Haemophilia is a blood-related disease, which can impair coagulation function. There are two main types of haemophilia, including haemophilia A and haemophilia B. They occur due to low amounts of clotting factor VIII and factor IX, respectively. Individuals with severe haemophilia A and B experience frequent bleeding episodes, which most commonly affect the joints and muscles. Recurrent joint bleeding can cause irreversible damage to cartilage and bone. Moreover, this irreversible damage can translate into the development of chronic arthropathy.

Tissue factor pathway inhibitor (TFPI), an anticoagulant protein, is the major inhibitor of the tissue factor-initiated extrinsic coagulation pathway in blood. It inhibits the TF:FVIIa complex, a primary element of the coagulation cascade. Within the extrinsic coagulation pathway, TFPI binds and inhibits FXa and tissue factor (TF)-bound FVIIa, resulting in the formation of the FXa-TFPI-TF-FVIIa quaternary complex. Furthermore, the prothrombinase complex, which consists of activated factor V (FVa) and FXa, converts prothrombin to thrombin as a final step in blood clot formation in the intrinsic pathway. TFPI blocks thrombin generation by inhibiting the prothrombinase complex.

Befovacimab (BAY 1093884) is a fully human anti-TFPI monoclonal antibody that restores hemostatic dysfunction due to hemophilia.

From: Mancuso ME, et al. Haemophilia. 2022 Sep;28(5):702-712.

Befovacimab binds human TFPI with high affinity (<10 pM) via the K1 and K2 domains, inhibiting its interactions with both FXa and FVIIa and thus restoring their activity. Thus, Befovacimab can restore thrombin burst for stable clot formation in hemophilic conditions in vitro.

Following the in vivo experiments results, in monkey plasma, Befovacimab exhibits IC50s of 4.65 and 6.19 nM for free TFPI and diluted prothrombin time (dPT), respectively. In addition, Befovacimab (5, 20 mg/kg, IV and SC) dose-dependent decreases in TFPI concentration and clotting time in female cynomolgus monkeys in vivo.

All in all, Befovacimab is a potent anti-TFPI mAb, and has the potential to research haemophilia.


    1. Mancuso ME, et al. Haemophilia. 2022 Sep;28(5):702-712. 
    2. Gu JM, et al. AAPS J. 2017 Jul;19(4):1186-1195.