Anticoagulation with the mechanistically distinct FXI/FXIa antibodies amrecibart (REGN9933A2) and cenvacibart (REGN7508Cat).

FXI-targeting monoclonal antibodies amrecibart and cenvacibart inhibit intrinsic pathway-triggered coagulation without affecting extrinsic pathway in humans and primates.

• Why it matters: Thrombosis causes significant health issues, and current anticoagulants increase bleeding risk, creating a need for safer, targeted therapies that do not impair normal clotting functions.
• What they did: Researchers developed two FXI monoclonal antibodies with distinct mechanisms: cenvacibart blocks FXI activity completely, while amrecibart specifically inhibits FXIIa-induced FXI activity; their effects were tested in vitro, in vivo in primates, and in healthy volunteers.
• The result: Both mAbs prolonged aPTT and prevented thrombosis in nonhuman primates without increasing bleeding, and in humans, they showed dose-dependent coagulation inhibition with durable effects and good tolerability, suggesting potential for tailored anticoagulant therapies.