One of the first completed trials using a passive antibody approach for tau clearance was a Phase 1 study involving RG7345 (RO 6,926,496), which targeted a phosphorylated epitope at serine 422 (pS422) near the C-terminal end of tau. The rationale for the development of this epitope target was that pS422 was thought to undergo phosphorylation only in pathologic tau aggregates, e.g. NFTs. [101] This hypothesis was supported by preclinical work targeting passive immunization with a monoclonal antibody against pS422 that resulted in selective clearance of pS422 in triple transgenic mouse models (TauPS1APP) [102]. Unfortunately, despite trial completion in October 2015, results from the Phase 1 study were not released, but Hoffman La-Roche discontinued development.
