Evaluation Of A Next-Generation Fviii Mimetic Antibody, Mim8, In Combination With Recombinant Fviia, Fviii And Activated Prothrombin Complex Concentrate

Introduction: Coagulation Factor VIII (FVIII) mimetics is a new class of molecules restoring the hemostatic capacity in blood lacking FVIII irrespective of the presence of inhibitory anti-FVIII antibodies. FVIII mimetics are bispecific antibodies bridging FIXa and FX on platelet surface, enhancing FX activation and thereby coagulation. Despite a significant reported prophylactic effect of the FVIII-mimetic emicizumab (Hemlibra®) in persons with Hemophilia A with and without inhibitors [Oldenburg et al., NEJM, 2017; Mahlangu et al., NEJM, 2018], bleeding may still occur during treatment, requiring intervention with FVIII or bypassing agents, i.e. recombinant FVIIa (rFVIIa) or activated prothrombin complex concentrate (aPCC). The combined treatment with emicizumab and aPCC has under certain conditions led to thrombotic events and microangiopathies in the treated patients, whereas the combination with rFVIIa has been safe [Levy et al., J Thromb Haemost, 2019]. We have developed a novel, next-generation FVIII mimetic antibody, Mim8, that potently enhances coagulation in pre-clinical models [manuscript in preparation]. We evaluated the combination of Mim8 with recombinant FVIII (rFVIII), rFVIIa, and aPCC by thrombin generation assay (TGA) and by thromboelastography (TEG), in haemophilia A condition.