Factor XI (FXI) is a serine protease that in humans is encoded by the F11 gene. FXI mainly exists in the liver and is present in the circulation as an inactive zymogen, and FⅪa can activate it. Unlike other coagulation factors, the FⅪ zymogen exists as a homodimer. FⅪ is important for normal hemostasis in the body and is part of the intrinsic coagulation pathway. It can participate in thrombin production and the pro-inflammatory kinase-releasing enzyme-kinin system.

FXI circulates as an enzyme proliferator and is activated to its enzymatic form by FXIIa, thrombin, or by self-activation of FXIa in the presence of an anionic polymer. Upon activation of its enzymatic form, FXIa increases thrombin production and reduces fibrinolysis. On the one hand, FXI deficiency leads to coagulation disorders with a variety of bleeding manifestations, such as the rare hemophilia C. On the other hand, high levels of FXI can lead to thrombosis.

Abelacimab (MAA868) is a fully human IgG1 mAb that binds to factor XI.

From: Nopp S, et al. Front Cardiovasc Med. 2022 May 12;9:903029.

It binds with high affinity to the catalytic structural domain of FXI and locks it in the zymogen conformation. So that, it prevents its activation by FXIIa or thrombin. Following the in vitro experiments results, Abelacimab  (0.0001-1 μM) prolongs the clotting time and reduces the amount of thrombin in human plasma in a concentration-dependent manner. Besides, Abelacimab (s.c., 3-30 mg/kg, on day 1, 85, 114) exhibits strong and sustained anticoagulant effects in crab-eating monkeys. Also, it significantly prolongs aPTT and has a good safety profile, with no significant toxic findings or signs of bleeding observed. Moreover, Abelacimab (i.v., 0.6 mg/kg) exhibits good anticoagulant activity to prevent carotid artery occlusion in iron chloride-induced thrombosis FXI^-/- C57BL/6 mice model.

In conclusion, Abelacimab (MAA868) is a human IgG1 monoclonal antibody that targets FXI and can be used in anti-thrombotic studies.

References:

[1] Lewandowska MD, et al. Hematol Oncol Clin North Am. 2021 Dec;35(6):1157-1169.

[2]  Alexander W Koch, et al. Blood. 2019 Mar 28;133(13):1507-1516.