Voyager Therapeutics Advances Single-Dose AAV Gene Therapy VY-1706 for Alzheimer's Disease, Targeting IND Filing in 2026
核心洞察
Voyager Therapeutics presented preclinical data on VY-1706, a single-dose AAV gene therapy that delivers tau-silencing siRNA intravenously to treat Alzheimer's disease (搜索).
The therapy demonstrated over 50% tau protein (搜索) reduction in key brain regions including cortex and hippocampus in nonhuman primate studies, with no observed toxicity or clinical signs.
VY-1706 showed robust pharmacologic activity in the P301S mouse model of tauopathy (搜索), significantly reducing tau mRNA, protein expression, and pathologic tau accumulation.
Voyager Therapeutics has reported promising preclinical results for VY-1706, an investigational gene therapy designed to treat Alzheimer's disease (搜索) through a single intravenous dose of adeno-associated virus (AAV) delivering tau-silencing siRNA. The data was presented at the American Society of Gene & Cell Therapy 28th Annual Meeting held May 13-17, 2025, in New Orleans, Louisiana.
Robust Preclinical Efficacy in Animal Models
VY-1706 demonstrated strong pharmacologic activity in the P301S mouse model of tauopathy (搜索), which exhibits early and progressive tau accumulation characteristic of Alzheimer's disease (搜索) pathology. A single IV administration resulted in broad central nervous system biodistribution and significantly reduced tau mRNA and protein expression, including reductions in pathologic tau.
"We treated these mice with a 1-time intravenous delivery of VY-1706 which actually resulted in broad delivery of this tau silencing siRNA in key regions of the brain impacted in AD, including the cortex, hippocampus, and brain stem, and showed robust lowering of the tau mRNA and tau protein (搜索), as well, as importantly, pathological tau," said Rajeev Sivasankaran, PhD, vice president of neuroscience at Voyager Therapeutics.
Promising Safety Profile in Nonhuman Primates
In nonhuman primate studies, VY-1706 achieved dose-dependent delivery and greater than 50% knockdown of tau protein (搜索) in the cortex, hippocampus, and other brain regions relevant to Alzheimer's disease (搜索). The treatment was well-tolerated over an 11-week study period, with no clinical signs or changes in cardiac or liver enzymes observed.
Importantly, the therapy showed no elevation of neurofilament light chain (搜索) (NfL), 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 noted. "Also, importantly, we looked at a surrogate marker for neuronal toxicity, or dorsal root ganglion toxicity, which is often associated with AAVs, and we found that the neurofilament light chain levels were not elevated at all during the entire course of this study."
Selective and Potent siRNA Design
The therapy utilizes a potent and selective siRNA payload that demonstrated minimal off-target activity in global transcriptomic analyses. The siRNA component showed strong in vitro potency and selectivity for tau targeting.
Clinical Development Timeline
Voyager Therapeutics expects to initiate good laboratory practice (GLP) toxicology studies later this year and aims to submit an investigational new drug application in 2026. The company views the pharmacology data as consistent with what would be expected for a therapeutic dose range.
Dual Approach to Tau Targeting
VY-1706 represents one of two tau-targeting programs at Voyager Therapeutics. The company is also developing a monoclonal antibody (搜索) approach currently in human trials with a multiple ascending dose study. This dual strategy underscores the company's commitment to tau as a therapeutic target for Alzheimer's disease (搜索).
"The idea that tau is a really important target is validated by the recent advances in the field," Sivasankaran explained. "Tau accumulation seems to really correlate very well with cognitive decline and some of the recent AD therapies where you've seen improvements or suggestions of improvement in cognitive function, or slowing of cognitive decline, seem to correlate really well with slowing down tau accumulation."
Potential Clinical Advantages
The single-dose intravenous delivery approach could offer significant advantages over current treatment paradigms requiring repeated administration. "One of the key advantages of this approach would be that it would be a single IV delivery, so it would have ease of administration and a lot less burden on the patients of the healthcare system because it's expected to be a one-time delivery," Sivasankaran noted. "I think that's a big differentiator compared to routine delivery for the life of the patient."