Voyager Therapeutics Faces Setback in ALS Gene Therapy Development

Voyager Therapeutics, a leading gene therapy company, has announced a significant delay in its amyotrophic lateral sclerosis (ALS) program due to unexpected preclinical results. The company's candidate, VY9323, will not advance to clinical trials as originally planned, prompting a search for an alternative payload.

Preclinical Data Reveals Safety Concerns

New data from a three-month non-human primate study has indicated that the siRNA payload component of VY9323 does not meet Voyager's safety standards. CEO Alfred Sandrock, M.D., Ph.D., explained, "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."

This setback has forced Voyager to postpone its planned mid-2025 phase 1 trial for VY9323 in ALS patients. The company is now focusing on identifying an alternate payload that can achieve the desired product profile while maintaining safety standards.

Impact on Pipeline and Financial Outlook

Despite the disappointment surrounding VY9323, Voyager remains optimistic about its overall gene therapy pipeline. The company has confirmed that no changes are required for the capsid component of the therapy, which is also used in its VY1706 Alzheimer's disease program. This program has shown promise in preclinical studies, demonstrating the ability to reduce tau protein levels.

Voyager's other key programs remain on track:

• The GBA1 program for Parkinson's disease, partnered with Neurocrine, is expected to submit an Investigational New Drug (IND) filing this year.
• An IND filing for the Alzheimer's candidate VY1706 is planned for next year.

The delay in the ALS program has a silver lining for Voyager's finances. The company now expects to extend its cash runway into mid-2027, excluding potential milestone payments from various partnerships.

Strategic Partnerships and Future Directions

Voyager continues to leverage its partnerships to advance its gene therapy platform. The company recently strengthened its collaboration with Novartis, signing deals related to its RNA-based screening platform for discovering adeno-associated virus capsids that can penetrate the blood-brain barrier and target the central nervous system.

As Voyager works to overcome the challenges in its ALS program, the company remains committed to addressing unmet needs in neurodegenerative diseases. CEO Sandrock emphasized, "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."

Voyager has promised to provide an updated timeline for its ALS program when appropriate, as it continues to explore alternative approaches to deliver effective gene therapies for this devastating disease.