The Leiderman lab published “Mathematical analysis of emicizumab: affinity-driven complex formation and lipid-surface reactions” in the Journal of Thrombosis and Haemostasis.
The bispecific antibody emicizumab is designed to replace the function of clotting factor VIII in hemophilia A by bridging factor IXa and factor X. In normal clotting, activated FVIII serves as a cofactor for FIXa, promoting FX activation by colocalizing the enzyme and substrate on lipid membranes. Our study shows that although emicizumab does not bind lipid, its activity is enhanced in the presence of lipid surfaces. Using experiments and mechanistic mathematical modeling, we demonstrate that emicizumab interacts with proteins already bound to the membrane, providing quantitative insight into its mechanism and informing the design of next-generation bispecific antibodies. Read more: https://www.sciencedirect.com/science/article/pii/S1538783625004258