| Background | Zagotenemab is a humanized anti-tau antibody derived from MCI-1, Peter Davies' mouse monoclonal antibody against an early pathological conformation of tau. Zagotenemab binds and neutralizes soluble tau aggregates.Preclinical studies in tau transgenic mice showed that immunotherapy with MCI-1 reduced levels of hyperphosphorylated insoluble tau levels and neurofibrillary pathology (Chai et al., 2011).At the 2017 AAIC meeting, Lilly presented data from surface plasmon resonance binding and ELISA assays to assess LY3303560's selectivity to aggregates over monomer and characterize its epitope. LY3303560 reportedly had high affinity to soluble tau aggregate in vitro, at a KD of below 220 picomolar, compared to monomer, KD of 235 nanomolar. The antibody reportedly recognizes a conformational epitope whose primary epitope is in tau's N-terminal region. Intravenous administration to monkeys indicated clearance of 0.15 ml/h/kg and a half-life of 13 days. SC administration indicated a bioavailability of 79 percent, and rat CSF concentration was 0.1 percent of plasma at 24 hours after IV administration (Alam et al., 2017). |
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