Factor XI Program Overview - Regeneron is developing two Factor XI antibodies, REGN7508Cat and REGN9933A2, targeting various indications with different bleeding risk profiles[51] - The company aims to address unmet needs in anticoagulation by potentially reducing bleeding risk while maintaining efficacy[64] - Genetics support targeting Factor XI, as lower FXI levels are associated with reduced VTE and cardioembolic stroke risk[16, 20] Clinical Data and Development - ROXI-VTE-I and ROXI-VTE-II studies showed REGN7508Cat had a numerically lower VTE rate compared to apixaban, while REGN9933A2 had a numerically lower VTE rate compared to enoxaparin in TKR patients[33, 36] - In a pooled analysis, REGN7508Cat showed a 13.6% risk difference reduction in VTE incidence compared to pooled enoxaparin[35] - Interim results from the ROXI-CATH study in catheter-associated thrombosis showed a 66% relative risk reduction in VTE with REGN7508Cat versus placebo[40] - A Phase 1 GI bleed study indicated that REGN7508/REGN9933 resulted in 14% less bleeding risk compared to rivaroxaban + aspirin[46] Commercial Opportunity - The current global anticoagulation market is \$20 billion, with standard-of-care DOAC utilization at approximately 50% due to bleeding risk[12] - The U S Factor XI total addressable market in post-TKR VTE is estimated to be ~800K patients, with a ~40% class share anticipated[56, 75] - The U S Factor XI total addressable market in cancer VTE is estimated to be ~300K patients, with a ~30-35% class share anticipated[56, 85]