Apixaban

On April 26, 2023, Bristol-Myers Squibb (BMS) announced a significant development that placed the company in the spotlight. The announcement revealed a major leadership change: after eight years as CEO, Dr. Giovanni Caforio would step down, passing leadership to Chief Commercialization Officer Chris Boerner. This leadership transition not only marked the end of a chapter in Caforio’s career but also posed unprecedented challenges for Boerner. Bristol-Myers Squibb is facing the severe challenge of a patent cliff, which is a critical test for the company. To ensure a smooth transition, Caforio’s resignation did not take immediate effect; instead, a carefully planned transition period lasted until November 1, 2023, when he formally handed over leadership, ushering in a new era for Bristol-Myers Squibb. This leadership change has profound implications for BMS and its closely associated biotechnology partners. Recently, the company announced the termination of cell therapy collaboration agreements with Century Therapeutics and Immatics, marking significant decisions under Boerner’s tenure—and they are unlikely to be the last. Under Caforio's leadership, BMS achieved remarkable milestones. The official statement highly praised Caforio’s contributions, including his leadership of the landmark merger with Celgene, the launch of 12 new drugs, and the doubling of company revenues. These achievements have fostered a high-performance corporate culture and an engaged workforce. However, these accomplishments present both inspiration and pressure for Boerner. BMS faces challenges in innovative drug development due to the expiration of patents on its three revenue pillars: Revlimid, Eliquis, and Opdivo. Together, these drugs generated $26 billion in sales in 2023, accounting for nearly 60% of the company's total revenue. The impending patent expirations create a sense of urgency for the company. In response, BMS has been actively engaged in the M&A market, acquiring companies such as Karuna, Mirati, and RayzeBio for a combined total of approximately $22.9 billion. The company is also investing significantly in introducing innovative drugs, exemplified by the $8.3 billion licensing deal with Brii Biosciences for its dual-target ADC drug BL-B01D1. For Boerner, these extensive acquisitions and introductions pose a formidable challenge, requiring time for integration and digestion. At the financial report meeting on February 2, 2024, Boerner made his debut, presenting his comprehensive insights on the company’s future. Despite challenges like the patent cliff and the Inflation Reduction Act (IRA), Boerner emphasized that core products such as Revlimid, Eliquis, and Opdivo will continue to generate cash flow, supporting the company’s innovative R&D pipeline. Boerner identified 2026 as the company's most challenging period, describing it as the “most critical risk exposure” due to the IRA’s impact taking effect in that year. Boerner’s strategic focus in the current phase is to "shorten the transition period as much as possible" by accelerating R&D while maintaining strict cost control. His core strategy involves prioritizing investments in high-potential projects and suspending lower-priority ones. For example, the acquisition of Karuna is not just about acquiring assets but also involves integrating its operating expenses. BMS needs to centralize management, improve efficiency, and free up resources for new assets. From the outset of his tenure, Boerner has emphasized the importance of repositioning underperforming products such as Abecma and Zeposia, ensuring they receive adequate resources to succeed. In July 2024, Eisai announced that its FRα ADC drug MORAb-202, which was part of a $3.1 billion collaboration, was returned by BMS. Despite high investment and strong performance in key areas, treatment-related adverse events such as interstitial lung disease/pneumonia limited its competitiveness. In August 2024, BMS terminated its partnership with Agenus for TIGIT/CD96 dual antibodies, leading to a $200 million loss. Similarly, collaborations such as the $3 billion investment with Immatics have also been terminated. These actions reflect Boerner's strategy of shortening transition periods and focusing on the future. So, who will be the next to face "return" at BMS?

Investigational REGN7508 (catalytic domain) and REGN9933 (A2 domain) are being evaluated for their potential to control thrombosis while minimizing bleeding risk in a variety of patient populations and clinical settings Evaluated against current standards of care, single doses of REGN7508 and REGN9933 administered 12 to 24 hours after total knee replacement demonstrated robust antithrombotic effects Phase 3 program to be initiated in 2025 TARRYTOWN, NY, USA I December 19, 2024 I Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced positive Phase 2 results for two novel monoclonal antibodies targeting distinct domains of Factor XI. REGN7508 (catalytic domain) is designed to maximize anticoagulant activity while minimizing bleeding risk, and REGN9933 (A2 domain) is designed to provide an additional option for patients with the highest bleeding risk who would otherwise not be candidates for currently available anticoagulants. Per the Phase 2 results, there was a robust antithrombotic effect for each antibody, and no clinically relevant bleeding was observed in any treatment arm. “Our Factor XI antibodies targeting the catalytic and A2 domains were rigorously evaluated alongside current standards of care and showed clear evidence of antithrombotic effect with an encouraging safety profile after a convenient single dose,” said George D. Yancopoulos, M.D., Ph.D., Board Co-Chair, President and Chief Scientific Officer at Regeneron. “These latest Phase 2 results add to our preclinical data that showed prolongation of activated partial thromboplastin clotting time was greater with REGN7508 and similar with REGN9933, compared to other Factor XI-targeted agents. Together, these clinical and preclinical data, along with compelling genetic evidence, give us confidence in targeting multiple distinct domains of Factor XI to potentially offer tailored therapies for patients with different bleeding risk profiles and in a variety of treatment settings. We are eager to advance REGN7508 and REGN9933 into a broad Phase 3 program beginning in 2025.” Regeneron conducted two open-label, active-controlled Phase 2 trials (ROXI-VTE-I and ROXI-VTE-II) in the same centers under similar protocols to evaluate REGN7508 and REGN9933 for the prevention of asymptomatic (detected by venogram between day 8 and 12) or symptomatic venous thromboembolism (VTE) after unilateral total knee arthroplasty. In ROXI-VTE-I, patients were randomized to receive either a single intravenous (IV) dose of REGN9933, daily enoxaparin, or twice daily doses of apixaban until the time of venography. In ROXI-VTE-II, patients were randomized to receive a single IV dose of REGN7508 or daily enoxaparin until the time of venography. In contrast to trials evaluating other Factor XI antibodies, administration of all treatments began 12 to 24 hours after surgery (generally one day post-operation) in both trials, consistent with the approved administration of the active comparators. On the measure of VTE rates at venogram following surgery, a pooled analysis across both trials showed REGN7508 was superior to enoxaparin and non-inferior to apixaban, and REGN9933 was non-inferior to enoxaparin. All VTE events were asymptomatic, except for one symptomatic case of pulmonary embolism in the apixaban arm. Results were as follows: * Superiority met ^ Non-inferiority met with a margin of 9% There was no major bleeding (including surgical site bleeding) or clinically relevant non-major bleeding in any arm; the only treatment-related adverse events (AE) in any arm was one case of minimal bleeding (contusion) reported in the enoxaparin arm of ROXI-VTE-I. There were no treatment-related serious AEs (SAEs) in any arm. There were also no AEs in any arm leading to trial discontinuation or dose interruption/modification, and no AEs of special interest or deaths in these trials. Across both trials, AE rates were generally similar among the treatment arms (ROXI-VTE-I: REGN9933=22%, enoxaparin=21%, apixaban: 25%; ROXI-VTE-II: REGN7508=22%, enoxaparin: 25%). The safety and efficacy of REGN7508 and REGN9933 have not been evaluated by any regulatory authority. About Thrombosis Thrombosis, otherwise known as clot formation, is responsible for one in four deaths worldwide. Due to bleeding concerns, current standard-of-care anticoagulants are underutilized and current oral agents are often associated with poor adherence. There is an unmet need for treatments that can help prevent thrombosis without increased bleeding risk. About Regeneron’s VelocImmune ® Technology Regeneron’s VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron’s co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite ® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved fully human monoclonal antibodies. This includes Dupixent ® (dupilumab), Libtayo ® (cemiplimab-rwlc), Praluent ® (alirocumab), Kevzara ® , Evkeeza ® (evinacumab-dgnb), Inmazeb ® (atoltivimab, maftivimab and odesivimab-ebgn) and Veopoz ® (pozelimab-bbfg). In addition, REGEN-COV ® (casirivimab and imdevimab) had been authorized by the FDA during the COVID-19 pandemic until 2024. About Regeneron Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for over 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases and rare diseases. Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite ® technologies, such as VelocImmune, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center ® , which is conducting one of the largest genetics sequencing efforts in the world. For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn . SOURCE: Regeneron Pharmaceuticals