Mode of action of FVIIIa-mimetics emicizumab and Mim8. Schematic representation and comparison of the mode of action of the bispecific antibodies emicizumab (A) and Mim8 (B) that, in part, mimic the FVIIIa cofactor function on negatively charged phospholipid surfaces such as that of activated platelets. (A) Emicizumab interacts with the FIX(a) EGF1 and FX(a) EGF2 domains, thereby bringing FIX(a) and its substrate in close proximity, facilitating FIXa-mediated FX activation. (B) Mim8 specifically binds to the FIX(a) serine protease domain Leu337-Thr343 (Leu169_c-Thr174_c) and the FX(a) serine protease and EGF2 domains. In addition to localizing FIX(a) and FX close to each other on the membrane surface, Mim8 conformationally activates FIXa catalytic activity directly in a manner similar to FVIIIa. Professional illustration by Somersault18:24.