Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) 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