ponezumab

Ponezumab is a humanized monoclonal antibody (IgG2δA) developed as a passive immunotherapy targeting amyloid beta (Aβ) peptides. It specifically binds to the free carboxy terminal amino acids 33–40 of the Aβ1–40 peptide, which is predominantly found in blood vessel walls. The antibody was engineered with mutations in its Fc region to minimize complement activation and reduce the risk of antibody-dependent cell-mediated cytotoxicity. Its primary mechanism involves sequestration of soluble Aβ in the blood, shifting the brain-blood equilibrium toward peripheral clearance—a process known as the "peripheral sink" hypothesis—aiming to deplete central nervous system amyloid stores and potentially reverse or prevent amyloid aggregation and deposition. Ponezumab was originally developed by Rinat Neuroscience and later acquired by Pfizer for further development in Alzheimer's disease and cerebral amyloid angiopathy; however, clinical development for both indications has been discontinued after phase II trials failed to meet efficacy endpoints[2][3][4][5][6].

Other names

Anti-human beta-amyloid Monoclonal Antibody PF-043603651TG15H1XE9Anti-human Aβ 28–40IgG1Antibody 2286Antibody2286Antibody-2286PF-4,360,365RN 1219RN1219RN-1219