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The investigational factor XI (FXI) monoclonal antibodies amrecibart and cenvacibart demonstrated successful anticoagulation with a favorable safety profile in preclinical and phase 1 clinical studies, representing a novel treatment strategy for patients with thrombosis. The results were published in Blood by Dan Chalothorn, PhD, of Regeneron Pharmaceuticals, and colleagues. The research team first compared the mechanisms and coagulation effects of amrecibart and cenvacibart with other FXI-targeted monoclonal antibodies in both human and nonhuman primate plasma using an in vitro functional clotting assay.1Targeting the Intrinsic PathwayWith unique FXI/FXIa-binding mechanisms, amrecibart and cenvacibart address an unmet need for novel treatments with a favorable risk-benefit profile because current standard-of-care anticoagulants carry a high risk for bleeding. Cenvacibart and amrecibart block FXI activity by targeting the catalytic domain and the apple 2 domain of FXI/FXIa, respectively. Although standard-of-care anticoagulants target the extrinsic coagulation pathway, these monoclonal antibodies specifically target the intrinsic coagulation pathway.