Astellas Advances New “MyoAAV” Gene Therapy to Clinical Phase

SAN FRANCISCO — During the J.P. Morgan 44th Annual Healthcare Conference, Astellas Gene Therapies announced a major pivot in its quest to treat X-linked Myotubular Myopathy (XLMTM). Moving away from the troubled AAV8-based AT132 program, the company has officially opened the Phase I/II VALOR trial (NCT07052929) for ASP2957, a next-generation AAV therapy utilizing a muscle-tropic MyoAAV capsid.

Decoupling Muscle Efficacy from Liver Toxicity

The decision follows a multi-year investigation into the deaths of four boys in the previous ASPIRO AAV trial. Astellas pinpointed a “cholestatic tendency” inherent to XLMTM that, when combined with high AAV viral loads, leads to fatal liver toxicity.

To solve this, ASP2957 (licensed from Kate Therapeutics, now part of Novartis) utilizes an engineered MyoAAV3.8 capsid. The advantages of this new AAV delivery vehicle include:

• High Muscle Affinity: Uses integrin receptors to enter muscle cells more efficiently than standard AAV serotypes.

• Dramatic Dose Reduction: Achieves therapeutic protein levels at a much lower AAV dose, significantly reducing the burden on the liver.

• Enhanced Safety: Designed to “de-target” the liver while maintaining potent expression of the MTM1 gene in skeletal and cardiac muscle.

Parallel Pipeline Updates: Pompe and FTD

Astellas also provided updates on its broader AAV portfolio, signaling a busy 2026 for the genetic medicine division:

• Pompe Disease (AT845): Dosing is complete in the Phase I/II study for late-onset Pompe. A “proof-of-concept” decision is expected by March 31, 2026.

• Frontotemporal Dementia (AVB-101): In partnership with AviadoBio, this AAV program is expected to release early biomarker data from the ASPIRE-FTD trial later this year.

• Observational Liver Study (EXCEL): To better understand the risks of AAV in this population, Astellas is tracking 50 patients to map the natural course of liver health in XLMTM.