Voyager Pauses IND Filing while Assessing Alternate Payloads for SOD1 ALS Gene Therapy Program

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Voyager Therapeutics, a biotechnology company focused on neurogenetic medicines, announced on Feb. 11, 2025 that it will be assessing alternate payloads related to VY9323, its gene therapy program for superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS), based on emerging three-month data from a study in non-human primates (NHPs). These data suggest that it would be necessary to use an alternate payload in order to achieve the desired product profile (1). This change of plan shifts the company’s investigational new drug (IND) application filing, which was originally intended to be filed in mid-2025. The company’s cash runway is now expected to extend out into mid-2027, not including potential milestone payments from existing partnerships.

The company also reported that it had no changes planned to the novel capsid component of the SOD1 ALS gene therapy program. That same capsid in its VY1706 (tau silencing) gene therapy program achieved desired activity levels and was shown to be well-tolerated in three-month NHP studies.

“Emerging preclinical data indicate the siRNA [small interfering RNA] 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. 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,” said Alfred W. Sandrock, Jr., MD, PhD, chief executive officer of Voyager, in a company press release (1).

Given the need to assess alternate payloads, Voyager’s IND application and Canadian clinical trial application (CTA) for VY9323, whose filings were anticipated in mid-2025, have been paused. The company expects to provide an update on the new expected timing for its SOD1 ALS program when appropriate.

This decision on the SOD1 ALS program does not impact the company’s other gene therapy programs, however, and the company continues to expect IND filings in 2025 from Neurocrine Biosciences for a gene therapy program in glucosylceramidase beta 1 (GBA1) Parkinson’s and other GBA1-mediated diseases, as well as a program in Friedreich’s ataxia (FA). Voyager formed a collaboration with Neurocrine Biosciences in January 2023 (1), under which the companies will work on three gene therapy programs directed at rare central nervous system (CNS) targets. Each program leverages Voyager’s novel tropism redirection of adeno-associated virus by cell-type-specific expression of RNA (TRACER) capsids. The agreement called for a $175 million upfront payment to Voyager by Neurocrine Biosciences. Neurocrine Biosciences has also agreed to fund all costs incurred under the collaboration (2).

Meanwhile, Voyager remains on track with VY1706 and still expects to file an IND for this gene therapy program in 2026. The company’s overall pipeline includes programs for Alzheimer’s disease, ALS, Parkinson’s disease, and multiple other CNS diseases. Many of the company’s programs derive from its TRACER platform, which the company uses to generate novel capsids and identify associated receptors in an effort to potentially enable high brain penetration following intravenous dosing of genetic medicines.

“We are encouraged that our novel TRACER capsids continue to perform consistently across multiple programs, and we believe they have the potential to transform gene therapy for CNS diseases. We continue to expect IND filings in 2025 for our gene therapy candidates for GBA1 and FA, and in 2026 for VY1706,” said Sandrock, Jr., in the press release (1).

References

1. Voyager Therapeutics. Voyager Provides Update on SOD1 ALS Gene Therapy Program. Press Release. Feb. 11, 2025.
2. Voyager Therapeutics. Neurocrine Biosciences and Voyager Therapeutics Enter Strategic Collaboration for Development and Commercialization of Voyager’s GBA1 Program and Other Next-Generation Gene Therapies for Neurological Diseases. Press Release. Jan. 9, 2023.