Lynparza reduced risk of death by 32% in the adjuvant treatment of patients with germline BRCA-mutated high-risk early breast cancer

On March 16, 2022 AstraZeneca reported that Further positive results from the OlympiA Phase III trial showed MSD’s Lynparza (olaparib) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo in the adjuvant treatment of patients with germline BRCA-mutated (gBRCAm) high-risk human epidermal growth factor receptor 2 (HER2)-negative early breast cancer who had completed local treatment and standard neoadjuvant or adjuvant chemotherapy (Press release, AstraZeneca, MAR 16, 2022, View Source [SID1234610162]).

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These results were presented today at a European Society for Medical Oncology Virtual Plenary. The OlympiA trial is led by the Breast International Group (BIG) in partnership with the Frontier Science & Technology Research Foundation (FSTRF), NRG Oncology, AstraZeneca and MSD.1

In the key secondary endpoint of OS, Lynparza reduced the risk of death by 32% versus placebo (based on a HR of 0.68; 98.5% CI 0.47-0.97; p=0.009). Lynparza improved the three-year survival rate to 92.8% versus 89.1% for those on placebo. At four years, the survival benefit was maintained with 89.8% of patients treated with Lynparza alive versus 86.4% of those on placebo. The safety and tolerability profile of Lynparza in this trial was in line with that observed in prior clinical trials.

Primary results from the OlympiA Phase III trial were first presented during the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and are published in The New England Journal of Medicine.2 The OS data and the primary results formed the basis for the recent approval by the US Food and Drug Administration (FDA) of Lynparza in this setting.

Breast cancer is the most diagnosed cancer worldwide with an estimated 2.3 million patients diagnosed in 2020.3 Nearly 91% of all breast cancer patients in the US are diagnosed at an early stage of disease and BRCA mutations are found in approximately 5-10% of patients.4,5

Professor Andrew Tutt, Global Chair of the OlympiA Phase III trial and Professor of Oncology at The Institute of Cancer Research, London and King’s College London, said: "OlympiA’s latest results are great news for patients with a specific inherited form of breast cancer. Most breast cancers are identified in the early stages and many patients will do very well, but for those with higher risk disease at diagnosis, the risk of cancer returning can be unacceptably high. OlympiA has now shown that olaparib not only reduced the risk of recurrence but also improved overall survival for women with high risk early-stage breast cancer and a BRCA1/2 mutation and is an exciting demonstration of the benefits of targeting the specific biology of disease for these women."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "These exciting results further support how Lynparza could significantly change the way people with germline BRCA-mutated early breast cancer are treated. The OlympiA trial is the first time we’ve seen a PARP inhibitor deliver survival benefit in early breast cancer, highlighting the importance of persistent innovation in tackling cancer early."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "The results from the OlympiA trial highlight that patients with germline BRCA-mutated, HER2-negative, high-risk early breast cancer can both live longer and with reduced risk of disease recurrence when treated with Lynparza in the adjuvant setting, compared to placebo. These data further reinforce the importance of germline BRCA testing immediately after diagnosis to help identify patients who may be eligible for treatment with Lynparza."

Lynparza is approved in the US, EU, Japan and several other countries for the treatment of patients with gBRCAm, HER2-negative, metastatic breast cancer previously treated with chemotherapy based on results from the OlympiAD Phase III trial. In the EU, this indication also includes patients with locally advanced breast cancer.

Notes

Early 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.6 In the US, the 5-year survival is 99% for localised breast cancer (only found in the breast area) and 86% for regional breast cancer (cancer that has spread outside the breast to nearby structures or lymph nodes).4 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.7

Breast cancer is one of the most biologically diverse tumour types with various factors fuelling its development and progression.8 The discovery of biomarkers in the development of breast cancer has greatly impacted scientific understanding of the disease.9

OlympiA
OlympiA is a Phase III, double-blind, parallel group, placebo-controlled, multicentre 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.1

The primary endpoint of the trial is invasive disease-free survival defined as time from randomisation to date of first loco-regional or distant recurrence or new cancer or death from any cause.1

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

Founded by leading European opinion leaders in 1999, the organisation aims to address fragmentation in breast cancer research and now represents a network of over 50 like-minded research groups affiliated with specialised hospitals, research centres 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 programmes.

FSTRF
Frontier Science & Technology Research Foundation (FSTRF) is a non-profit, research organisation 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 centres 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.

NRG Oncology
NRG Oncology is a network group funded by the US National Cancer Institute (NCI), a part of the National Institutes of Health. NRG Oncology brings together the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG), with the mission to improve the lives of cancer patients by conducting practice-changing multi-institutional clinical and translational research. NRG Oncology sponsored OlympiA in the US and collaborated with the other adult cancer clinical trials research groups funded by the NCI, Alliance, ECOG/ACRIN and the Southwest Oncology Group. The NCI and AstraZeneca are collaborating under a Cooperative Research and Development Agreement between the parties.

BRCA
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role maintaining the genetic stability of cells.10 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.10-13

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 homologous recombination repair (HRR), such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as new hormonal agents – NHAs).

Inhibition of PARP proteins 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 currently approved in a number of countries across PARP-dependent tumour types with defects and dependencies in the DDR pathway including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and homologous recombination repair deficient (HRD)-positive advanced ovarian cancer, respectively; for germline BRCAm, HER2-negative metastatic breast cancer (in the EU and Japan this includes locally advanced breast cancer); for germline BRCAm metastatic pancreatic cancer; and HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm only in the EU and Japan).

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, 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. The companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines independently.

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 tumour environment.

AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex and Zoladex and the next-generation oral SERD and potential new medicine camizestrant.

The PARP inhibitor, Lynparza, is an approved targeted treatment option for early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD continue to research Lynparza in breast cancer patients with an inherited BRCA mutation.

Building on the first approval of Enhertu, 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 Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu, evaluating 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 is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

Adagene Announces FDA Clearance to Proceed with Phase 1b/2 Trial of Anti-CTLA-4 ADG126 SAFEbody® in Combination Therapy With Anti-PD-1 Antibody Pembrolizumab

On March 16, 2022 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported FDA clearance to proceed with a Phase 1b/2 clinical trial of its anti-CTLA-4 monoclonal antibody (mAb), ADG126, in combination with the anti-PD-1 antibody pembrolizumab (Press release, Adagene, MAR 16, 2022, View Source [SID1234610161]). The global trial (ADG126-P001 / KEYNOTE-C98) will evaluate patients with advanced/metastatic solid tumors at multiple sites in the U.S. and Asia Pacific (APAC).

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ADG126 SAFEbody is designed for conditional activation in the tumor microenvironment (TME), as well as to enhance the efficacy profile by potent Treg depletion and to maintain its physiological function by soft ligand blocking in order to expand the therapeutic index and further address safety concerns with existing CTLA-4 therapies.

"The FDA clearance of this trial represents a major step forward in our wholly-owned CTLA-4 program. It builds on a strong safety profile for ADG126 SAFEbody and its parental antibody ADG116, respectively, as a single agent and the ability to achieve doses that may unlock the full potential of CTLA-4 as a proven target for strong ADCC-mediated Treg depletion in the TME. Our goal is to establish the CTLA-4 pathway as the cornerstone of cancer treatment in both single-agent and combination regimens," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. "We are excited to initiate our clinical trial evaluating combination therapy with ADG126, which leverages SAFEbody precision masking technology to address toxicity limitations. This multi-regional trial of ADG126 with pembrolizumab also reflects our commitment to bringing highly differentiated therapies to cancer patients globally."

SAFEbody technology is designed to address safety and tolerability challenges associated with many antibody therapeutics by using precision masking technology to shield the binding domain of the biologic therapy. Through activation in the TME, this allows for tumor-specific targeting of antibodies, while minimizing on-target off-tumor toxicity in healthy tissues.

The ADG126-P001 trial is expected to dose the first patients soon. The trial is designed to evaluate safety and tolerability, and to determine the recommended Phase 2 dose for ADG126 in combination with pembrolizumab. The trial will begin with dose-escalation (ADG126 at 6 mg/kg) followed by dose expansion at the recommended dose for early efficacy evaluation. A combination cohort of ADG126 with the anti-PD-1 therapy, toripalimab is also being initiated in Australia.

2seventy bio Secures $170 Million in Private Placement Equity Financing

On March 16, 2022 2seventy bio, Inc. (Nasdaq: TSVT), a leading immuno-oncology cell therapy company, reported that it has agreed to sell approximately 13,934,427 shares of its common stock to a select group of institutional and accredited investors in a private placement (Press release, 2seventy bio, MAR 16, 2022, View Source [SID1234610160]). Upon the closing of the financing, 2seventy bio will receive gross proceeds of approximately $170 million, before payment of offering commissions and expenses, based on a price of $12.20 per share, the closing price of 2seventy bio’s common stock on Nasdaq on March 15, 2022. The financing is expected to close on March 17, 2022, subject to customary closing conditions. Proceeds from the financing will support 2seventy bio’s ongoing research and development activities as well as general corporate purposes and working capital.

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The private placement included top healthcare investors: 683 Capital, Armistice Capital, Bain Capital Life Sciences, Boxer Capital, CaaS Capital, Casdin Capital, Cowen Healthcare Investments, EcoR1 Capital, Heights Capital, Janus Henderson Investors, Madison Avenue Partners, Newtyn Management, Nick Leschly & family, RTW Investments, LP, and existing investors.

"Roughly 100 days into the launch of 2seventy bio, we have taken important steps to secure the company’s financial foundation. We have increasing conviction in the ABECMA U.S. commercial launch, we are executing on a plan to rebalance our burn, and we have secured important funding from leading healthcare investors. Taken together, we expect these steps will get us through critical milestones and into 2025," said Nick Leschly, chief kairos officer. "After conducting diligence to understand our platform, pipeline and the commercial outlook for ABECMA, we are pleased to welcome many new investors to our shareholder base. We believe you end up with the investors you deserve, and we have a shareholder base that has a common belief in our mission, an un-incremental, long-term orientation, and the ability to go deep on the science."

2seventy bio ended 2021 with cash, cash equivalents and marketable securities of $362.2 million. Combined with the company’s expectations for U.S. ABECMA commercial sales in 2022, a reduction in expected net cash spend for 2022 to a range of $190 to $220 million, and the net proceeds from the private placement, the company anticipates that it will have sufficient cash and cash equivalents to fund current planned operations into 2025. 2seventy bio anticipates that this runway will bring the company through meaningful clinical data updates, new INDs and continued progress in the commercialization of ABECMA.

Goldman Sachs & Co. LLC acted as exclusive placement agent. The shares of common stock described above are being sold in a private placement and have not been registered under the Securities Act of 1933, as amended, and may not be offered or sold in the United States absent registration or an applicable exemption from registration requirements. The company has agreed to file a resale registration statement with the Securities and Exchange Commission, for purposes of registering the resale of the shares of common stock issued in the offering.

This press release does not constitute an offer to sell or the solicitation of an offer to buy the shares of common stock described above, nor shall there be any sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state. Any offering of the shares or common stock described above under the resale registration statement will only be by means of a prospectus.

Navidea Biopharmaceuticals to Host Fourth Quarter 2021 Earnings Conference Call and Business Update

On March 16, 2022 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported it will host a conference call and webcast on Wednesday, March 23, 2022 at 5:00 p.m. (EDT) to discuss corporate developments and financial results for the fourth quarter ended December 31, 2021 (Press release, Navidea Biopharmaceuticals, MAR 16, 2022, View Source [SID1234610155]).

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Dr. Michael Rosol, Chief Medical Officer, and Erika Eves, Vice President of Finance and Administration, will host the call and webcast to discuss the financial results and provide an update on recent developments and clinical progress. Management will be available to answer questions live immediately following the earnings announcement and prepared remarks portion of the call.

To participate in the call and webcast, please refer to the information below:

A live audio webcast of the conference call will also be available on the investor relations page of Navidea’s corporate website at www.navidea.com. In addition, the recorded conference call can be replayed and will be available for 90 days following the call on Navidea’s website.

Iovance Biotherapeutics to Present at Upcoming Conferences

On March 16, 2022 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported that senior leadership plans to present at the following conferences in March (Press release, Iovance Biotherapeutics, MAR 16, 2022, View Source [SID1234610154]):

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Oppenheimer Healthcare Conference
Fireside Chat: March 16 at 12:40 p.m. ET
Barclays Global Healthcare Conference
Fireside Chat: March 17 at 10:45 a.m. ET
The live and archived webcasts will be available at View Source