armanezumab

Armanezumab is a humanized IgG1 monoclonal antibody that selectively recognizes a phosphatase activation domain (PAD) epitope in the N-terminus of pathological tau, spanning approximately amino acids 3–8, which becomes exposed in misfolded and aggregated tau associated with Alzheimer’s disease and other tauopathies.[1][5] Developed from a murine precursor (1C9) and produced in CHO cells at commercial-like yields (>1.5 g/L), the antibody binds monomeric and aggregated human tau with high affinity, labels pathological tau in human Alzheimer’s, frontotemporal dementia, and Pick’s disease brain tissue, and does not bind normal control brain.[1][3][6] In preclinical models, armanezumab inhibits seeding activity of aggregated tau, neutralizes tau oligomer cytotoxicity in neuronal and neuroblastoma cell assays, and acutely reduces total and multiple phosphorylated tau species in tau transgenic mice after intracranial administration, supporting its potential as a passive tau-targeted immunotherapy for advanced stages of Alzheimer’s disease and related tauopathies.[1][3][6]