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Drug Discovery targeting coagulation Factor XIIIa (F13a)

Blocking Coagulation Factor XIIIa (FXIIIa) in at-risk patients

The physiological functions of coagulation factor XIIIa - also called plasma transglutaminase - are well known. Factor XIII is activated by thrombin to factor XIIIa and subsequently cross-links fibrin fibers. This covalent cross-linking reaction augments blood clot strength while also improving the visco-elastic properties. Further, the clot is covalently decorated with α2-antiplasmin, increasing clot stability against premature fibrinolysis by plasmin. In summary, factor XIII is the major factor influencing clot stability, clot maturation, and clot lysis.
Using a rabbit animal model, Zedira showed the proof-of-principle of “safe” anticoagulation therapy by the inhibition of factor XIIIa published in the Journal of Thrombosis and Haemostasis: “Novel inhibitor ZED3197 as potential drug candidate in anticoagulation targeting coagulation FXIIIa (F13a)”.
The crucial difference compared with the existing anticoagulants lies in the fact that a soft and easily degradable blood clot can still be formed while thrombin generation – and therefore platelet activation – is not affected.
A significant reduction in the life-threatening tendency to bleed as provoked by current drugs is thus likely to be achieved. Today about 50% of patients are excluded from anticoagulation therapy due to the risk of bleeding events.
Zedira’s factor XIIIa blockers have the highest efficacy demonstrated to date. Our compounds have the potential to provide a novel therapeutic option with a superior benefit/risk ratio in hypercoagulable disease states.