Voyager Therapeutics no longer expects to sail its amyotrophic lateral sclerosis (ALS) candidate into the clinic in the coming months as the gene therapy company looks to rejig the asset’s payload.
The candidate in question is VY9323, an AAV gene therapy combining a highly potent pri-miRNA against superoxide dismutase 1 (SOD1) with an intravenous-delivered, blood-brain barrier-penetrant TRACER capsid. The company originally planned to begin a phase 1 trial of VY9323 in ALS in mid-2025.
But the biotech announced this morning that new three-month data from a non-human primate study suggest “an alternate payload" will be "necessary to achieve the desired product profile.”
No changes are expected to be required to the capsid component of the therapy, Voyager said, noting that the same capsid is used in the VY1706 Alzheimer’s disease program. That drug has been shown to reduce tau in preclinical studies.
“Emerging preclinical data indicate the siRNA payload component of VY9323 does not meet our high standards due to what appears to be an off-target effect resulting in a narrowed therapeutic window,” Voyager CEO Alfred Sandrock, M.D., Ph.D., explained in the release.
“While we are disappointed that the development candidate VY9323 will not advance, we hope that we may be able to identify an alternate payload and find a path forward for this program, given the unmet need in ALS,” Sandrock added.
There is a financial upside to the delay, as it means Voyager will be able to extend its cash runway into mid-2027, excluding milestone payments from its various partnerships.
Voyager will provide an updated timeline for its ALS program “when appropriate,” but in the meantime the biotech said its other gene therapies remain on track.
They include the GBA1 program for Parkinson’s disease, for which Voyager’s partner Neurocrine is expected to submit an Investigational New Drug (IND) filing this year. Voyager is also planning to file an IND next year for the Alzheimer’s candidate VY1706.
Last year, Voyager signed a pair of deals with long-time collaborator Novartis related to the biotech’s RNA-based screening platform for discovering adeno-associated virus capsids that penetrate the blood-brain barrier and head to the central nervous system.