    The table below presents our operating expenses for the years ended December 31, 2020 and 2019:

    In thousands of eurosDecember 31, 2020December 31, 2019
    Research and development expenses(58,613)(78 844)
    Selling, general and administrative expenses(31,246)(25 803)
    Operating expenses(89,859)(104 647)

    Research and development expenses

    Research and development ("R&D") expenses decreased by €20.2 million, or 25.7%, to €58.6 million for the year ended December 31, 2020, as compared to €78.8 million for the year ended December 31, 2019. R&D expenses represented a total of 65.2% and 75.3% of the total operating expenses for the years ended December 31, 2020 and 2019, respectively.

    They include direct R&D expenses (subcontracting costs and consumables), depreciation and amortization, and personnel expenses. Direct expenses decreased by €16.4 million, or 37.0%, to €28.0 million for the year ended December 31, 2020, as compared to €44.4 million for the year ended December 31, 2019. This decrease is mainly explained by lower expenses on Lumoxiti (completion in 2019 of certain work in relation to the regulatory submission in Europe) and IPH5201 and IPH5301 (completion of certain preclinical work).

    Personnel and other expenses allocated to R&D decreased by €3.8 million, or 11.1%, to €30.6 million for the year ended December 2020, as compared to an amount of €34.4 million for the year ended December 31, 2019. This decrease is mainly due to the decrease by €3.5 million in depreciation and amortization relating to monalizumab rights (extension of the depreciation horizon due to a mechanical adjustment after the completion of a cohort in 2020) and IPH5201 rights (full amortization at December 31, 2020).

    Selling, general and administrative expenses

    Selling, general and administrative ("SG&A") expenses increased by €5.4 million, or 21.1% to €31.2 million for the year ended December 31, 2020 as compared to €25.8 million for the year ended December 31, 2019. SG&A expenses represented a total of 34.8% and 24.7% of the total operating expenses for the years ended December 31, 2020 and 2019, respectively.

    Personnel expenses (including share-based compensation) include the compensation paid to our employees and consultants, and increased by €2.1 million, or 20.3%, to €12.7 million for the year ended December 31, 2020, as compared to €10.6 million for the year ended December 31, 2019. This increase mainly results from the full-year effect of personnel costs related to our US subsidiary, including personnel assigned to Lumoxiti commercial activities. This increase is partially offset by the drop in share-based payments by €1.2 million.

    SG&A expenses also include non-scientific advisory and consulting expenses which mostly consist of auditing, accounting, tax advisory, legal, business and hiring fees. These expenses increased by €0.7 million, or 8.2%, to €9.1 million for the year ended December 31, 2020, compared to an amount of €8.4 million for the year ended December 31, 2019. This increase results mainly from the costs incurred for the marketing of Lumoxiti and the operation of our US subsidiary until the decision to return the US and EU commercialization rights to AstraZeneca at the end of 2020.

    Other SG&A expenses relate to intellectual property, the costs of maintaining laboratory equipment and our premises, depreciation and amortization and other general, administrative and commercial expenses. It notably includes insurance costs, that increased following the listing of the Company in the US in October 2019.

    Net income (loss) from distribution agreements

    When product sales are performed by a partner in the context of collaboration or transition agreements, the Company must determine if the partner acts as an agent or a principal. The Company concluded that AstraZeneca acted as a principal in the context of the production and commercialization of Lumoxiti until September 30, 2020. Consequently, the global inflows and outflows received from or paid to AstraZeneca are presented on a single line in the statement of income of Innate Pharma. This amount does not include the R&D costs which are recognized as R&D operating expenses.

    We recognized a net income of €0.9 million from the Lumoxiti license agreement in the year ended December 31, 2020, covering the first three quarters, to be compared to a net loss of €8.2 million for the year ended December 31, 2019, which reflected revenue from sales of Lumoxiti in the period, less administrative and selling expenses associated with the sales revenue allocated to us, following the sale in the United States.

    As of December 31, 2020, following the end of the transition period for the commercialization of Lumoxiti in the United States on September 30, 2020, the Company recognized fourth quarter net sales of Lumoxiti in the total amount of €0.7 million.

    Impairment of intangible assets

    As of December 31, 2020, impairment of intangible assets is linked to the full depreciation of Lumoxiti rights for an amount of €43.5 million, following the Company's decision to return the US and EU commercialization rights of Lumoxiti to AstraZeneca.

    Financial income (loss), net

    We recognized a net financial loss of €1.9 million for the year ended December 31, 2020, as compared to €6.3 million net financial gain for the year ended December 31, 2019. This change results mainly from the change in the fair value of certain financial instruments (gain of €4.1 million in 2019 as compared to a loss of €0.6 million in 2020) and a net foreign exchange loss of €1,5 million in 2020 as compared to a net foreign exchange gain of €0.8 million in 2019.

    Balance sheet items

    Cash, cash equivalents, short-term investments and financial assets (current and non-current) amounted to €190.6 million as of December 31, 2020, as compared to €255.9 million as of December 31, 2019. Net cash as of December 31, 2020 (cash, cash equivalents and current financial assets less current financial liabilities) amounted to €149.5 million (€216.7 million as of December 31, 2019).

    The other key balance sheet items as of December 31, 2020 are:

    • Deferred revenue of €44.0 million (including €31.5 million booked as ‘Deferred revenue – non-current portion') and collaboration liabilities of €46.7 million (including €44.9 million booked as ‘Collaboration liability – non-current portion') relating to the remainder of the initial payment received from AstraZeneca with respect to monalizumab, not yet recognized as revenue or used to co-fund the research and the development work performed by AstraZeneca including co-funding of the monalizumab program with AstraZeneca, notably the INTERLINK-1 Phase 3 trial;
    • Deferred revenue of €17.4 million relating to the initial payment for preclinical molecules, entirely classified as ‘Deferred revenue – non-current portion';
    • Intangible assets for a net book value of €46.3 million, mainly corresponding to the rights and licenses relating to the acquisitions relating to the monalizumab, IPH5201, avdoralimab (€97.0 million as of December 30, 2019); variation between the two periods is mainly explained by the full depreciation of Lumoxiti rights for an amount of €47.2 million, following the Company's decision to return the US and EU commercialization rights of Lumoxiti to AstraZeneca.
    • Non-current receivables from the French government in relation to the research tax credit for 2019 and 2020 of €29.9 million;
    • Shareholders' equity of €156.0 million, including the net loss of the period of €64.0 million;
    • Financial liabilities amounting to €19.1 million (€18.7 million as of December 31, 2019).

    Cash-flow items

    The net cash flow used over the year ended December 31, 2020 amounted to €66.1 million, compared to a net cash flow generated of €50.6 million for the year ended December 31, 2019.

    The net cash flow used during the period under review mainly results from the following:

    • Net cash used from operating activities of €51.8 million, mainly explained by the net cash consumption of operating activities less the receipt in December 2020 of the milestone payment of $50.0m (€41.2m) following the inclusion by AstraZeneca of the first patient in the Phase 3 clinical trial INTERLINK-1. In April 2020, Innate Pharma received €4.6 million payment from AstraZeneca following the dosing of the first patient in the IPH5201 Phase 1 clinical trial.
    • Net cash used in investing activities for an amount of €13.4 million, which mainly resulted from (i) a €13.4 million ($15.0 million) additional consideration paid to AstraZeneca regarding Lumoxiti following the submission of the Biologics License Application to the European Medicine Agency (EMA) in November 2019 (ii) a €2.7 million additional consideration paid to Orega Biotech in April 2020 relating to IPH5201 following the dosing of a first patient in a Phase 1 clinical trial and (iii) the acquisition of financial assets for a net amount of €3.0 million. Such items were partially offset by the reimbursement by AstraZeneca in relation to the 2019 cost sharing mechanism for the commercialization of Lumoxiti (€7.0 million).
    • Net cash flows used in financing activities for an amount of €1.1 million. On August 11, 2020, following the signing of a financing contract with BpiFrance Financement as part of the program set up by the French government to help develop a therapeutic solution with a preventive or curative aim against COVID-19, the Company received a repayable advance of €1.4 million. Loan repayments amounted to €2.2 million for the year ended December 31, 2020 compared to 2.0 million euros for the year ended December 31, 2019.

    Post period event

    • Laure-Helene Mercier, Executive Vice President, Chief Financial Officer and member of the Executive Board, has decided to step down from her position, after leading the Company through more than 14 years of growth, including an initial public offering in the US. Frederic Lombard will join the company as CFO on April 1, 2021. Mr. Lombard will be joining Innate with more than 20 years of financial experience in the pharmaceutical industry, holding senior finance roles at Ipsen, AstraZeneca and Novartis. Ms. Mercier will remain at the Company until the end of the year to ensure a smooth transition of responsibilities.

    Contingent liabilities

    At the date of this press release, discussions on the transition plan with AstraZeneca are ongoing including timing and costs, notably the split of certain manufacturing costs which are to date estimated at a maximum of $12.8 million.

    Nota

    This press release contains financial data not yet approved by the Executive Board based on our consolidated financial statements for the year ended December 31, 2020. The audit is in progress at the date of this communication.

    Our consolidated financial statements for the year ended December 31, 2020 will be approved by the Executive Board and reviewed by the Supervisory Board of the Company on April 26, 2021.

    Risk factors

    Risk factors ("Facteurs de Risque") identified by the Company are presented in section 3 of the registration document ("Universal Registration Document") filed with the French Financial Markets Authority ("Autorité des Marchés Financiers" or "AMF"), which is available on the AMF website http://www.amf-france.org or on the Company's website as well as in the Risk Factors section of the Company's Annual Report on Form 20-F for the year ended December 31, 2019 filed with the U.S. Securities and Exchange Commission, and subsequent filings and reports filed with the AMF or SEC, or otherwise made public, by the Company.


    1 This press release contains financial data not yet approved by the Executive Board based on our consolidated financial statements for the year ended December 31, 2020. The audit is in progress at the date of this communication.

    2 Including short term investments (€14.8m) and non-current financial instruments (€38.9m).

    3 Lumoxiti is licensed from MedImmune, a subsidiary of AstraZeneca.

    4 This press release contains financial data not yet approved by the Executive Board based on our consolidated financial statements for the year ended December 31, 2020. The audit is in progress at the date of this communication.

    5 This press release contains financial data not yet approved by the Executive Board based on our consolidated financial statements for the year ended December 31, 2020. The audit is in progress at the date of this communication.



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  4. – FOTIVDA® (tivozanib) Approved for Adult Patients with Relapsed or Refractory Advanced Renal Cell Carcinoma Following Two or More Prior Systemic Therapies; AVEO Plans to Make FOTIVDA Available to Patients in the U.S. by March 31, 2021 –

    - Entered Clinical Trial Collaboration and Supply Agreement with Bristol Myers Squibb for Planned Pivotal Phase 3 TiNivo-2 Study of FOTIVDAin Combination with OPDIVO® (nivolumab); Trial Expected to Commence Mid-2021 -

    – Enrollment Complete in Phase 2 Open Label Randomized Study of Ficlatuzumab in HNSCC; Results and Phase 3 Decision on Track for Mid-2021 –

    - Regained Ex-North American Rights to AV-203; AVEO Now Holds Global Rights to Three Clinical Assets in Addition to FOTIVDA North American Rights -

    -

    – FOTIVDA® (tivozanib) Approved for Adult Patients with Relapsed or Refractory Advanced Renal Cell Carcinoma Following Two or More Prior Systemic Therapies; AVEO Plans to Make FOTIVDA Available to Patients in the U.S. by March 31, 2021 –

    - Entered Clinical Trial Collaboration and Supply Agreement with Bristol Myers Squibb for Planned Pivotal Phase 3 TiNivo-2 Study of FOTIVDA in Combination with OPDIVO® (nivolumab); Trial Expected to Commence Mid-2021 -

    – Enrollment Complete in Phase 2 Open Label Randomized Study of Ficlatuzumab in HNSCC; Results and Phase 3 Decision on Track for Mid-2021 –

    - Regained Ex-North American Rights to AV-203; AVEO Now Holds Global Rights to Three Clinical Assets in Addition to FOTIVDA North American Rights -

    - $20M Tranche Drawdown Complete in Connection with FOTIVDA Approval Under Amended Hercules Loan Agreement -

    – Announced IP Strategy to Potentially Extend FOTIVDA Exclusivity to November 2028 –

    AVEO Oncology (NASDAQ:AVEO) today reported financial results for the full year ended December 31, 2020 and provided a business update.

    "The U.S. Food and Drug Administration's (FDA) recent approval of FOTIVDA marks a transformative event for AVEO, and we are eager to demonstrate FOTIVDA's potential to serve as a meaningful new treatment option within the growing relapsed or refractory advanced renal cell carcinoma (RCC) patient population. We look forward to bringing this meaningful new therapy to patients in the U.S. by the end of this month," said Michael Bailey, president and chief executive officer of AVEO. "In parallel, we remain focused on the evaluation of FOTIVDA in the immunotherapy combination setting, with the pivotal Phase 3 TiNivo-2 study of FOTIVDA in combination with OPDIVO expected to commence patient enrollment mid-year."

    "We also anticipate notable progress within our clinical programs, with several key inflection points expected to occur in the coming year. This includes a decision on the initiation of a pivotal study of ficlatuzumab in head and neck squamous cell carcinoma (HNSCC), and advancement of our Phase 1 study of AV-380. We look forward to providing updates on our progress in the coming months."

    FOTIVDA U.S. Regulatory, Commercial, and IP Updates

    • FOTIVDA Approved by the FDA for the Treatment of Adult Patients with Relapsed or Refractory Advanced RCC Following Two or More Prior Systemic Therapies. On March 10, 2021, AVEO announced FDA approval of FOTIVDA in the United States for the treatment of adults with relapsed or refractory advanced RCC following two or more prior systemic therapies. FOTIVDA is an oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI). AVEO plans to make FOTIVDA available to patients in the U.S. by March 31, 2021.
    • Presented New Analyses from the Phase 3 TIVO-3 Study at ASCO 2021 GU Cancers Symposium. In February 2021, AVEO presented key subgroup and quality of life analyses from the Phase 3 TIVO-3 study, its pivotal Phase 3 trial comparing tivozanib to sorafenib in RCC patients who are relapsed or refractory to two or more prior therapies, at the American Society of Clinical Oncology (ASCO) 2021 Genitourinary (GU) Cancers Symposium. The results further demonstrate the benefits of tivozanib over sorafenib. A copy of each presentation is available in the Scientific Publications & Presentations section of AVEO's website.
    • Updated IP Strategy Offers Potential for Tivozanib Patent Term Extension to November 2028. AVEO holds an exclusive license to two issued U.S. patents for tivozanib, one pertaining to the tivozanib composition of matter, which expires in April 2022, and the other pertaining to a crystalline form of tivozanib, which expires in November 2023. A patent term extension of up to five years may be available under the Hatch-Waxman Act, although only one patent can be extended under the Act. AVEO currently intends to file applications for patent term extension on both patents in parallel to provide optionality in its exclusivity strategy. Depending upon which patent AVEO ultimately chooses to extend, if a full five-year extension is granted for such patent, tivozanib's exclusivity period could reach either April 2027 or November 2028.

    Tivozanib Immuno-Oncology Updates

    • Announced Collaboration with Bristol Myers Squibb to Evaluate FOTIVDA in Combination with OPDIVO in Pivotal Phase 3 TiNivo-2 Trial in IO Relapsed or Refractory RCC. In March 2021, AVEO announced that it has entered into a clinical trial collaboration and supply agreement with Bristol Myers Squibb to evaluate FOTIVDA in combination with OPDIVO, Bristol Myers Squibb's anti-PD-1 therapy, in the pivotal Phase 3 TiNivo-2 trial in patients with advanced relapsed or refractory RCC following prior immunotherapy exposure. Bristol Myers Squibb will provide OPDIVO clinical drug supply for the study. AVEO will serve as the study sponsor and will be responsible for costs associated with the trial execution. AVEO expects to begin enrollment in the trial in mid-2021 subject to FDA feedback on the trial design anticipated in the second quarter of 2021.
    • Results from Phase 1b Portion of DEDUCTIVE Study in Hepatocellular Carcinoma (HCC) Presented at 2021 ASCO GI Cancer Symposium. In January 2021, results from the Phase 1b portion of the Phase 1b/2 DEDUCTIVE clinical trial of tivozanib in combination with IMFINZI® (durvalumab), AstraZeneca's (NASDAQ:AZN) human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with HCC were presented at the 2021 ASCO Gastrointestinal (GI) Cancers Symposium. There were no dose-limiting toxicities with the combination. In addition, the combination demonstrated a 29% partial response (PR) rate and 71% disease control rate (PR + stable disease), which is comparable to findings with bevacizumab and TECENTRIQ® (atezolizumab), an emerging standard of care in the same setting. Completion of enrollment in the ongoing Phase 2 portion of the study, which is expected to enroll up to an additional 30 subjects, is anticipated later this year.
    • Results from Phase 1b/2 TiNivo Study of Tivozanib in Combination with OPDIVO® (nivolumab) in RCC Published in Annals of Oncology. In November 2020, AVEO announced that previously reported results from the Phase 1b/2 TiNivo study of oral tivozanib in combination with intravenous OPDIVO (nivolumab) , an immune checkpoint, or PD-1, inhibitor, for the treatment of advanced RCC, were published in Annals of Oncology. The article, titled "TiNivo: Safety and Efficacy of Tivozanib-Nivolumab Combination Therapy in Patients with Metastatic Renal Cell Carcinoma", is available online via this link.

    Ficlatuzumab Update

    • Enrollment Complete in Phase 2 Open Label Randomized Study of Ficlatuzumab in HNSCC; Results Expected to Be Presented at a Medical Meeting in Mid-2021; Phase 3 Decision on Track for Mid-2021. In January 2021, AVEO announced completion of enrollment in its randomized confirmatory Phase 2 study of ficlatuzumab as a single agent or in combination with cetuximab, an EGFR-targeted antibody, in metastatic HNSCC patients who have failed prior immunotherapy, chemotherapy and cetuximab (ERBITUX®). Ficlatuzumab is AVEO's potent humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets hepatocyte growth factor (HGF). The study was designed to confirm findings from a Phase 1/2 study of ficlatuzumab and cetuximab where the combination was well tolerated and resulted in a disease control rate of 67%, as well as prolonged progression-free survival and overall survival compared to historical controls.



      Results from the Phase 2 study are expected to be presented at a medical meeting in mid-2021. In that timeframe, AVEO plans to announce a Phase 3 decision for ficlatuzumab. In September 2020, AVEO regained full global rights to ficlatuzumab and has initiated clinical manufacture of ficlatuzumab to supply a potential Phase 3 clinical trial in HNSCC, as well as additional potential Phase 2 studies in pancreatic cancer and acute myeloid leukemia.

    AV-380 Update

    • Phase 1 Clinical Study Initiated Following FDA Acceptance of IND Filing. In January 2021, AVEO announced that its Investigational New Drug (IND) application for AV-380, a potent humanized IgG1 monoclonal antibody that targets growth differentiation factor 15 (GDF15), for the potential treatment of cancer cachexia, was accepted by the FDA. A Phase 1 study in healthy subjects has been initiated.

    AV-203 Update

    • Regained Ex-North American Rights to AV-203. In March 2021, AVEO announced it will regain rights to AV-203 outside of North America, its clinical-stage potent humanized IgG1 monoclonal antibody that targets ErbB3 (also known as HER3), following the voluntary termination of its collaboration and license agreement by CANbridge Life Sciences. AVEO will regain rights to AV-203 in all territories globally, and CANbridge has initiated the process to transfer all preclinical data and materials to AVEO.

    Corporate Updates

    • Announced Drawdown of $20 Million Tranche Under $45 Million Debt Facility with Hercules Capital. In March 2021, AVEO announced that it completed a drawdown of $20 million under its previously announced $45 million loan and security agreement with Hercules Capital, Inc. (NYSE:HTGC, Hercules))) and its affiliates. With the closing of the second tranche, which was made available in connection with the recent FDA approval of FOTIVDA, AVEO has drawn down a total of $35 million under its loan and security agreement with Hercules. Under the terms of the loan agreement, an additional $10 million will become available if certain sales criteria and other conditions are met.
    • Announced Appointment of Mike Ferraresso to Chief Commercial Officer. In March 2021, AVEO announced the appointment of Mike Ferraresso to chief commercial officer. He will be responsible for managing AVEO's commercial strategy and operations, including the commercialization of FOTIVDA. Mr. Ferraresso, who joined AVEO in December 2017, most recently served as AVEO's senior vice president, business analytics and commercial operations. He has over 20 years of commercial pharmaceutical and biotechnology experience, including 15 years developing and commercializing oncology products.
    • Announced Appointment of Corinne D. Epperly, MD, MPH to Board of Directors. In January 2021, AVEO announced the appointment of Corinne D. Epperly, MD, MPH, to its Board of Directors. Dr. Epperly brings over 15 years of experience in oncology as a physician and scientist, blending medicine and business with a proven track record in oncology drug development and launches, commercial and medical strategy, marketing, M&A, and operations gained at Iovance Biotherapeutics, VBL Therapeutics, Bristol Myers Squibb, Goldman Sachs, and the National Cancer Institute of the NIH.
    • Announced Appointment of David Crist as Vice President of Sales. In October 2020, AVEO announced the appointment of David W. Crist as vice president of sales. Mr. Crist, who brings to AVEO over 20 years of oncology sales experience in both launch-stage and late-stage companies, is responsible for building out AVEO's sales force in preparation for the commercial launch of FOTIVDA in the U.S.

    A current summary of AVEO's activities and corporate updates is available in AVEO's Corporate Presentation on the Investors portion of AVEO's website at investor.aveooncology.com.

    Full Year 2020 Financial Highlights

    • AVEO ended 2020 with $61.8 million in cash, cash equivalents, and marketable securities as compared with $47.7 million at December 31, 2019.
    • Total revenue for 2020 was approximately $6.0 million compared with $28.8 million for 2019, which included the $25.0 million upfront payment in connection with Kyowa Kirin's buy back of tivozanib non-oncology rights.
    • Research and development expense for 2020 was $22.7 million compared with $18.0 million for 2019.
    • General and administrative expense for 2020 was $22.2 million compared with $11.2 million for 2019.
    • Net loss for 2020 was $35.6 million, or net loss of $1.66 per basic and diluted share, compared with a net income of $9.4 million, or net income of $0.61 per basic and diluted share, in 2019.
      • Net loss in 2020 reflects an approximate $4.9 million non-cash gain attributable to the decrease in the fair value of the 2016 private placement warrant liability that principally resulted from decreases in the stock price and stock volatility rate that occurred within the fiscal year, as well as a shorter remaining term as the warrants approach expiration. Net income in 2019 reflects an approximate $11.6 million non-cash gain attributable to the decrease in the fair value of the 2016 private placement warrant liability that principally resulted from the decrease in the stock price that occurred within the fiscal year.

    Financial Guidance

    AVEO believes that its $61.8 million in cash and cash equivalents as of December 31, 2020, along with proceeds from the $20 million drawdown under the Hercules loan facility in March 2021 and from warrant exercises to date, together with anticipated partnership cost sharing reimbursements, royalties from EUSA Pharma (UK) Limited's (EUSA) FOTIVDA sales, product revenues upon the commercial launch of FOTIVDA in the United States and the potential additional $10 million in credit under the Hercules loan agreement, would allow AVEO to fund planned operations into 2022.

    The above guidance estimates the expenses associated with the commercial launch of FOTIVDA in the United States will be approximately $40 million during the year ended December 31, 2021.

    About FOTIVDA® (tivozanib)

    FOTIVDA® (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models1. FOTIVDA was discovered by Kyowa Kirin.

    INDICATIONS

    FOTIVDA is indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

    IMPORTANT SAFETY INFORMATION

    WARNINGS AND PRECAUTIONS

    Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

    Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

    Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

    Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

    Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

    Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

    Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

    Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

    Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

    Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

    Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

    ADVERSE REACTIONS

    The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

    DRUG INTERACTIONS

    Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

    USE IN SPECIFIC POPULATIONS

    Lactation: Advise not to breastfeed.

    Females and Males of Reproductive Potential: Can impair fertility.

    Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

    To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    Please see FOTIVDA Full Prescribing Information which is available at www.AVEOoncology.com.

    About Advanced Renal Cell Carcinoma

    According to the American Cancer Society's 2021 statistics, renal cell carcinoma (RCC) is the most common type of kidney cancer, which is among the ten most common cancers in both men and women. Approximately 73,750 new cases of kidney cancer will be diagnosed annually and about 14,830 people will die from this disease. In patients with late-stage disease, the five-year survival rate is 13%. Agents that target the vascular endothelial growth factor (VEGF) pathway have shown significant antitumor activity in RCC.2 According to a 2019 publication, 50% of the approximately 10,000 patients who progress following two or more lines of therapy choose not to receive further treatment,3 which may be attributable to tolerability concerns and a lack of data to support evidence-based treatment decisions in this highly relapsed or refractory patient population.

    About AVEO Pharmaceuticals, Inc.

    AVEO is an oncology-focused biopharmaceutical company committed to delivering medicines that provide a better life for cancer patients. AVEO's strategy is to focus its resources toward the development and commercialization of its product candidates in North America, while leveraging partnerships to support development and commercialization in other geographies. AVEO's lead candidate, FOTIVDA® (tivozanib), received U.S. Food and Drug Administration (FDA) approval on March 10, 2021 for the treatment of adult patients with relapsed or refractory renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA® was approved in August 2017 in the European Union and other countries in the EUSA territory for the treatment of adult patients with advanced RCC. AVEO has previously reported promising early clinical data on ficlatuzumab (anti-HGF IgG1 mAb) in head and neck cancer, pancreatic cancer and acute myeloid leukemia and is conducting a randomized Phase 2 confirmatory clinical trial of ficlatuzumab for the potential treatment of head and neck cancer. AVEO's pipeline of product candidates also includes AV-380 (anti-GDF15 IgG1 mAb). AVEO has previously reported the acceptance of its investigational new drug application in the U.S. for AV-380 and its initiation of a Phase 1 clinical trial for the potential treatment of cancer cachexia. AVEO's earlier-stage pipeline includes monoclonal antibodies in oncology development, including AV-203 (anti-ErbB3 mAb) and AV-353 (anti-Notch 3 mAb). AVEO is committed to creating an environment of diversity and inclusion.

    Cautionary Note Regarding Forward-Looking Statements

    This press release contains forward-looking statements of AVEO within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. The words "anticipate," "believe," "design," "expect," "hope," "intend," "may," "plan," "potential," "could," "should," "would," "seek," "look forward," "advance," "goal," "strategy," or the negative of these terms or other similar expressions, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, among others, statements about: AVEO's planned timing for making FOTIVDA available to patients in the U.S.; the potential for FOTIVDA as a treatment option for patients with relapsed or refractory advanced RCC; the potential efficacy, safety, and tolerability of tivozanib, both as a stand-alone drug candidate and in combination with other therapies in several indications; AVEO's execution of its clinical and regulatory strategy for tivozanib; AVEO's plans and strategies for current and future clinical trials of tivozanib, ficlatuzumab and AV-380 and for commercialization of FOTIVDA in the United States; the advancement of AVEO's pipeline, including the advancement of ficlatuzumab in multiple clinical studies; the potential outcomes from studies of ficlatuzumab to provide AVEO with opportunities to pursue regulatory strategies; the potential clinical utility of ficlatuzumab and AV-380 in areas of unmet need and AVEO's strategy, prospects, plans and objectives for FOTIVDA and its product candidates and for AVEO generally. AVEO has based its expectations and estimates on assumptions that may prove to be incorrect. As a result, readers are cautioned not to place undue reliance on these expectations and estimates. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that AVEO makes due to a number of important factors, including risks relating to: AVEO's ability to successfully implement its strategic plans, including its ability to successfully commercialize FOTIVDA and to obtain and maintain market and third party payor acceptance of FOTIVDA; AVEO's ability to raise the substantial additional funds required to achieve its goals, including those goals pertaining to the commercialization of FOTIVDA; AVEO's ability, and the ability of its licensees, to demonstrate to the satisfaction of applicable regulatory agencies such as the FDA the safety, efficacy, and clinically meaningful benefit of AVEO's product candidates, and risks relating to the timing and costs of seeking and obtaining regulatory approvals; AVEO's dependence on third-party vendors for the development, manufacture and supply of FOTIVDA and its product candidates; and AVEO's ability to enter into and maintain its third party collaboration and license agreements, and its ability, and the ability of its strategic partners, to achieve development and commercialization objectives under these arrangements; AVEO's and its collaborators' ability to successfully enroll and complete clinical trials; AVEO's ability to maintain compliance with regulatory requirements applicable to FOTIVDA and its product candidates; AVEO's ability to obtain and maintain adequate protection for intellectual property rights relating to FOTIVDA and its product candidates; unplanned capital requirements; uncertainties related to AVEO's ability to access future borrowings under the Hercules loan agreement, which turns on the achievement of milestones related to the commercialization of FOTIVDA in the U.S., which milestones may not be achieved; adverse general economic, political and industry conditions; the potential adverse effects of the COVID-19 pandemic on AVEO's business continuity, financial condition, results of operations, liquidity and ability to successfully and timely enroll, complete and read-out data from its clinical trials; competitive factors; and those risks discussed in the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations—Liquidity and Capital Resources" included in AVEO's quarterly and annual reports on file with the Securities and Exchange Commission (SEC) and in other filings that AVEO makes with the SEC. The forward-looking statements in this press release represent AVEO's views as of the date of this press release, and subsequent events and developments may cause its views to change. While AVEO may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. You should, therefore, not rely on these forward-looking statements as representing AVEO's views as of any date other than the date of this press release.

    Any reference to AVEO's website address in this press release is intended to be an inactive textual reference only and not an active hyperlink.

    References

    1. Pawlowski N et al. AACR 2013. Poster 3971
    2. J Angulo and O Shapiro, Cancers (Basel) 2019 Sep; 11(9): 1227. [10.3390/cancers11091227]
    3. Decision Resources. RCC landscape and forecast. December 12, 2019.

    AVEO PHARMACEUTICALS, INC.

    Condensed Consolidated Statements of Operations

    (In thousands, except per share amounts)

    (Unaudited)

     

     

     

    Three Months Ended

    December 31,

     

     

    Year Ended

    December 31,

     

     

     

    2020

     

     

    2019

     

     

    2020

     

     

    2019

     

    Revenues:

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

    Collaboration and licensing revenue

     

    $

    494

     

     

    $

    493

     

     

    $

    4,774

     

     

    $

    27,934

     

    Partnership royalties

     

     

    392

     

     

     

    271

     

     

     

    1,245

     

     

     

    861

     

     

     

     

    886

     

     

     

    764

     

     

     

    6,019

     

     

     

    28,795

     

    Operating expenses:

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

    Research and development

     

     

    4,574

     

     

     

    4,512

     

     

     

    22,679

     

     

     

    17,958

     

    Selling, general and administrative

     

     

    9,008

     

     

     

    2,886

     

     

     

    22,217

     

     

     

    11,211

     

     

     

     

    13,582

     

     

     

    7,398

     

     

     

    44,896

     

     

     

    29,169

     

    Loss from operations

     

     

    (12,696

    )

     

     

    (6,634

    )

     

     

    (38,877

    )

     

     

    (374

    )

    Other income (expense), net:

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

    Interest expense, net

     

     

    (522

    )

     

     

    (333

    )

     

     

    (1,605

    )

     

     

    (1,815

    )

    Change in fair value of PIPE Warrant liability

     

     

    1,714

     

     

     

    2,506

     

     

     

    4,898

     

     

     

    11,577

     

    Other income (expense), net

     

     

    1,192

     

     

     

    2,173

     

     

     

    3,293

     

     

     

    9,762

     

    Net income (loss)

     

    $

    (11,504

    )

     

    $

    (4,461

    )

     

    $

    (35,584

    )

     

    $

    9,388

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

    Basic net income (loss) per share

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

    Net income (loss) per share

     

    $

    (0.44

    )

     

    $

    (0.28

    )

     

    $

    (1.66

    )

     

    $

    0.61

     

    Weighted average number of common shares outstanding

     

     

    26,252

     

     

     

    16,077

     

     

     

    21,402

     

     

     

    15,331

     

    Diluted net income (loss) per share

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

     

    Net income (loss) per share

     

    $

    (0.44

    )

     

    $

    (0.28

    )

     

    $

    (1.66

    )

     

    $

    0.61

     

    Weighted average number of common shares and dilutive common share equivalents outstanding

     

     

    26,252

     

     

     

    16,077

     

     

     

    21,402

     

     

     

    15,376

     

    Consolidated Balance Sheet Data

    (In thousands)

    (Unaudited)

     

     

     

    December 31,

    2020

     

     

    December 31,

    2019

     

    Assets

     

     

     

     

     

     

     

     

    Cash, cash equivalents and marketable securities

     

    $

    61,761

     

     

    $

    47,745

     

    Accounts receivable

     

     

    1,197

     

     

     

    1,631

     

    Prepaid expenses and other current assets

     

     

    2,550

     

     

     

    1,224

     

    Property and equipment, net

     

     

    343

     

     

     

     

    Operating lease right-of-use asset

     

     

    903

     

     

     

     

    Other assets

     

     

    158

     

     

     

     

    Total assets

     

    $

    66,912

     

     

    $

    50,600

     

     

     

     

     

     

     

     

     

     

    Liabilities and stockholders' equity

     

     

     

     

     

     

     

     

    Accounts payable and accrued expenses

     

    $

    12,393

     

     

    $

    9,482

     

    Loans payable, net of discount

     

     

    13,772

     

     

     

    15,766

     

    Deferred revenue and research and development reimbursements

     

     

    2,716

     

     

     

    4,619

     

    PIPE Warrant liability

     

     

    199

     

     

     

    5,097

     

    Operating lease liability

     

     

    705

     

     

     

     

    Other liabilities

     

     

    1,833

     

     

     

    790

     

    Stockholder's equity

     

     

    35,294

     

     

     

    14,846

     

    Total liabilities and stockholders' equity

     

    $

    66,912

     

     

    $

    50,600

     

     

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  5. SAN FRANCISCO, March 01, 2021 (GLOBE NEWSWIRE) -- FibroGen, Inc. (NASDAQ:FGEN) and its partner, AstraZeneca (NASDAQ:AZN), today announced that the Cardiovascular and Renal Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) will hold an advisory committee (AdCom) meeting to review the new drug application for roxadustat in the U.S. The companies have not received a confirmed AdCom meeting date from the FDA.

    "While disappointed with the news today, FibroGen and AstraZeneca are committed to working with the FDA to bring roxadustat to patients with anemia of CKD in the U.S. as soon as possible," said Enrique Conterno, Chief Executive Officer, FibroGen. "We continue to be confident in the efficacy and safety profile of…

    SAN FRANCISCO, March 01, 2021 (GLOBE NEWSWIRE) -- FibroGen, Inc. (NASDAQ:FGEN) and its partner, AstraZeneca (NASDAQ:AZN), today announced that the Cardiovascular and Renal Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) will hold an advisory committee (AdCom) meeting to review the new drug application for roxadustat in the U.S. The companies have not received a confirmed AdCom meeting date from the FDA.

    "While disappointed with the news today, FibroGen and AstraZeneca are committed to working with the FDA to bring roxadustat to patients with anemia of CKD in the U.S. as soon as possible," said Enrique Conterno, Chief Executive Officer, FibroGen. "We continue to be confident in the efficacy and safety profile of this potential new medicine based on positive results from a global Phase 3 program encompassing more than 8,000 patients."

    Roxadustat has been approved in China, Japan and Chile for the treatment of anemia of CKD in both non-dialysis dependent (NDD) and dialysis-dependent (DD) adult patients.

    Roxadustat, an oral small molecule hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, is the first HIF-PH inhibitor accepted by the FDA for review for the treatment of anemia of CKD.

    About Anemia of CKD

    Chronic kidney disease (CKD) is generally a progressive disease characterized by gradual loss of kidney function that may eventually lead to kidney failure or end stage renal disease, requiring dialysis or kidney transplant. CKD is estimated to occur in approximately 10-12% of adults worldwide and is predicted to become the fifth most common cause of premature death globally by 2040.

    Anemia, a serious medical condition in which patients have insufficient red blood cells and low levels of hemoglobin, is a common early complication of CKD, affecting approximately 20% of CKD patients. Anemia of CKD is associated with an increased risk of hospitalization, cardiovascular complications, and death, and can also cause significant fatigue, cognitive dysfunction and reduced quality of life. Blood transfusions are used for treating severe anemia, however, they may reduce a patient's opportunity for kidney transplant and can increase the risk of infection and/or complications such as heart failure and allergic reactions.

    About Roxadustat

    Roxadustat, an oral medicine, is the first in a new class of medicines, HIF-PH inhibitors that promote erythropoiesis, or red blood cell production, through increased endogenous production of erythropoietin; improved iron absorption and mobilization; and downregulation of hepcidin. Roxadustat is also in clinical development for anemia associated with myelodysplastic syndromes (MDS) and for chemotherapy-induced anemia (CIA).

    Roxadustat is approved in China, Japan, and Chile for the treatment of anemia of CKD in adult patients on dialysis (DD) and not on dialysis (NDD). In Europe, the Marketing Authorization Application for roxadustat for the treatment of anemia in with chronic kidney disease (CKD) in NDD and DD patients was filed by Astellas Pharma Inc. (Astellas) and accepted by the European Medicines Agency for review in May 2020. Several other licensing applications for roxadustat have been submitted by Astellas and AstraZeneca to regulatory authorities across the globe, and are currently in review.

    Astellas and FibroGen are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in territories including Japan, Europe, Turkey, Russia and the Commonwealth of Independent States, the Middle East, and South Africa. FibroGen and AstraZeneca are collaborating on the development and commercialization of roxadustat for the potential treatment of anemia in the U.S., China, other markets in the Americas, in Australia/New Zealand, and Southeast Asia.

    About FibroGen

    FibroGen, Inc. is a biopharmaceutical company committed to discovering, developing, and commercializing a pipeline of first-in-class therapeutics. The Company applies its pioneering expertise in hypoxia-inducible factor (HIF) and connective tissue growth factor (CTGF) biology to advance innovative medicines for the treatment of unmet needs. The Company is currently developing and commercializing roxadustat, an oral small molecule inhibitor of HIF prolyl hydroxylase activity, for anemia associated with chronic kidney disease (CKD). Roxadustat is also in clinical development for anemia associated with myelodysplastic syndromes (MDS) and for chemotherapy-induced anemia (CIA). Pamrevlumab, an anti-CTGF human monoclonal antibody, is in clinical development for the treatment of locally advanced unresectable pancreatic cancer (LAPC), Duchenne muscular dystrophy (DMD), and idiopathic pulmonary fibrosis (IPF). For more information, please visit www.fibrogen.com.

    Forward-Looking Statements

    This release contains forward-looking statements regarding our strategy, future plans and prospects, including statements regarding the development and commercialization of the company's product candidates, the potential safety and efficacy profile of our product candidates, our clinical programs and regulatory events, and those of our partners. These forward-looking statements include, but are not limited to, statements about our plans, objectives, representations and contentions and are not historical facts and typically are identified by use of terms such as "may," "will", "should," "on track," "could," "expect," "plan," "anticipate," "believe," "estimate," "predict," "potential," "continue" and similar words, although some forward-looking statements are expressed differently. Our actual results may differ materially from those indicated in these forward-looking statements due to risks and uncertainties related to the continued progress and timing of our various programs, including the enrollment and results from ongoing and potential future clinical trials, and other matters that are described in our Annual Report on Form 10-K for the fiscal year ended December 31, 2020 and our Quarterly Report on Form 10-Q for quarter ended September 30, 2020 filed with the Securities and Exchange Commission (SEC), including the risk factors set forth therein. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and we undertake no obligation to update any forward-looking statement in this press release, except as required by law.

    Contacts:

    FibroGen, Inc.

    Investors:

    Michael Tung, M.D.

    Corporate Strategy / Investor Relations

    1.415.978.1434

    Media:

    Jennifer Harrington

    +1.610.574.9196



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  6. Tezepelumab demonstrated superiority versus placebo across every primary and key secondary endpoint in NAVIGATOR Phase III trial

    Positive full results from the pivotal NAVIGATOR Phase III trial showed AstraZeneca and Amgen's tezepelumab demonstrated a statistically significant and clinically meaningful1 reduction in the annualized asthma exacerbation rate (AAER) in severe, uncontrolled asthma patients.2 The results were presented at the American Academy of Asthma Allergy & Immunology Virtual Annual Meeting.2

    Tezepelumab demonstrated superiority versus placebo across every primary and key secondary endpoint in NAVIGATOR Phase III trial

    Positive full results from the pivotal NAVIGATOR Phase III trial showed AstraZeneca and Amgen's tezepelumab demonstrated a statistically significant and clinically meaningful1 reduction in the annualized asthma exacerbation rate (AAER) in severe, uncontrolled asthma patients.2 The results were presented at the American Academy of Asthma Allergy & Immunology Virtual Annual Meeting.2

    Tezepelumab, a potential first-in-class medicine, when added to standard of care (SoC) achieved a 56% reduction (p<0.001) in AAER over 52 weeks in the overall patient population, compared to placebo when added to SoC.2 SoC was medium- or high-dose inhaled corticosteroids (ICS) plus at least one additional controller medication with or without oral corticosteroids (OCS).2

    Tezepelumab is the only biologic medicine to consistently and significantly reduce AAER in a broad population of severe asthma patients irrespective of baseline eosinophil count across Phase II and Phase III clinical trials.2-9

    In a pre-planned subgroup analysis, tezepelumab achieved a statistically significant and clinically meaningful 41% reduction (p<0.001) in AAER in patients with baseline eosinophil counts less than 300 cells per microliter.2 Importantly, clinically meaningful reductions in AAER were also observed in two additional subgroups: 39% in patients with baseline eosinophil counts less than 150 cells per microliter and 70% in patients with greater than or equal to 300 cells per microliter.2

    Additionally, clinically meaningful reductions in AAER compared to placebo were observed in the tezepelumab-treated patients irrespective of allergy status and fractional exhaled nitric oxide (FeNO) level, biomarkers used by clinicians to inform treatment options.2

    Professor Andrew Menzies-Gow, Director of the Lung Division, Royal Brompton Hospital, London, UK, and principal investigator of the NAVIGATOR Phase III trial, said: "These are ground-breaking results for the many patients with severe asthma who continue to face debilitating symptoms despite receiving standard of care inhaled medicines and currently approved biologics. Tezepelumab has the potential to transform treatment for a broad population of patients with severe asthma regardless of their type of inflammation, including those with and without an eosinophilic phenotype."

    Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: "The unprecedented results from the NAVIGATOR Phase III trial show tezepelumab is the first and only asthma biologic to demonstrate in randomized trials clinically meaningful exacerbation reductions, irrespective of blood eosinophil counts, allergy status and fractional exhaled nitric oxide. There is now a strong body of evidence showing the benefit of targeting the top of the inflammatory cascade with tezepelumab, and we look forward to bringing this potential first-in-class medicine to a broad population of severe asthma patients as soon as possible."

    Tezepelumab demonstrated statistically significant improvements in every key secondary endpoint compared to placebo, including lung function measurements, asthma control and health-related quality of life.2

    There were no clinically meaningful differences in safety results between the tezepelumab and placebo groups. The most frequently reported adverse events were nasopharyngitis, upper respiratory tract infection and headache.2

    NAVIGATOR is a pivotal Phase III trial that will form the basis of regulatory submission.

    Tezepelumab blocks the action of thymic stromal lymphopoietin (TSLP), an epithelial cytokine that plays a key role across the spectrum of asthma inflammation.3,10 NAVIGATOR is the first Phase III trial to show benefit in severe asthma by targeting TSLP.2

    The statistically significant and clinically meaningful exacerbation rate reductions demonstrated with tezepelumab in patients with baseline eosinophil counts less than 300 cells per microliter support the US Food and Drug Administration Breakthrough Therapy Designation granted to tezepelumab in September 2018 for patients with severe asthma, without an eosinophilic phenotype.2,3 Tezepelumab is being developed by AstraZeneca in collaboration with Amgen.

    Severe asthma

    Asthma is a heterogeneous disease affecting an estimated 339 million people worldwide.11,12 Approximately 10% of asthma patients have severe asthma.12,13 Despite the use of inhaled asthma controller medicine, currently available biologic therapies and OCS, many severe asthma patients remain uncontrolled.12-14 Due to the complexity of severe asthma, many patients have unclear or multiple drivers of inflammation and may not qualify for or respond well to a current biologic medicine.13-16

    Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life.12,13,17 Patients with severe asthma are at an increased risk of mortality and have twice the risk of asthma-related hospitalizations.18-20 There is also a significant socio-economic burden, with these patients accounting for 50% of asthma-related costs.21

    NAVIGATOR and the PATHFINDER clinical trial program

    Building on the Phase IIb PATHWAY trial, the Phase III PATHFINDER program included two trials, NAVIGATOR and SOURCE.22,23 The program includes additional planned mechanistic and long-term safety trials.

    NAVIGATOR is a Phase III, randomized, double-blinded, placebo-controlled trial in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma, who were receiving treatment with medium- or high-dose ICS plus at least one additional controller medication with or without OCS. The trial population included approximately equal proportions of patients with high (≥ 300 cells/µL) and low (< 300 cells/µL) blood eosinophil counts. The trial comprised a five to six week screening period, a 52-week treatment period and a 12-week post-treatment follow-up period. All patients received their prescribed controller medications without change throughout the trial.22

    The primary efficacy endpoint was the AAER during the 52-week treatment period. Key secondary endpoints included the effect of tezepelumab on lung function, asthma control and health-related quality of life.22

    NAVIGATOR primary endpoints2

    Endpoint

    Timepoint

    Results

    Tezepelumab added to SoC vs placebo added to SoC

    AAER – overall patient population

    Over 52 weeks

    56% reduction (95% CI: 47, 63; p<0.001)

    AAER – baseline eosinophil counts < 300 cells/µL

    Over 52 weeks

    41% reduction (95% CI: 25, 54; p<0.001)

    CI: confidence interval

    As part of prespecified analyses, the AAER over 52 weeks was also assessed in patients grouped by baseline blood eosinophil count, fractional exhaled nitric oxide (FeNO) level, serum specific immunoglobin E (IgE) status (perennial allergen sensitivity positive or negative). These are inflammatory biomarkers used by clinicians to inform treatment options and involve tests analysing a patient's blood (eosinophils / IgE) and exhaled air (FeNO).

    SOURCE is a Phase III multicenter, randomized, double-blinded, parallel-group, placebo-controlled trial for 48 weeks in adult patients with severe asthma who require continuous treatment with ICS plus long-acting beta2-agonists (LABA), and chronic treatment with maintenance OCS therapy. The primary endpoint is the categorized percentage reduction from baseline in the daily OCS dose, while not losing asthma control.23

    Patients who participated in the NAVIGATOR and SOURCE trials were eligible to continue in DESTINATION, a Phase III extension trial assessing long-term safety and efficacy.24

    Tezepelumab

    Tezepelumab is a potential first-in-class human monoclonal antibody that inhibits the action of TSLP, a key epithelial cytokine that sits at the top of multiple inflammatory cascades and is critical in the initiation and persistence of allergic, eosinophilic and other types of airway inflammation associated with severe asthma.3,10 TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles.3,10 Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity.3,25 Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control.3,25 Tezepelumab acts at the top of the inflammation cascade and has the potential to treat a broad population of severe asthma patients regardless of their type of inflammation.3,25

    AstraZeneca and Amgen collaboration

    In 2020, Amgen and AstraZeneca updated the 2012 collaboration agreement for tezepelumab. Both companies will continue to share costs and profits equally after payment by AstraZeneca of a mid single-digit inventor royalty to Amgen. AstraZeneca continues to lead development and Amgen continues to lead manufacturing. All aspects of the collaboration are under the oversight of joint governing bodies. Under the amended agreement in North America, Amgen and AstraZeneca will jointly commercialize tezepelumab; Amgen will record sales in the US and AstraZeneca will record sales in Canada. AstraZeneca's share of gross profits from tezepelumab in the US will be recognized as collaboration revenue. In all countries outside the US and Canada, AstraZeneca will solely commercialize tezepelumab. AstraZeneca will record all sales outside of the US as product sales and recognise Amgen's share of gross profit as cost of sales.

    AstraZeneca in Respiratory & Immunology

    Respiratory & Immunology is one of AstraZeneca's three therapy areas and is a key growth driver for the Company.

    AstraZeneca is an established leader in respiratory care, and its inhaled and biologic medicines reached more than 53 million patients in 2019. Building on a 50-year heritage, the Company aims to transform the treatment of asthma and COPD by focusing on earlier biology-led treatment, eliminating preventable asthma attacks, and removing COPD as a top-three leading cause of death. The Company's early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell-repair processes in disease and neuronal dysfunction.

    With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immunology-driven disease areas. The Company's growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential, in areas including rheumatology (including Systemic Lupus Erythematosus), dermatology, gastroenterology, and systemic eosinophilic-driven diseases. AstraZeneca's ambition in Respiratory & Immunology is to achieve disease modification and durable remission for millions of patients worldwide.

    About AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

    References

    1. Bonini M, Di Paolo M, Bagnasco D, et al. Minimal clinically important difference for asthma endpoints: an expert consensus report. Eur Respir Rev. 2020; 29: 190137.
    2. Menzies-Gow A, Corre J, Bourdin A, et al. Efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma: results from the phase 3 NAVIGATOR study. L 46. AAAAI poster. February 2021.
    3. Corren J, Parnes JR, Wang L, et al. Tezepelumab in Adults with Uncontrolled Asthma [published correction appears in N Engl J Med. 2019 May 23; 380 (21): 2082]. N Engl J Med. 2017; 377 (10): 936-946.
    4. Wenzel S, Castro M, Corren J, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016;388 (10039): 31-44.
    5. Castro M, Corren J, Pavord I.D, et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N Engl J Med 2018; 378:2486-2496.
    6. Bleecker ER, FitzGerald JM, Chanez P, et al, on behalf of the SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 2016: 388 (10056): 2115-2127.
    7. FitzGerald JM, Bleecker ER, Nair P, et al, on behalf of the CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2016: 388(10056): 2128-2141.
    8. FitzGerald JM, Bleecker ER, Menzies-Gow A, et al. Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies. Lancet Respir Med. 2017; 6 (1): 51-64.
    9. Ortega HG, Liu MC, Pavord ID, et al; on behalf of the MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198-207.
    10. Varricchi G, Pecoraro A, Marone G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018; 9: 1595.
    11. The Global Asthma Network. The Global Asthma Report 2018. [Online]. Available at: http://www.globalasthmareport.org/Global%20Asthma%20Report%202018.pdf.[Last accessed: February 2021].
    12. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014; 43: 343–73.
    13. Wenzel S. Severe Asthma in Adults. Am J Respir Crit Care Med. 2005; 172; 149–60.
    14. Peters SP, Ferguson G, Deniz Y, et al. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med. 2006; 100 (7): 1139-51.
    15. Hyland ME, Masoli M, Lanario JW, et al. A Possible Explanation for Non-responders, Responders and Super-responders to Biologics in Severe Asthma. Explor Res Hypothesis Med. 2019; 4:35–38.
    16. Tran TN, Zeiger RS, Peters SP, et al. Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma. Ann Allergy Asthma Immunol. 2016; 116:37–42.
    17. Fernandes AG, Souza-Machado C, Coelho RC, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014; 40 (4): 364-372.
    18. Chastek B, Korrer S, Nagar SP, et al. Economic Burden of Illness Among Patients with Severe Asthma in a Managed Care Setting. J Manag Care Spec Pharm. 2016; 22: 848–861.
    19. Hartert TV, Speroff T, Togias A, et al. Risk factors for recurrent asthma hospital visits and death among a population of indigent older adults with asthma. Ann Allergy Asthma Immunol. 2002; 89: 467–73.
    20. Price D, Fletcher M, van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014; 12; 24: 14009.
    21. World Allergy Organization (WAO). The management of severe asthma: economic analysis of the cost of treatments for severe asthma. Available at: https://www.worldallergy.org/educational_programs/world_allergy_forum/anaheim2005/blaiss.php [Last accessed: February 2021].
    22. Menzies-Gow A, Colice G, Griffiths JM et al. NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Respir Res. 2020; 21(1): 266.
    23. Weschler ME, Colice G, Griffiths JM, et al. SOURCE: A Phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of Tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma. Respir Res. 2020; 21(1), 264.
    24. Clinicaltrials.gov. Extension Study to Evaluate the Safety and Tolerability of Tezepelumab in Adults and Adolescents With Severe, Uncontrolled Asthma (DESTINATION) [Online]. Available at: https://clinicaltrials.gov/ct2/show/NCT03706079. [Last accessed: February 2021].
    25. Li Y, Wang W, LV Z et al. Elevated Expression of IL-33 and TSLP in the Airways of Human Asthmatics In Vivo: A Potential Biomarker of Severe Refractory Disease. The Journal of Immunology. 2018; 200: 2253–2262.

    US-49744 Last Updated 2/21

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  7. OlympiA Phase III trial of LYNPARZA in the adjuvant treatment of BRCA-mutated high-risk HER2-negative early breast cancer will be analyzed and reported early

    AstraZeneca and Merck & Co., Inc., known as MSD outside the US and Canada, today announced the OlympiA Phase III trial for LYNPARZA® (olaparib) will move to early primary analysis and reporting following a recommendation from the Independent Data Monitoring Committee (IDMC).

    Based on the planned interim analysis, the IDMC concluded that the trial crossed the superiority boundary for its primary endpoint of invasive disease-free survival (iDFS) and demonstrated a sustainable, clinically relevant treatment effect for LYNPARZA versus placebo for patients with germline BRCA-mutated (gBRCA

    OlympiA Phase III trial of LYNPARZA in the adjuvant treatment of BRCA-mutated high-risk HER2-negative early breast cancer will be analyzed and reported early

    AstraZeneca and Merck & Co., Inc., known as MSD outside the US and Canada, today announced the OlympiA Phase III trial for LYNPARZA® (olaparib) will move to early primary analysis and reporting following a recommendation from the Independent Data Monitoring Committee (IDMC).

    Based on the planned interim analysis, the IDMC concluded that the trial crossed the superiority boundary for its primary endpoint of invasive disease-free survival (iDFS) and demonstrated a sustainable, clinically relevant treatment effect for LYNPARZA versus placebo for patients with germline BRCA-mutated (gBRCAm) high-risk human epidermal growth factor receptor 2 (HER2)-negative early breast cancer, and recommend primary analysis now take place.

    The OlympiA Phase III trial is a partnership between Breast International Group (BIG), NRG Oncology, the US National Cancer Institute (NCI), Frontier Science & Technology Research Foundation (FSTRF), AstraZeneca and Merck.1 The trial is sponsored by NRG Oncology in the US and by AstraZeneca outside the US.

    An estimated 2.3 million women were diagnosed with breast cancer worldwide in 2020, and BRCA mutations are found in approximately 5% of breast cancer patients.2-10 Around 55-65% of women with a BRCA1 mutation and approximately 45% with a BRCA2 mutation will develop breast cancer before the age of 70.11

    Andrew Tutt, Global Chair of the OlympiA Phase III trial and Professor, Institute of Cancer Research and Kings College London, said: "We are delighted that our global academic and industry partnership has been able to help investigate a possible personalized treatment for women with hereditary breast cancer. The most common cause of hereditary breast cancer is an inherited mutation in the BRCA1 or BRCA2 genes which also may cause the disease to develop at a significantly earlier age than is usual. The OlympiA trial has allowed us to go beyond using genetic testing to identify patients who are at risk of this disease and explore the potential of LYNPARZA to prevent disease recurrence for these patients. We look forward to analyzing and presenting the full results of the trial at a forthcoming medical meeting."

    José Baselga, Executive Vice President, Oncology R&D, said: "Breast cancer remains one of the most common cancers globally and despite advances in treatment, many patients with high-risk disease will unfortunately develop a recurrence. We look forward to reviewing the results."

    Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck, said: "Analysis of the OlympiA trial, based upon the IDMC recommendation, could represent a potential step forward for patients with early-stage, high-risk primary breast cancer with a germline BRCA mutation."

    In its communication, the IDMC did not raise any new safety concerns. The trial will continue to assess the key secondary endpoints of overall survival and distant disease-free survival.

    In the US, LYNPARZA is approved for the treatment of adult patients with deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA. LYNPARZA is not currently approved for the adjuvant treatment of gBRCAm high-risk HER2-negative early breast cancer.

    IMPORTANT SAFETY INFORMATION

    CONTRAINDICATIONS

    There are no contraindications for LYNPARZA.

    WARNINGS AND PRECAUTIONS

    Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some also had a history of more than one primary malignancy or of bone marrow dysplasia.

    Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

    If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

    Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

    Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for females of reproductive potential prior to initiating treatment.

    Females

    Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

    Males

    Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

    Venous Thromboembolic Events: Including pulmonary embolism, occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. Patients receiving LYNPARZA and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.

    ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer

    Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), UTI (13%), thrombocytopenia (11%), and stomatitis (11%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

    ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab

    Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab compared to a ≥5% frequency for placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%) and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%) and headache (14%).

    In addition, venous thromboembolic events occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%) and decrease in platelets (35%).

    ADVERSE REACTIONS—Maintenance Recurrent Ovarian Cancer

    Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

    Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%) and dyspepsia (20%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

    ADVERSE REACTIONS—Advanced gBRCAm Ovarian Cancer

    Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular volume elevation (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

    ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer

    Most common adverse reactions (Grades 1-4) in ≥20% of patients in OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

    ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma

    Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).

    ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

    Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of LYNPARZA for PROfound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%).

    Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).

    DRUG INTERACTIONS

    Anticancer Agents: Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

    CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

    CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using LYNPARZA.

    USE IN SPECIFIC POPULATIONS

    Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

    Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

    Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).

    Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

    INDICATIONS

    LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

    First-Line Maintenance BRCAm Advanced Ovarian Cancer

    For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    First-Line Maintenance HRD Positive Advanced Ovarian Cancer in Combination with Bevacizumab

    In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

    • a deleterious or suspected deleterious BRCA mutation, and/or
    • genomic instability

    Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    Maintenance Recurrent Ovarian Cancer

    For the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy.

    Advanced gBRCAm Ovarian Cancer

    For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    gBRCAm, HER2-Negative Metastatic Breast Cancer

    For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer

    For the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

    For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    Please click here for complete Prescribing Information, including Patient Information (Medication Guide).

    Early breast cancer

    Breast cancer is the most common cancer among women worldwide and an estimated 90% of all breast cancer is diagnosed at an early stage.12,13 Breast cancer is one of the most biologically diverse tumor types with various factors fuelling its development and progression.14 The discovery of biomarkers in the development of breast cancer has greatly impacted scientific understanding of the disease.15

    BRCA1 and BRCA2

    BRCA1 and BRCA2 (breast cancer susceptibility genes 1/2) are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells. When either of these genes is mutated or altered such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer and confer sensitivity to PARP inhibitors including LYNPARZA.16-19

    OlympiA

    OlympiA is a Phase III, double-blind, parallel group, placebo-controlled, multicenter trial testing the efficacy and safety of LYNPARZA tablets versus placebo as adjuvant treatment in patients with gBRCAm high-risk HER2-negative early breast cancer, who have completed definitive local treatment and neoadjuvant or adjuvant chemotherapy. The primary endpoint of the trial is iDFS defined as time from randomization to date of first treatment failure that is loco-regional or distant recurrence or new cancer or death from any cause.1

    NRG Oncology

    NRG Oncology is a network group funded by the NCI, a part of the National Institutes of Health. All of the NCI funded network groups participated in the trial. The NCI and AstraZeneca are collaborating under a Cooperative Research and Development Agreement.

    NRG Oncology brings together the National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group, with the mission to improve the lives of cancer patients by conducting practice-changing multi-institutional clinical and translational research.

    BIG

    The Breast International Group (BIG) is an international not-for-profit organization for academic breast cancer research groups from around the world, based in Brussels, Belgium.

    Founded by leading European opinions leaders in 1999, the organization aims to address fragmentation in European breast cancer research and now represents a network of over 55 like-minded research groups affiliated with specialized hospitals, research centers and leading experts across approximately 70 countries on six continents.

    BIG's research is supported in part by its philanthropy unit, known as BIG against breast cancer, which is used to interact with the general public and donors, and to raise funds for BIG's purely academic breast cancer trials and research programs.

    FSTRF

    Frontier Science & Technology Research Foundation (FSTRF) is a non-profit, research organization which supports research networks, pharmaceutical companies and investigators to conduct scientifically meaningful high-quality clinical trials. The OlympiA trial involved research staff in the US and in the Affiliate office in Scotland.

    FSTRF works with scientists and technicians in more than 800 laboratories, universities and medical centers around the world to provide a comprehensive range of research services throughout the clinical trial process including design, analysis and reporting.

    Through its work, FSTRF aims to advance the application of statistical science and practice and data management techniques in science, healthcare and education.

    LYNPARZA

    LYNPARZA (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumors harboring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with LYNPARZA leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. LYNPARZA is being tested in a range of PARP-dependent tumor types with defects and dependencies in the DDR pathway.

    LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has been used to treat over 40,000 patients worldwide. LYNPARZA has the broadest and most advanced clinical trial development program of any PARP inhibitor, and AstraZeneca and Merck are working together to understand how it may affect multiple PARP-dependent tumors as a monotherapy and in combination across multiple cancer types. LYNPARZA is the foundation of AstraZeneca's industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

    The AstraZeneca and Merck strategic oncology collaboration

    In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize LYNPARZA, the world's first PARP inhibitor, and selumetinib, a mitogen-activated protein kinase (MEK) inhibitor, for multiple cancer types. Working together, the companies will develop LYNPARZA and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop LYNPARZA and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

    AstraZeneca in breast cancer

    Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

    AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumor environment. AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines fulvestrant and goserelin and the next-generation selective estrogen receptor degrader (SERD) and potential new medicine camizestrant (AZD9833). PARP inhibitor, LYNPARZA is a targeted treatment option for patients with germline BRCA-mutated HER2-negative metastatic breast cancer. AstraZeneca with Merck continue to research LYNPARZA in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease state.

    Building on the first approval of fam-trastuzumab deruxtecan-nxki, a HER2-directed antibody-drug conjugate (ADC), in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings. To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy durvalumab in combination with other oncology medicines, including LYNPARZA and fam-trastuzumab deruxtecan-nxki, assessing the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

    AstraZeneca in oncology

    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of six scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

    AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit astrazeneca-us.com and follow the Company on Twitter @AstraZenecaUS.

    References

    1. ClinicalTrials.gov. Olaparib as Adjuvant Treatment in Patients with Germline BRCA Mutated High Risk HER2 Negative Primary Breast Cancer (OlympiA). Available at https://clinicaltrials.gov/ct2/show/NCT02032823. Accessed February 2021.

    2. GLOBOCAN. Breast Cancer. Available at https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf. Accessed February 2021.

    3. Gomes M.C, et al. Prevalence of BRCA1 and BRCA2 Mutations in Breast Cancer Patients from Brazil. Breast Cancer Res Treat. 2007 Jul;103(3):349-53.

    4. Hernandez J.E, et al. Prevalence of BRCA1 and BRCA2 Mutations in Unselected Breast Cancer Patients from Medellín, Colombia. Hered Cancer in Clin Pract. 2014;12:11.

    5. Bu R, et al. Identification of Novel BRCA Founder Mutations in Middle Eastern Breast Cancer Patients Using Capture and Sanger Sequencing Analysis. Int J Cancer. 2016;139:1091-1097.

    6. Abugattas J, et al. Prevalence of BRCA1 and BRCA2 Mutations in Unselected Breast Cancer Patients From Peru. Clin Genet. 2015 October;88(4):371-375.

    7. Kast K, et al. Prevalence of BRCA1/2 Germline Mutations in 21,401 Families with Breast and Ovarian Cancer. J Med Genet. 2016;53:465-471.

    8. Winter C, et al. Targeted Sequencing of BRCA1 and BRCA2 Across a Large Unselected Breast Cancer Cohort Suggests That One-third of Mutations Are Somatic. Ann Oncol. 2016;27:1532-1538.

    9. Hoberg-Vetti H, et al. BRCA1/2 Testing in Newly Diagnosed Breast and Ovarian Cancer Patients Without Prior Genetic Counselling: the DNA-BONus Study. Eur J HumGenetic. 2016;24:881-888.

    10. Kim R, et al. Incidence of germline BRCA1- and BRCA2-mutated Breast Cancer in the US. SABCS. 2017;poster P5-08-28.

    11. National Breast Cancer Foundation. BRCA: The Breast Cancer Gene. Available at https://www.nationalbreastcancer.org/what-is-brca. Accessed February 2021.

    12. SEER. SEER Cancer Statistics Review, 1975-2013. Available at http://seer.cancer.gov/csr/1975_2013/. Accessed February 2021.

    13. Bertozzi S, et al. Biomarkers in Breast Cancer. Intechopen. 2018.

    14. Yersal O, and Barutca S. Biological Subtypes of Breast Cancer: Prognostic and therapeutic implications. World J Clin Oncol. 2014;5(3):412-424.

    15. Rivenbark A, et al. Molecular and Cellular Heterogeneity in Breast Cancer: Challenges for Personalized Medicine. Am J Pathol. 2013;183(4):1113-1124.

    16. Roy R, et al. BRCA1 and BRCA2: Different Roles in a Common Pathway of Genome Protection. Nat Rev Cancer. 12(1):68-78.

    17. Wu J, et al. The Role of BRCA1 in DNA Damage Response. Protein Cell. 2010;1(2):117-123.

    18. Gorodetska I, et al. BRCA Genes: The Role in Genome Stability, Cancer Stemness and Therapy Resistance. J Cancer. 2019;10(9):2109-2127.

    19. Li H, et al. PARP Inhibitor Resistance: The Underlying Mechanisms and Clinical Implications. Mol Cancer. 2020;19:107.

    US-50210 | 2/21

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  8. MOUNTAIN VIEW, Calif., Feb. 16, 2021 /PRNewswire/ -- AliveCor, the leader in AI-based personal ECG technology and provider of enterprise cardiology solutions, today announced a new collaboration with AstraZeneca (NASDAQ:AZN), a global science-led biopharmaceutical company, to research new disease management solutions in cardiovascular, renal, and metabolism (CVRM) therapeutic areas. The collaboration will translate AliveCor's potassium detection technology and science, which enables potassium measurement outside of blood draws, into real-world disease management applications and solutions.

    The cross-industry collaboration expands the research and development of AliveCor's Kardia-K AI platform, which received "Breakthrough Device Designation" status from the FDA to screen for elevated levels of blood potassium. Kardia-K is being built using AliveCor's proprietary deep neural network, and analyzes electrocardiograms (ECGs) to measure a patient's potassium levels without requiring any blood from the patient. AliveCor's neural network was trained in collaboration with Mayo Clinic using more than 1.5 million ECGs and was validated on approximately 62,000 ECGs. The research was published in JAMA Cardiology in April 2019.

    "By collaborating across industries, AliveCor is leading the way in the development of non- invasive, more accessible medical solutions for patients and health organizations worldwide," said Aman Bhatti, Head of BioPharma Relationships at AliveCor. "Our collaboration with AstraZeneca exemplifies how pharmaceutical and digital health companies can work together to drive the future of medicine."

    For the nearly 30 million U.S. adults with chronic kidney disease, the one-day likelihood of a fatality is 3 to 13 times higher if potassium is elevated. The current standard practice for measuring potassium levels is a blood test, which is invasive, inconvenient, and poses safety risks for patients during the pandemic. A remote, easy-to-use potassium test could help track for increased potassium levels in those patients, as well as the 500,000 Americans with end stage kidney disease and on dialysis, where high potassium may contribute to up to 40% of fatalities.

    The collaboration seeks to improve the delivery of life-changing medicines that are fueling growth in the industry and providing value to patients and society. Its initiative accelerates AliveCor's work with key players in the BioPharma industry and demonstrates diverse interest in AliveCor's technology, from clinical research organizations to health systems to pharmaceutical companies' digital therapeutic programs.

    About AliveCor

    AliveCor, Inc. is transforming cardiological care using deep learning. The FDA-cleared KardiaMobile device is the most clinically validated personal ECG solution in the world. KardiaMobile provides instant detection of Atrial Fibrillation, Bradycardia, Tachycardia, Sinus Rhythm with Supraventricular Ectopy, Sinus Rhythm with Premature Ventricular Contractions, Sinus Rhythm with Wide QRS and Normal Heart Rhythm in an ECG. Kardia is the first AI-enabled platform to aid patients and clinicians in the early detection of atrial fibrillation, the most common arrhythmia and one associated with a highly-elevated risk of stroke. AliveCor's enterprise platform allows third party providers to manage their patients' and customers' heart conditions simply and profitably using state-of-the-art tools that provide easy front-end and back-end integration to AliveCor technologies. AliveCor protects its customers with stringent data security and compliance practices, achieving HIPAA compliance and SOC2 Type 1 and Type 2 attestations. AliveCor is a privately-held company headquartered in Mountain View, Calif. "Consumer" or "Personal" ECGs are ECG devices available for direct sale to consumers. For more information, visit alivecor.com.

     

    Cision View original content to download multimedia:http://www.prnewswire.com/news-releases/alivecor-announces-collaboration-with-astrazeneca-to-develop-non-invasive-potassium-monitoring-solutions-301228042.html

    SOURCE AliveCor

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  9. Following the European Medicines Agency (EMA) approval, millions of AstraZeneca vaccines began shipping on 5 February as part of the initial 17m doses that are due to be delivered over the next weeks, with more planned in March.

    AstraZeneca and IDT Biologika are exploring options to accelerate output of finished COVID-19 Vaccine AstraZeneca in the second quarter of 2021 in order to help support Europe's immediate vaccination needs during the pandemic.

    AstraZeneca and IDT Biologika also intend to strengthen Europe's vaccine manufacturing capability with a joint investment to build large additional drug substance capacity for the future. Details of the agreement are to be finalised. Both companies plan to invest in capacity expansion at IDT…

    Following the European Medicines Agency (EMA) approval, millions of AstraZeneca vaccines began shipping on 5 February as part of the initial 17m doses that are due to be delivered over the next weeks, with more planned in March.

    AstraZeneca and IDT Biologika are exploring options to accelerate output of finished COVID-19 Vaccine AstraZeneca in the second quarter of 2021 in order to help support Europe's immediate vaccination needs during the pandemic.

    AstraZeneca and IDT Biologika also intend to strengthen Europe's vaccine manufacturing capability with a joint investment to build large additional drug substance capacity for the future. Details of the agreement are to be finalised. Both companies plan to invest in capacity expansion at IDT Biologika's production site in Dessau, Germany to build up to five 2,000-litre bioreactors capable of making tens of millions of doses per month of AstraZeneca's COVID-19 vaccine. The new assets are estimated to be operational by the end of 2022.

    The investment could also allow for the manufacture of other vaccines sharing a similar manufacturing process, greatly expanding Europe's domestic vaccine production capability. IDT Biologika will have among the largest vaccine manufacturing capacities of its kind in Europe and play an important part in ensuring Europe's future vaccine supply independence.

    Jürgen Betzing, Chief Executive Officer, IDT Biologika, said: “We are proud that AstraZeneca has chosen us as a strategic partner for the manufacturing of their vaccines. The agreement underscores our expertise in the production of demanding vector-based vaccines and our ability to provide a one-stop solution, from creating drug substance, through to “fill and finish” and secondary packaging. I would like to thank the German Ministry of Health for their support in making this cooperation happen, which marks a great day for Germany and Europe.”

    Pascal Soriot, Chief Executive Officer, said: “This agreement will greatly help Europe build an independent vaccine manufacturing capability that will allow it to meet the challenges of the current pandemic and create strategic supply capacity for the future. We are delighted to be investing with our partner IDT Biologika in the future health, security and wellbeing of millions of citizens across Europe. I would like to thank the German Federal Government and the European Commission for their support in our efforts.”

    On 29 January, COVID-19 Vaccine AstraZeneca was granted a conditional marketing authorisation (CMA) in the European Union (EU) for active immunisation to prevent COVID-19 caused by SARS-CoV-2, in individuals 18 years of age and older. The vaccine's flexible dosing regimen allows an interval of up to three months between first and second dose, allowing public health authorities to rapidly deploy the vaccine to large numbers of people.

    COVID-19 Vaccine AstraZeneca, formerly AZD1222
    COVID-19 Vaccine AstraZeneca was co-invented by the University of Oxford and its spin-out company, Vaccitech. It uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body.

    In addition to the programme led by Oxford University, AstraZeneca is conducting a large trial in the US and globally. In total, Oxford University and AstraZeneca expect to enrol up to 60,000 participants globally.

    COVID-19 Vaccine AstraZeneca has already been granted a conditional marketing authorisation or emergency use in over 50 countries, spanning four continents including in the EU, a number of Latin American countries, India, Morocco and the UK.

    AstraZeneca
    AstraZeneca (NASDAQ:AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com 

    — WebWireID270231 —


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  10. The KESTREL Phase III trial for AstraZeneca's Imfinzi (durvalumab) did not meet the primary endpoint of improving overall survival (OS) versus the EXTREME treatment regimen (chemotherapy plus cetuximab), a standard of care, in the 1st-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose tumours expressed high levels of PD-L1. Also, the combination of Imfinzi plus tremelimumab did not indicate an OS benefit in 'all-comer' patients, a secondary endpoint.

    Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “Metastatic head and neck cancer is a complex and challenging disease with a poor prognosis. While we are disappointed by these results, insights from the KESTREL…

    The KESTREL Phase III trial for AstraZeneca's Imfinzi (durvalumab) did not meet the primary endpoint of improving overall survival (OS) versus the EXTREME treatment regimen (chemotherapy plus cetuximab), a standard of care, in the 1st-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose tumours expressed high levels of PD-L1. Also, the combination of Imfinzi plus tremelimumab did not indicate an OS benefit in 'all-comer' patients, a secondary endpoint.

    Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “Metastatic head and neck cancer is a complex and challenging disease with a poor prognosis. While we are disappointed by these results, insights from the KESTREL Phase III trial will advance our understanding and application of immunotherapy across our clinical development programme. We will continue to build on the established benefits of Imfinzi in early lung cancer and small cell lung cancer, to bring immunotherapy treatment options to all patients who may benefit.”

    The safety and tolerability profiles for Imfinzi as a monotherapy and in combination with tremelimumab were consistent with previous trials. The data will be shared in due course.

    HNSCC
    Nearly 750,000 patients were diagnosed with head and neck cancer around the world in 2020.1 Two thirds of these patients are diagnosed in advanced stages, and more than half of those treated eventually relapse.2,3 Median survival for a patient with an uncurable or metastatic relapse remains under one year.More than 90% of all head and neck cancers start in the squamous cells that line the mouth, nose and throat and are called head and neck squamous cell carcinomas.4

    KESTREL
    The KESTREL Phase III trial was a randomised, open-label, multi-centre, global trial in the 1st-line treatment of recurrent or metastatic HNSCC. The trial tested Imfinzi or Imfinzi plus a second immunotherapy, tremelimumab, versus the EXTREME treatment regimen (cetuximab with cisplatin or carboplatin plus 5-fluorouracil), a standard of care treatment. High PD-L1 was defined as either 50% or more tumour cells or 25% or more tumour-infiltrating immune cells expressing PD-L1.

    The trial was conducted in more than 200 centres across 23 countries, including centres in the US, Europe, South America and Asia. The primary endpoint was OS in patients with high PD-L1 expression in the Imfinzi monotherapy arm. OS in 'all-comer' patients treated with the combination of Imfinzi plus tremelimumab was being tested as a key secondary endpoint.

    Imfinzi
    Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.

    Imfinzi is approved in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) after chemoradiation therapy in the EU, US, Japan, China and many other countries, based on the PACIFIC Phase III trial. Additionally, it is approved in the EU, US, Japan and many other countries for the treatment of extensive-stage small cell lung cancer (SCLC) based on the CASPIAN Phase III trial. Imfinzi&#8239;is also approved for previously treated patients with advanced bladder cancer in the US and several other countries.

    As part of a broad development programme, Imfinzi is being tested as a monotherapy and in combination with other anti-cancer treatments for patients with NSCLC, SCLC, bladder cancer, hepatocellular carcinoma (HCC), biliary tract cancer, oesophageal cancer, gastric and gastroesophageal cancer, cervical cancer, ovarian cancer, endometrial cancer and other solid tumours.

    Tremelimumab
    Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation, priming the immune response to cancer and fostering cancer cell death. Tremelimumab is being tested in a clinical trial programme in combination with Imfinzi in NSCLC, SCLC, bladder cancer and HCC.

    AstraZeneca in immunotherapy
    Immunotherapy is a therapeutic approach designed to stimulate the body's immune system to attack tumours. The Company's Immuno-Oncology (IO) portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

    The Company is pursuing a comprehensive clinical trial programme that includes Imfinzi as a monotherapy and in combination with tremelimumab in multiple tumour types, stages of disease, and lines of therapy, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, and small, targeted molecules from across AstraZeneca's oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

    In head and neck cancer, the Company is also testing monalizumab, a first-in-class humanised anti-NKG2A antibody, in combination with cetuximab in the INTERLINK-1 Phase III trial in patients with recurrent or metastatic HNSCC previously treated with IO and chemotherapy. AstraZeneca obtained full oncology rights to monalizumab from Innate Pharma in October 2018 through a co-development and commercialisation agreement initiated in 2015.

    AstraZeneca in oncology
    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of six scientific platforms - Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies - and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

    AstraZeneca
    AstraZeneca (NASDAQ:AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com 

    1. World Health Organization. World GLOBOCAN 2020. Available at https://gco.iarc.fr/today/home. Accessed January 2021.

    2. Heriou A, et al. Multiple Cancers of the Head and Neck. MAEDICA – a Journal of Clinical Medicine 2013;8(1):80-852.

    3. Rothschild U, et al. Immunotherapy in head and neck cancer – scientific rationale, current treatment options and future directions. Swiss Med Wkly. 2018;148:w14625.

    4. Palka K, et al. Update in Molecular Diagnostic Tests in Head and Neck Cancer. Semin Oncol. 2008 June;35(3):198-210.

     

    — WebWireID270057 —


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  11. AstraZeneca has agreed, subject to certain limited exceptions, to divest its 26.7% ownership in Viela Bio, Inc. (Viela), as part of the proposed acquisition of Viela by Horizon Therapeutics plc (Nasdaq: HZNP).

    AstraZeneca is anticipating to receive cash proceeds and profit of c.$760-$780m upon closing for the sale of the holding, which will be recorded in Reported and Core Other Operating Income and Expense in the Company's financial statements. The divestment is expected to complete by the end of the first quarter of 2021.

    The divestment does not impact the Company's financial guidance for 2020. Guidance for 2021 is anticipated to be issued with full-year 2020 results on 11 February 2021.

    Viela
    Viela (NASDAQ:VIE), headquartered in Gaithersburg…

    AstraZeneca has agreed, subject to certain limited exceptions, to divest its 26.7% ownership in Viela Bio, Inc. (Viela), as part of the proposed acquisition of Viela by Horizon Therapeutics plc (Nasdaq: HZNP).

    AstraZeneca is anticipating to receive cash proceeds and profit of c.$760-$780m upon closing for the sale of the holding, which will be recorded in Reported and Core Other Operating Income and Expense in the Company's financial statements. The divestment is expected to complete by the end of the first quarter of 2021.

    The divestment does not impact the Company's financial guidance for 2020. Guidance for 2021 is anticipated to be issued with full-year 2020 results on 11 February 2021.

    Viela
    Viela (NASDAQ:VIE), headquartered in Gaithersburg, Maryland, is a biotechnology company dedicated to the discovery, development and commercialisation of novel treatments for autoimmune and severe inflammatory diseases. Viela was founded in 2018 as a spinout from AstraZeneca, with clinical and pre-clinical projects from AstraZeneca's inflammation and autoimmunity pipeline.

    AstraZeneca
    AstraZeneca (NASDAQ:AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com 

    — WebWireID269806 —


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  12. Data at WCLC showed patients in the practice-changing ADAURA Phase III trial maintained their quality of life based on patient-reported outcomes

    New data reinforce the ability of TAGRISSO to penetrate the blood-brain barrier in patients with central nervous system metastases

    Results from an exploratory analysis of the positive ADAURA Phase III trial showed AstraZeneca's TAGRISSO® (osimertinib) extended disease-free survival (DFS) in patients with epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) regardless of prior adjuvant chemotherapy treatment or stage of disease, building on the unprecedented primary DFS results for TAGRISSO in the adjuvant setting announced last year. Results from ADAURA were presented…

    Data at WCLC showed patients in the practice-changing ADAURA Phase III trial maintained their quality of life based on patient-reported outcomes

    New data reinforce the ability of TAGRISSO to penetrate the blood-brain barrier in patients with central nervous system metastases

    Results from an exploratory analysis of the positive ADAURA Phase III trial showed AstraZeneca's TAGRISSO® (osimertinib) extended disease-free survival (DFS) in patients with epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) regardless of prior adjuvant chemotherapy treatment or stage of disease, building on the unprecedented primary DFS results for TAGRISSO in the adjuvant setting announced last year. Results from ADAURA were presented during the 2020 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer (IASLC) and featured in the Press Program.

    In this exploratory analysis of the overall trial population, adjuvant TAGRISSO reduced the risk of disease recurrence or death by 84% in patients who had been treated with prior adjuvant chemotherapy (based on a hazard ratio [HR] of 0.16, 95% confidence interval [CI] 0.10-0.26) and by 77% in patients who had not (HR 0.23; 95% CI 0.13-0.40). DFS benefits were similar across each stage of disease.

    In addition, a separate exploratory post-hoc analysis of patient-reported outcomes in ADAURA showed that patients treated with TAGRISSO maintained their quality of life, with no clinically meaningful differences in physical or mental health measures in the TAGRISSO and placebo arms.

    Yi-Long Wu, MD, FACS, Tenured Professor of the Lung Cancer Institute at Guangdong Provincial People's Hospital and Academy of Medical Sciences in Guangzhou, China, and a principal investigator in the ADAURA Phase III trial, said: "The overwhelming disease-free survival benefit in patients in ADAURA already supported the role of TAGRISSO as a pioneering therapy in the adjuvant treatment of EGFR-mutated non-small cell lung cancer. This latest analysis shows the magnitude of that benefit is consistent with or without prior adjuvant chemotherapy, and regardless of disease stage, reinforcing the critical role of TAGRISSO in this setting."

    Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "These new data show that TAGRISSO provides transformative benefits independent of prior chemotherapy treatment, preventing lung cancer from returning while allowing patients to sustain their quality of life. Following the recent approval of TAGRISSO in the US in the adjuvant setting, we continue to work urgently with regulatory authorities globally to bring this new standard of care to patients with early-stage lung cancer."

    Exploratory DFS analysis with and without chemotherapy (CTx)

    OSI: TAGRISSO; PBO: placebo

     

     

       

    Stage IB

       

    Stage II

       

    Stage IIIA

       

    Stage IB-IIIA

     
     

     

       

    OSI

       

    PBO

       

    OSI

       

    PBO

       

    OSI

       

    PBO

       

    OSI

       

    PBO

     
     

    With CTx

       

    n=28

       

    n=30

       

    n=81

       

    n=85

       

    n=94

       

    n=92

       

    n=203

       

    n=207

     
     

    DFS events

    patients (%)

       

    4 (14)

       

    11 (37)

       

    6 (7)

       

    36 (42)

       

    12 (13)

       

    56 (61)

       

    22 (11)

       

    103 (50)

     
     

    DFS HR

    (95% CI)

       

    NC

    (NC, NC)

       

    0.15

    (0.06, 0.32)

       

    0.13

    (0.06, 0.23)

       

    0.16

    (0.10, 0.26)

     
     

     

     
     

    Without CTx

       

    n=78

       

    n=76

       

    n=37

       

    n=33

       

    n=21

       

    n=27

       

    n=136

       

    n=136

     
     

    DFS events

    patients (%)

       

    7 (9)

       

    18 (24)

       

    5 (14)

       

    16 (48)

       

    3 (14)

       

    22 (81)

       

    15 (11)

       

    56 (41)

     
     

    DFS HR

    (95% CI)

       

    0.38

    (0.15, 0.88)

       

    0.20

    (0.07, 0.52)

       

    0.10

    (0.02, 0.29)

       

    0.23

    (0.13, 0.40)

     

    In the ADAURA Phase III trial, chemotherapy use was balanced across the two treatment arms, with 60% of patients receiving prior adjuvant chemotherapy. In line with uptake observed in prior studies and clinical practice, younger patients (<70 years) and those with more advanced disease were more likely to have prior adjuvant chemotherapy.1,2 Treatment with chemotherapy did not vary according to a patient's performance status.

    The safety and tolerability of TAGRISSO was consistent with previous trials in the metastatic EGFRm NSCLC setting. Adverse events at Grade 3 or higher from all causes occurred in 20% of patients in the TAGRISSO arm versus 13% in the placebo arm as assessed by investigators.

    Primary results of ADAURA, which were published in The New England Journal of Medicine in September 2020, showed adjuvant treatment with TAGRISSO reduced the risk of disease recurrence or death by 83% (HR 0.17; 95% CI 0.12-0.23; p<0.0001) among patients with Stage II and IIIA EGFRm NSCLC and, as shown in a prespecified exploratory analysis, demonstrated a clinically meaningful improvement in central nervous system (CNS) DFS compared to placebo.

    Additional TAGRISSO highlights at WCLC

    In addition to these ADAURA analyses, several other presentations and posters for TAGRISSO across lung cancer settings and in novel combinations were featured during WCLC, including:

    • Results from the ODIN BM Phase I trial, which support the efficacy and uniform brain penetration of TAGRISSO in patients with CNS metastases as reported in previous clinical trials. This trial used a micro dose of intravenous TAGRISSO detectable on PET scans, which showed rapid, high and widespread brain exposure of TAGRISSO in both the healthy tissue and CNS metastases of four patients with EGFRm NSCLC. Results also showed that TAGRISSO markedly reduced CNS metastases in patients following three to four weeks of daily oral treatment
    • Final results from two expansion cohorts of the TATTON Phase Ib trial, which support the potential of TAGRISSO plus savolitinib, a selective inhibitor of mesenchymal epithelial transition (c-MET) factor receptor tyrosine kinase, to overcome MET-based resistance in patients with NSCLC whose disease has progressed on prior EGFR-tyrosine kinase inhibitor (TKI) treatment. The safety profile of TAGRISSO plus savolitinib was consistent with previous reports. The combination is currently being tested in the ongoing SAVANNAH and ORCHARD Phase II trials
    • The design of a Phase I study exploring TAGRISSO in combination with patritumab deruxtecan (U3-1402) in patients with locally advanced or metastatic EGFRm NSCLC who progressed during or after prior treatment with TAGRISSO alone3
    • The design of the NeoADAURA Phase III trial testing the benefit of treating patients with resectable Stage II-IIIB NSCLC with neoadjuvant TAGRISSO as monotherapy or in combination with a choice of standard platinum-based chemotherapies versus chemotherapy with placebo. Patient recruitment for this trial is ongoing

    TAGRISSO was recently approved in the US for the adjuvant treatment of adult patients with early-stage EGFRm NSCLC after tumor resection with curative intent based on the ADAURA Phase III trial. This indication is under priority review in China and regulatory review in the EU; additional global submission discussions are ongoing. TAGRISSO is also approved for the 1st-line treatment of patients with metastatic EGFRm NSCLC and for the treatment of metastatic EGFR T790M mutation-positive NSCLC in the US, Japan, China, the EU and many other countries around the world.

    TAGRISSO Important Safety Information

    • There are no contraindications for TAGRISSO
    • Interstitial lung disease (ILD)/pneumonitis occurred in 3.7% of the 1479 TAGRISSO-treated patients; 0.3% of cases were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed
    • Heart rate-corrected QT (QTc) interval prolongation occurred in TAGRISSO-treated patients. Of the 1479 TAGRISSO-treated patients in clinical trials, 0.8% were found to have a QTc >500 msec, and 3.1% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
    • Cardiomyopathy occurred in 3% of the 1479 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 3.2% of 1233 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. Conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO
    • Keratitis was reported in 0.7% of 1479 patients treated with TAGRISSO in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist
    • Postmarketing cases consistent with Stevens-Johnson syndrome (SJS) and erythema multiforme major (EMM) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if SJS or EMM is suspected and permanently discontinue if confirmed
    • Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity
    • Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose
    • Most common (≥20%) adverse reactions, including laboratory abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough

    INDICATIONS

    • TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
    • TAGRISSO is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
    • TAGRISSO is indicated for the treatment of adult patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy

    For additional information, please see the complete Prescribing Information, including Patient Information.

    Lung cancer

    Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.4 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.5 The majority of all NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.6-8

    For those with resectable tumors, the majority of patients eventually develop recurrence despite complete tumor resection and adjuvant chemotherapy.9 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.10,11

    Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.12-14 These patients are particularly sensitive to treatment with EGFR-tyrosine kinase inhibitors (TKIs) which block the cell-signaling pathways that drive the growth of tumor cells.15

    About ADAURA

    ADAURA is a randomized, double-blinded, global, placebo-controlled Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, IIIA EGFRm NSCLC following complete tumor resection and adjuvant chemotherapy as indicated. Patients were treated with TAGRISSO 80 mg once-daily oral tablets or placebo for three years or until disease recurrence.

    The trial enrolled in more than 200 centers across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was DFS in Stage II and IIIA patients and a key secondary endpoint was DFS in Stage IB, II and IIIA patients. The data readout was originally anticipated in 2022. The trial will continue to assess overall survival.

    About TAGRISSO

    TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with clinical activity against central nervous system metastases. TAGRISSO 40 mg and 80 mg once-daily oral tablets have received approval in the US, Japan, China, the EU and many countries around the world for 1st-line EGFRm metastatic NSCLC and EGFR T790M mutation-positive metastatic NSCLC.

    AstraZeneca in lung cancer

    AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.

    AstraZeneca aims to address the unmet needs of patients with EGFRm tumors as a genetic driver of disease with the approved medicines gefitinib and TAGRISSO, and its ongoing LAURA, NeoADAURA, and FLAURA2 Phase III trials.

    AstraZeneca is committed to addressing tumor mechanisms of resistance through the ongoing Phase II trials SAVANNAH and ORCHARD which test TAGRISSO in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines.

    AstraZeneca in oncology

    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of six scientific platforms - Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies - and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

    AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit https://www.astrazeneca-us.com/ and follow us on Twitter @AstraZenecaUS.

    References

    1. Chouaid C, et al. Adjuvant treatment patterns and outcomes in patients with stage IB-IIIA non-small cell lung cancer in France, Germany, and the United Kingdom based on the LuCaBIS burden of illness study. Lung Cancer. 2018;124:310-316.
    2. Buck PO, et al. Treatment Patterns and Health Resource Utilization Among Patients Diagnosed With Early Stage Resected Non-Small Cell Lung Cancer at US Community Oncology Practices. Clin Lung Cancer. 2015;16:486-495.
    3. Trial collaboration with Daiichi Sankyo which maintains exclusive rights to patritumab deruxtecan.
    4. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. https://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed January 2021.
    5. LUNGevity Foundation. Types of Lung Cancer. https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed January 2021.
    6. Cagle P, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med. 2013;137:1191-1198.
    7. Le Chevalier T, et al. Adjuvant Chemotherapy for Resectable Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol. 2010;21:196-198.
    8. Datta D, et al. Preoperative Evaluation of Patients Undergoing Lung Resection Surgery. Chest. 2003;123:2096-2103.
    9. Pignon JP, et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26:3552-3559.
    10. Sethi S, et al. Incidental Nodule Management – Should There Be a Formal Process? J Thorac Onc. 2016:8;S494-S497.
    11. LUNGevity Foundation. Screening and Early Detection. https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection. Accessed January 2021.
    12. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013;6:2800-2812.
    13. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011;2:2121-2127.
    14. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013;66:79-89.
    15. Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4(9):1046-1061.

    US-49454 Last Updated 1/21

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  13. AstraZeneca's Symbicort Turbuhaler (budesonide/formoterol 160/4.5mcg) has been approved in China as an anti-inflammatory reliever to be taken as-needed in response to symptoms to achieve asthma control in patients with mild asthma aged 12 years and older.

    The approval by the National Medical Products Administration (NMPA) was based on positive results from the SYGMA 1 and SYGMA 2 Phase III trials, published in The New England Journal of Medicine, which evaluated the efficacy of Symbicort Turbuhaler taken as-needed as an anti-inflammatory reliever compared with standard of care (SoC) therapies in mild asthma. SoC included short-acting beta2-agonist (SABA) taken as-needed or regular maintenance controller therapy (twice-daily budesonide, an…

    AstraZeneca's Symbicort Turbuhaler (budesonide/formoterol 160/4.5mcg) has been approved in China as an anti-inflammatory reliever to be taken as-needed in response to symptoms to achieve asthma control in patients with mild asthma aged 12 years and older.

    The approval by the National Medical Products Administration (NMPA) was based on positive results from the SYGMA 1 and SYGMA 2 Phase III trials, published in The New England Journal of Medicine, which evaluated the efficacy of Symbicort Turbuhaler taken as-needed as an anti-inflammatory reliever compared with standard of care (SoC) therapies in mild asthma. SoC included short-acting beta2-agonist (SABA) taken as-needed or regular maintenance controller therapy (twice-daily budesonide, an inhaled corticosteroid (ICS)) plus SABA taken as-needed.1,2

    Symbicort Turbuhaler is the first dual-combination therapy approved in China as an anti-inflammatory reliever to treat mild asthma. It is already approved in China for patients with moderate to severe asthma as an anti-inflammatory reliever plus maintenance therapy, and as maintenance therapy only.

    Asthma is a chronic, variable, inflammatory disease which can cause asthma attacks and symptoms including breathlessness and wheezing.3 Asthma affects an estimated 46 million adults in China, including an estimated 34 million with mild asthma.4,5

    Professor Xin Zhou, Vice President of the 10th China Thoracic Society and the respiratory discipline leader, Shanghai General Hospital, China, said: “This approval aligns to the latest National Asthma Guidelines from the Chinese Thoracic Society as well as international recommendations from the Global Initiative for Asthma which recommend a low dose corticosteroid-formoterol combination therapy taken as-needed as the preferred reliever therapy in mild asthma. Now doctors in China can prescribe Symbicort Turbuhaler to reduce the impact of asthma on their patients with mild, moderate and severe disease.”

    Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “Everyone with asthma is at risk of an attack, regardless of their age, disease severity, adherence to treatment or level of control. This approval means people with mild asthma in China can now take Symbicort Turbuhaler as an anti-inflammatory reliever to treat their symptoms and also to reduce the likelihood of an attack by treating the underlying inflammation in their airways. This approval builds on Symbicort's established role in treating moderate to severe disease.”

    The safety and tolerability data for Symbicort Turbuhaler in the SYGMA trials were consistent with the known profile of the medicine.1,2

    Symbicort is a combination of an ICS that treats underlying inflammation and a long-acting beta2-agonist (LABA) bronchodilator with a fast onset of action in a single inhaler. Symbicort Turbuhaler has been approved as an anti-inflammatory reliever taken as-needed in mild asthma in 35 countries, and regulatory reviews are ongoing in additional countries.

    Asthma 
    Asthma is a common chronic respiratory disease, and it affects the health and day-to-day lives of as many as 339 million adults and children worldwide.6 It is characterised by recurrent breathlessness and wheezing which varies over time, and in severity and frequency from person to person.3

    All asthma patients are at risk of severe exacerbations regardless of their disease severity, adherence to treatment or level of control.7,8,9 There are an estimated 176 million asthma exacerbations globally per year;10 these are physically threatening and emotionally significant for many patients.11 However, despite asthma being a chronic, variable inflammatory disease, many patients are either under-prescribed or under-use their anti-inflammatory maintenance therapy and may over-rely on their SABA reliever, which can mask symptom worsening.12,13,14,15 Taking a SABA inhaler alone during a worsening of symptoms does not address the underlying inflammation, leaving patients at risk of asthma exacerbations and potential exposure to frequent bursts of oral corticosteroids.16 The Global Initiative for Asthma no longer recommends SABA taken as-needed as the preferred reliever therapy.17

    SYGMA
    The Symbicort Given as-needed in Mild Asthma (SYGMA) trial programme comprised SYGMA 1 and 2: two 52-week Phase III trials in more than 8,000 patients.18 SYGMA 1 evaluated Symbicort Turbuhaler (200/6mcg*) as-needed, compared with terbutaline (0.5mg) as-needed and budesonide (200mcg**) twice-daily plus terbutaline (0.5mg) as-needed.1 Results from SYGMA 1 were published in The New England Journal of Medicine.1 SYGMA 2 evaluated Symbicort Turbuhaler (200/6mcg*) as-needed, compared with budesonide (200mcg**) twice-daily maintenance plus terbutaline (0.5mg) as-needed.2 Results were published in The New England Journal of Medicine.2

    Symbicort
    Symbicort&#8239;(budesonide/formoterol) is the number one ICS/LABA combination therapy in asthma and chronic obstructive pulmonary disease (COPD) in China. It is a combination formulation containing budesonide, an ICS that treats underlying inflammation, and formoterol, a LABA with a fast onset of action, in a single inhaler.&#8239;Symbicort&#8239;was launched in 2000 and is approved in approximately 120 countries to treat asthma and/or COPD either as&#8239;Symbicort Turbuhaler&#8239;or&#8239;Symbicort&#8239;pMDI (pressurised metered-dose inhaler).

    Symbicort Turbuhaler is the first dual-combination therapy approved in China as an anti-inflammatory reliever to treat mild asthma. It is already approved in China for patients with moderate to severe asthma as an anti-inflammatory reliever plus maintenance therapy (12 years and older) and as maintenance therapy only (six years and older).

    AstraZeneca in Respiratory & Immunology
    Respiratory & Immunology is one of AstraZeneca's three therapy areas and is a key growth driver for the Company.

    AstraZeneca is an established leader in respiratory care, and its inhaled and biologic medicines reached more than 53 million patients in 2019. Building on a 50-year heritage, the Company aims to transform the treatment of asthma and COPD by focusing on earlier biology-led treatment, eliminating preventable asthma attacks, and removing COPD as a top-three leading cause of death. The Company's early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell-repair processes in disease and neuronal dysfunction.

    With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immunology-driven disease areas. The Company's growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential, in areas including rheumatology (including systemic lupus erythematosus), dermatology, gastroenterology, and systemic eosinophilic-driven diseases. AstraZeneca's ambition in Respiratory & Immunology is to achieve disease modification and durable remission for millions of patients worldwide.

    AstraZeneca
    AstraZeneca (NASDAQ:AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com 

    * Corresponds to a delivered dose of budesonide/formoterol of 160/4.5mcg.
    ** Corresponds to a delivered dose of budesonide of 160mcg.
    † Corresponds to a delivered dose of terbutaline of 0.4mg, delivered by a Turbuhaler.

    References

    1.     O'Byrne PM, FitzGerald JM, Bateman ED, et al. Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J Med. 2018; 378: 1865-1876.
    2.     Bateman ED, Reddel HK, O'Byrne PM, et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N Engl J Med. 2018; 378: 1877-1887.
    3.     National Heart, Lung, and Blood Institute. Guidelines for the Diagnosis and Management of Asthma (EPR-3). [Online]. Available at: https://www.nhlbi.nih.gov/health-topics/guidelines-for-diagnosis-management-of-asthma. [Accessed December 2020]
    4.     Huang K, Yang T, Xu J, et al. Prevalence, risk factors, and management of asthma in China: a national cross-sectional study. Lancet. 2019; 394:407-418.
    5.     Ding B, Small M, Wang W, et al. The disease burden of mild asthmatics in China. European Respiratory Journal. 2016; 48 (suppl 60): PA4208.
    6.     The Global Asthma Network. The Global Asthma Report 2018. [Online]. Available at: http://www.globalasthmanetwork.org/. [Accessed December 2020]
    7.    Olaguibel JM, Quirce S, Julia B, et al. Measurement of asthma control according to Global Initiative for Asthma guidelines: a comparison with the Asthma Control Questionnaire. Respir Res. 201; 13: 50.
    8.    Price D, Fletcher M, van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014; 24: 14009.
    9.    Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J. 2008; 31: 143–78.
    10.  AstraZeneca Pharmaceuticals. Data on file. Budesonide/formoterol: Annual Rate of Exacerbations Globally (ID:SD-3010-ALL-0017).
    11.  Sastre J, Fabbri LM, Price D, et al. Insights, attitudes, and perceptions about asthma and its treatment: a multinational survey of patients from Europe and Canada. World Allergy Organ J. 2016; 9: 13.
    12.  Humbert M, Andersson TL, Buhl R. Budesonide/formoterol for maintenance and reliever therapy in the management of moderate to severe asthma. Allergy. 2008; 63: 1567–80.
    13.  Rabe KF, Vermeire PA, Soriano JB, Maier WC. Clinical management of asthma in 1999: the asthma insights and reality in Europe (AIRE) study. Eur Respir J. 2000; 16: 802–7.
    14.  Tattersfield AE, Postma DS, Barnes PJ, et al. on behalf of the FACET International Study Group. Exacerbations of asthma: a descriptive study of 425 severe exacerbations. Am J Respir Crit Care Med. 1999; 160: 594–9.
    15.  Adams RJ, Fuhlbrigge A, Guilbert T, et al. Inadequate use of asthma medication in the United States: results of the asthma in America national population survey. J Allergy Clin Immunol. 2002; 110: 58–64.
    16.  Price DB, Trudo F, Voorham J, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy. 2018; 11: 193–204.
    17.  Global Initiative for Asthma. 2020 GINA Report, Global Strategy for Asthma Management and Prevention. [Online]. Available at: https://ginasthma.org/gina-reports/. [Accessed December 2020]
    18.  O'Byrne PM, FitzGerald JM, Zhong N, et al. The SYGMA programme of phase 3 trials to evaluate the efficacy and safety of budesonide/formoterol given “as needed” in mild asthma: study protocols for two randomised controlled trials. Trials. 2017; 18: 12.

    Adrian Kemp
    Company Secretary
    AstraZeneca PLC

     

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  14. AstraZeneca's Calquence (acalabrutinib), a next-generation, selective Bruton's tyrosine kinase (BTK) inhibitor, has been approved in Japan for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) (including small lymphocytic lymphoma [SLL]).

    The approval by the Japanese Ministry of Health, Labour and Welfare was based on positive results from the ASCEND Phase III trial and a Phase I trial in Japanese patients, showing Calquence monotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus a standard treatment of rituximab, a monoclonal antibody, combined with the physician's choice of idelalisib, a PI3-kinase inhibitor or bendamustine…

    AstraZeneca's Calquence (acalabrutinib), a next-generation, selective Bruton's tyrosine kinase (BTK) inhibitor, has been approved in Japan for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) (including small lymphocytic lymphoma [SLL]).

    The approval by the Japanese Ministry of Health, Labour and Welfare was based on positive results from the ASCEND Phase III trial and a Phase I trial in Japanese patients, showing Calquence monotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus a standard treatment of rituximab, a monoclonal antibody, combined with the physician's choice of idelalisib, a PI3-kinase inhibitor or bendamustine, a chemotherapy.

    In the ASCEND trial, Calquence reduced the risk of disease progression or death by 69% (hazard ratio, 0.31; 95% confidence interval, 0.20-0.49). These results were published in Journal of Clinical Oncology in 2020.1

    CLL is the most common type of adult leukaemia across the globe but is considered a rare disease in Japan and East Asia, representing between 1% and 2% of patients diagnosed with leukaemia.2-4

    Dai Maruyama, MD, PhD, Director, Department of Hematology and Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan said: “Today's news marks great progress for patients with chronic lymphocytic leukaemia in Japan. As the ASCEND trial showed, Calquence provides a significant improvement in progression-free survival compared with current standard therapies. Treatment with a safe and tolerable regimen remains paramount for these patients who often require ongoing therapy for many years.”

    Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “Chronic lymphocytic leukaemia is less prevalent in Japan than other regions, yet patients remain in need of innovative treatment options. This approval of Calquence offers patients in Japan a new, chemo-free, tolerable treatment option with uncompromised efficacy and the potential to positively impact quality of life.”

    In the ASCEND Phase III trial, an estimated 88% of patients with relapsed or refractory CLL treated with Calquence remained alive and free from disease progression after 12 months compared with 68% of patients on rituximab combined with idelalisib or bendamustine. After a median follow up of 16.1 months, median PFS was not reached with Calquence monotherapy versus 16.5 months in the control arm.1

    The safety and tolerability of Calquence were consistent with its established profile.1 Final results of the ASCEND Phase III trial were presented at the 2020 American Society of Clinical Oncology and 2020 European Hematology Association virtual meetings and demonstrated the long-term (median 22-month follow-up) efficacy and tolerability of Calquence in CLL.5,6

    Calquence is approved for the treatment of CLL and SLL in the US and is approved for the treatment of CLL in the EU and in several other countries worldwide in the 1st-line and relapsed or refractory settings. Calquence is also approved in the US and several other countries for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Calquence is not currently approved for the treatment of MCL in Japan or the EU.

    As part of a broad development programme, Calquence is being assessed in more than 20 AstraZeneca-sponsored clinical trials for the treatment of patients with B-cell malignancies including CLL, MCL, diffuse large B-cell lymphoma, Waldenström's macroglobulinaemia, follicular lymphoma, and other haematologic malignancies.

    A Japanese Phase I/II trial based on the ELEVATE TN Phase III trial is currently underway for the treatment of 1st-line CLL.

    CLL
    CLL is the most common type of leukaemia in adults, with an estimated 114,000 new cases globally in 2017, and the number of people living with CLL is expected to grow with improved treatment as patients live longer with the disease.7-10 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells, and platelets. This could result in anaemia, infection, and bleeding.7 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.

    ASCEND
    ASCEND (ACE-CL-309) was a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy of Calquence in patients with relapsed or refractory CLL. In the trial, 310 patients were randomised (1:1) into two arms. Patients in the first arm received Calquence monotherapy (100mg twice daily until disease progression or unacceptable toxicity). Patients in the second arm received physician's choice of either rituximab, a CD20 monoclonal antibody, in combination with idelalisib, a PI3-kinase inhibitor, or rituximab in combination with bendamustine, a chemotherapy.1

    The primary endpoint was PFS assessed by an Independent Review Committee (IRC), and key secondary endpoints included investigator-assessed PFS, IRC- and investigator-assessed overall response rate and duration of response, as well as overall survival, patient-reported outcomes and time to next treatment.1 ASCEND is the first randomised Phase III trial to directly compare a BTK inhibitor as monotherapy to these combinations in relapsed or refractory CLL.

    AstraZeneca in haematology
    Leveraging its strength in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus. The Company's haematology franchise includes two medicines approved in the US and a robust global development programme for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca's haematology research and development arm. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.

    AstraZeneca in oncology
    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of six scientific platforms - Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies - and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

    AstraZeneca
    AstraZeneca (NASDAQ:AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com

    References

    1. Ghia P, et al. ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia [published online ahead of print, 2020 May 27]. J Clin Oncol. 2020; JCO1903355. doi:10.1200/JCO.19.03355.
    2. Mahlich J, Okamoto S, Tsubota A. Cost of Illness of Japanese Patients with Chronic Lymphocytic Leukemia (CLL), and Budget Impact of the Market Introduction of Ibrutinib. Pharmacoecon Open. 2017;1(3):195-202. doi:10.1007/s41669-017-0024-5.
    3. National Cancer Institute Cancer Information Service. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Available at: https://ganjoho.jp/public/cancer/CLL/index.html. Accessed January 2021.
    4. Takizawa J, et al. Comparative Analysis of Japanese and European Typical CLL Patients. Blood. 02 December 2016;128(22):5564.
    5. Ghia P, et al. Acalabrutinib (Acala) vs Idelalisib plus Rituximab (IdR) or Bendamustine plus Rituximab (BR) in Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): ASCEND Final Results. Abstract S159 at the Virtual Edition of the European Hematology Association 25th EHA Annual Congress.
    6. Ghia P, et al. Acalabrutinib Vs Idelalisib Plus Rituximab (IdR) or Bendamustine Plus Rituximab (BR) in Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): ASCEND Final Results. Abstract 8015 at the American Society of Clinical Oncology ASCO20 Virtual Session.
    7. American Cancer Society. What is Chronic Lymphocytic Leukemia? Available at https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/what-is-cll.html. Accessed January 2021.
    8. National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version. Available at https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq. Accessed January 2021.
    9. Global Burden of Disease Cancer Collaboration. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017. JAMA Oncol. 2019;5(12):1749-1768.
    10. Jain N, et al. Prevalence and Economic Burden of Chronic Lymphocytic Leukemia (CLL) in the Era of Oral Targeted Therapies. Blood. 2015;126:871.

    — WebWireID269425 —


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  15. Superior safety on key secondary endpoint of atrial fibrillation

    Positive high-level results from the ELEVATE-RR Phase III trial showed AstraZeneca's CALQUENCE® (acalabrutinib) met the primary endpoint demonstrating non-inferior progression-free survival (PFS) for adults with previously treated, high-risk chronic lymphocytic leukemia (CLL) compared to ibrutinib.

    The trial also met a key secondary endpoint for safety, showing patients treated with CALQUENCE had statistically significantly lower incidence of atrial fibrillation compared to patients treated with ibrutinib. Atrial fibrillation is an irregular heart rate that can increase the risk of stroke, heart failure and other heart-related complications.1 Further hierarchical testing revealed…

    Superior safety on key secondary endpoint of atrial fibrillation

    Positive high-level results from the ELEVATE-RR Phase III trial showed AstraZeneca's CALQUENCE® (acalabrutinib) met the primary endpoint demonstrating non-inferior progression-free survival (PFS) for adults with previously treated, high-risk chronic lymphocytic leukemia (CLL) compared to ibrutinib.

    The trial also met a key secondary endpoint for safety, showing patients treated with CALQUENCE had statistically significantly lower incidence of atrial fibrillation compared to patients treated with ibrutinib. Atrial fibrillation is an irregular heart rate that can increase the risk of stroke, heart failure and other heart-related complications.1 Further hierarchical testing revealed no difference for Grade 3 or higher infections or Richter's transformation. There was a descriptive trend for numerically favorable overall survival. Overall, the safety and tolerability of CALQUENCE were consistent with the profile seen in the broader CALQUENCE clinical development program.

    ELEVATE-RR is the first Phase III trial to compare two Bruton's tyrosine kinase (BTK) inhibitors in patients with CLL, the most common type of leukemia in adults.2 Patients diagnosed with high-risk CLL may experience rapid worsening of their disease, requiring treatment.3

    José Baselga, Executive Vice President, Oncology R&D, said: "With over forty months of follow-up, today's results confirm that CALQUENCE, a selective BTK inhibitor, displays superior safety in atrial fibrillation without compromising efficacy. The totality of the data confirm our confidence in the favorable benefit-risk profile of CALQUENCE."

    The data will be presented at a forthcoming medical meeting and shared with health authorities.

    INDICATION AND USAGE

    CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

    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.

    CALQUENCE is also indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

    IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE® (acalabrutinib) capsules

    Serious and Opportunistic Infections

    Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE.

    Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 19% of 1029 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (11% of all patients, including pneumonia in 6%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 1.9% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jiroveci pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor patients for signs and symptoms of infection and treat promptly.

    Hemorrhage

    Fatal and serious hemorrhagic events have occurred in patients with hematologic malignancies treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 3.0% of patients, with fatal hemorrhage occurring in 0.1% of 1029 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 22% of patients.

    Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 2.7% of patients taking CALQUENCE without antithrombotic agents and 3.6% of patients taking CALQUENCE with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with CALQUENCE. Monitor patients for signs of bleeding.

    Consider the benefit-risk of withholding CALQUENCE for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

    Cytopenias

    Grade 3 or 4 cytopenias, including neutropenia (23%), anemia (8%), thrombocytopenia (7%), and lymphopenia (7%), developed in patients with hematologic malignancies treated with CALQUENCE. Grade 4 neutropenia developed in 12% of patients. Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted.

    Second Primary Malignancies

    Second primary malignancies, including skin cancers and other solid tumors, occurred in 12% of 1029 patients exposed to CALQUENCE in clinical trials. The most frequent second primary malignancy was skin cancer, reported in 6% of patients. Monitor patients for skin cancers and advise protection from sun exposure.

    Atrial Fibrillation and Flutter

    Grade 3 atrial fibrillation or flutter occurred in 1.1% of 1029 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 4.1% of all patients. The risk may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (e.g., palpitations, dizziness, syncope, dyspnea) and manage as appropriate.

    ADVERSE REACTIONS

    The most common adverse reactions (≥ 20%) of any grade in patients with relapsed or refractory MCL were anemia,* thrombocytopenia,* headache (39%), neutropenia,* diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%). The most common Grade ≥ 3 non-hematological adverse reaction (reported in at least 2% of patients) was diarrhea (3.2%).

    *Treatment-emergent decreases (all grades) of hemoglobin (46%), platelets (44%), and neutrophils (36%) were based on laboratory measurements and adverse reactions.

    Dose reductions or discontinuations due to any adverse reaction were reported in 1.6% and 6.5% of patients, respectively. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.

    The most common adverse reactions (≥ 30%) of any grade in patients with CLL were anemia,* neutropenia,* thrombocytopenia,* headache, upper respiratory tract infection, and diarrhea.

    *Treatment-emergent decreases (all grades) of hemoglobin, platelets, and neutrophils were based on laboratory measurements and adverse reactions.

    In patients with previously untreated CLL exposed to CALQUENCE, fatal adverse reactions that occurred in the absence of disease progression and with onset within 30 days of the last study treatment were reported in 2% for each treatment arm, most often from infection. Serious adverse reactions were reported in 39% of patients in the CALQUENCE plus obinutuzumab arm and 32% in the CALQUENCE monotherapy arm, most often due to events of pneumonia (7% and 2.8%, respectively).

    Adverse reactions led to CALQUENCE dose reduction in 7% and 4% of patients in the CALQUENCE plus obinutuzumab arm (N=178) and CALQUENCE monotherapy arm (N=179), respectively. Adverse events led to discontinuation in 11% and 10% of patients, respectively. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 3.9% and 2.8% of patients in the CALQUENCE combination arm and monotherapy arm, respectively.

    In patients with relapsed/refractory CLL exposed to CALQUENCE, serious adverse reactions occurred in 29% of patients. Serious adverse reactions in > 5% of patients who received CALQUENCE included lower respiratory tract infection (6%). Fatal adverse reactions within 30 days of the last dose of CALQUENCE occurred in 2.6% of patients, including from second primary malignancies and infection.

    Adverse reactions led to CALQUENCE dose reduction in 3.9% of patients (N=154), dose interruptions in 34% of patients, most often due to respiratory tract infections followed by neutropenia, and discontinuation in 10% of patients, most frequently due to second primary malignancies followed by infection. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 1.3% of patients who received CALQUENCE.

    DRUG INTERACTIONS

    Strong CYP3A Inhibitors: Avoid co-administration with a strong CYP3A inhibitor. If a strong CYP3A inhibitor will be used short-term, interrupt CALQUENCE.

    Moderate CYP3A Inhibitors: When CALQUENCE is co-administered with a moderate CYP3A inhibitor, reduce CALQUENCE dose to 100 mg once daily.

    Strong CYP3A Inducers: Avoid co-administration with a strong CYP3A inducer. If a strong CYP3A inducer cannot be avoided, increase the CALQUENCE dose to 200 mg approximately every 12 hours.

    Gastric Acid Reducing Agents: If treatment with a gastric acid reducing agent is required, consider using an H2-receptor antagonist or an antacid. Take CALQUENCE 2 hours before taking an H2-receptor antagonist. Separate dosing with an antacid by at least 2 hours.

    Avoid co-administration with proton pump inhibitors. Due to the long-lasting effect of proton pump inhibitors, separation of doses may not eliminate the interaction with CALQUENCE.

    SPECIFIC POPULATIONS

    Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Advise pregnant women of the potential risk to a fetus.

    Pregnancy testing is recommended for females of reproductive potential prior to initiating CALQUENCE therapy. Advise female patients of reproductive potential to use effective contraception during treatment with CALQUENCE and for at least 1 week following the last dose of CALQUENCE.

    It is not known if CALQUENCE is present in human milk. Advise lactating women not to breastfeed while taking CALQUENCE and for at least 2 weeks after the final dose.

    Avoid administration of CALQUENCE in patients with severe hepatic impairment. Dose modifications are not required for patients with mild or moderate hepatic impairment.

    Please see full Prescribing Information, including Patient Information.

    CLL

    CLL is the most common type of leukemia in adults, with an estimated 114,000 new cases globally in 2017 and 21,250 new cases in the US in 2021, and the number of people living with CLL is expected to grow with improved treatment as patients live longer with the disease.2,4-7 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows, there is less room for healthy white blood cells, red blood cells, and platelets. This could result in anemia, infection, and bleeding.4 B-cell receptor signaling through BTK is one of the essential growth pathways for CLL.

    ELEVATE-RR

    ELEVATE-RR (ACE-CL-006) is a randomized, multicenter, open-label Phase III non-inferiority trial of CALQUENCE versus ibrutinib in patients with previously treated CLL with high-risk features (presence of 17p deletion and/or 11q deletion). In the trial, 533 patients were randomized (1:1) into two arms. Patients in the first arm received CALQUENCE (100mg, orally, twice daily) until disease progression or unacceptable toxicity. Patients in the second arm received ibrutinib (420mg orally once daily) until disease progression or unacceptable toxicity.8

    The primary endpoint for the trial was PFS assessed by an independent review committee (non-inferiority; tested after 250 events). Secondary endpoints included incidence of atrial fibrillation, incidence of treatment-emergent Grade 3 or higher infections, incidence of Richter's transformation (a condition in which CLL changes into an aggressive form of lymphoma) and overall survival.8

    CALQUENCE

    CALQUENCE (acalabrutinib) is a next-generation, selective inhibitor of BTK. CALQUENCE binds covalently to BTK, thereby inhibiting its activity.9,10 In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.9

    CALQUENCE is approved for the treatment of CLL and small lymphocytic lymphoma in the US and approved for CLL in the EU and several other countries worldwide. CALQUENCE is under regulatory review in Japan for relapsed or refractory CLL. A Phase I trial is currently underway in Japan for the treatment of 1st-line CLL.

    In the US and several other countries, CALQUENCE is also approved for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. The US MCL 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. CALQUENCE is not currently approved for the treatment of MCL in Europe or Japan.

    As part of an extensive clinical development program, AstraZeneca and Acerta Pharma are currently evaluating CALQUENCE in more than 20 company-sponsored clinical trials. CALQUENCE is being developed for the treatment of multiple B-cell blood cancers including CLL, MCL, diffuse large B-cell lymphoma, Waldenström's macroglobulinaemia, follicular lymphoma, and other hematologic malignancies.

    AstraZeneca in hematology

    Leveraging its strength in oncology, AstraZeneca has established hematology as one of four key oncology disease areas of focus. The Company's hematology franchise includes two medicines approved in the US and a robust global development program for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca's hematology research and development arm. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.

    AstraZeneca in oncology

    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of six scientific platforms - Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies - and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

    AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

    References

    1. Mayo Clinic. Patient Care & Health Information, Diseases & Conditions - Atrial Fibrillation.

    Available at: https://www.mayoclinic.org/diseases-conditions/atrial-fibrillation/symptoms-causes/syc-20350624. Accessed January 2021.

    2. American Cancer Society. What is Chronic Lymphocytic Leukemia. Available at: https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/what-is-cll.html. Accessed January 2021.

    3. Cancer.net. Leukemia-Chronic Lymphocytic – CLL: Stages. Available at: https://www.cancer.net/cancer-types/leukemia-chronic-lymphocytic-cll/stages. Accessed January 2021.

    4. National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version. Available at: https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq. Accessed January 2021.

    5. Global Burden of Disease Cancer Collaboration. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017. JAMA Oncol. 2019;5(12):1749-1768.

    6. American Cancer Society. Cancer Facts & Figures 2021. Key Statistics for Chronic Lymphocytic Leukemia. 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.

    7. Jain N, et al. Prevalence and Economic Burden of Chronic Lymphocytic Leukemia (CLL) in the Era of Oral Targeted Therapies. Blood. 2015;126:871.5.

    8. Clinicaltrials.gov. NCT02477696. Accessed September 18, 2020. Study started in October 2015.

    9. CALQUENCE (acalabrutinib) [U.S. prescribing information]. Wilmington, DE; AstraZeneca Pharmaceuticals LP; 2019.

    10. Wu J, Zhang M & Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016;9(21).

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  16. AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)'s Enhertu (trastuzumab deruxtecan) has been approved in the US for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

    In the US, gastric cancer is most frequently diagnosed in the advanced stage, with only approximately 5% of patients surviving beyond five years.1,2 Approximately one in five gastric cancers are HER2 positive.3

    The approval by the Food and Drug Administration (FDA) was based on the positive results from the randomised DESTINY-Gastric01 Phase II trial conducted in Japan and South Korea. In the trial, Enhertu demonstrated…

    AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)'s Enhertu (trastuzumab deruxtecan) has been approved in the US for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

    In the US, gastric cancer is most frequently diagnosed in the advanced stage, with only approximately 5% of patients surviving beyond five years.1,2 Approximately one in five gastric cancers are HER2 positive.3

    The approval by the Food and Drug Administration (FDA) was based on the positive results from the randomised DESTINY-Gastric01 Phase II trial conducted in Japan and South Korea. In the trial, Enhertu demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and objective response rate (ORR) versus chemotherapy (irinotecan or paclitaxel) in patients with advanced gastric cancer or GEJ adenocarcinoma who had progressed on at least two or more prior regimens including trastuzumab plus a fluoropyrimidine- and platinum-based chemotherapy combination.4

    Ronan Kelly, MD, MBA, Director of the Charles A. Sammons Cancer Center and the W.W. Caruth, Jr. Chair of Immunology at Baylor University Medical Center, Dallas, Texas, US, said: “Patients with metastatic HER2-positive gastric cancer with progression following 1st-line treatment have historically faced poor outcomes, including low response to treatment and rapid disease progression. This approval represents the first time a HER2-directed medicine has demonstrated a significant improvement in survival compared to chemotherapy following initial treatment in the metastatic setting, and it has the potential to become the new standard of care for this patient population.”

    Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “Today's approval of Enhertu represents the first HER2-directed medicine approved in a decade for patients with HER2-positive metastatic gastric cancer. The results from the DESTINY-Gastric01 trial highlight the potential to change clinical practice, showing a 41 per cent improvement in survival and a response rate more than three times higher with Enhertu compared to chemotherapy. We are thrilled to bring this important medicine to more patients and physicians in the US.”

    Antoine Yver, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo, said: “Enhertu is the first antibody drug conjugate to receive approval in the US for the treatment of patients with metastatic gastric cancer, and represents a major advance in managing this difficult-to-treat disease. This second indication in the US represents an important step forward in our ambitious plan to accelerate the development of Enhertu across a broad range of HER2-targetable cancers.”

    In a pre-specified interim analysis from the DESTINY-Gastric01 trial, patients treated with Enhertu had a 41% reduction in the risk of death versus patients treated with chemotherapy (based on a hazard ratio [HR] of 0.59; 95% confidence interval [CI] 0.39-0.88; p=0.0097) with a median OS of 12.5 months versus 8.4 months.3

    Confirmed ORR, assessed by independent central review was a major efficacy outcome. Results showed a confirmed ORR of 40.5% in patients treated with Enhertu (n=126) compared to 11.3% in patients treated with chemotherapy (n=62). Patients treated with Enhertu had a 7.9% complete response rate and a 32.5% partial response rate compared to a complete response rate of 0% and a partial response rate of 11.3% for patients treated with chemotherapy.4

    Enhertu demonstrated a median progression-free survival (PFS) of 5.6 months compared to 3.5 months with chemotherapy (HR=0.47; 95% CI 0.31-0.71). Additionally, Enhertu showed a median duration of response (DoR) of 11.3 months versus 3.9 months with chemotherapy.4

    Results from the DESTINY-Gastric01 trial were published in The New England Journal of Medicine in June 2020.5

    The most common adverse reactions, including laboratory abnormalities, of any grade (greater than or equal to 20%) for patients treated with Enhertu (n=125) in the DESTINY-Gastric01 trial were anaemia, leukopenia, neutropenia, lymphocytopenia, thrombocytopenia, nausea, decreased appetite, increased aspartate aminotransferase, fatigue, increased blood alkaline phosphatase, increased alanine aminotransferase, diarrhoea, hypokalaemia, vomiting, constipation, increased blood bilirubin, pyrexia and alopecia. Interstitial lung disease or pneumonitis occurred in 10% of patients.4

    This is the second indication approved for Enhertu in the US following the accelerated approval for adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 trial.

    Enhertu was previously granted Priority Review, Breakthrough Therapy Designation (BTD) in HER2-positive metastatic gastric cancer and Orphan Drug Designation for gastric cancer by the FDA. Two additional Phase II trials, DESTINY-Gastric02 and DESTINY-Gastric03, are underway, further evaluating treatment with Enhertu in patients with HER2-positive metastatic gastric cancer.

    Financial considerations
    Following US approval, an amount of $115m is due from AstraZeneca to Daiichi Sankyo as a combined 2nd-line and 3rd-line milestone payment in HER2-positive gastric cancer. In AstraZeneca, the milestones paid will be capitalised as an addition to the upfront payment made in 2019 and subsequent capitalised milestones and amortised through the profit and loss.

    Sales of Enhertu in the US are recognised by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from Enhertu sales in the US as collaboration revenue in the Company's financial statements. For further details on the financial arrangements, please consult the collaboration agreement from March 2019.

    Gastric cancer
    Gastric (stomach) cancer is the fifth most common cancer worldwide and the third leading cause of cancer mortality with a five-year survival rate of 5% for metastatic disease; there were approximately one million new cases reported in 2020 and more than 768,000 deaths.6 In the US, it is estimated that 27,600 new cases of gastric cancer were diagnosed in 2020 and more than 11,000 people died from the disease.7

    Approximately one in five gastric cancers are HER2 positive.1 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers. Gastric cancer is usually diagnosed in the advanced stage, but even when diagnosed in earlier stages of the disease the survival rate remains modest.2 Recommended 1st-line treatment for HER2-positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve survival outcomes when added to chemotherapy. For patients with metastatic gastric cancer that progresses following initial treatment with a trastuzumab-based regimen, there were previously no other approved HER2-targeted medicines prior to the approval of Enhertu.8

    DESTINY-Gastric01
    DESTINY-Gastric01 is a Phase II, open-label, multi-centre, randomised controlled trial testing the safety and efficacy of Enhertu (6.4 mg/kg) versus investigator's choice of chemotherapy in a primary cohort of patients from Japan and South Korea with HER2-positive (defined as IHC3+ or IHC2+/ISH+), locally advanced or metastatic gastric cancer or GEJ adenocarcinoma who have progressed on at least two or more prior regimens including trastuzumab plus a fluoropyrimidine- and platinum-based chemotherapy combination. Patients (n=188) were randomised 2:1 to receive Enhertu or physician's choice of chemotherapy (paclitaxel or irinotecan monotherapy). Patients were treated with Enhertu 6.4mg/kg once every three weeks or chemotherapy.

    The main efficacy outcome measures were ORR, assessed by independent central review, and OS. Additional efficacy outcome measures were PFS and DoR.4

    Enhertu
    Enhertu (trastuzumab deruxtecan; fam-trastuzuab deruxtecan-nxki in the US) is a HER2-directed antibody drug conjugate (ADC). It is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca's ADC scientific platform.

    ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ('payload') to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Enhertu is comprised of a humanised anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable linker.

    Enhertu (5.4mg/kg) is approved in the US under accelerated approval, and in Japan under the conditional early approval system, for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 trial. In addition to the US, Enhertu (6.4mg/kg) is also approved in Japan for patients with HER2-positive unresectable advanced or recurrent gastric cancer that progressed after chemotherapy based on the DESTINY-Gastric01 trial.

    Development programme
    A comprehensive development programme is underway globally, with nine registrational trials evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2 cancers, including breast, gastric and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

    In May 2020, Enhertu received a BTD for the treatment of patients with metastatic non-small cell lung cancer whose tumours have a HER2 mutation and with disease progression on or after platinum-based therapy.

    Daiichi Sankyo collaboration
    Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.

    AstraZeneca in gastrointestinal cancers
    AstraZeneca has a broad development programme for the treatment of gastrointestinal (GI) cancers across several medicines spanning a variety of tumour types and stages of disease. In 2020, GI cancers collectively represented over five million new cancer cases leading to more than 3.5 million deaths.6 Within this programme, the Company is committed to improving outcomes in gastric, liver, oesophageal, pancreatic, and colorectal cancers.

    The Company aims to understand the potential of Enhertu in the two most common GI cancers, colorectal and gastric cancers. Imfinzi (durvalumab) is being assessed as both as monotherapy and in combinations including with tremelimumab across the two main types of liver cancer, hepatocellular carcinoma and biliary tract cancer, and in oesophageal and gastric cancers. Lynparza (olaparib) is a first-in-class PARP inhibitor with a broad and advanced clinical trial programme across multiple GI tumour types including pancreatic and colorectal cancers. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada).

    AstraZeneca in oncology
    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of&#8239;new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline&#8239;of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

    AstraZeneca
    AstraZeneca (NASDAQ:AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

    References

    1. Curea F.G, et al. Current Targeted Therapies in HER2-Positive Gastric Adenocarcinoma. Cancer Biotherapy & Radiopharmaceuticals. 2017;32 (10).

    2. American Cancer Society. Stomach Cancer: Early Detection, Diagnosis, and Staging. Available at: https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/survival-rates.html.

    3. American Cancer Society. Stomach Cancer: Treating Stomach Cancer. Available at: https://www.cancer.org/cancer/stomach-cancer/treating/targeted-therapies.html.

    4. ENHERTU® [fam-trastuzumab deruxtecan-nxki] US prescribing information; 2021.

    5. Shitara, K et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020;382(25):2419-2430. DOI: 10.1056/NEJMoa2004413.

    6. Global Cancer Observatory. Cancer Today. Lyon, France: International Agency for Research on Cancer. Available at: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf .

    7. American Cancer Society. Stomach Cancer: About Stomach Cancer. Available at: https://www.cancer.org/cancer/stomach-cancer/about/key-statistics.html.

    8. NCCN Guidelines® Gastric Cancer. Version 4.2019. December 20, 2019: MS-22-36.

    — WebWireID269135 —


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  17. First HER2-directed medicine approved for patients with gastric cancer in a decade

    AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)'s ENHERTU® (fam-trastuzumab deruxtecan-nxki) has been approved in the US for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

    In the US, gastric cancer is more frequently diagnosed in the advanced stage with only approximately 5% of patients surviving beyond five years.1,2 Approximately one in five gastric cancers are HER2 positive.3

    The approval by the Food and Drug Administration (FDA) was based on the positive results from the randomized DESTINY-Gastric01…

    First HER2-directed medicine approved for patients with gastric cancer in a decade

    AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)'s ENHERTU® (fam-trastuzumab deruxtecan-nxki) has been approved in the US for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

    In the US, gastric cancer is more frequently diagnosed in the advanced stage with only approximately 5% of patients surviving beyond five years.1,2 Approximately one in five gastric cancers are HER2 positive.3

    The approval by the Food and Drug Administration (FDA) was based on the positive results from the randomized DESTINY-Gastric01 Phase II trial conducted in Japan and South Korea. In the trial, ENHERTU demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) and objective response rate (ORR) versus chemotherapy (irinotecan or paclitaxel) in patients with advanced gastric cancer or GEJ adenocarcinoma who had progressed on at least two or more prior regimens including trastuzumab plus a fluoropyrimidine- and a platinum-containing chemotherapy combination.4

    Ronan Kelly, MD, MBA, Director of the Charles A. Sammons Cancer Center and the W.W. Caruth, Jr. Chair of Immunology at Baylor University Medical Center, Dallas, Texas, said: "Patients with metastatic HER2-positive gastric cancer with progression following 1st-line treatment have historically faced poor outcomes, including low response to treatment and rapid disease progression. This approval represents the first time a HER2-directed medicine has demonstrated a significant improvement in survival compared to chemotherapy following initial treatment in the metastatic setting, and it has the potential to become the new standard of care for this patient population."

    Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "Today's approval of ENHERTU represents the first HER2-directed medicine in a decade for patients with HER2-positive metastatic gastric cancer. The results from the DESTINY-Gastric01 trial highlight the potential to change clinical practice, showing a 41 percent improvement in survival and a response rate more than three times higher with ENHERTU compared to chemotherapy. We are thrilled to bring this important medicine to more patients and physicians in the US."

    Antoine Yver, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo, said: "ENHERTU is the first antibody drug conjugate to receive approval in the US for the treatment of patients with metastatic gastric cancer, and represents a major advance in managing this difficult-to-treat disease. This second indication in the US represents an important step forward in our ambitious plan to accelerate the development of ENHERTU across a broad range of HER2-targetable cancers."

    In a pre-specified interim analysis from the DESTINY-Gastric01 trial, patients treated with ENHERTU had a 41% reduction in the risk of death versus patients treated with chemotherapy (based on a hazard ratio [HR] of 0.59; 95% confidence interval [CI] 0.39-0.88; p=0.0097) with a median OS of 12.5 months versus 8.4 months.3

    Confirmed ORR, assessed by independent central review was a major efficacy outcome. Results showed a confirmed ORR of 40.5% in patients treated with ENHERTU (n=126) compared to 11.3% in patients treated with chemotherapy (n=62). Patients treated with ENHERTU had a 7.9% complete response rate and a 32.5% partial response rate compared to a complete response rate of 0% and a partial response rate of 11.3% for patients treated with chemotherapy.4

    ENHERTU demonstrated a median progression-free survival (PFS) of 5.6 months compared to 3.5 months with chemotherapy (HR=0.47; 95% CI 0.31-0.71). Additionally, ENHERTU showed a median duration of response (DoR) of 11.3 months versus 3.9 months with chemotherapy.4

    Results from the DESTINY-Gastric01 trial were published in The New England Journal of Medicine in June 2020.5

    ENHERTU is approved with Boxed WARNINGS for interstitial lung disease (ILD) or pneumonitis and embryo-fetal toxicity. The most common adverse reactions, including laboratory abnormalities, of any grade (greater than or equal to 20%) for patients treated with ENHERTU (n=125) in the DESTINY-Gastric01 trial were anemia, leukopenia, neutropenia, lymphocytopenia, thrombocytopenia, nausea, decreased appetite, increased aspartate aminotransferase, fatigue, increased blood alkaline phosphatase, increased alanine aminotransferase, diarrhea, hypokalaemia, vomiting, constipation, increased blood bilirubin, pyrexia and alopecia. Interstitial lung disease (ILD) or pneumonitis occurred in 10% of patients.4

    This is the second indication approved for ENHERTU in the US following the accelerated approval for adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 trial.

    ENHERTU was previously granted Priority Review, Breakthrough Therapy Designation (BTD) in HER2-positive metastatic gastric cancer and Orphan Drug Designation (ODD) for gastric cancer by the FDA. Two additional Phase II trials, DESTINY-Gastric02 and DESTINY-Gastric03, are underway, further evaluating treatment with ENHERTU in patients with HER2-positive metastatic gastric cancer.

    Please visit www.ENHERTU.com for full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

    Financial considerations

    Following US approval, an amount of $115m is due from AstraZeneca to Daiichi Sankyo as a combined 2nd-line and 3rd-line milestone payments in HER2-positive gastric cancer. In AstraZeneca, the milestones paid will be capitalized as an addition to the upfront payment made in 2019 and subsequent capitalized milestones and amortised through the profit and loss.

    Sales of ENHERTU in the US are recognized by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from ENHERTU sales in the US as collaboration revenue in the Company's financial statements. For further details on the financial arrangements, please consult the collaboration agreement from March 2019.

    Important Safety Information

    Indications

    ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:

    • Unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.



      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 a confirmatory trial.

    Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.

    WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

    • Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.
    • Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

    Contraindications

    None.

    Warnings and Precautions

    Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.

    Metastatic Breast Cancer

    In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3).

    Locally Advanced or Metastatic Gastric Cancer

    In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21.0).

    Neutropenia

    Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level.

    Metastatic Breast Cancer

    In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU 5.4mg/kg, a decrease in neutrophil count was reported in 62% of patients. Sixteen percent had Grade 3 or 4 decrease in neutrophil count. Median time to first onset of decreased neutrophil count was 23 days (range: 6 to 547). Febrile neutropenia was reported in 1.7% of patients.

    Locally Advanced or Metastatic Gastric Cancer

    In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.

    Left Ventricular Dysfunction

    Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

    Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure.

    Embryo-Fetal Toxicity

    ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.

    Additional Dose Modifications

    Thrombocytopenia

    For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less. Reduce dose by one level.

    Adverse Reactions

    Metastatic Breast Cancer

    The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).

    Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

    ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.

    The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (79%), white blood cell count decreased (70%), hemoglobin decreased (70%), neutrophil count decreased (62%), fatigue (59%), vomiting (47%), alopecia (46%), aspartate aminotransferase increased (41%), alanine aminotransferase increased (38%), platelet count decreased (37%), constipation (35%), decreased appetite (32%), anemia (31%), diarrhea (29%), hypokalemia (26%), and cough (20%).

    Locally Advanced or Metastatic Gastric Cancer

    The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg once every three weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) in the ENHERTU group and 2.8 months (range: 0.5 to 13.1) in the irinotecan/paclitaxel group.

    Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%).

    ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and hypokalemia. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.

    The most common (≥20%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (75%), white blood cell count decreased (74%), neutrophil count decreased (72%), lymphocyte count decreased (70%), platelet count decreased (68%), nausea (63%), decreased appetite (60%), anemia (58%), aspartate aminotransferase increased (58%), fatigue (55%), blood alkaline phosphatase increased (54%), alanine aminotransferase increased (47%), diarrhea (32%), hypokalemia (30%), vomiting (26%), constipation (24%), blood bilirubin increased (24%), pyrexia (24%), and alopecia (22%).

    Use in Specific Populations

    • Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of ENHERTU.
    • Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
    • Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
    • Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
    • Geriatric Use: Of the 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (53%) as compared to younger patients (42%). Of the 125 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients.
    • Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.

    To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

    Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

    Notes

    Gastric cancer

    Gastric (stomach) cancer is the fifth most common cancer worldwide and the third leading cause of cancer mortality with a five-year survival rate of 5% for metastatic disease; there were approximately one million new cases reported in 2020 and more than 768,000 deaths.6 In the US, it is estimated that 27,600 new cases of gastric cancer will be diagnosed in 2020 and more than 11,000 people will die from the disease.7

    Approximately one in five gastric cancers are HER2 positive.1 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers. Gastric cancer is usually diagnosed in the advanced stage, but even when diagnosed in earlier stages of the disease the survival rate remains modest.1,2 Recommended 1st-line treatment for HER2-positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve survival outcomes when added to chemotherapy. For patients with metastatic gastric cancer that progresses following initial treatment with a trastuzumab-based regimen, there were previously no other approved HER2-targeted medicines prior to the approval of ENHERTU.8

    DESTINY-Gastric01

    DESTINY-Gastric01 is a Phase II, open-label, multi-center, randomized controlled trial testing the safety and efficacy of ENHERTU (6.4 mg/kg) versus investigator's choice of chemotherapy in a primary cohort of patients from Japan and South Korea with HER2-positive (defined as IHC3+ or IHC2+/ISH+), locally advanced or metastatic gastric cancer or GEJ adenocarcinoma who have progressed on two or more prior regimens including trastuzumab plus a fluoropyrimidine- and platinum-containing chemotherapy. Patients (n=188) were randomized 2:1 to receive ENHERTU or physician's choice of chemotherapy (paclitaxel or irinotecan monotherapy). Patients were treated with ENHERTU 6.4mg/kg once every three weeks or chemotherapy.

    The main efficacy outcome measures were ORR assessed by independent central review and OS. Additional efficacy outcome measures were PFS and DoR.4

    ENHERTU

    ENHERTU (fam-trastuzumab deruxtecan-nxki) is a HER2-directed antibody drug conjugate (ADC). It is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca's ADC scientific platform.

    ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. ENHERTU is comprised of a humanized anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable linker.

    ENHERTU (5.4mg/kg) is approved in the US under accelerated approval, and in Japan under conditional early approval system, for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 trial. In addition to the US, ENHERTU (6.4mg/kg) is also approved in Japan for patients with HER2-positive unresectable advanced or recurrent gastric cancer that progressed after chemotherapy based on the DESTINY-Gastric01 trial.

    Development program

    A comprehensive development program is underway globally, with nine registrational trials evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 cancers including breast, gastric and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

    In May 2020, ENHERTU received BTD for the treatment of patients with metastatic non-small cell lung cancer whose tumors have a HER2 mutation and with disease progression on or after platinum-based therapy.

    Daiichi Sankyo collaboration

    Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of ENHERTU and datopotamab deruxtecan.

    AstraZeneca in gastrointestinal (GI) cancers

    AstraZeneca has a broad development program for the treatment of GI cancers across several medicines spanning a variety of tumor types and stages of disease. In 2020, GI cancers collectively represented over 5 million new cancer cases leading to more than 3.5 million deaths.6 Within this program, the Company is committed to improving outcomes in gastric, liver, oesophageal, pancreatic, and colorectal cancers.

    The Company aims to understand the potential of ENHERTU in the two most common GI cancers, colorectal and gastric cancers.6 Durvalumab is being assessed as both as monotherapy and in combinations including with tremelimumab across the two main types of liver cancer, hepatocellular carcinoma and biliary tract cancer, and in oesophageal and gastric cancers. Olaparib is a PARP inhibitor with a broad and advanced clinical trial program across multiple GI tumor types including pancreatic and colorectal cancers. Olaparib is developed and commercialized in collaboration with MSD (Merck & Co., Inc. inside the US and Canada).

    AstraZeneca in oncology

    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

    AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

    References

    1. Curea F.G, et al. Current Targeted Therapies in HER2-Positive Gastric Adenocarcinoma. Cancer Biotherapy & Radiopharmaceuticals. 2017;32 (10).
    2. American Cancer Society. Stomach Cancer: Early Detection, Diagnosis, and Staging. Available at: https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/survival-rates.html.
    3. American Cancer Society. Stomach Cancer: Treating Stomach Cancer. Available at: https://www.cancer.org/cancer/stomach-cancer/treating/targeted-therapies.html.
    4. ENHERTU® [fam-trastuzumab deruxtecan-nxki] US prescribing information; 2021.
    5. Shitara, K et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020;382(25):2419-2430. DOI: 10.1056/NEJMoa2004413.
    6. Global Cancer Observatory. Cancer Today. Lyon, France: International Agency for Research on Cancer. Available at: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf .
    7. American Cancer Society. Stomach Cancer: About Stomach Cancer. Available at: https://www.cancer.org/cancer/stomach-cancer/about/key-statistics.html.
    8. NCCN Guidelines® Gastric Cancer. Version 4.2019. December 20, 2019: MS-22-36.

    US-49031 Last Updated: 1/2021

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  18. – Data Presented at the 2021 ASCO GI Cancers Symposium –

    AVEO Oncology (NASDAQ:AVEO) today announced the presentation of results from the Phase 1b portion of the Phase 1b/2 DEDUCTIVE clinical trial of tivozanib (FOTIVDA®), AVEO's vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) drug candidate, in combination with IMFINZI® (durvalumab), AstraZeneca's (NASDAQ:AZN) human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with advanced or metastatic hepatocellular carcinoma (HCC). The results are being presented today in a poster session at the 2021 American Society of Clinical Oncology Gastrointestinal (ASCO GI) Cancers Symposium being held virtually.

    A total of seven patients…

    – Data Presented at the 2021 ASCO GI Cancers Symposium –

    AVEO Oncology (NASDAQ:AVEO) today announced the presentation of results from the Phase 1b portion of the Phase 1b/2 DEDUCTIVE clinical trial of tivozanib (FOTIVDA®), AVEO's vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) drug candidate, in combination with IMFINZI® (durvalumab), AstraZeneca's (NASDAQ:AZN) human monoclonal antibody directed against programmed death-ligand 1 (PD-L1), in patients with advanced or metastatic hepatocellular carcinoma (HCC). The results are being presented today in a poster session at the 2021 American Society of Clinical Oncology Gastrointestinal (ASCO GI) Cancers Symposium being held virtually.

    A total of seven patients with advanced or metastatic HCC were enrolled in the Phase 1b portion of the study, which was designed to determine the recommended Phase 2 dose and assess preliminary safety and efficacy of the tivozanib/durvalumab combination. Patients received 1.0 mg of tivozanib for 21 days followed by 7 days off therapy combined with 1500 mg of durvalumab every 28 days. The combination was well tolerated, with no dose-limiting toxicities. The combination demonstrated a 29% partial response (PR) rate and 71% disease control rate (PR + stable disease). Completion of enrollment in the ongoing Phase 2 portion of the study, which is expected to enroll up to an additional 30 subjects, is anticipated later this year.

    "With a five-year survival rate of less than 5%, advanced or metastatic HCC represents an area of high unmet need," said Renuka Iyer, M.D., Professor of Oncology and Co-Director, Liver and Pancreas Tumor Center, Roswell Park Comprehensive Cancer Center. "These data demonstrated the tolerability of the tivozanib and immunotherapy combination, and I look forward to its further evaluation in the Phase 2 portion of the study."

    "We believe that data observed in the Phase 1b portion of the DEDUCTIVE study continue to support tivozanib's potential to serve as an attractive VEGFR TKI to use in the immunotherapy combination setting," said Michael Bailey, president and chief executive officer of AVEO. "As we await a decision on our New Drug Application for single agent tivozanib in relapsed or refractory renal cell carcinoma (RCC), we remain focused on executing on our combination strategy, including in metastatic RCC and HCC."

    About Tivozanib (FOTIVDA®)

    Tivozanib is an oral, once-daily, next-generation VEGFR TKI discovered by Kyowa Kirin Co. and approved as FOTIVDA® for the treatment of adult patients with advanced RCC in the European Union and other countries in the territory of the Company's partner, EUSA Pharma (UK) Limited (EUSA territory). It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib is being studied in the TIVO-3 trial, which is supporting a regulatory submission of tivozanib in the U.S. seeking marketing approval as a treatment for adult patients with relapsed or refractory advanced RCC. Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC.4 Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers. Tivozanib is also being studied by partner Kyowa Kirin Co. in non-oncology indications.

    About AVEO Pharmaceuticals, Inc.

    AVEO is an oncology-focused biopharmaceutical company committed to delivering medicines that provide a better life for cancer patients. AVEO's strategy is to focus its resources toward development and commercialization of its product candidates in North America, while leveraging partnerships to support development and commercialization in other geographies. AVEO's lead candidate, tivozanib, is approved as FOTIVDA® in the European Union and other countries in the EUSA territory for the treatment of adult patients with advanced RCC. Tivozanib is being studied in the TIVO-3 trial, which is supporting a regulatory submission of tivozanib in the U.S. seeking marketing approval as a treatment for relapsed or refractory RCC. AVEO has previously reported promising early clinical data on ficlatuzumab (anti-HGF mAb) in head and neck cancer, acute myeloid leukemia and pancreatic cancer and is conducting a randomized Phase 2 confirmatory clinical trial of ficlatuzumab in head and neck cancer. AVEO's earlier-stage pipeline includes several monoclonal antibodies in oncology development, including AV-203 (anti-ErbB3 mAb), AV-380 (anti-GDF15 mAb) and AV-353 (anti-Notch 3 mAb). AVEO is committed to creating an environment of diversity and inclusion as a foundation for innovation.

    Cautionary Note Regarding Forward Looking Statements

    This press release contains forward-looking statements of AVEO within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. The words "anticipate," "believe," "design," "expect," "hope," "intend," "may," "plan," "potential," "could," "should," "would," "seek," "look forward," "advance," "goal," "strategy," or the negative of these terms or other similar expressions, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, among others, statements about: the potential for tivozanib as a treatment option for patients with advanced HCC or relapsed/refractory or advanced RCC; the potential efficacy, safety, and tolerability of tivozanib, both as a stand-alone drug candidate and in combination with other therapies in several indications; AVEO's execution of its clinical and regulatory strategy for tivozanib; AVEO's plans and strategies for current and future clinical trials of tivozanib, ficlatuzumab and AV-380 and for commercialization of tivozanib in the United States; the advancement of AVEO's pipeline, including the advancement of ficlatuzumab in multiple clinical studies; the potential efficacy, safety and tolerability of ficlatuzumab, both as a stand-alone drug candidate and in combination with other therapies; the potential outcomes from studies of ficlatuzumab to provide AVEO with opportunities to pursue regulatory strategies; the potential clinical utility of ficlatuzumab in areas of unmet need; and AVEO's strategy, prospects, plans and objectives for its product candidates and for the Company generally. AVEO has based its expectations and estimates on assumptions that may prove to be incorrect. As a result, readers are cautioned not to place undue reliance on these expectations and estimates. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that AVEO makes due to a number of important factors, including risks relating to: whether the results of TIVO-3 are sufficient to obtain marketing approval for tivozanib in the U.S., which turns on the ability of AVEO to demonstrate to the satisfaction of the FDA the safety and efficacy of tivozanib based upon the findings of TIVO-3, including its data with respect to progression-free survival, the rate of adverse events, overall survival and other information that the FDA may consider to be relevant to an approval determination; AVEO's ability to successfully implement its strategic plans, including its ability to successfully launch and commercialize tivozanib if it may be approved for commercialization by the FDA and to obtain and maintain market and third party payor acceptance of tivozanib if it may be approved for commercialization by the FDA; AVEO's ability to raise the substantial additional funds required to achieve its goals, including those goals pertaining to the launch and commercialization of tivozanib; AVEO's ability, and the ability of its licensees, to demonstrate to the satisfaction of applicable regulatory agencies such as the FDA the safety, efficacy and clinically meaningful benefit of AVEO's product candidates, and risks relating to the timing and costs of seeking and obtaining regulatory approvals; and AVEO's ability to enter into and maintain its third party collaboration and license agreements, and its ability, and the ability of its strategic partners, to achieve development and commercialization objectives under these arrangements; AVEO's and its collaborators' ability to successfully enroll and complete clinical trials; AVEO's ability to maintain compliance with regulatory requirements applicable to its product candidates; AVEO's ability to obtain and maintain adequate protection for intellectual property rights relating to its product candidates; unplanned capital requirements; uncertainties related to AVEO's ability to access future borrowings under the Hercules loan facility, which turns on the achievement of milestones related to the approval and commercialization of tivozanib in the U.S., which milestones may not be achieved; adverse general economic and industry conditions; the potential adverse effects of the COVID-19 pandemic on AVEO's business continuity, financial condition, results of operations, liquidity and ability to successfully and timely enroll, complete and read-out data from its clinical trials; competitive factors; and those risks discussed in the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations—Liquidity and Capital Resources" included in AVEO's quarterly and annual reports on file with the Securities and Exchange Commission (SEC) and in other filings that AVEO makes with the SEC. The forward-looking statements in this press release represent AVEO's views as of the date of this press release, and subsequent events and developments may cause its views to change. While AVEO may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. You should, therefore, not rely on these forward-looking statements as representing AVEO's views as of any date other than the date of this press release.

    Any reference to AVEO's website address in this press release is intended to be an inactive textual reference only and not an active hyperlink.

    References

    1. Fotivda (Tivozanib) SmPC August 2017
    2. Motzer RJ, Nosov D, Eisen T, et al. J Clin Oncol 2013; 31(30): 3791-9
    3. Pawlowski N et al. AACR 2013. Poster 3971
    4. Barthelemy et al. ESMO 2018. Poster 878P

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  19. HONG KONG, SHANGHAI and FLORHAM PARK, N.J., Jan. 14, 2021 (GLOBE NEWSWIRE) -- Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM) today announces that the final analysis of savolitinib in Phase Ib TATTON study Parts B and D will be presented at the upcoming virtual 2020 World Conference on Lung Cancer (WCLC 2020), taking place on January 28-31, 2021, virtually.

    Further details of the featured poster presentation are as follows:

    Title:Osimertinib + savolitinib in patients with EGFRm MET-amplified/overexpressed NSCLC: Phase Ib TATTON Parts B and D final analysis
    Lead Author:Ji-Youn Han, Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea
    Session:FP14 - Targeted Therapy - Clinically Focused
    Abstract # / Link:#FP14.03

    HONG KONG, SHANGHAI and FLORHAM PARK, N.J., Jan. 14, 2021 (GLOBE NEWSWIRE) -- Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM) today announces that the final analysis of savolitinib in Phase Ib TATTON study Parts B and D will be presented at the upcoming virtual 2020 World Conference on Lung Cancer (WCLC 2020), taking place on January 28-31, 2021, virtually.

    Further details of the featured poster presentation are as follows:

    Title:Osimertinib + savolitinib in patients with EGFRm MET-amplified/overexpressed NSCLC: Phase Ib TATTON Parts B and D final analysis
    Lead Author:Ji-Youn Han, Center for Lung Cancer, National Cancer Center, Goyang, Republic of Korea
    Session:FP14 - Targeted Therapy - Clinically Focused
    Abstract # / Link:#FP14.03 / Link
    Availability Date:Thursday, January 28, 2021 (from midnight Singapore time)

    About Savolitinib

    Savolitinib is an oral, potent, and highly selective small molecule inhibitor of MET, a receptor tyrosine kinase which has been shown to function abnormally in many types of solid tumors promoting tumor growth, angiogenesis, and metastasis. Savolitinib has been studied in over 1,000 patients to date. In clinical studies, it has shown promising clinical efficacy in patients with MET gene alterations in multiple tumor types with an acceptable safety profile.

    In 2011, Chi-Med entered into a global licensing and joint development and commercialization agreement with AstraZeneca PLC (NYSE:AZN) for savolitinib. Savolitinib's global development plan includes non-small cell lung cancer ("NSCLC") and kidney cancer, and additional MET-driven tumors are being explored.

    Savolitinib development in NSCLC:

    Phase II in MET Exon 14 alteration NSCLC (NCT02897479) – In May 2020, data from an ongoing open-label, Phase II registration study was presented as part of the American Society of Clinical Oncology 2020 Virtual Scientific Program ("ASCO 2020"). In patients with MET Exon 14 skipping alteration NSCLC in the efficacy evaluable population, savolitinib demonstrated a 49.2% objective response rate ("ORR"), a 93.4% disease control rate (DCR) and a 9.6 months interim duration of response ("DoR"). 36% of patients in the study have pulmonary sarcomatoid carcinoma (PSC), an aggressive subtype of NSCLC. Data were not yet mature for DoR, progression-free survival (PFS) or overall survival ("OS"). Clinical data indicated an acceptable safety profile, with a low adverse event (AE) related discontinuations rate of 14.3%. This data supported the China new drug application ("NDA") acceptance in May 2020.

    SAVANNAH Phase II study of savolitinib in combination with Tagrisso® in patients who have progressed following Tagrisso® due to MET amplification or overexpression (NCT03778229) – The SAVANNAH study is a single-arm, open-label study in epidermal growth factor receptor ("EGFR") mutation positive NSCLC patients with MET amplified/overexpressed tumors following progression after treatment with Tagrisso®, an EGFR-tyrosine kinase inhibitor owned by AstraZeneca.

    Savolitinib development in kidney cancer:

    MET-driven papillary renal cell carcinoma ("RCC") (NCT03091192) – In May 2020, data from 60 patients in the SAVOIR global study of savolitinib monotherapy compared with sunitinib monotherapy in MET-driven papillary RCC was presented at ASCO 2020. Savolitinib demonstrated encouraging activity, including an ORR of 27% versus 7% for sunitinib, with no savolitinib responding patients with disease progression at data cut-off, and an encouraging OS hazard ratio of 0.51 (95% CI: 0.21–1.17; p=0.110) with median not reached at data cut-off.

    CALYPSO Phase II of savolitinib in combination with Imfinzi® PD-L1 inhibitor in RCC (NCT02819596) – The CALYPSO study is an investigator initiated open-label Phase I/II study of savolitinib in combination with Imfinzi®, a PD-L1 antibody owned by AstraZeneca. The study is evaluating the safety and efficacy of the savolitinib/Imfinzi® combination in patients with papillary RCC and clear cell RCC.

    Based on these data, AstraZeneca and Chi-Med are actively evaluating the opportunity to progress clinical work in papillary RCC for savolitinib.

    Savolitinib development in other cancer indications:

    Savolitinib opportunities are also continuing to be explored in multiple other MET-driven tumor settings via investigator-initiated studies including gastric cancer and colorectal cancer.

    About Chi-Med

    Chi-Med (Nasdaq/AIM: HCM) is an innovative biopharmaceutical company committed, over the past twenty years, to the discovery and global development of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has a portfolio of nine cancer drug candidates currently in clinical studies around the world and extensive commercial infrastructure in its home market of China. For more information, please visit: www.chi-med.com.

    Forward-Looking Statements

    This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect Chi-Med's current expectations regarding future events, including its expectations regarding the therapeutic potential of savolitinib for the treatment of patients with NSCLC, the further clinical development of savolitinib in this and other indications, its expectations as to whether clinical studies of savolitinib would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the sufficiency of its data to support NDA approval of savolitinib for the treatment of patients with NSCLC in China, its potential to gain expeditious approvals for savolitinib in other jurisdictions such as the U.S., E.U. or Japan, the safety profile of savolitinib, the potential for savolitinib to become a new standard of care for NSCLC patients, its ability to implement and complete its further clinical development plans for savolitinib, its potential commercial launch of savolitinib in China and other jurisdictions, the timing of these events, and the impact of the COVID-19 pandemic on general economic, regulatory and political conditions. In addition, as certain studies rely on the use of Tagrisso® and Imfinzi® as combination therapeutics with savolitinib, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of Tagrisso® and Imfinzi®. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see Chi-Med's filings with the U.S. Securities and Exchange Commission and on AIM. Chi-Med undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

    CONTACTS

    Investor Enquiries 
    Mark Lee, Senior Vice President+852 2121 8200
    Annie Cheng, Vice President+1 (973) 567 3786
      
    Media Enquiries 
    Americas – Brad Miles, Solebury Trout+1 (917) 570 7340 (Mobile)

    Europe – Ben Atwell / Alex Shaw, FTI Consulting+44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile)

    Asia – Joseph Chi Lo / Zhou Yi, Brunswick+852 9850 5033 (Mobile), /

    +852 9783 6894 (Mobile), y
      
    Nominated Advisor 
    Freddy Crossley / Atholl Tweedie, Panmure Gordon (UK) Limited+44 (20) 7886 2500

     



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  20. Data for datopotamab deruxtecan (DS-1062) and ENHERTU® signal strong potential of these antibody drug conjugates in advanced lung cancer

    New non-small cell lung cancer data for TAGRISSO® and IMFINZI® further demonstrate the impact of treating patients in early stages of the disease

    AstraZeneca will present new data from across the innovative lung cancer portfolio at the IASLC 2020 World Conference on Lung Cancer (WCLC), hosted by the International Association for the Study of Lung Cancer, 28 to 31 January 2021.

    Eleven AstraZeneca medicines and potential new medicines from the pipeline feature in 39 abstracts showcasing the Company's leadership across different types and stages of lung cancer, including eight oral presentations with two…

    Data for datopotamab deruxtecan (DS-1062) and ENHERTU® signal strong potential of these antibody drug conjugates in advanced lung cancer

    New non-small cell lung cancer data for TAGRISSO® and IMFINZI® further demonstrate the impact of treating patients in early stages of the disease

    AstraZeneca will present new data from across the innovative lung cancer portfolio at the IASLC 2020 World Conference on Lung Cancer (WCLC), hosted by the International Association for the Study of Lung Cancer, 28 to 31 January 2021.

    Eleven AstraZeneca medicines and potential new medicines from the pipeline feature in 39 abstracts showcasing the Company's leadership across different types and stages of lung cancer, including eight oral presentations with two late breakers.

    Presentations include:

    • Updated data from the TROPION-PanTumor01 Phase I trial of datopotamab deruxtecan (Dato-DXd; DS-1062) with additional patients, supporting its potential to redefine treatment outcomes in advanced non-small cell lung cancer (NSCLC) Datopotamab deruxtecan is a novel trophoblast cell-surface antigen 2 (TROP2)-directedantibody drug conjugate (ADC)
    • New data from the DESTINY-Lung01 Phase II trial highlighting the potential of ENHERTU® (trastuzumab deruxtecan) in HER2-expressing metastatic NSCLC, and data in metastatic HER2-mutant (HER2m) NSCLC, two groups of patients for whom no HER2-directed medicine is currently approved
    • New analyses from the ADAURA Phase III trial featured in two oral presentations reinforcing the unprecedented benefit of TAGRISSO® (osimertinib) regardless of prior adjuvant chemotherapy or disease stage in the adjuvant treatment of epidermal growth factor receptor-mutated (EGFRm) NSCLC, and showing patients treated with TAGRISSO maintained their quality of life

    José Baselga, Executive Vice President, Oncology R&D, said: "AstraZeneca is leading the next wave of precision-medicine innovations in lung cancer that aim to change clinical practice and ultimately alter the course of the disease. Our data at WCLC for datopotamab deruxtecan and ENHERTU (trastuzumab deruxtecan) illustrate the potentially transformative role next-generation antibody drug conjugates may play in advanced non-small cell lung cancer. New results for TAGRISSO and IMFINZI® (durvalumab) continue to validate our strategy to treat patients earlier, as we progress the science of identifying patients most likely to respond to treatment."

    Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "AstraZeneca is committed to advancing early detection and treatment of lung cancer - and the urgency to achieve this goal has only increased during the pandemic, which has significantly impacted cancer care for patients around the world. Our TAGRISSO and IMFINZI data at WCLC show how we are driving progress in early-stage lung cancer, while also pushing the scientific boundaries in resistant and advanced disease to identify new solutions for patients."

    Harnessing the emerging potential of ADCs to treat different types of lung cancer

    Updated data from the TROPION-PanTumor01 Phase I trial of the novel ADC datopotamab deruxtecan will be featured in an oral presentation, demonstrating early antitumor activity in patients with advanced/metastatic NSCLC who had progressed on standard treatment. Additionally, two presentations on the data from the DESTINY-Lung01 Phase II trial will show results of ENHERTU patients with NSCLC, including new data from the HER2-expressing cohort and data from the HER2 mutant cohort.

    Collaboration in the scientific community is critical to improving outcomes for patients. AstraZeneca is collaborating with Daiichi Sankyo Company, Limited (Daiichi Sankyo) to develop and commercialize ENHERTU and datopotamab deruxtecan globally.

    Treating patients with NSCLC in early stages

    A late-breaking analysis from the ADAURA Phase III trial will underscore the practice-changing results for adjuvant TAGRISSO in Stage IB-IIIA EGFRm NSCLC and show the disease-free survival results for patients who had been treated with adjuvant chemotherapy prior to TAGRISSO and those who were not by stage of disease. A second exploratory analysis from the Phase III ADAURA trial will highlight the impact of treatment with adjuvant TAGRISSO on quality of life based on patient-reported outcomes. TAGRISSO was recently approved in the adjuvant setting in the US.

    The ongoing NeoADAURA Phase III trial testing the benefit of treating patients with resectable EGFRm NSCLC with neoadjuvant TAGRISSO will be highlighted in a poster presentation.

    The MERMAID-1 Phase III trial testing IMFINZI in patients with completely resected, Stage II and III NSCLC who show evidence of minimal residual disease (MRD), will also be highlighted in a poster. MERMAID-1 is an early-stage NSCLC Phase III trial evaluating circulating tumor DNA measurements to monitor for MRD and to identify patients at high risk of recurrence after surgery who may benefit from intervention with immunotherapy.

    Progressing research in advanced lung cancer

    AstraZeneca will also present data from several trials exploring targeted therapies and novel combinations for advanced lung cancer, including:

    • Additional data from the CASPIAN Phase III trial of IMFINZI in extensive-stage small cell lung cancer (ES-SCLC) showing exposure response and pharmacokinetics as well as exploratory analyses based on extent of disease
    • The biomarker-directed HUDSON Phase II platform trial of IMFINZI in combination with LYNPARZA© (olaparib) and other novel anti-cancer medicines, including danvatirsen (STAT3 antisense oligonucleotide), ceralasertib (ATR inhibitor) and oleclumab (anti-CD73), in patients with NSCLC who progressed on anti-PD(L)1 therapy
    • The ODIN BM Phase I trial assessing TAGRISSO brain exposure in patients with EGFRm NSCLC central nervous system (CNS) metastases
    • The TATTON Phase Ib trial of TAGRISSO plus savolitinib in patients with EGFRm MET-overexpressed/amplified NSCLC
    • A trial-in-progress update on the Phase I trial of TAGRISSO in combination with patritumab deruxtecan (HER3-DXd; U3-1402) in patients with locally advanced or metastatic EGFRm NSCLC

    Key AstraZeneca presentations during WCLC 20201

    Lead author

    Abstract title

    Presentation details

    Immuno-Oncology

     

    Reinmuth, N

    First-line durvalumab plus platinum-etoposide in ES-SCLC: exploratory analyses based on extent of disease in CASPIAN

     

    Abstract #P48.03

    Poster: P48 – Small Cell Lung Cancer/NET – Chemo – IO

    28 January 2021

    Zheng, Y

    Population pharmacokinetics and exposure-response with durvalumab plus platinum-etoposide in ES-SCLC: Results from CASPIAN

     

    Abstract #P48.21

    Poster: P48 – Small Cell Lung Cancer/NET – Chemo – IO

    28 January 2021

    Besse, B

    HUDSON: An open-label, multi-drug, biomarker-directed Phase II platform study in patients with NSCLC, who progressed on anti-PD(L)1 therapy

     

    Abstract #OA07.08

    Oral Session: OA07 – Immuno-biology and Novel Immunotherapeutics from Bench to Bed

    30 January 2021

    11:05-11:10 SGT

    Besse, B

    Immuno-modulatory effects of ceralasertib in combination with durvalumab in NSCLC with progression on anti-PD(L)1 treatment (HUDSON)

     

    Abstract #P16.07

    Poster: P16 – Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)

    Peters, S

    MERMAID-1: A Phase III study of adjuvant durvalumab plus chemotherapy in resected NSCLC patients with MRD+ post-surgery

     

    Abstract #P03.03

    Poster: P03 – Early Stage/Localized Disease – Clinical Trials in Progress

    28 January 2021

    Tumor drivers and resistance

     

    Wu, Y-L

    Postoperative chemotherapy use and outcomes from ADAURA: osimertinib as adjuvant therapy for resected EGFR mutated NSCLC

     

    Abstract #OA06.04

    Oral Session: OA06 – Updates on EGFR Targeted Perioperative Therapy​ and Precision Adjuvant Chemotherapy

    29 January 2021

    16:55-17:05 SGT

    Majem, M

    Patient-reported outcomes from ADAURA: osimertinib as adjuvant therapy in patients with resected EGFR mutated (EGFRm) NSCLC

     

    Abstract #OA06.03

    Oral Session: OA06 – Updates on EGFR Targeted Perioperative Therapy​ and Precision Adjuvant Chemotherapy

    29 January 2021

    16:45-16:55 SGT

    Tsuboi, M

    Neoadjuvant osimertinib with/without chemotherapy vs chemotherapy for EGFR mutated resectable NSCLC: neoADAURA

     

    Abstract #P03.02

    Poster: P03 – Early Stage/Localized Disease – Clinical Trials in Progress

    28 January 2021

    Cho, BC

    ORCHARD: A biomarker-directed Phase 2 platform study in pts with advanced EGFRm NSCLC progressing on first-line osimertinib

     

    Abstract #P76.27

    Poster: P76 – Targeted Therapy – Clinically Focused – EGFR

    28 January 2021

    Jänne, PA

    Phase 1 study of patritumab deruxtecan (HER3-DXd; U3-1402) in combination with osimertinib in patients with locally advanced or metastatic EGFR-mutated NSCLC2

    Abstract #P01.03

    Poster: P01 – Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics

    28 January 2021

    Han, J-Y

    Osimertinib+savolitinib in pts with EGFRm MET-amplified/overexpressed NSCLC: Phase Ib TATTON parts B and D final analysis​

     

    Abstract #FP14.03

    Featured Poster Session: FP14 – Targeted Therapy – Clinically Focused ​

    28 January 2021

    Ekman, S

    A PET and MRI study exploring osimertinib brain exposure and efficacy in EGFRm NSCLC CNS metastases

     

    Abstract #P76.72

    Poster: P76 – Targeted Therapy – Clinically Focused – EGFR

    28 January 2021

    Antibody drug conjugates

     

    Spira, A

    Datopotamab deruxtecan (dato-DXd; DS-1062), a TROP2 ADC, in patients with advanced NSCLC: updated results of TROPION-PanTumor01 Phase 1 study3

    Abstract #OA03.03

    Oral Session: OA03 – Promising Antibody-Drug Conjugate and Cytotoxic Therapy in NSCLC

    29 January 2021

    10:30-10:40 SGT

    Nakagawa, K

    Trastuzumab deruxtecan in HER2-overexpressing metastatic non-small cell lung cancer: interim results of DESTINY-Lung013

    Abstract #OA04.05

    Oral Session: OA04 – New Data from Rare EGFR Alterations

    29 January 2021

    12:05-12:15 SGT

    Smit, EF

    Trastuzumab deruxtecan in HER2-mutated metastatic non-small cell lung cancer (NSCLC): interim results of DESTINY-Lung013

    Abstract #MA11.03

    Mini Oral Session: MA11 – Expanding Targetable Genetic Alterations in NSCLC

    31 January 2021

    14:15-14:20 SGT

    1 39 abstracts at WCLC 2020 will feature AstraZeneca medicines and pipeline molecules, of which 24 are company-sponsored or supported.

    2 Trial collaboration with Daiichi Sankyo which maintains exclusive rights to patritumab deruxtecan.

    3 ENHERTU and datapotamab deruxtecan are developed and commercialized in collaboration with Daiichi Sankyo worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights.

    U.S. FDA-APPROVED INDICATION for ENHERTU® (trastuzumab deruxtecan)

    ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

    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 a confirmatory trial.

    ENHERTU IMPORTANT SAFETY INFORMATION

    WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

    • Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.
    • Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

    Contraindications

    None.

    WARNINGS AND PRECAUTIONS

    Interstitial Lung Disease / Pneumonitis

    Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3).

    Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg prednisolone or equivalent). Upon improvement, follow by gradual taper (e.g., 4 weeks).

    Neutropenia

    Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, a decrease in neutrophil count was reported in 30% of patients and 16% had Grade 3 or 4 events. Median time to first onset was 1.4 months (range: 0.3 to 18.2). Febrile neutropenia was reported in 1.7% of patients.

    Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. Based on the severity of neutropenia, ENHERTU may require dose interruption or reduction. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level.

    Left Ventricular Dysfunction

    Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

    Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. Permanently discontinue ENHERTU if LVEF of <40% or absolute decrease from baseline of >20% is confirmed. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure.

    Embryo-Fetal Toxicity

    ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.

    Adverse Reactions

    The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).

    Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

    ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.

    The most common adverse reactions (frequency ≥20%) were nausea (79%), fatigue (59%), vomiting (47%), alopecia (46%), constipation (35%), decreased appetite (32%), anemia (31%), neutropenia (29%), diarrhea (29%), leukopenia (22%), cough (20%), and thrombocytopenia (20%).

    Use in Specific Populations

    • Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of ENHERTU.
    • Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
    • Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.
    • Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
    • Geriatric Use: Of the 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (53%) as compared to younger patients (42%).
    • Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.

    To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

    Please see accompanying full Prescribing Information, including Boxed WARNING, and Medication Guide.

    SELECT SAFETY INFORMATION FOR TAGRISSO® (osimertinib)

    • There are no contraindications for TAGRISSO
    • TAGRISSO is associated with several serious and sometimes fatal adverse reactions, including interstitial lung disease (ILD)/pneumonitis, QTc interval prolongation, cardiomyopathy, keratitis, erythema multiforme and Stevens-Johnson syndrome, cutaneous vasculitis, and embryo-fetal toxicity
    • The most common (≥20%) adverse reactions, including lab abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough

    For additional information, please refer to the complete Important Safety Information.

    INDICATIONS

    • TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
    • TAGRISSO is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
    • TAGRISSO is indicated for the treatment of adult patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy

    For additional information, please see the complete Prescribing Information, including Patient Information.

    SELECT SAFETY INFORMATION FOR IMFINZI® (durvalumab)

    Stage III:

    Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, and solid organ transplant rejection. IMFINZI can cause severe or life-threatening infusion-related reactions. Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody.

    Advise women not to become pregnant or breastfeed during treatment with IMFINZI and for at least 3 months after the last dose.

    In the PACIFIC trial, the most frequent serious adverse reactions reported in at least 2% of patients were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%).

    The most common adverse reactions were cough, fatigue, pneumonitis or radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash.

    The safety and effectiveness of IMFINZI have not been established in pediatric patients.

    SCLC:

    Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, and solid organ transplant rejection. IMFINZI can cause severe or life-threatening infusion-related reactions. Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody.

    Advise women not to become pregnant or breastfeed during treatment with IMFINZI and for at least 3 months after the last dose.

    In the CASPIAN trial, the most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%) and COPD (1.1%).

    The most common adverse reactions (≥20%) were nausea, fatigue/asthenia and alopecia.

    The safety and effectiveness of IMFINZI have not been established in pediatric patients.

    Please refer to the complete Important Safety Information and the full Prescribing Information for important dosage modification and management information specific to adverse reactions, here.

    SELECT SAFETY INFORMATION for LYNPARZA® (olaparib) tablets

    LYNPARZA is associated with serious, potentially fatal risks, including myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), pneumonitis. Additionally, serious, potentially fatal risk of venous thromboembolic events has been reported with LYNPARZA in mCRPC. LYNPARZA can also cause fetal harm.

    U.S. FDA-APPROVED INDICATIONS

    LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

    First-Line Maintenance BRCAm Advanced Ovarian Cancer

    For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab

    In combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:

    • a deleterious or suspected deleterious BRCA mutation, and/or
    • genomic instability

    Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer

    For the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

    Please see complete Prescribing Information, including Patient Information.

    NOTES TO EDITORS

    AstraZeneca in lung cancer

    AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.

    AstraZeneca aims to address the unmet needs of patients with EGFRm tumors as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with the approved medicines gefitinib and TAGRISSO® (osimertinib) and its ongoing LAURA, NeoADAURA and FLAURA2 Phase III trials.1-3 AstraZeneca is committed to addressing tumor mechanisms of resistance through the ongoing SAVANNAH and ORCHARD Phase II trials, which test TAGRISSO in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines.

    The Company is also evaluating the potential of ADCs to improve patient outcomes in tumors with targetable gene alterations, including HER2m NSCLC which affects approximately 2-4% of patients with NSCLC.4,5 ENHERTU® (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, is in development for metastatic non-squamous HER2-overexpressing or HER2m NSCLC including trials in combination with other anticancer treatments. In addition, a broad and comprehensive clinical development program is evaluating the efficacy and safety of datopotamab deruxtecan (a TROP2-directed ADC) across multiple TROP2 cancers, as both a monotherapy and in combination with other anticancer treatments.

    An extensive Immuno-Oncology (IO) development program focuses on lung cancer patients without a targetable genetic mutation, which represent up to three-quarters of all patients with lung cancer.6 IMFINZI® (durvalumab), an anti-PDL1 antibody, is in development for patients with advanced disease (POSEIDON and PEARL Phase III trials) and for patients in earlier stages of disease, including potentially curative settings (MERMAID-1, MERMAID-2, AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC Phase III trials) both as monotherapy and in combination with tremelimumab and/or chemotherapy. IMFINZI is also in development in the NeoCOAST, COAST and HUDSON Phase II trials in combination with potential new medicines from the early-stage pipeline, including ENHERTU.

    About AstraZeneca in Oncology

    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of six scientific platforms - Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies - and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

    AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

    Reference

    1. Szumera-Ciećkiewicz A, et al. EGFR mutation testing on cytological and histological samples in non-small cell lung cancer: a Polish, single institution study and systematic review of European incidence. Int J Clin Exp Pathol. 2013;6:2800-12.
    2. Keedy VL, et al. American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J Clin Oncol. 2011;29:2121-27.
    3. Ellison G, et al. EGFR mutation testing in lung cancer: a review of available methods and their use for analysis of tumor tissue and cytology samples. J Clin Pathol. 2013;66:79-89.
    4. Campbell JD, et al. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat Genet. 2016;48(6):607-16.
    5. Li BT, et al. HER2 amplification and HER2 mutation are distinct molecular targets in lung cancers. J Thorac Oncol. 2016;11(3): 414-419.
    6. Pakkala, S, et al. Personalized therapy for lung cancer: striking a moving target. JCI Insight. 2018;3(15):e120858.

    US-49317 Last Updated 1/21

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  21. EAGAN, Minn., Jan. 12, 2021 /PRNewswire/ --  Recombinetics Inc., a leading gene editing company with platform technology applied to biomedicine and animal agriculture, today announced a research collaboration with AstraZeneca(NASDAQ:AZN)  in a first of its kind study to inform the knowledge base of Neurofibromatosis Type 1 (NF1).

    NF1 is a pediatric disease that affects 1 in 3,000 births. NF1 patients suffer from a variety of manifestations including learning disabilities, scoliosis, and are predisposed to tumor development. In April 2020, selumetinib became the first FDA approved therapy for NF1 patients for the treatment of symptomatic, inoperable plexiform neurofibromas. 

    Surrogen, a subsidiary of Recombinetics Inc., has developed several…

    EAGAN, Minn., Jan. 12, 2021 /PRNewswire/ --  Recombinetics Inc., a leading gene editing company with platform technology applied to biomedicine and animal agriculture, today announced a research collaboration with AstraZeneca(NASDAQ:AZN)  in a first of its kind study to inform the knowledge base of Neurofibromatosis Type 1 (NF1).

    NF1 is a pediatric disease that affects 1 in 3,000 births. NF1 patients suffer from a variety of manifestations including learning disabilities, scoliosis, and are predisposed to tumor development. In April 2020, selumetinib became the first FDA approved therapy for NF1 patients for the treatment of symptomatic, inoperable plexiform neurofibromas. 

    Surrogen, a subsidiary of Recombinetics Inc., has developed several large animal models of neurofibromatoses that exhibit the clinical features seen in patients with these diseases. In particular, Surrogen's NF1 minipig displays café-au-lait macules, a diagnostic marker of NF1.  In addition, the model also develops both optic pathway glioma and cutaneous neurofibromas, both of which are manifestations of the disease that have been challenging to study preclinically, until now.  

    Surrogen's NF1 minipig platform presents an exceptional opportunity to better understand this disease and pilot much needed treatments and cures to the millions of people throughout the world suffering  from this disease.  

    Together, AstraZeneca and Recombinetics Inc. will now undertake a study to assess selumetinib for the treatment of cutaneous neurofibromas, using Surrogen's NF1 preclinical platform. The results of this study will provide key insights into whether selumetinib can also be used as an effective treatment for cutaneous neurofibromas, which occur in nearly all NF1 patients.

     "Bringing new therapies to the clinic that are poised to have a meaningful impact on patient lives is the most important thing we can do," says Dr. Adrienne Watson, Recombinetics Inc. Vice President of Research and Development, "Utilizing a preclinical model that most closely resembles the patient population is critical to these efforts."

    According to Recombinetics' CEO, Mark Platt, "Dr. Watson and her team have shown incredible skill, dedication, and focus in bringing this powerful genetic model to bear in the fight to treat and cure NF1.  It is an honor to partner with AstraZeneca to combine our efforts and make a difference for NF1 patients and their families."

    About Recombinetics

    Founded in 2008, Recombinetics Inc. is a recognized global leader in the development, deployment, and commercialization of genetically engineered animals.  Its four subsidiaries, Regenevida, Surrogen, Makana, and Acceligen, have delivered hundreds of animals to enable drug, device and therapeutic discovery, generate transplantable cells, tissues and organs, and provide improved health, well-being and productivity of agricultural animals.

    Contact:

    Nikki Rockstroh

    https://recombinetics.com/

    Cision View original content:http://www.prnewswire.com/news-releases/recombinetics-inc--announces-neurofibromatosis-type-1-research-collaboration-with-astrazeneca-301205934.html

    SOURCE Recombinetics, Inc.

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  22. Multi-year, pan-portfolio deal extends Adaptive's proprietary immunoSEQ T-MAP offering, originally launched for COVID-19, into oncology

    This transaction highlights the value of immune receptor data generated by Adaptive's proprietary immune medicine platform

    SEATTLE, Jan. 11, 2021 (GLOBE NEWSWIRE) -- Adaptive Biotechnologies Corporation (NASDAQ:ADPT), a commercial stage biotechnology company that aims to translate the genetics of the adaptive immune system into clinical products to diagnose and treat disease, today announced a translational collaboration with AstraZeneca (NASDAQ:AZN) to investigate the use of immunoSEQ T-MAP, a product that combines the sequencing and mapping capabilities of Adaptive's proprietary immune medicine platform…

    Multi-year, pan-portfolio deal extends Adaptive's proprietary immunoSEQ T-MAP offering, originally launched for COVID-19, into oncology

    This transaction highlights the value of immune receptor data generated by Adaptive's proprietary immune medicine platform

    SEATTLE, Jan. 11, 2021 (GLOBE NEWSWIRE) -- Adaptive Biotechnologies Corporation (NASDAQ:ADPT), a commercial stage biotechnology company that aims to translate the genetics of the adaptive immune system into clinical products to diagnose and treat disease, today announced a translational collaboration with AstraZeneca (NASDAQ:AZN) to investigate the use of immunoSEQ T-MAP, a product that combines the sequencing and mapping capabilities of Adaptive's proprietary immune medicine platform to map T-cell receptors (TCRs) to antigens, across AstraZeneca's oncology portfolio.         

    Under this collaboration, AstraZeneca will provide biological samples from patients with cancer; Adaptive will sequence these samples and deliver TCR-antigen mapping data using its growing and dynamic clinical immunomics database of more than 58 billion immune cell receptors and thousands of antigens. This mapping data may inform signatures of immune response (or resistance) to cancer therapies which may provide information to guide treatment decisions. Additionally, mapping of unique TCRs to antigens at scale can provide powerful information regarding the potential for early and accurate detection of a disease and the specificity of a given patient's immune response to therapy.

    "We continue to demonstrate that specific T-cell immune receptor data can be utilized to inform the diagnosis and treatment for most diseases," said Sharon Benzeno, Chief Business Development Officer, Adaptive Biotechnologies. "We are thrilled to partner with AstraZeneca to realize the value of antigen-specific T-cell response data across their portfolio of transformative cancer medicines."

    Adaptive will receive from AstraZeneca quarterly payments plus sequencing and data mapping fees. In addition, AstraZeneca has an option to enter into a separate agreement with Adaptive for the development and commercialization of a companion diagnostic or therapeutic application based on T-MAP data. Specific financial terms of the agreement will not be disclosed.

    The scope of this non-exclusive, pan-portfolio oncology collaboration may be expanded to cover additional therapeutic areas, including autoimmunity and infectious diseases.

    About Adaptive

    Adaptive Biotechnologies is a commercial-stage biotechnology company focused on harnessing the inherent biology of the adaptive immune system to transform the diagnosis and treatment of disease. We believe the adaptive immune system is nature's most finely tuned diagnostic and therapeutic for most diseases, but the inability to decode it has prevented the medical community from fully leveraging its capabilities. Our proprietary immune medicine platform reveals and translates the massive genetics of the adaptive immune system with scale, precision and speed to develop products in life sciences research, clinical diagnostics, and drug discovery. We have three commercial products, and a robust clinical pipeline to diagnose, monitor and enable the treatment of diseases such as cancer, autoimmune conditions and infectious diseases. Our goal is to develop and commercialize immune-driven clinical products tailored to each individual patient. For more information, please visit adaptivebiotech.com and follow us on www.twitter.com/adaptivebiotech.

    Forward Looking Statements

    This press release contains forward-looking statements that are based on management's beliefs and assumptions and on information currently available to management. All statements contained in this release other than statements of historical fact are forward-looking statements. These statements involve risks, uncertainties and other factors that may cause actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. These risks, uncertainties and other factors are described under "Risk Factors," "Management's Discussion and Analysis of Financial Condition and Results of Operations" and elsewhere in the documents we file with the Securities and Exchange Commission from time to time. We caution you that forward-looking statements are based on a combination of facts and factors currently known by us and our projections of the future, about which we cannot be certain. As a result, the forward-looking statements may not prove to be accurate. The forward-looking statements in this press release represent our views as of the date hereof. We undertake no obligation to update any forward-looking statements for any reason, except as required by law.

    ADAPTIVE MEDIA

    Beth Keshishian

    917-912-7195

    ADAPTIVE INVESTORS

    Karina Calzadilla, Vice President, Investor Relations

    201-396-1687

    Carrie Mendivil, Gilmartin Group



    Primary Logo

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  23. GRAIL, Inc., a healthcare company whose mission is to detect cancer early, today announced collaborations with global biopharmaceutical companies Amgen (NASDAQ:AMGN), AstraZeneca (NASDAQ:AZN), and Bristol Myers Squibb (NYSE:BMY) to evaluate GRAIL's methylation-based technology for the detection of minimal residual disease (MRD).

    Cancer MRD testing is used in clinical and research applications to detect the presence or absence of residual disease. Many MRD tests available today for solid tumors require tissue samples and development of patient-specific assays, which contributes to longer turnaround times and potential delay in treatment decisions. GRAIL's targeted methylation platform could enable a blood-based MRD detection assay for solid…

    GRAIL, Inc., a healthcare company whose mission is to detect cancer early, today announced collaborations with global biopharmaceutical companies Amgen (NASDAQ:AMGN), AstraZeneca (NASDAQ:AZN), and Bristol Myers Squibb (NYSE:BMY) to evaluate GRAIL's methylation-based technology for the detection of minimal residual disease (MRD).

    Cancer MRD testing is used in clinical and research applications to detect the presence or absence of residual disease. Many MRD tests available today for solid tumors require tissue samples and development of patient-specific assays, which contributes to longer turnaround times and potential delay in treatment decisions. GRAIL's targeted methylation platform could enable a blood-based MRD detection assay for solid tumors that perform comparably to bespoke tissue-based assays, while reducing complexity and processing times.

    "GRAIL has developed and validated a novel approach to detect early cancer signals in blood and now we are excited to collaborate with leading companies Amgen, AstraZeneca, and Bristol Myers Squibb to evaluate the benefits of using our technology to find minimal residual disease after treatment or to detect early recurrent cancers," said Joshua Ofman, MD, MSHS, GRAIL chief medical officer and head of external affairs. "Cancer never quits, making the detection of residual disease and early recurrences critical to helping patients and care providers stay ahead of the disease."

    "Amgen is pleased to partner with GRAIL to understand how this technology can provide deeper insights into tumor biology and a patient's prognosis," said Narimon Honarpour, vice president, Translational Medicine, Amgen. "Achieving better clinical outcomes relies upon our understanding of cancer progression and the field needs more robust testing capabilities."

    "Research has shown that we can improve outcomes across cancer types by treating patients as early as possible and intervening early if cancer recurs, which underpins our strategy," said Carl Barrett, vice president, Translational Science, Oncology R&D, AstraZeneca. "This collaboration with GRAIL will allow us to test a promising approach for monitoring MRD and detecting recurrence – tools that will provide critical information that we hope can optimize patient treatment plans."

    "We are committed to leveraging the latest science and technologies to bring continued innovation to the healthcare community and patients we serve," said Sarah Hersey, vice president, Precision Medicine, Translational Medicine, Bristol Myers Squibb. "Our collaboration with GRAIL and other leaders in the industry will help enhance our ability to address the outstanding challenges of detecting and treating cancer head-on."

    About GRAIL

    GRAIL is a healthcare company whose mission is to detect cancer early, when it can be cured. GRAIL is focused on saving lives and improving health by pioneering new technologies for early cancer detection. The company is using the power of next-generation sequencing, population-scale clinical studies, and state-of-the-art computer science and data science to overcome one of medicine's greatest challenges with Galleri™, GRAIL's multi-cancer early detection test. An earlier version of Galleri demonstrated the ability to detect more than 50 types of cancers -- over 45 of which lack recommended screening tests today -- with a low false-positive rate of less than 1%. When cancer is detected, Galleri localizes the cancer signal with high accuracy, all from a single blood draw. GRAIL is headquartered in Menlo Park, California, with locations in Washington, D.C., North Carolina, and the United Kingdom. It is supported by leading global investors and pharmaceutical, technology, and healthcare companies.

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  24. AstraZeneca's COVID-19 vaccine has been granted emergency use authorisation in India as well as Argentina, Dominican Republic, El Salvador, Mexico and Morocco for the active immunisation of adults.

    The vaccine was shown in clinical trials to be safe and effective at preventing symptomatic COVID-19, with no severe cases and no hospitalisations more than 14 days after the second dose.

    The approval in India is an important milestone as it will enable to supply India but also a large number of countries around the world. AstraZeneca has partnered with Serum Institute of India (SII), the world's largest vaccine manufacturer, for the supply of the vaccine to the Indian Government but also to a large number of low and middle-income countries.

    AstraZeneca's COVID-19 vaccine has been granted emergency use authorisation in India as well as Argentina, Dominican Republic, El Salvador, Mexico and Morocco for the active immunisation of adults.

    The vaccine was shown in clinical trials to be safe and effective at preventing symptomatic COVID-19, with no severe cases and no hospitalisations more than 14 days after the second dose.

    The approval in India is an important milestone as it will enable to supply India but also a large number of countries around the world. AstraZeneca has partnered with Serum Institute of India (SII), the world's largest vaccine manufacturer, for the supply of the vaccine to the Indian Government but also to a large number of low and middle-income countries.

    Pascal Soriot, Chief Executive Officer, AstraZeneca, said: “These emergency use authorisations will soon bring the vaccine to many millions of people and are proof of our long-held commitment to broad and equitable access around the world. We hope this effective, well-tolerated and simple-to-administer vaccine will now begin to have a real impact on this deadly virus. We would like to thank the regulators for their swift and decisive actions and our partner, Serum Institute of India, for its substantial contribution to this global effort.”

    Adar Poonawalla, Chief Executive Officer, Serum Institute of India, said: "The emergency licensure in India marks an important milestone for all of us. The regulatory decisions are welcoming and encouraging towards ensuring equitable access to a safe, immunogenic, and affordable vaccine for millions of people worldwide. The pandemic of 2020, however devastating - brought public and private institutions, health authorities, governments of various countries, and most importantly the global communities together to pose a resilient front against the virus. That said, we would like to thank all the stakeholders at various levels who have continually supported and motivated us to fortify our commitment of health for all."

    AstraZeneca has already submitted a substantial data package to support a conditional marketing authorisation for its COVID-19 vaccine to the European Medicines Agency (EMA), as part of an ongoing rolling review process and will continue to work closely with the EMA to seek approval in the coming weeks. AstraZeneca is also seeking Emergency Use Listing from the World Health Organization for an accelerated pathway to vaccine availability in low-income countries during this health crisis and has ongoing rolling reviews with many other regulatory authorities around the world.

    In addition to the University of Oxford-led trials, the Company is conducting a large trial in the US as part of a global programme. In total, the University of Oxford and AstraZeneca expect to enrol more than 60,000 participants worldwide. Additional safety and efficacy data will continue to accumulate from ongoing clinical trials.

    AstraZeneca is working with its global partners to continue building manufacturing capacity of up to three billion doses of the vaccine globally in 2021 on a rolling basis, pending regulatory approvals. The vaccine can be stored, transported and handled at normal refrigerated conditions (two-eight degrees Celsius/ 36-46 degrees Fahrenheit) for at least six months and administered within existing healthcare settings.

    AstraZeneca continues to engage with governments, multilateral organisations and other partners around the world to ensure broad and equitable access to the vaccine at no profit for the duration of the pandemic.

    COVID-19 Vaccine AstraZeneca, formerly AZD1222
    AZD1222 was co-invented by the University of Oxford and its spin-out company, Vaccitech. It uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body.

    The interim analysis for efficacy was based on 11,636 participants accruing 131 symptomatic infections from the UK and Brazil Phase III trials conducted by Oxford University. As published in The Lancet on 8 December 2020, the primary efficacy endpoint based on a pooled analysis showed that the vaccine was 70.4% (confidence interval: 54.8% to 80.6%) effective at preventing symptomatic COVID-19 occurring more than 14 days after receiving two doses of the vaccine. A secondary efficacy endpoint of prevention of severe disease demonstrated no cases of severe infections or hospitalisations in the vaccine group.

    The safety data published so far is from over 20,000 participants enrolled across four clinical trials in the UK and Brazil and South Africa. The Lancet publication confirmed that AZD1222 was well tolerated and that there were no serious safety events confirmed related to the vaccine. The participants were from diverse racial and geographic groups who are healthy or have stable underlying medical conditions. This analysis provides safety data on 74,341 person-months of follow-up after first dose (median 3.4 months) and 29,060 person-months of follow-up after two doses (median 2.0 months). The overall reported rates of serious adverse events were 0.7% in the vaccine group and 0.8% in the control group.

    In addition to the programme led by Oxford University, AstraZeneca is conducting a large trial in the US and globally. In total, Oxford University and AstraZeneca expect to enrol up to 60,000 participants globally.

    On 29 December 2020, the UK Medicines and Healthcare products Regulatory Agency (MHRA) has provided authorisation for emergency supply of COVID-19 Vaccine AstraZeneca for the active immunisation of individuals 18 years or older.

    AstraZeneca
    AstraZeneca (NASDAQ:AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com 

    — WebWireID268740 —


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  25. FARXIGA could become the first SGLT2 inhibitor approved to treat patients with chronic kidney disease, with and without type 2 diabetes

    AstraZeneca's FARXIGA (dapagliflozin) has been granted Priority Review in the US for the treatment of new or worsening chronic kidney disease (CKD) in adults with and without type 2 diabetes (T2D).

    The Food and Drug Administration (FDA) grants Priority Review to regulatory submissions for medicines that offer significant advances over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance. The Prescription Drug User Fee Action date, the day the FDA targets for their regulatory decision, will be during the second quarter of 2021.

    CKD…

    FARXIGA could become the first SGLT2 inhibitor approved to treat patients with chronic kidney disease, with and without type 2 diabetes

    AstraZeneca's FARXIGA (dapagliflozin) has been granted Priority Review in the US for the treatment of new or worsening chronic kidney disease (CKD) in adults with and without type 2 diabetes (T2D).

    The Food and Drug Administration (FDA) grants Priority Review to regulatory submissions for medicines that offer significant advances over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance. The Prescription Drug User Fee Action date, the day the FDA targets for their regulatory decision, will be during the second quarter of 2021.

    CKD, a condition defined by decreased kidney function, is often associated with a heightened risk of heart disease or stroke, or the need for dialysis or kidney transplant. CKD is expected to become the world's fifth leading cause of mortality by 2040. Currently in the US, 37 million people are estimated to have CKD.

    Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: "This decision brings us a step closer to delivering this new treatment option for the millions of patients living with chronic kidney disease in the US. FARXIGA has the potential to be a truly transformational medicine across a breadth of diseases, including type 2 diabetes, heart failure with reduced ejection fraction and, if approved, chronic kidney disease."

    The acceptance of the regulatory submission by the FDA and the granting of Priority Review was based on clinical evidence from the DAPA-CKD Phase III trial showing that FARXIGA, on top of standard of care consisting of an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB), reduced the risk of the composite of worsening of renal function or risk of cardiovascular (CV) or renal death by 39%, the primary endpoint, compared to placebo (absolute risk reduction [ARR] 5.3%, p<0.0001) in patients with CKD Stages 2-4 and elevated urinary albumin excretion. It also significantly reduced the risk of death from any cause by 31% (ARR 2.1%, p=0.0035) compared to placebo. The safety and tolerability of FARXIGA were consistent with the well-established safety profile of the medicine.

    In March 2020, an independent Data Monitoring Committee recommended the trial be stopped early, based on its determination of overwhelming efficacy. Detailed results from the DAPA-CKD trial were shared in August 2020 and published in The New England Journal of Medicine.

    In October 2020, FARXIGA received Breakthrough Therapy Designation in the US for patients with CKD with and without T2D. In the US, FARXIGA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D and to reduce the risk of hospitalization for heart failure in patients with T2D and established CV disease or multiple CV risk factors. In May 2020 FARXIGA was approved in the US to reduce the risk of CV death and hospitalization for heart failure (hHF) in adults with heart failure (NYHA class II-IV) with reduced ejection fraction (HFrEF) with and without T2D. FARXIGA is not indicated to reduce the worsening of renal function or death in patients with CKD.

    INDICATIONS AND LIMITATIONS OF USE for FARXIGA® (dapagliflozin)

    FARXIGA is indicated:

    • as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
    • to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and established cardiovascular (CV) disease or multiple CV risk factors
    • to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction

    FARXIGA is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

    IMPORTANT SAFETY INFORMATION for FARXIGA® (dapagliflozin) 5 mg and 10 mg tablets

    Contraindications

    • Prior serious hypersensitivity reaction to FARXIGA
    • Patients with severe renal impairment (eGFR <30 mL/min/1.73 m2) being treated for glycemic control without established CV disease or multiple CV risk factors
    • Patients on dialysis

    Warnings and Precautions

    • Volume Depletion: FARXIGA can cause intravascular volume depletion which may manifest as symptomatic hypotension or acute transient changes in creatinine. Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes receiving SGLT2 inhibitors, including FARXIGA. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating FARXIGA in these patients, assess volume status and renal function. After initiating therapy, monitor for signs and symptoms of hypotension and renal function
    • Ketoacidosis in Diabetes Mellitus has been reported in patients with type 1 and type 2 diabetes receiving FARXIGA. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue FARXIGA, evaluate and treat promptly. Before initiating FARXIGA, consider risk factors for ketoacidosis. Patients on FARXIGA may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis
    • Urosepsis and Pyelonephritis: SGLT2 inhibitors increase the risk for urinary tract infections (UTIs) and serious UTIs have been reported with FARXIGA. Evaluate for signs and symptoms of UTIs and treat promptly
    • Hypoglycemia: FARXIGA can increase the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with FARXIGA
    • Necrotizing Fasciitis of the Perineum (Fournier's Gangrene): Rare but serious, life-threatening cases have been reported in patients with diabetes mellitus receiving SGLT2 inhibitors including FARXIGA. Cases have been reported in females and males. Serious outcomes have included hospitalization, surgeries, and death. Assess patients presenting with pain or tenderness, erythema, swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment and discontinue FARXIGA
    • Genital Mycotic Infections: FARXIGA increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately

    Adverse Reactions

    In a pool of 12 placebo-controlled studies, the most common adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and placebo respectively were female genital mycotic infections (8.4% vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract infections (5.7% vs 4.3% vs 3.7%).

    Use in Specific Populations

    • Pregnancy: Advise females of potential risk to a fetus especially during the second and third trimesters
    • Lactation: FARXIGA is not recommended when breastfeeding

    DOSING

    • To improve glycemic control in patients with T2D, the recommended starting dose of FARXIGA is 5 mg orally once daily, taken in the morning. In patients tolerating FARXIGA 5 mg once daily who require additional glycemic control, the dose can be increased to 10 mg once daily
    • To reduce the risk of hospitalization for heart failure in patients with T2D and established CV disease or multiple CV risk factors, the recommended dose of FARXIGA is 10 mg orally once daily
    • To reduce the risk of CV death and hospitalization for heart failure in patients with HFrEF, the recommended dose of FARXIGA is 10 mg orally once daily

    Please see accompanying US Full Prescribing Information and Medication Guide for FARXIGA.

    Chronic kidney disease

    CKD is a serious, progressive condition defined by decreased kidney function (shown by reduced estimated glomerular filtration rate [eGFR] or markers of kidney damage, or both, for at least three months) affecting nearly 700 million people worldwide, many of them still undiagnosed. The most common causes of CKD are diabetes, hypertension and glomerulonephritis. CKD is associated with significant patient morbidity and an increased risk of CV events, such as heart failure (HF) and premature death. In its most severe form, known as end-stage kidney disease (ESKD), kidney damage and deterioration of kidney function have progressed to the stage where dialysis or kidney transplantation are required. The majority of patients with CKD will die from CV causes before reaching ESKD.

    DAPA-CKD

    DAPA-CKD was an international, multi-center, randomized, double-blinded trial in 4,304 patients designed to evaluate the efficacy of dapagliflozin 10mg, compared with placebo, in patients with CKD Stages 2-4 and elevated urinary albumin excretion, with and without T2D. FARXIGA was given once daily in addition to standard of care consisting of an ACEi or an ARB. The primary composite endpoint was worsening of renal function or risk of death (defined as a composite of an eGFR decline ≥50%, onset of ESKD and death from CV or renal cause). The secondary endpoints included the time to first occurrence of the renal composite (sustained ≥50% eGFR decline, ESKD and renal death), the composite of CV death or hHF, and death from any cause. The trial was conducted in 21 countries.

    AstraZeneca in CV, Renal & Metabolism (CVMD)

    CV, renal and metabolism together form one of AstraZeneca's main therapy areas and a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection and improving outcomes by slowing disease progression, reducing risks and tackling co-morbidities. Our ambition is to modify or halt the natural course of CVMD diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide.

    About AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

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  26. AstraZeneca has completed the divestment of commercial rights to Atacand (candesartan cilexetil) and Atacand Plus (a fixed-dose combination of candesartan cilexetil and hydrochlorothiazide) in over 70 countries to Cheplapharm Arzneimittel GmbH (Cheplapharm).

    Financial considerations
    Under the terms of the agreement AstraZeneca received a payment of $250m from Cheplapharm. AstraZeneca will receive further non-contingent payments equal to $150m during the first half of 2021. The present value of all payments, totalling $400m, will be reported in AstraZeneca's financial statements within Other Operating Income in the fourth quarter of 2020.

    Pursuant to London Stock Exchange listing rule 10.4.1R (notification of class 2 transactions), in 2019…

    AstraZeneca has completed the divestment of commercial rights to Atacand (candesartan cilexetil) and Atacand Plus (a fixed-dose combination of candesartan cilexetil and hydrochlorothiazide) in over 70 countries to Cheplapharm Arzneimittel GmbH (Cheplapharm).

    Financial considerations
    Under the terms of the agreement AstraZeneca received a payment of $250m from Cheplapharm. AstraZeneca will receive further non-contingent payments equal to $150m during the first half of 2021. The present value of all payments, totalling $400m, will be reported in AstraZeneca's financial statements within Other Operating Income in the fourth quarter of 2020.

    Pursuant to London Stock Exchange listing rule 10.4.1R (notification of class 2 transactions), in 2019 Atacand and Atacand Plus generated product sales of $148m and profit before tax of $89m in the countries covered by the agreement. The gross book value of assets subject to the divestment at 31 December 2019 was $nil. The consideration was and will be paid in cash, and the proceeds used for general corporate purposes.

    Atacand
    Atacand (candesartan cilexetil) is a selective AT1 subtype angiotensin II receptor antagonist that is indicated for the management of hypertension in adults and children/adolescents, as well as heart failure in adults. Atacand Plus is indicated for the management of hypertension when candesartan or hydrochlorothiazide monotherapy is not sufficiently effective. Atacand was developed in collaboration with Takeda Pharmaceutical Company Limited. Each company held the exclusive rights to the medicine in certain countries; in other countries, Atacand was co-marketed.

    AstraZeneca
    AstraZeneca (NASDAQ:AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com 

    — WebWireID268551 —


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  27. AstraZeneca and MSD's Lynparza (olaparib) has been approved in Japan for the treatment of advanced ovarian, prostate and pancreatic cancers.

    The three approvals authorise Lynparza for: maintenance treatment after 1st-line chemotherapy containing bevacizumab (genetical recombination) for patients with homologous recombination repair deficient (HRD) ovarian cancer; the treatment of patients with BRCA gene-mutated (BRCAm) castrate-resistant prostate cancer with distant metastasis (mCRPC); and as maintenance treatment after platinum-based chemotherapy for patients with BRCAm curatively unresectable pancreas cancer.

    The concurrent approvals by the Japanese Ministry of Health, Labour, and Welfare are based on positive results from the PAOLA-1

    AstraZeneca and MSD's Lynparza (olaparib) has been approved in Japan for the treatment of advanced ovarian, prostate and pancreatic cancers.

    The three approvals authorise Lynparza for: maintenance treatment after 1st-line chemotherapy containing bevacizumab (genetical recombination) for patients with homologous recombination repair deficient (HRD) ovarian cancer; the treatment of patients with BRCA gene-mutated (BRCAm) castrate-resistant prostate cancer with distant metastasis (mCRPC); and as maintenance treatment after platinum-based chemotherapy for patients with BRCAm curatively unresectable pancreas cancer.

    The concurrent approvals by the Japanese Ministry of Health, Labour, and Welfare are based on positive results from the PAOLA-1PROfound and POLO Phase III trials, which each were published in The New England Journal of Medicine.

    Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “These three approvals allow patients in Japan to be treated with Lynparza, a targeted treatment personalised to their specific biomarkers. They further underline the critical importance of biomarker testing at diagnosis, which helps physicians determine a course of treatment tailored to individual patients to substantially delay disease progression.”

    Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: “For patients in Japan diagnosed with each of these types of cancer there are very few treatment options. Approvals for treatments such as Lynparza, the first PARP inhibitor to be approved in these specific types of metastatic castration-resistant prostate cancer and metastatic pancreatic cancer in Japan, enable us to advance this evolving era of personalised medicine and change how these cancers are treated.”

    Lynparza in ovarian cancer
    The approval as 1st-line maintenance treatment with bevacizumab for patients with HRD-positive advanced ovarian cancer is based on a biomarker subgroup analysis of the PAOLA-1 Phase III trial which showed Lynparza, in combination with bevacizumab maintenance treatment, demonstrated a substantial progression-free survival (PFS) improvement versus bevacizumab alone, for patients with HRD-positive advanced ovarian cancer.

    In 2020, nearly 11,000 women in Japan were diagnosed with ovarian cancer, with more than 5,000 women dying of the disease.One in two women with advanced ovarian cancer has an HRD-positive tumour.2,3

    Lynparza in prostate cancer
    The approval for the treatment of BRCAm mCRPC is based on a subgroup analysis of the PROfound Phase III trial which showed Lynparza demonstrated a substantial improvement in radiographic progression-free survival (rPFS) and overall survival (OS) versus enzalutamide or abiraterone in men with BRCA1/2 mutations. Lynparza is the first and only PARP inhibitor approved in Japan in advanced prostate cancer.

    Prostate cancer is the third most common type of cancer in Japan and in 2020, accounted for over 100,000 new cases.With limited treatment options, the average survival for men with mCRPC is only 9-13 months.8 Approximately 12% of men with mCRPC have a BRCA mutation,a subgroup of patients with a particularly poor prognosis.

    Lynparza in pancreatic cancer
    The approval for BRCAm metastatic pancreatic cancer is based on the results of the POLO Phase III trial which showed Lynparza demonstrated a statistically significant and clinically meaningful improvement in PFS versus placebo in patients with germline BRCAm metastatic pancreatic cancer. Lynparza is the first and only PARP inhibitor approved in this disease.

    Pancreatic cancer has one of the lowest survival rates of the most common cancers and in Japan was responsible for almost 40,000 deaths in 2020 – the fourth most common cause of cancer death.1,5 Japan has the third-highest rate of pancreatic cancer in the world with 44,000 new cases diagnosed in 2020.1,6 Approximately 5-7% of patients with metastatic pancreatic cancer have a germline BRCA mutation.7

    AstraZeneca and MSD are exploring additional trials in advanced prostate cancer including the ongoing PROpel Phase III trial testing Lynparza as a 1st-line treatment for patients with mCRPC in combination with abiraterone versus abiraterone alone. Data are anticipated in the second half of 2021. AstraZeneca is exploring additional trials in advanced ovarian cancer, including the DUO-O Phase III trial testing Imfinzi (durvalumab) in combination with chemotherapy and bevacizumab, followed by maintenance treatment with Imfinzi, bevacizumab, and Lynparza in newly diagnosed advanced ovarian cancer patients.

    PAOLA-1
    PAOLA-1 is a double-blinded Phase III trial testing the efficacy and safety of&#8239;Lynparza&#8239;added to standard-of-care bevacizumab versus bevacizumab alone, as a 1st-line maintenance treatment for newly diagnosed advanced FIGO Stage III-IV high-grade serous or endometroid ovarian, fallopian tube, or peritoneal cancer patients who had a complete or partial response to 1st-line treatment with platinum-based chemotherapy and bevacizumab. AstraZeneca and MSD announced in August 2019 that the trial met its primary endpoint of PFS in the overall trial population.

    The PAOLA-1 Phase III trial showed that Lynparza, in combination with bevacizumab maintenance treatment, reduced the risk of disease progression or death by 67% (based on a hazard ratio [HR] of 0.33, 95% confidence interval [CI] 0.25-0.45). The addition of Lynparza improved PFS to a median of 37.2 months versus 17.7 with bevacizumab alone in patients with HRD-positive advanced ovarian cancer.

    PROfound
    PROfound is a prospective, multicentre, randomised, open-label, Phase III trial testing the efficacy and safety of Lynparza versus enzalutamide or abiraterone in patients with mCRPC who have progressed on prior treatment that included new hormonal agents (abiraterone or enzalutamide) and have a qualifying tumour mutation in BRCA1/2, ATM or one of 12 other genes involved in the homologous recombination repair (HRR) pathway.

    The trial was designed to analyse patients with HRR gene mutations in two cohorts: the primary endpoint was rPFS in those with mutations in BRCA1/2 or ATM genes and then, if Lynparza showed clinical benefit, a formal analysis was performed of the overall trial population of patients with HRR gene mutations (BRCA1/2, ATM, CDK12 and 11 other HRR gene mutations). AstraZeneca and MSD announced in August 2019 that the trial met its primary endpoint of rPFS.

    The subgroup analysis from the PROfound Phase III trial showed Lynparza reduced the risk of disease progression or death by 78% (based on a HR of 0.22, 95% CI, 0.15-0.32;) and improved rPFS to a median of 9.8 months versus 3.0 with enzalutamide or abiraterone in men with mCRPC with BRCA1/2 mutations. Lynparza reduced the risk of death by 37% (based on a HR of 0.63, 95% CI 0.42-0.95) with median OS of 20.1 months versus 14.4 with enzalutamide or abiraterone.

    POLO
    POLO is a randomised, double-blinded, placebo-controlled, multi-centre Phase III trial of Lynparza tablets (300mg twice daily) as maintenance monotherapy versus placebo. The trial randomised 154 patients with germline BRCAm metastatic pancreatic cancer whose disease had not progressed on 1st-line platinum-based chemotherapy. Patients were randomised (3:2) to receive Lynparza or placebo until disease progression. The primary endpoint was PFS and key secondary endpoints included OS, time to second disease progression, overall response rate and health-related quality of life.

    Data from the Phase III POLO trial showed Lynparza nearly doubled the time patients with germline BRCAm metastatic pancreatic cancer lived without disease progression or death to a median of 7.4 months versus 3.8 on placebo and reduced the risk of disease progression or death by 47% (based on a HR of 0.53, 95% CI 0.35-0.82; p=0.004).

    BRCA
    BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells. When either of these genes are mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer and confer sensitivity to PARP inhibitors including Lynparza.8-11

    HRD
    HRD, which defines a subgroup of ovarian cancer, encompasses a wide range of genetic abnormalities, including BRCA mutations and beyond. As with BRCA gene mutations, HRD interferes with normal cell DNA repair mechanisms and confers sensitivity to PARP inhibitors including Lynparza.12

    Lynparza
    Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in HRR, such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.

    Lynparza is currently approved in a number of countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer. It is approved in the US, the EU, Japan, China, and several other countries as 1st-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in the US and EU as a 1st-line maintenance treatment with bevacizumab for patients with HRD-positive advanced ovarian cancer (BRCAm and/or genomic instability). Lynparza is approved in the US, Japan, and a number of other countries for germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer. It is also approved in the US, the EU and several other countries for the treatment of germline BRCAm metastatic pancreatic cancer. Lynparza is approved in the US for HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm and other HRR gene mutations) and in the EU for BRCAm metastatic castration-resistant prostate cancer. Regulatory reviews are underway in several countries for ovarian, breast, pancreatic and prostate cancers.

    Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, has been used to treat over 40,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca's industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

    The AstraZeneca and MSD strategic oncology collaboration
    In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world's first PARP inhibitor, and Koselugo (selumetinib), a mitogen-activated protein kinase (MEK) inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines.

    AstraZeneca in oncology
    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

    AstraZeneca
    AstraZeneca (NASDAQ:AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com 

    -------

     

    References

    1. The World Health Organization. IARC. Globocan. (2020). Japan Factsheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/392-japan-fact-sheets.pdf [Accessed December 2020].
    2. Moschetta et al. (2016). BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer. Annals of Oncology, 27(8), pp.1449-1455.
    3. Bonadio et al. (2018). Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management. Clinics, 73(Suppl 1): e450s.
    4. Abida et al. (2020). Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. Journal of Clinical Oncology, 38.
    5. Rawla et al. (2019). Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World Journal of Oncology, 10(1), pp.10-27.
    6. The World Health Organization. IARC. Globocan. (2020). Estimated age-standardized incidence rates (World) in 2020, pancreas, both sexes, all ages. Available here [Accessed December 2020].
    7. Golan et al. (2020). Geographic and Ethnic Heterogeneity of Germline BRCA1 or BRCA2 Mutation Prevalence Among Patients With Metastatic Pancreatic Cancer Screened for Entry Into the POLO Trial. Journal of Clinical Oncology 2020; 38(13): 1442-1454.
    8. Kirby, M. (2011). Characterising the castration-resistant prostate cancer population: a systematic review. International Journal of Clinical Practice, 65(11), pp.1180-1192.
    9. Roy R, et al. (2012). BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer. 2011;12(1):68-78. Published 2011 Dec 23. doi:10.1038/nrc3181.
    10. Wu J, et al. (2010) The role of BRCA1 in DNA damage response. Protein Cell. 2010;1(2):117-123.
    11. Gorodetska I, et al. (2019). BRCA Genes: The Role in Genome Stability, Cancer Stemness and Therapy Resistance. J Cancer. 2019;10(9):2109-2127.
    12. Moore, K. (2018). Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. New England Journal of Medicine, 379(26), pp.2495-2505.

    — WebWireID268312 —


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  28. HOLON, Israel, Dec. 23, 2020 /PRNewswire/ -- Compugen Ltd. (NASDAQ:CGEN), a clinical-stage cancer immunotherapy company and a leader in predictive target discovery, announced today progress from its ongoing license agreement with AstraZeneca (LSE: AZN) (STO: AZN) (NASDAQ:AZN) under which the program has achieved a preclinical milestone. Under the terms of the agreement, Compugen provided an exclusive license to AstraZeneca for the development of bispecific and multi-specific antibody products based on one of Compugen's pipeline programs, with AstraZeneca responsible for all research, development and commercial activities. In connection with this first milestone, Compugen is entitled to receive a $2 million payment from AstraZeneca.

    "AstraZeneca…

    HOLON, Israel, Dec. 23, 2020 /PRNewswire/ -- Compugen Ltd. (NASDAQ:CGEN), a clinical-stage cancer immunotherapy company and a leader in predictive target discovery, announced today progress from its ongoing license agreement with AstraZeneca (LSE: AZN) (STO: AZN) (NASDAQ:AZN) under which the program has achieved a preclinical milestone. Under the terms of the agreement, Compugen provided an exclusive license to AstraZeneca for the development of bispecific and multi-specific antibody products based on one of Compugen's pipeline programs, with AstraZeneca responsible for all research, development and commercial activities. In connection with this first milestone, Compugen is entitled to receive a $2 million payment from AstraZeneca.

    "AstraZeneca choosing Compugen as a partner for its bispecific and multi-specific development plans is testament to the power of our platform, and we are proud that this program has now advanced to demonstrate therapeutic potential," said Anat Cohen-Dayag, Ph.D., President and CEO of Compugen. "This license agreement has enabled Compugen to monetize one of our programs outside our development focus and is part of our larger strategy to selectively collaborate with biopharmaceutical companies to leverage our diverse, computationally-discovered pipeline for the development of novel cancer immunotherapies. We are delighted that AstraZeneca has chosen to continue the development of this bispecific program, providing further validation of Compugen's discovery and development capabilities."

    About the Compugen-AstraZeneca License Agreement

    In April 2018, Compugen and AstraZeneca entered into an agreement by which Compugen provided an exclusive license to AstraZeneca for the development of bispecific and multi-specific antibody products derived from one of Compugen's pipeline programs. AstraZeneca has the right to create multiple products under this license and is solely responsible for all research, development and commercial activities. Compugen received a $10 million upfront payment and is eligible to receive up to $200 million in development, regulatory and commercial milestones for the first product as well as tiered royalties on future product sales. If additional products are developed, additional milestones and royalties would be due to Compugen. Under the terms of the license agreement, Compugen retained all other rights to its entire pipeline of programs as monotherapies and in combination with other products.

    About Compugen

    Compugen is a clinical-stage therapeutic discovery and development company utilizing its broadly applicable, predictive computational discovery platforms to identify novel drug targets and develop therapeutics in the field of cancer immunotherapy. The Company's lead product candidate, COM701, a first-in-class anti-PVRIG antibody, for the treatment of solid tumors, is undergoing a Phase 1 clinical study. In addition, COM902, Compugen's antibody targeting TIGIT, is in a Phase 1 clinical study. The Company's therapeutic pipeline also includes early stage immuno-oncology programs focused largely on myeloid targets. The Company is headquartered in Israel, with offices in South San Francisco, CA. Compugen's shares are listed on the Nasdaq and the Tel Aviv Stock Exchange under the ticker symbol CGEN. For additional information, please visit Compugen's corporate website at www.cgen.com .

    Forward-Looking Statement

    This press release contains "forward-looking statements" within the meaning of the Securities Act of 1933, as amended, the Securities Exchange Act of 1934, as amended, and the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements are based on the current beliefs, expectations and assumptions of Compugen. Forward-looking statements can be identified by the use of terminology such as "will," "may," "expects," "anticipates," "believes," "potential," "plan," "goal," "estimate," "likely," "should," "confident," and "intends," and similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements, including statements related to the payment of the milestone payment and our strategy to selectively collaborate with biopharmaceutical companies, involve known and unknown risks and uncertainties that may cause the actual results, performance or achievements of Compugen to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Among these risks: Compugen's operations could be affected by the outbreak and spread of COVID-19; clinical development involves a lengthy and expensive process, with an uncertain outcome and Compugen may encounter substantial delays or even an inability to begin clinical trials for any specific product, or may not be able to conduct or complete its trials on the timelines it expects; Compugen relies, and expects to continue to rely, on third parties to conduct its clinical trials and if these third parties do not successfully carry out their contractual duties, comply with regulatory requirements or meet expected deadlines (including as a result of the effect of the COVID-19), Compugen may experience significant delays in the conduct of its clinical trials; Compugen's approach to the discovery of therapeutic products is based on its proprietary computational target discovery infrastructure, which is unproven clinically; There can be no assurance that Compugen will be able to discover and develop additional potential product candidates or products of commercial value; Compugen's business model is substantially dependent on entering into collaboration agreements with third parties; and Compugen may not be successful in generating adequate revenues or commercializing aspects of its business model. These risks and other risks are more fully discussed in the "Risk Factors" section of Compugen's most recent Annual Report on Form 20-F as filed with the Securities and Exchange Commission (SEC) as well as other documents that may be subsequently filed by Compugen from time to time with the SEC. In addition, any forward-looking statements represent Compugen's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. Compugen does not assume any obligation to update any forward-looking statements unless required by law. 

    Company contact:

    Elana Holzman

    Director, Investor Relations and Corporate Communications Compugen Ltd.

    Email:

    Tel: +972-(3)-765-8124

    Investor Relations contact:

    Bob Yedid

    LifeSci Advisors, LLC

    Email:  

    Tel: +1-(646)-597-6989

    Media contact:

    Josephine Belluardo, Ph.D.

    LifeSci Communications  

    Email:   

    Tel: +1-(646)-751-4361

    Cision View original content:http://www.prnewswire.com/news-releases/compugen-announces-first-development-milestone-in-license-agreement-with-astrazeneca-for-the-development-of-bispecific-and-multi-specific-antibody-products-301198009.html

    SOURCE Compugen Ltd.

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  29. AstraZeneca's Tagrisso (osimertinib) has been approved in the US for the adjuvant treatment of adult patients with early-stage epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after tumour resection with curative intent. Tagrisso is indicated for EGFRm patients whose tumours have exon 19 deletions or exon 21 L858R mutations as detected by an approved test.

    The approval was granted under the US Food and Drug Administration's (FDA) Real-Time Oncology Review (RTOR) pilot program. Five other countries participated in a concurrent submission and review process through FDA's Project Orbis.

    While up to 30% of all patients with NSCLC may be diagnosed early enough to have potentially curative surgery, disease recurrence…

    AstraZeneca's Tagrisso (osimertinib) has been approved in the US for the adjuvant treatment of adult patients with early-stage epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after tumour resection with curative intent. Tagrisso is indicated for EGFRm patients whose tumours have exon 19 deletions or exon 21 L858R mutations as detected by an approved test.

    The approval was granted under the US Food and Drug Administration's (FDA) Real-Time Oncology Review (RTOR) pilot program. Five other countries participated in a concurrent submission and review process through FDA's Project Orbis.

    While up to 30% of all patients with NSCLC may be diagnosed early enough to have potentially curative surgery, disease recurrence is still common in early-stage disease and nearly half of patients diagnosed in Stage IB, and over three quarters of patients diagnosed in Stage IIIA, experience recurrence within five years.1-4

    The approval was based on results from the ADAURA Phase III trial where Tagrisso demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) in the primary analysis population of patients with Stage II and IIIA EGFRm NSCLC, and also in the overall trial population of patients with Stage IB-IIIA disease, a key secondary endpoint.

    Roy S. Herbst, MD, PhD, chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, New Haven, CT and principal investigator in the ADAURA Phase III trial, said: “Adjuvant Tagrisso has demonstrated an unprecedented disease-free survival benefit for early-stage lung cancer patients with EGFR mutations who face high rates of recurrence even after successful surgery and subsequent chemotherapy. This approval reinforces how critical it is to test all lung cancer patients for EGFR mutations before deciding how to treat them and regardless of their stage at diagnosis. This will help ensure as many patients as possible can benefit from this potentially practice-changing treatment.”

    Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “For the first time, a targeted, biomarker-driven treatment option is available to patients in the US with early-stage EGFR-mutated lung cancer. This approval dispels the notion that treatment is over after surgery and chemotherapy, as the ADAURA results show that Tagrisso can dramatically change the course of this disease. We remain committed to treating cancer patients earlier, when they may still have a chance of being cured.”

    Adjuvant treatment with Tagrisso reduced the risk of disease recurrence or death by 83% in the primary endpoint of DFS in patients with Stage II and IIIA disease (hazard ratio [HR] 0.17; 95% confidence interval [CI] 0.12-0.23; p-0.0001). DFS results in the overall trial population of patients with Stage IB-IIIA disease showed Tagrisso reduced the risk of disease recurrence or death by 80% (HR 0.20; 95% CI 0.15-0.27; p-0.0001). At two years, 89% of patients treated with Tagrisso remained alive and disease free versus 52% on placebo after surgery, the current standard of care. The safety and tolerability of Tagrisso in this trial was consistent with previous trials in the metastatic setting.

    Tagrisso was recently granted Breakthrough Therapy Designation for patients in the early-stage disease setting by the US FDA. In April 2020, an Independent Data Monitoring Committee recommended for the ADAURA trial to be unblinded two years early based on a determination of overwhelming efficacy. Investigators and patients continue to participate in the trial and remain blinded to treatment. The results from the ADAURA trial were presented during the plenary session of the American Society of Clinical Oncology ASCO20 Virtual Scientific Program in May 2020 and were recently published in The New England Journal of Medicine.

    The US regulatory submission was reviewed under the FDA's RTOR pilot program which aims to ensure that safe and effective treatments are available to patients as early as possible. Five national health authorities collaborated with the FDA on this review through Project Orbis, an initiative of the FDA Oncology Center of Excellence, which provides a framework for concurrent submission and review of oncology medicines among international partners. These included Health Canada, the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (Anvisa), Swissmedic, and Singapore Health Sciences Authority. The UK Medicines and Healthcare products Regulatory Agency participated in the review as an observer.

    In China, Tagrisso is under priority review for the adjuvant treatment of patients with early-stage EGFRm NSCLC based on the ADAURA Phase III trial. This indication is also under regulatory review in the EU and additional global submission discussions are ongoing.  

    Tagrisso is a once-daily oral tablet approved for the 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC and for the treatment of locally advanced or metastatic EGFR T790M mutation-positive NSCLC in the US, Japan, China, the EU and many other countries around the world.

    Lung cancer
    Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.5 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.6 The majority of all NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.1-3

    For patients with resectable tumours, the majority of patients eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.4 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.7-8

    Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.9-11 These patients are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which block the cell-signalling pathways that drive the growth of tumour cells.12

    ADAURA
    ADAURA is a randomised, double-blinded, global, placebo-controlled Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, IIIA EGFRm NSCLC following complete tumour resection and adjuvant chemotherapy as indicated. Patients were treated with Tagrisso 80mg once-daily oral tablets or placebo for three years or until disease recurrence.

    The trial enrolled in more than 200 centres across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was DFS in Stage II and IIIA patients and a key secondary endpoint was DFS in Stage IB, II and IIIA patients. The data readout was originally anticipated in 2022. The trial will continue to assess overall survival.

    Tagrisso
    Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with clinical activity against central nervous system metastases Tagrisso 40mg and 80mg once-daily oral tablets have received approval in the US, Japan, China, the EU and many countries around the world for 1st-line EGFRm advanced NSCLC and EGFR T790M mutation-positive advanced NSCLC.

    AstraZeneca in lung cancer
    AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.

    AstraZeneca aims to address the unmet needs of patients with EGFRm tumours as a genetic driver of disease with the approved medicines Iressa (gefitinib) and Tagrisso, and its ongoing Phase III trials LAURA, NeoADAURA, and FLAURA2.

    AstraZeneca is committed to addressing tumour mechanisms of resistance through the ongoing Phase II trials SAVANNAH and ORCHARD which test Tagrisso in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines.

    AstraZeneca in oncology
    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of six scientific platforms - Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies - and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

    AstraZeneca
    AstraZeneca (NASDAQ:AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

    References

    1. Cagle P, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Archives Pathology Lab Med. 2013;137:1191-1198.
    2. Le Chevalier T. Adjuvant Chemotherapy for Resectable Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol. 2010;21:196-8.
    3. Datta D, et al. Preoperative Evaluation of Patients Undergoing Lung Resection Surgery. Chest. 2003;123: 2096–2103.
    4. Pignon et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol 2008;26:3552-3559.
    5. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed August 2020.
    6. LUNGevity Foundation. Types of Lung Cancer. Available at https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer. Accessed August 2020.
    7. Sethi S, et al. Incidental Nodule Management – Should There Be a Formal Process?. Journal of Thorac Onc. 2016:8;S494-S497.
    8. LUNGevity Foundation. Screening and Early Detection. Available at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection#1. Accessed August 2020.
    9. Szumera-Cie&#263;kiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013:6;2800-12.
    10. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-27.
    11. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013:66;79-89.
    12. Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4(9):1046-1061.

    — WebWireID268107 —


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  30. Approval based on unprecedented results from the ADAURA Phase III trial where TAGRISSO reduced the risk of disease recurrence or death by 80%

    AstraZeneca's TAGRISSO® (osimertinib) has been approved in the US for the adjuvant treatment of adult patients with early-stage epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after tumor resection with curative intent. TAGRISSO is indicated for EGFRm patients whose tumors have exon 19 deletions or exon 21 L858R mutations as detected by an approved test.

    The approval was granted under the US Food and Drug Administration's (FDA) Real-Time Oncology Review (RTOR) pilot program. Five other countries participated in a concurrent submission and review process through FDA's…

    Approval based on unprecedented results from the ADAURA Phase III trial where TAGRISSO reduced the risk of disease recurrence or death by 80%

    AstraZeneca's TAGRISSO® (osimertinib) has been approved in the US for the adjuvant treatment of adult patients with early-stage epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after tumor resection with curative intent. TAGRISSO is indicated for EGFRm patients whose tumors have exon 19 deletions or exon 21 L858R mutations as detected by an approved test.

    The approval was granted under the US Food and Drug Administration's (FDA) Real-Time Oncology Review (RTOR) pilot program. Five other countries participated in a concurrent submission and review process through FDA's Project Orbis.

    While up to 30% of all patients with NSCLC may be diagnosed early enough to have potentially curative surgery, disease recurrence is still common in early-stage disease and nearly half of patients diagnosed in Stage IB, and over three quarters of patients diagnosed in Stage IIIA, experience recurrence within five years.1-4

    The approval was based on results from the ADAURA Phase III trial where TAGRISSO demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) in the primary analysis population of patients with Stage II and IIIA EGFRm NSCLC, and also in the overall trial population of patients with Stage IB-IIIA disease, a key secondary endpoint.

    Roy S. Herbst, MD, PhD, chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, New Haven, CT and principal investigator in the ADAURA Phase III trial, said: "Adjuvant TAGRISSO has demonstrated an unprecedented disease-free survival benefit for early-stage lung cancer patients with EGFR mutations who face high rates of recurrence even after successful surgery and subsequent chemotherapy. This approval reinforces how critical it is to test all lung cancer patients for EGFR mutations before deciding how to treat them and regardless of their stage at diagnosis. This will help ensure as many patients as possible can benefit from this potentially practice-changing treatment."

    Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "For the first time, a targeted, biomarker-driven treatment option is available to patients in the US with early-stage EGFR-mutated lung cancer. This approval dispels the notion that treatment is over after surgery and chemotherapy, as the ADAURA results show that TAGRISSO can dramatically change the course of this disease. We remain committed to treating cancer patients earlier, when they may still have a chance of being cured."

    Adjuvant treatment with TAGRISSO reduced the risk of disease recurrence or death by 83% in the primary endpoint of DFS in patients with Stage II and IIIA disease (hazard ratio [HR] 0.17; 95% confidence interval [CI] 0.12-0.23; p<0.0001). DFS results in the overall trial population of patients with Stage IB-IIIA disease showed TAGRISSO reduced the risk of disease recurrence or death by 80% (HR 0.20; 95% CI 0.15-0.27; p<0.0001). At two years, 89% of patients treated with TAGRISSO remained alive and disease free versus 52% on placebo after surgery, the current standard of care. The safety and tolerability of TAGRISSO in this trial was consistent with previous trials in the metastatic setting.

    TAGRISSO was recently granted Breakthrough Therapy Designation for patients in the early-stage disease setting by the US FDA. In April 2020, an Independent Data Monitoring Committee recommended for the ADAURA trial to be unblinded two years early based on a determination of overwhelming efficacy. Investigators and patients continue to participate in the trial and remain blinded to treatment. The results from the ADAURA trial were presented during the plenary session of the American Society of Clinical Oncology ASCO20 Virtual Scientific Program in May 2020 and were recently published in The New England Journal of Medicine.

    The US regulatory submission was reviewed under the FDA's RTOR pilot program which aims to ensure that safe and effective treatments are available to patients as early as possible. Five national health authorities collaborated with the FDA on this review through Project Orbis, an initiative of the FDA Oncology Center of Excellence, which provides a framework for concurrent submission and review of oncology medicines among international partners. These included Health Canada, the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (Anvisa), Swissmedic, and Singapore Health Sciences Authority. The UK Medicines and Healthcare products Regulatory Agency participated in the review as an observer.

    In China, TAGRISSO is under priority review for the adjuvant treatment of patients with early-stage EGFRm NSCLC based on the ADAURA Phase III trial. This indication is also under regulatory review in the EU and additional global submission discussions are ongoing.

    TAGRISSO is a once-daily oral tablet approved for the 1st-line treatment of patients with metastatic EGFRm NSCLC and for the treatment of metastatic EGFR T790M mutation-positive NSCLC in the US, Japan, China, the EU and many other countries around the world.

    TAGRISSO Important Safety Information

    • There are no contraindications for TAGRISSO
    • Interstitial lung disease (ILD)/pneumonitis occurred in 3.7% of the 1479 TAGRISSO-treated patients; 0.3% of cases were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed
    • Heart rate-corrected QT (QTc) interval prolongation occurred in TAGRISSO-treated patients. Of the 1479 TAGRISSO-treated patients in clinical trials, 0.8% were found to have a QTc >500 msec, and 3.1% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
    • Cardiomyopathy occurred in 3% of the 1479 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 3.2% of 1233 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. Conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO
    • Keratitis was reported in 0.7% of 1479 patients treated with TAGRISSO in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist
    • Postmarketing cases consistent with Stevens-Johnson syndrome (SJS) and erythema multiforme major (EMM) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if SJS or EMM is suspected and permanently discontinue if confirmed
    • Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity
    • Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose
    • Most common (≥20%) adverse reactions, including laboratory abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough

    INDICATIONS

    • TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
    • TAGRISSO is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
    • TAGRISSO is indicated for the treatment of adult patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy

    For additional information, please see the complete Prescribing Information, including Patient Information.

    Lung cancer

    Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.5 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.6 The majority of all NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.1-3

    For those with resectable tumors, the majority of patients eventually develop recurrence despite complete tumor resection and adjuvant chemotherapy.4 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.7,8

    Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.9-11 These patients are particularly sensitive to treatment with EGFR-tyrosine kinase inhibitors (TKIs) which block the cell-signaling pathways that drive the growth of tumor cells.12

    About ADAURA

    ADAURA is a randomized, double-blinded, global, placebo-controlled Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, IIIA EGFRm NSCLC following complete tumor resection and adjuvant chemotherapy as indicated. Patients were treated with TAGRISSO 80 mg once-daily oral tablets or placebo for three years or until disease recurrence.

    The trial enrolled in more than 200 centers across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was DFS in Stage II and IIIA patients and a key secondary endpoint was DFS in Stage IB, II and IIIA patients. The data readout was originally anticipated in 2022. The trial will continue to assess overall survival.

    About TAGRISSO

    TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with clinical activity against central nervous system metastases. TAGRISSO 40 mg and 80 mg once-daily oral tablets have received approval in the US, Japan, China, the EU and many countries around the world for 1st-line EGFRm metastatic NSCLC and EGFR T790M mutation-positive metastatic NSCLC.

    AstraZeneca in lung cancer

    AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.

    AstraZeneca aims to address the unmet needs of patients with EGFRm tumors as a genetic driver of disease with the approved medicines gefitinib and TAGRISSO, and its ongoing LAURA, NeoADAURA, and FLAURA2 Phase III trials.

    AstraZeneca is committed to addressing tumor mechanisms of resistance through the ongoing Phase II trials SAVANNAH and ORCHARD which test TAGRISSO in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines.

    AstraZeneca in oncology

    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of six scientific platforms - Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies - and by championing the development of personalized combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

    AstraZeneca

    AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit https://www.astrazeneca-us.com/ and follow us on Twitter @AstraZenecaUS.

    References

    1. Cagle P, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med. 2013;137:1191-1198.
    2. Le Chevalier T. Adjuvant Chemotherapy for Resectable Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol. 2010;21:196-198.
    3. Datta D, et al. Preoperative Evaluation of Patients Undergoing Lung Resection Surgery. Chest. 2003;123:2096-2103.
    4. Pignon et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26:3552-3559.
    5. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed August 2020.
    6. LUNGevity Foundation. Types of Lung Cancer. https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer. Accessed August 2020.
    7. Sethi S, et al. Incidental Nodule Management – Should There Be a Formal Process? J Thorac Dis. 2016;8:S494-S497.
    8. LUNGevity Foundation. Screening and Early Detection. https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection#1. Accessed August 2020.
    9. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013;6:2800-2812.
    10. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011;29:2121-2127.
    11. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013:66:79-89.
    12. Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4(9):1046-1061.

    US-43163 Last Updated 12/20

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  31. AstraZeneca's Imfinzi (durvalumab) has been recommended for marketing authorisation in the European Union (EU) for an additional dosing option, 1,500mg fixed dose every four weeks, in the approved indication of locally advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on at least 1% of tumour cells and whose disease has not progressed following platinum-based chemoradiation therapy (CRT).

    This new dosing option is consistent with the approved Imfinzi dosing in extensive-stage small cell lung cancer (ES-SCLC) and once approved, will be available to patients with locally advanced, unresectable NSCLC weighing more than 30kg.

    Following review of the application under its accelerated assessment procedure…

    AstraZeneca's Imfinzi (durvalumab) has been recommended for marketing authorisation in the European Union (EU) for an additional dosing option, 1,500mg fixed dose every four weeks, in the approved indication of locally advanced, unresectable non-small cell lung cancer (NSCLC) in adults whose tumours express PD-L1 on at least 1% of tumour cells and whose disease has not progressed following platinum-based chemoradiation therapy (CRT).

    This new dosing option is consistent with the approved Imfinzi dosing in extensive-stage small cell lung cancer (ES-SCLC) and once approved, will be available to patients with locally advanced, unresectable NSCLC weighing more than 30kg.

    Following review of the application under its accelerated assessment procedure, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on data from several Imfinzi clinical trials, including the PACIFIC Phase III trial which supported the two-week, weight-based dosing of 10mg/kg every two weeks already approved in locally advanced, unresectable NSCLC, and the CASPIAN Phase III trial which used fixed dosing every four weeks during maintenance treatment in ES-SCLC.

    José Baselga, Executive Vice President, Oncology R&D, said: “The four-week dosing regimen will decrease the risk of exposure to infection in the healthcare setting, furthering our efforts to ensure continuity of care for cancer patients at high risk of complications during the pandemic. We look forward to offering non-small cell lung cancer patients in Europe an option that would reduce medical visits by extending dosing from two to four weeks.”

    Imfinzi was recently approved in the US for this dosing regimen. Imfinzi is approved in the curative-intent setting of unresectable, Stage III (locally advanced) NSCLC after CRT in the EU, US, Japan, China and many other countries, based on the PACIFIC Phase III trial. Additionally, it is approved in the EU, US, Japan and many other countries around the world for the treatment of ES-SCLC based on the CASPIAN Phase III trial.

    Stage III NSCLC

    Stage III (locally advanced) NSCLC is commonly divided into three subcategories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally and the possibility of surgery.1 Stage III disease is different from Stage IV disease, when the cancer has spread (metastasised), as the majority of Stage III patients are currently treated with curative intent.1,2

    Stage III NSCLC represents approximately one third of NSCLC incidence and in 2015 was estimated to affect nearly 200,000 patients in the following eight large countries: China, France, Germany, Italy, Japan, Spain, UK, and the US, with approximately 43,000 cases in the US alone.3,4 The majority of Stage III NSCLC patients are diagnosed with unresectable tumours.5 Prior to approval of Imfinzi in this setting, no new treatments beyond CRT had been available to patients for decades.6-8

    Small cell lung cancer

    SCLC is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly, despite initial response to chemotherapy.9,10 About two thirds of SCLC patients are diagnosed with extensive-stage disease, in which the cancer has spread widely through the lung or to other parts of the body.11 Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.11

    Imfinzi

    Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.

    Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and several other countries.

    As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combinations including with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, oesophageal cancer, gastric cancer, cervical cancer and other solid tumours.

    AstraZeneca in lung cancer

    AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action.

    An extensive Immuno-Oncology (IO) development programme focuses on lung cancer patients without a targetable genetic mutation which represents up to three-quarters of all patients with lung cancer.12 Imfinzi, an anti-PDL1 antibody, is in development for patients with advanced disease (POSEIDON and PEARL Phase III trials) and for patients in earlier stages of disease including potentially-curative settings (MERMAID-1, MERMAID-2, AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC Phase III trials) both as monotherapy and in combination with tremelimumab and/or chemotherapy.

    Imfinzi is also in development in the NeoCOAST, COAST and HUDSON Phase II trials in combination with potential new medicines from the early-stage pipeline including Enhertu (trastuzumab deruxtecan).

    AstraZeneca's approach to IO

    IO is a therapeutic approach designed to stimulate the body's immune system to attack tumours. The Company's IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

    The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a monotherapy and in combination with tremelimumab in multiple tumour types, stages of disease, and lines of therapy, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small targeted molecules from across AstraZeneca's Oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

    AstraZeneca in oncology

    AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients' lives and the Company's future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

    By harnessing the power of six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

    AstraZeneca

    AstraZeneca (NASDAQ:AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com

    ------

    1. ASCO. Cancer.net. Lung Cancer – Non-Small Cell. Available at: https://www.cancer.net/cancer-types/lung-cancer/view-all. Accessed September 2020.

    2. Cheema PK, et al. Perspectives on Treatment Advances For Stage III Locally Advanced Unresectable Non-Small-Cell Lung Cancer. Curr Oncol. 2019;26(1):37-42. Accessed September 2020.

    3. Antonia SJ, et al. PACIFIC Investigators. Durvalumab After Chemoradiotherapy In Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377(20):1919-1929.

    4. EpiCast Report: NSCLC Epidemiology Forecast to 2025. GlobalData. 2016.

    5. Provencio M, et al. Inoperable Stage III Non-Small Cell Lung Cancer: Current Treatment And Role Of Vinorelbine. J Thorac Dis. 2011;3:197-204. Accessed September 2020.

    6. Curran WJ, et al. Sequential vs Concurrent Chemoradiation for Stage III Non–Small Cell Lung Cancer: Randomized Phase III Trial RTOG 9410. J Natl Cancer Inst. 2011;103(19):1452-1460.

    7. NCCN. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) - Non-Small Cell Lung Cancer. Version 8. 2017. https://www.nccn.org/professionals/physician_gls/pdf/nscl_blocks.pdf. Accessed September 2020.

    8. Hanna N, et al. Current Standards and Clinical Trials in Systemic Therapy for Stage III Lung Cancer: What is New? Am Soc Clin Oncol Educ Book. 2015:e442-447.

    9. Kalemkerian GP, et al. Treatment Options for Relapsed Small-Cell Lung Cancer: What Progress Have We Made? J Oncol Pract. 2018;14(6):369-370.

    10. National Cancer Institute. NCI Dictionary – Small Cell Lung Cancer. Available at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer. Accessed November 2020.

    11. Cancer.Net. Lung Cancer - Small Cell. Available at https://www.cancer.net/cancer-types/lung-cancer-small-cell. Accessed November 2020.

    12. Pakkala, S, et al. Personalized therapy for lung cancer: striking a moving target. JCI Insight. 2018;3(15):e120858.

    — WebWireID267959 —


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  32. Greater scientific presence in immunology by adding Alexion's innovative complement-technology platforms and strong pipeline 

    Dedicated rare disease unit to be headquartered in Boston

     Geographical presence to be enhanced with broad coverage across primary, speciality and highly specialised care

     Double-digit revenue growth through 2025; acquisition strengthens AstraZeneca's broad-based revenue and the company will further globalise Alexion's portfolio 

    Enhanced operating margin and cash flow to enable rapid debt reduction with an ambition to increase the dividend

    The acquisition will be immediately core earnings-accretive and value-enhancing, and is aligned with stated capital-allocation priorities

    AstraZeneca and Alexion Pharmaceuticals…

    Greater scientific presence in immunology by adding Alexion's innovative complement-technology platforms and strong pipeline 

    Dedicated rare disease unit to be headquartered in Boston

     Geographical presence to be enhanced with broad coverage across primary, speciality and highly specialised care

     Double-digit revenue growth through 2025; acquisition strengthens AstraZeneca's broad-based revenue and the company will further globalise Alexion's portfolio 

    Enhanced operating margin and cash flow to enable rapid debt reduction with an ambition to increase the dividend

    The acquisition will be immediately core earnings-accretive and value-enhancing, and is aligned with stated capital-allocation priorities

    AstraZeneca and Alexion Pharmaceuticals, Inc. (Alexion) have entered into a definitive agreement for AstraZeneca to acquire Alexion.

    This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20201212005016/en/

    Alexion shareholders will receive $60 in cash and 2.1243 AstraZeneca American Depositary Shares (ADSs) (each ADS representing one-half of one (1/2) ordinary share of AstraZeneca, as evidenced by American Depositary Receipts (ADRs)) for each Alexion share. Based on AstraZeneca's reference average ADR price of $54.14, this implies total consideration to Alexion shareholders of $39bn or $175 per share.

    The boards of directors of both companies have unanimously approved the acquisition. Subject to receipt of regulatory clearances and approval by shareholders of both companies, the acquisition is expected to close in Q3 2021, and upon completion, Alexion shareholders will own c.15% of the combined company.

    Pascal Soriot, Chief Executive Officer, AstraZeneca, said: "Alexion has established itself as a leader in complement biology, bringing life-changing benefits to patients with rare diseases. This acquisition allows us to enhance our presence in immunology. We look forward to welcoming our new colleagues at Alexion so that we can together build on our combined expertise in immunology and precision medicines to drive innovation that delivers life-changing medicines for more patients."

    Ludwig Hantson, Ph.D., Chief Executive Officer, Alexion, said: "For nearly 30 years Alexion has worked to develop and deliver transformative medicines to patients around the world with rare and devastating diseases. I am incredibly proud of what our organisation has accomplished and am grateful to our employees for their contributions. This transaction marks the start of an exciting new chapter for Alexion. We bring to AstraZeneca a strong portfolio, innovative rare disease pipeline, a talented global workforce and strong manufacturing capabilities in biologics. We remain committed to continuing to serve the patients who rely on our medicines and firmly believe the combined organisation will be well positioned to accelerate innovation and deliver enhanced value for our shareholders, patients and the rare disease communities."

    Strategic rationale

    Both companies share the same dedication to science and innovation to deliver life-changing medicines. The capabilities of both organisations will create a company with great strengths across a range of technology platforms, with the ability to bring innovative medicines to millions of people worldwide. The combined company will also have an enhanced global footprint and broad coverage across primary, speciality and highly specialised care.

    Scientific leadership - accelerated presence in immunology

    AstraZeneca has built a growing scientific presence in oncology, and in cardiovascular, renal and metabolism, and respiratory diseases, with a focus on organ protection. AstraZeneca has developed a broad range of technologies, initially focused on small molecules and biologics and with a growing focus in precision medicine, genomics, oligonucleotides and epigenetics. More recently, AstraZeneca has increased its efforts in immunology research and the development of medicines for immune-mediated diseases.

    Alexion has pioneered complement inhibition for a broad spectrum of immune-mediated rare diseases caused by uncontrolled activation of the complement system, a vital part of the immune system. Alexion's franchise includes Soliris (eculizumab), a first-in-class anti-complement component 5 (C5) monoclonal antibody. The medicine is approved in many countries for the treatment of patients with paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uremic syndrome, generalized myasthenia gravis and neuromyelitis optica spectrum disorder. More recently, Alexion launched Ultomiris (ravulizumab), a second-generation C5 monoclonal antibody with a more convenient dosing regimen.

    Alexion's immunology expertise extends to other targets in the complement cascade beyond C5 as well as additional modalities, with its dee