Factor XI/XIa (FXI/FXIa)

Class

Anti-FXI/FXIa dual-domain antibody

Factor XI (FXI) is a plasma protein that circulates as an inactive precursor (zymogen) and becomes an active enzyme, factor XIa, during blood clotting. FXIa amplifies the coagulation cascade by activating factor IX, contributing to sustained thrombin generation and stable clot formation, particularly in the intrinsic pathway that is triggered by contact with negatively charged surfaces such as those found in medical devices or within a growing thrombus. Unlike factors central to normal hemostasis (the process that stops bleeding after injury), FXI appears to contribute more to pathological clot amplification than to the initial sealing of a wound. This distinction, drawn from observations of people with inherited FXI deficiency who have a reduced tendency toward venous and some arterial clots without a strong predisposition to spontaneous bleeding, has made FXI/FXIa an attractive target for anticoagulant development. The goal is to reduce thrombotic risk in conditions such as venous thromboembolism, atrial fibrillation, or clot-related complications of surgery, while preserving the hemostatic reserve needed to prevent excessive bleeding. Antibodies directed at FXI/FXIa, including dual-domain designs that engage more than one region of the protein, aim to achieve thorough and durable neutralization of this pathway.