SAR447610

SAR447610 is a preclinical-stage bispecific antibody developed by Sanofi for the treatment of tauopathies, including Alzheimer's disease. It is engineered to cross the blood-brain barrier (BBB) via receptor-mediated transcytosis by targeting the transferrin receptor (TfR) while simultaneously binding to pathological tau protein. SAR447610 features an optimized structure combining two tau-binding moieties and one anti-TfR moiety. This design allows it to selectively bind to pathological tau fibrils with a low off-rate compared to tau monomers. Crucially, SAR447610 inhibits the neuronal uptake of tau fibrils and maintains its TfR binding off-rate when bound to fibrils, demonstrating superior tau reduction in vivo without the safety liabilities of other bispecific constructs that can inadvertently enhance tau uptake.