Voyager Therapeutics (Nasdaq: VYGR) reported six-month preclinical toxicology data for its tau-targeting Alzheimer's disease gene therapy candidate VY1706 at the Alzheimer's Association International Conference, showing durable tau reduction and a favorable safety profile in non-human primates ahead of planned first-in-human dosing in H2 2026.
In a GLP toxicology study, a single intravenous dose of VY1706 reduced MAPT mRNA and tau protein by up to 75% across Alzheimer's disease-relevant brain regions, including the hippocampus, entorhinal cortex, and frontal and temporal cortices, with effects maintained through six months. No adverse clinical pathology or histopathological findings were observed in the central nervous system, dorsal root ganglia, liver, or other peripheral organs at doses up to 5E13 vg/kg.
VY1706 combines a proprietary blood-brain barrier-penetrating AAV capsid from Voyager's TRACER platform with an siRNA targeting MAPT mRNA. The approach is designed to silence tau production throughout the brain following a single intravenous administration, distinguishing it from antibody therapies that target extracellular tau aggregates.
The absence of liver toxicity is particularly notable, as hepatotoxicity has limited several systemically administered AAV gene therapy programs. Voyager said its ALPL receptor-mediated transport mechanism, which facilitates delivery across the blood-brain barrier while reducing liver exposure, supports translation across species.
The results extend three-month data presented at the American Society of Gene & Cell Therapy meeting in May, demonstrating sustained target knockdown without evidence of emerging toxicity, although human efficacy and safety remain to be established.