Marstacimab

TFPI is a serine protease and primary inhibitor of the extrinsic coagulation pathway. It negatively regulates thrombin generation within the extrinsic pathway of coagulation by inhibiting tissue factor‐activated FVII (FVIIa) and activated FX (FXa). All three isoforms of TFPI have the Kunitz‐type inhibitor domain K2, which binds to the active site of activated FXa and inhibits its activity.

Hemophilia A and B are hereditary bleeding disorders associated with deficiencies in coagulation clotting factors VIII (FVIII) and IX (FIX), respectively, of the intrinsic coagulation pathway. Marstacimab is a human monoclonal IgG1 antibody directed against the K2 to neutralize TFPI. Even in the absence of FVIII or FIX, marstacimab-induced inhibition of TFPI leads to increased generation of FXa and, ultimately, thrombin production and clot formation.