Enoxaparin Sodium

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

Regeneron will start a “broad” Phase 3 program next year for its two factor XI antibodies, following open-label Phase 2 results for the experimental anti-clotting drugs. The company said Thursday that its experimental medicine REGN7508 was superior to the older blood thinner enoxaparin and non-inferior to Bristol Myers Squibb’s newer factor Xa inhibitor Eliquis in a pooled analysis of two Phase 2 studies. Meanwhile, the second factor XI drug, REGN9933, was non-inferior to enoxaparin in the trials, which looked at the prevention of thromboembolism after total knee replacement. It will enter late-stage testing a few years after other large pharmas began pivotal trials with their own experimental factor XI medicines. The drugs aim to take advantage of genetic studies that show factor XI deficiency could lead to reduced rates of myocardial infarction, stroke and other cardiovascular problems. A Regeneron spokesperson told Endpoints News the company won’t share details about its Phase 3 plans at this time. It anticipates a large market opportunity, having outlined a $20 billion atrial fibrillation market in its latest quarterly presentation . It’s attempting to dethrone direct oral anticoagulants, which can come with bleeding risk. After years of hype on factor XI’s potential for shaking up the blood thinner field, two leaders — Bayer, with its drug asundexian, and BMS-partnered Johnson & Johnson, with milvexian — ran into mixed results in Phase 2 testing in 2022. They pushed ahead into Phase 3. But last November, Bayer stopped its nearly 15,000-person study after lack of efficacy . The German drugmaker is pushing ahead with asundexian elsewhere in Phase 3. Novartis and Blackstone-backed Anthos are also testing a factor XI drug . Regeneron’s REGN9933 is an A2 domain-focused asset and REGN7508 is a catalytic domain drug. “Our A2 domain antibody is not a complete blocker of factor XI. It actually is more like a complete factor XII blocker. It’s expected to not have as profound an effect on the coagulation pathways but to have a much milder safety profile,” Regeneron chief scientific officer George Yancopoulos said on the company’s third-quarter earnings call . “In contrast, we believe that our catalytic domain antibody is the best-in-class blocker of factor XI,” Yancopoulos continued. “It will come with the best ability to control coagulation among all agents that are attacking this pathway.” In Thursday’s press release, Yancopoulos said Regeneron’s monoclonal antibodies “showed clear evidence of antithrombotic effect with an encouraging safety profile after a convenient single dose.” The company said there was “no clinically relevant bleeding” in any of the treatment arms.