LY2599666

LY2599666 is a humanized, affinity-optimized monoclonal antibody antigen-binding fragment (Fab) linked to polyethylene glycol (PEG), designed to target soluble amyloid-beta (Aβ) monomers. It is an Fc-less fragment, meaning it lacks the Fc region of a full antibody, and was developed for subcutaneous administration. The drug was investigated as a passive immunotherapy for Alzheimer's disease by Eli Lilly. Its mechanism of action involves binding to soluble Aβ monomers in plasma, aiming to reduce their levels and potentially modify disease progression. Clinical development included Phase 1 studies in healthy volunteers and patients with mild cognitive impairment or mild-to-moderate Alzheimer's disease; however, the program was terminated in 2017 due to low target engagement despite being generally well tolerated[1][2][3][5].