Rajeev Sivasankaran, PhD, on Voyager’s Single-Dose AAV Strategy for Silencing Tau for Alzheimer Disease

“I think we're very excited about the progress the preclinical data that we've generated so far, and we're on track for continuing to our GLP tox studies, and we look forward to an IND filing in 2026.”

CGTLive® spoke with Rajeev Sivasankaran, PhD, vice president of neuroscience at Voyager Therapeutics, who presented new preclinical data at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2025, in New Orleans, Louisiana. His presentation focused on VY-1706, an investigational gene therapy intended to treat Alzheimer disease by delivering tau-silencing siRNA through a single intravenous (IV) dose of adeno-associated virus (AAV).

VY-1706 is still in preclinical development and utilizes the AAV platform to deliver a potent, selective siRNA payload directly to affected brain regions. The therapy demonstrated strong pharmacologic activity in the P301S mouse model of tauopathy, which shows early and progressive tau accumulation. A single IV administration of VY-1706 resulted in broad central nervous system biodistribution and significantly reduced tau mRNA and protein expression, including reductions in pathologic tau.

In nonhuman primate studies, VY-1706 achieved dose-dependent delivery and greater than 50% knockdown of tau protein in the cortex, hippocampus, and other brain regions relevant to AD. Notably, the treatment was well-tolerated, with no clinical signs or changes in cardiac or liver enzymes and no elevation of neurofilament light chain, a surrogate marker for AAV-associated neurotoxicity. “We did not see any clinical signs or clinical chemistry changes, including cardiac enzymes and liver enzymes,” Sivasankaran told CGTLive.

The company expects to initiate GLP toxicology studies later this year and aims to submit an investigational new drug application in 2026. VY-1706 is 1 of 2 tau-targeting programs at Voyager, alongside a monoclonal antibody currently in human trials.

Click here to view more coverage of the 2025 ASGCT Annual Meeting.