BJTJ-1837, a novel FXI activation-blocking antibody

Area of Science:

• Hematology
• Immunology
• Pharmacology

Background:

• Factor XI (FXI) plays a significant role in thrombosis development.
• Targeting FXI offers potential for thrombosis treatment with a reduced risk of bleeding.
• FXI has a limited role in normal hemostasis, making it an attractive therapeutic target.

Purpose of the Study:

• To develop novel antibody therapeutics targeting FXI.
• To investigate the potential of these antibodies for treating thrombosis-related diseases.

Main Methods:

• Mouse hybridoma technology was used to generate anti-FXI antibodies.
• Antibody characterization involved surface plasmon resonance, enzyme inhibition assays, and coagulation tests (aPTT, PT).
• Antithrombotic activity was validated using a cynomolgus monkey arterial venous shunt model.

Main Results:

• A humanized antibody, BJTJ-1837, demonstrated high-affinity binding to the FXI protease domain and inhibited FXI activation.
• BJTJ-1837 exhibited strong anticoagulant effects in human and monkey plasma and dose-dependent antithrombotic activity in vivo.
• The antibody showed no adverse bleeding effects in the thrombosis model and favorable pharmacokinetic and pharmacodynamic properties.

Conclusions:

• BJTJ-1837 is a promising antibody candidate for blocking FXI activation.
• This FXI inhibitor demonstrates potential as an antithrombotic therapeutic agent with a favorable safety profile.