On August 25, 2022 Novartis reported its intention to separate Sandoz, its generics and biosimilars division into a new publicly traded standalone company, by way of a 100% spin-off (Press release, Novartis, AUG 25, 2022, View Source [SID1234618660]).

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The spin-off aims to maximize shareholder value by creating the #1 European generics company1 and a global leader in biosimilars, allowing Novartis shareholders to participate fully in the potential future upside for both Sandoz and Novartis Innovative Medicines.

For both the Innovative Medicines and Sandoz businesses, the spin-off would enable enhanced focus and the ability to pursue independent growth strategies. Sandoz is expected to deliver its next wave of growth based on the existing biosimilars pipeline of 15+ molecules, a strong and experienced management team and organization. Novartis aims to become a focused innovative medicines company with a stronger financial profile, and improved return on capital.

The standalone Sandoz would be headquartered in Switzerland and listed on the SIX Swiss Exchange, with an American Depositary Receipt (ADR) program in the US.

Joerg Reinhardt, Chair of the Board of Directors of Novartis, said: "Our strategic review examined all options for Sandoz and concluded that a 100% spin-off is in the best interest of shareholders. A spin-off would allow our shareholders to benefit from the potential future successes of a more focused Novartis and a standalone Sandoz, and would offer differentiated and clear investment theses for the individual businesses. Sandoz would become the publicly traded #1 European generics company and a global leader in biosimilars based in Switzerland."

Vas Narasimhan M.D., CEO of Novartis, said: "For Novartis, the separation of Sandoz would further support our strategy of building a focused innovative medicines company, with depth in five core therapeutic areas, and strength in technology platforms. In addition, both companies would be able to focus on maximizing value creation for their shareholders by prioritizing capital and resource allocation, employing separate capital structure policies, and increasing management focus on their respective business needs."

Novartis: Focused Innovative Medicines Company
Novartis will continue expanding its strong position in five core therapeutic areas (Hematology, Solid Tumors, Immunology, Neuroscience and Cardiovascular), strength in technology platforms (Gene Therapy, Cell Therapy, Radioligand Therapy, Targeted Protein Degradation and xRNA), and a balanced geographic footprint. Novartis will also continue progressing the implementation of its new organizational structure announced in April 2022, integrating the Pharmaceuticals and Oncology business units with separate US and International commercial organizations supported by a new Strategy & Growth function and Operations unit to increase focus, strengthen competitiveness and drive synergies. Novartis remains committed to its strong investment-grade credit rating and capital allocation priorities, including our growing (CHF) annual dividend.

Sandoz: #1 European Generics Company and a Global Leader in Biosimilars
Sandoz generated USD 9.6bn sales in 2021 sales and served 100+ markets globally with a strong presence in Europe as well as in the United States and Rest of World. Sandoz would leverage its strong brand and sustain its leading global position by continuing to invest in the key strategic areas of Biosimilars, Antibiotics and Generic Medicines.

As a standalone company, Sandoz would focus on its vision to deliver access to patients, leveraging the business’ strengths and purpose-driven workforce. Sandoz would execute on a growth strategy with a focused approach to deploy resources efficiently and effectively, strengthen key platforms and deliver launch excellence. Following the proposed spin-off, Sandoz would target an investment grade credit rating, providing sufficient financial flexibility to deliver on its growth plans, invest in incremental growth opportunities, with a vision to deliver attractive dividends. An update on Sandoz’s planned dividend policy will be provided in due course. Any Sandoz dividends would be incremental to Novartis dividends.

Additional Transaction Details
Completion of the proposed spin-off is subject to satisfaction of certain conditions, including consultation with works councils and employee representatives (as required), general market conditions, receipt of favorable tax rulings and opinions, final endorsement by the Board of Directors of Novartis AG and shareholder approval. There can be no assurance regarding the ultimate timing of the proposed transaction or that the transaction will be completed. Further details of the proposed spin-off, including the proposed distribution ratio, detailed timeline and the composition of the board of directors of Sandoz will be provided at a later date.

Conference call
Novartis will hold an investor and analyst webcast today at 16:00 CET

1 Based on IQVIA gross sales for combined Generics and Biosimilars market, referring to March 2022

On August 25, 2022 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported the preliminary results of its rights offering which expired at 5:00 P.M. Eastern Time on August 24, 2022 (Press release, Navidea Biopharmaceuticals, AUG 25, 2022, View Source [SID1234618659]). The Company estimates that the rights offering will result in total subscriptions of approximately $14.2 million. Navidea expects to receive from the rights offering aggregate gross cash proceeds of approximately $6.1 million (excluding additional proceeds of up to $15.8 million from the exercise of warrants issued in the rights offering, if any such exercises occur), and the exchange and cancellation of all of its outstanding shares of Series D, Series F and Series G preferred stock having an aggregate fair market value of $8.05 million, plus accrued dividends. The results of the rights offering are preliminary and subject to change pending finalization and verification by Navidea and its subscription agent, Broadridge Corporate Issuer Solutions, Inc.

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Each right entitled the holder to purchase one unit, at a subscription price of $1,000 per unit, consisting of one (1) share of the Company’s newly created Series I Convertible Preferred Stock with a face value of $1,000 (and immediately convertible into shares of Navidea’s common stock at a conversion price of $0.45 per share) and one (1) warrant to purchase 2,222 shares of Navidea’s common stock with an exercise price of $0.50 per share.

Navidea anticipates that closing of the rights offering will occur on or about August 29, 2022, subject to satisfaction or waiver of all conditions to closing. Upon the closing, the subscription agent will distribute, by way of direct registration in book-entry form or through the facilities of DTC, as applicable, shares of its Series I convertible preferred stock and warrants to holders of rights who have validly exercised their rights and paid the subscription price in full. No physical stock or warrant certificates will be issued to such holders.

Maxim Group LLC acted as dealer-manager for the rights offering. Questions about the rights offering or requests for copies of the preliminary and final prospectuses may be directed to Maxim Group LLC at 300 Park Avenue, New York, NY 10022, Attention Syndicate Department, or via email at [email protected] or telephone at (212) 895-3745.

The Company’s registration statement on Form S-1 was declared effective by the U.S. Securities and Exchange Commission (SEC) on August 3, 2022. The prospectus relating to and describing the terms of the rights offering has been filed with the SEC as a part of the registration statement and is available on the SEC’s web site at View Source This press release does not constitute an offer to sell or the solicitation of an offer to buy these securities, nor will there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On August 25, 2022 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported its corporate highlights and unaudited financial results for the first half-year of 2022 (Press release, Molecular Partners, AUG 25, 2022, View Source [SID1234618658]).

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"In the first half of this year, we have delivered a major clinical success with ensovibep, leading to its licensure by our partner Novartis and a position of financial strength to execute on the next phase of our strategy at full speed," said Patrick Amstutz, Ph.D., CEO of Molecular Partners. "Programs like ensovibep and our trispecific T-cell engager for AML, MP0533, represent our strategic focus: highly differentiated approaches to major diseases that leverage the strengths of the DARPin class. Using our leading platform, we are focused on advancing and growing our pipeline to meaningfully impact treatment for patients."

Research & Development Highlights:

MP0317 (FAP x CD40):

Phase 1 open-label dose escalation study continues in patients with solid tumors known to express FAP. Initial clinical data from this study expected to be presented at a conference in the second half of 2022
Preclinical data published in Cancer Immunology Research supporting MP0317’s potential to deliver tumor-localized immune activation while avoiding systemic toxicity seen with other CD40-targeting agents
MP0533 (CD3 x CD33 x CD70 x CD123)

Lead candidate, MP0533, selected, following continued promising preclinical data supporting its unique design and mechanism. It is expected to reach clinical development by year end
New in vivo data from the MP0533 program were presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in June 2022
DARPin-Radioligand Therapies

Novartis partnered program ongoing
Proprietary programs now advancing
Ensovibep COVID-19 antiviral program

In January 2022, Novartis exercised its option to in-license ensovibep and is now solely responsible for further development, manufacturing, and commercialization activities. Upon exercise of the option, Molecular Partners received a payment of CHF 150 million, which was in addition to the initial upfront payment of CHF 60 million, from Novartis
Novartis submitted an application for Emergency Use Authorization (EUA) to the
U.S. Food and Drug Administration (FDA) in February 2022, following positive, topline results from the primary analysis of the Phase 2 EMPATHY clinical trial. As previously announced, the FDA has asked that Phase 3 data be provided for their review. Novartis is currently engaged in developing a Phase 3 protocol
The primary analysis from Phase 2 of the EMPATHY clinical trial was presented at the 2022 European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in April 2022
Key preclinical data documenting the unique design and mechanism of action of ensovibep were published in Nature Biotechnology in July 2022, in a paper titled "The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants"
MP0310 (FAP x 4-1BB)

Amgen has returned the global rights for MP0310 following a strategic pipeline review. The last patient has been dosed in the Phase 1 study, and the study data are currently being collected and reviewed. The results of the full analysis will inform further business development activity. No additional internal investment in the program is currently planned
Abicipar for wet age-related macular degeneration

Evaluation of business development opportunities for pivotal-stage asset continues, informed by correspondence with the FDA and discussions with potential partners
Oncology: MP0533 approaching Phase 1 initiation; Phase 1 trials of MP0317 and MP0310; Development of a DARPin-based radioligand program

MP0533, Molecular Partners’ novel acute myeloid leukemia (AML) candidate, is a DARPin designed to engage CD3 on T cells while binding up to three tumor-associated antigens (CD33, CD70, and CD123) on AML cells. Preclinical studies have shown that MP0533 T cell activation and tumor killing increased significantly with the number of tumor-associated antigens present. This ‘avidity-dependent’ mechanism, enabled by the DARPin platform, can lead to preferential targeting of AML cells which, unlike healthy cells, generally express two or more of these antigens. Once bound, the AML cells are marked for termination by nearby T cells. Half-life extension of MP0533 is ensured by its HSA (human serum albumin)-binding DARPins, making the drug compatible with weekly dosing. MP0533 is on track to begin clinical development before the end of 2022.

MP0317 binds both the fibroblast activation protein (FAP) and the immunostimulatory protein CD40. It also contains an HSA-binding DARPin for half-life extension. It is designed to enable tumor-localized immune activation with fewer side effects compared to other CD40-targeting agents. The ongoing Phase 1 trial of MP0317 is expected to enroll up to 30 patients, dosed once every 3 weeks, across six dosing cohorts and up to 15 patients are then expected to be enrolled in a dose expansion cohort. Further, the Company plans to test a weekly dosing regimen to provide potential options for future combinations with either immunotherapy, radiation, or chemotherapy. In addition to evaluating safety, tolerability, and pharmacokinetics of a monotherapy, the study plans to gather a variety of biomarker data to support the establishment of combination therapies with MP0317 in specific indications.

MP0310 is designed to deliver tumor-localized activation of the immunostimulatory 4-1BB protein. A Phase 1 study of this candidate as a treatment for solid tumors has concluded patient enrollment and is expected to yield a full dataset in the second half of 2022. Following Amgen’s return of global rights to MP0310 to the Company, the Phase 1 dataset will inform potential further business development activity.

Thanks to their small size and their high specificity and affinity, DARPins represent ideal delivery vectors for therapeutic radionuclides to efficiently target cancer cells with minimal systemic side effects. Molecular Partners is developing new DARPin-based radioligand therapy (DARPin-RLT) candidates internally, and in collaboration with Novartis. DARPin-RLTs have the potential to selectively deliver targeted radionuclides deeply into the tumor, with long tumor retention, causing direct tumor cell killing. In the Novartis partnership, the two companies plan to combine DARPins’ unique properties, including small size and high affinity and specificity, with the RLT capabilities and expertise of Novartis. Under the terms of the agreement, Molecular Partners will collaborate with Novartis to discover DARPins that target specific tumor-associated antigens. Both parties will collaborate on the discovery and optimization of therapeutic DARPin-RLT candidates for further development.

Ensovibep for COVID-19: In partnership with Novartis

Pursuant to the Company’s Option and Equity Rights Agreement executed in October 2020 with Novartis, Novartis exercised its option to in-license ensovibep in January 2022, triggering a milestone payment of CHF 150 million to Molecular Partners. Novartis is now responsible for further development, manufacturing, distribution, and commercialization activities.

Ensovibep is an investigational treatment, designed specifically to inhibit SARS-CoV-2, the virus that causes COVID-19. It is made up of five DARPin domains, three domains that bind to the SARS-CoV-2 spike protein, and two domains that are intended to extend half-life. It is the first clinical-stage trispecific antiviral candidate for COVID-19.

As announced in January 2022, Phase 2 of the EMPATHY clinical trial – a randomized, placebo-controlled study which enrolled 407 symptomatic patients infected with SARS-CoV-2 – met its primary endpoint with a statistically significant reduction in viral load over eight days in the ensovibep arms, compared to placebo. The secondary endpoint of hospitalization and/or emergency room (ER) visits related to
COVID-19, or death was met by showing an overall 78% reduction in relative risk of events across all ensovibep arms, compared to placebo. Following discussions with the FDA, the Agency has asked that Phase 3 data be provided for their review. Novartis is currently engaged in developing a Phase 3 study protocol.

Based on the strong clinical performance of ensovibep, Molecular Partners is assessing further viral disease areas where DARPins may offer advantages over existing antivirals or where no effective treatments exist.

Ophthalmology

In August 2021, Molecular Partners regained global development and commercial rights to abicipar for the treatment of neovascular age-related macular degeneration (nAMD) and Diabetic Macular Edema (DME). Abicipar went through two positive Phase 3 studies, CEDAR and SEQUOIA, which supported the non-inferior efficacy of its quarterly dosing regimen compared to monthly ranibizumab.

The Company is currently evaluating potential business development opportunities for abicipar. Based on correspondence with the FDA and discussions with potential partners, the options for resumed development may include the development and commercialization program by a partner, or the formation of a new company focused on abicipar with new investors and a dedicated management team.

Leadership & Governance

Chief Executive Officer Patrick Amstutz was elected as President of the Swiss Biotech Association Board of Directors on May 3, 2022. Switzerland has become one of the global hubs for life sciences and this position will allow Dr. Amstutz the opportunity to provide leadership and influence in the biopharma industry both regionally and globally.

Alexander Zürcher was promoted to Chief Operating Officer, effective as of July 1, 2022. Coinciding with Alexander’s promotion, Michael Stumpp, the Company’s prior COO, transitioned to the newly formed position of EVP Projects while remaining a member of the Company’s Management Board. Renate Gloggner was promoted to EVP People and Community, effective as of July 1, 2022. Both Alexander and Renate were appointed to the Company’s Management Board, also effective as of July 1, 2022.

At the Company’s 2022 Annual General Meeting held on April 13, 2022, the Company’s shareholders approved all motions proposed by the Board of Directors, including the re-election of all members of the Board of Directors for a term of office of one year, as well as of William Burns as Chairman of the Board, the renewal of the authorized share capital for a period of two years until April 13, 2024, and all motions regarding compensation of the Board of Directors and the Management Board.

Expansion of ESG initiative

As an innovative biotechnology company, Molecular Partners’ purpose is to find, develop, and bring to market novel therapeutics to improve the lives of patients across the globe. Molecular Partners’ company-wide efforts to develop a COVID-19 treatment for the world, ensovibep, exemplify this well. When partnering with Novartis to fight COVID-19, the Company and Novartis agreed to waive profits from ensovibep in developing regions as part of a commitment to corporate social responsibility in a time of urgent global medical need. In oncology, Molecular Partners is focusing the powers of its platform toward finding truly innovative therapeutics for diseases that currently have no sustainable solution, such as in the Company’s recent work in AML, a blood cancer with no reliably effective treatment, where the Company advancing a differentiated potential option for patients through DARPins.

Molecular Partners believes that its growth and constant improvement as a company are closely linked to the well-being and growth of its employees. As a part of that, the Company is focused on programs to support its internal culture, encouraging employees to show initiative, integrity, and to strive to excellence in their work.

Finally, Molecular Partners’ believes it is crucial to foster a socially and environmentally aware company culture, which it believes helps its team to better appreciate their contribution to society and the importance of their work. To help accomplish all of this, the Company has engaged external support to help guide its ESG strategy development as the next step toward executing on an ESG plan with practical and best practice metrics.

Creation of Treasury Shares

The Company today reports that it has created 3,500,000 treasury shares with a nominal value of CHF 0.10 each, thereby increasing its registered share capital from CHF 3,229,264.80 to CHF 3,579,264.80. The new shares, created on August 25, 2022 out of the Company’s authorized share capital, were subscribed by Molecular Partners Inc., the Company’s wholly owned subsidiary, and subsequently transferred at nominal value to the Company, and are expected to be listed on the SIX Swiss Exchange on or around August 26, 2022. With this increase, the Company now holds treasury shares that can be used in the future to raise funds in an efficient manner, including in connection with the Company’s at-the-market sales program for American Depositary Shares that the Company established in July 2022.

H1 2022 operational and financial highlights:

Strong financial position with CHF 285.1 million in cash (including short term deposits)
as of June 30, 2022
Revenue of CHF 184.5 million primarily due to payment received from Novartis upon exercise of option to in-license global rights to ensovibep
Net cash from operating activities of CHF 151.0 million in H1 2022
Operating profit of CHF 146.3 million and net profit of CHF 148.6 million in H1 2022
Company expected to be funded into 2026, excluding any potential payments from R&D partnerships
The H1 2022 Financial Statements are available on the company’s website

Business Outlook and Priorities

With expected funding into 2026 and several programs across infectious diseases, immuno-oncology, and ophthalmology, Molecular Partners is well-resourced to continue expanding the capabilities of its DARPin platform and the breadth and differentiation of its DARPin therapeutic candidates.

Initial data for the Phase 1 open-label dose escalation study of MP0317 (FAP x CD40) are expected in the second half of 2022 and MP0533 (CD3 x CD33 x CD70 x CD123) for AML are expected to reach clinical development in the second half of 2022.

Financial outlook 2022

For the full year 2022, at constant exchange rates, the Company expects total expenses of CHF 70 – 80 million, of which approximately CHF 9 million will be non-cash effective costs for share-based payments, IFRS pension accounting and depreciation. This cash flow guidance does not include any potential receipts from R&D partnerships.

With CHF 285.1 million in cash and short-term time deposits and no debt as of June 30, 2022, the Company expects to be funded into 2026, excluding any potential receipts from R&D partners.

Documentation
The results presentation, this press release, and the half-year 2022 report will be made available on www.molecularpartners.com after 10pm CET on August 25, 2022.

Half year 2022 conference call & audio webcast – August 26, 2022 – 2pm CET, 8am ET

The half year 2022 results presentation will be webcast live and made available on the Company’s website under the investor section. The replay will be available for 90 days following the presentation.

In order to register for the H1 2022 conference call on Friday, August 26, 2pm CET / 8am ET, please dial the following numbers approximately 10 minutes before the start of the presentation:

The latest timing of the above events can always be viewed on the investor section of the website.

About DARPin therapeutics

DARPin therapeutics are a new class of custom-built protein therapeutics based on natural binding proteins that open a new dimension of multi-functionality and multi-target specificity in drug design. A single DARPin candidate can engage more than five targets, and its flexible architecture and small size offer benefits over other currently available protein therapeutics. DARPin therapeutics have been clinically validated through to registration via the development of abicipar, Molecular Partners’ most advanced DARPin drug candidate. The DARPin platform is a fast and cost-effective drug discovery engine, producing drug candidates with optimized properties for development and very high production yields.

On August 25, 2022 AstraZeneca and Merck, known as MSD outside of the United States and Canada, reported that LYNPARZA has been approved by the Japan Pharmaceuticals and Medical Devices Agency (PMDA) for the adjuvant treatment for patients with BRCA-mutated (BRCAm), human epidermal growth factor receptor 2 (HER2)-negative high recurrent risk breast cancer (Press release, Merck & Co, AUG 25, 2022, View Source [SID1234618657]).

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This approval was based on results from the Phase 3 OlympiA trial published in The New England Journal of Medicine in June 2021. In the trial, LYNPARZA demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS), reducing the risk of invasive breast cancer recurrences, new cancers, or death by 42% (HR=0.58 [99.5% CI, 0.41-0.82]; p<0.0001) versus placebo.

LYNPARZA also demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), reducing the risk of death by 32% (HR=0.68 [98.5% CI, 0.47-0.97]; p=0.009) versus placebo. The safety and tolerability profile of LYNPARZA in this trial was in line with that observed in prior clinical trials. The most common adverse reactions (ARs) ≥10% for LYNPARZA were nausea (57%), fatigue (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%) and stomatitis (10%). Approximately 10% of patients who received LYNPARZA discontinued treatment due to an AR. The most common Grade ≥3 ARs for LYNPARZA were anemia (9%), neutropenia (5%), leukopenia (3%) and fatigue (1.8%).

Breast cancer is the most commonly diagnosed cancer worldwide, with an estimated 2.3 million patients diagnosed in 2020. In 2022, breast cancer is estimated to account for 95,000 new cases and over 15,000 deaths in Japan. Over 90% of all breast cancer patients in Japan are diagnosed with early breast cancer. BRCA mutations are found in approximately 10% of HER2-negative patients.

Professor Andrew Tutt, global chair of the OlympiA trial and professor of oncology, The Institute of Cancer Research, London and King’s College London, said, "Today’s approval marks a new era of care for patients in Japan. For patients with high-risk early-stage breast cancer, including those with germline BRCA mutations, recurrence rates remain unacceptably high, with more than one in four of these patients seeing their cancer return following surgery and systemic treatment. Today’s approval offers eligible patients in Japan an effective and targeted treatment that improves survival and helps to prevent cancer recurrence."

Dave Fredrickson, executive vice president, oncology business unit, AstraZeneca, said, "Today’s approval marks a significant leap forward for breast cancer patients in Japan, where it is the most commonly diagnosed cancer among women. Patients with BRCA mutations have high rates of disease recurrence and lower survival, and LYNPARZA has been shown to significantly reduce both the risk of recurrence and death. We hope this approval sets a new, much-needed standard of care for these early breast cancer patients in Japan."

Dr Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, said, "With this approval, LYNPARZA becomes the first and only PARP inhibitor available for patients with BRCA-mutated, HER2-negative early breast cancer in Japan. This further reinforces the critical need to conduct BRCA testing at the point of diagnosis so that all eligible patients can be identified."

In March 2022, LYNPARZA was approved in the U.S. for the adjuvant treatment of patients with germline BRCAm (gBRCAm), HER2-negative high-risk early breast cancer, followed by approval in the European Union (EU) in August 2022, based on results from the OlympiA trial. LYNPARZA is also approved in the U.S., EU, Japan and several other countries for the treatment of adult patients with gBRCAm, HER2-negative, metastatic breast cancer previously treated with chemotherapy and, if hormone receptor-positive, endocrine therapy if appropriate based on results from the Phase 3 OlympiAD trial. In the EU, this indication also includes patients with locally advanced breast cancer.

About OlympiA

OlympiA is a Phase 3, double-blind, parallel-group, placebo-controlled, international trial evaluating the efficacy and safety of LYNPARZA 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 the time from randomization to the date of the first loco-regional or distant recurrence or new cancer or death from any cause. A key secondary efficacy outcome measure is OS.

The OlympiA trial is led by the Breast International Group in partnership with the Frontier Science & Technology Research Foundation, NRG Oncology, the U.S. National Cancer Institute, AstraZeneca and Merck. The trial is sponsored by NRG Oncology in the U.S. and by AstraZeneca outside of the U.S.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was 2 years (range: <6 months to >10 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

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 0.8% of patients exposed to LYNPARZA monotherapy, 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 who received 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%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received 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 who received 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 who received 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 After 3 or More Lines of Chemotherapy

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received 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 who received 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—Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: nausea (57%), fatigue (including asthenia) (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: decrease in lymphocytes (77%), increase in mean corpuscular volume (67%), decrease in hemoglobin (65%), decrease in leukocytes (64%), and decrease in absolute neutrophil count (39%).

ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the metastatic setting for 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 who received LYNPARZA in the metastatic setting for 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 who received 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 who received 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 who received 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 who received 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 for LYNPARZA in the United States

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

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.

Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer

For the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant 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 see complete Prescribing Information, including Medication Guide.

About LYNPARZA (olaparib)

LYNPARZA is a first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. 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 tumor types with defects and dependencies in the DDR.

LYNPARZA, which is being jointly developed and commercialized by AstraZeneca and Merck, has a broad and advanced clinical trial development program, 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.

About breast cancer

Early breast cancer is defined as cancer confined to the breast with or without regional lymph node involvement and the absence of distant metastatic disease. In Japan, breast cancer is both the most commonly diagnosed cancer overall and the most prevalent cancer among women. In 2020, breast cancer accounted for an estimated 2.3 million new cases and approximately 700,000 deaths worldwide. Despite advancements in the treatment of early breast cancer, up to 30% of patients with high-risk clinical and/or pathologic features recur within the first few years, and patients with gBRCA mutations are more likely to be diagnosed at a younger age than those without these mutations. Breast cancer is one of the most biologically diverse tumor types with various factors fueling its development and progression. The discovery of biomarkers in the development of breast cancer has greatly impacted scientific understanding of the disease.

About BRCA mutations

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.

About the AstraZeneca and Merck strategic oncology collaboration

In July 2017, AstraZeneca and Merck, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialize certain oncology products including LYNPARZA, the world’s first PARP inhibitor, for multiple cancer types. Working together, the companies will develop these products in combination with other potential new medicines and as monotherapies. Independently, the companies will develop these oncology products in combination with their respective PD-L1 and PD-1 medicines.

Merck’s focus on cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On August 25, 2022 Eli Lilly and Company (NYSE: LLY) reported that it will attend Citi’s 17th Annual BioPharma Conference on Wednesday, Sept. 7, 2022 (Press release, Eli Lilly, AUG 25, 2022, View Source [SID1234618655]). Daniel Skovronsky, M.D., Ph.D., Lilly’s chief scientific and medical officer, and president of Lilly Research Laboratories, will participate in a fireside chat at 3:30 p.m., Eastern time.

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A live audio webcast will be available on the "Webcasts & Presentations" section of Lilly’s Investor website at View Source A replay of the presentation will be available on this same website for approximately 90 days.