SOUTH SAN FRANCISCO, Calif. — September 14, 2026

Tenaya Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to TN-401, the company’s investigational gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC). The designation is supported by interim data from the ongoing RIDGE-1 Phase 1b/2 clinical trial, which demonstrated reductions in the daily rates of premature ventricular contractions (PVCs) and non-sustained ventricular tachycardias (NSVTs), alongside a favorable tolerability profile. RMAT designation adds another expedited regulatory designation to TN-401, following FDA Fast Track and Orphan Drug designations and the European Medicines Agency’s PRIME designation. Tenaya said the regulatory status could facilitate enhanced interaction with the FDA as it works toward a potential pivotal trial and continues discussions regarding the clinical development path for TN-401.

RIDGE-1 Data Support TN-401 Development

Interim findings from RIDGE-1 provide the clinical evidence supporting Tenaya’s RMAT application, with improvements observed across multiple measures of electrical stability in patients with PKP2-associated ARVC. PVCs and NSVTs are among the ventricular arrhythmias associated with the disease and can contribute to potentially life-threatening cardiac events. RIDGE-1 is a multicenter, open-label, dose-escalation Phase 1b/2 study evaluating the safety, tolerability and preliminary clinical efficacy of a one-time intravenous infusion of TN-401. The trial is designed to enroll up to 15 adults with PKP2-associated ARVC who have an implantable cardioverter-defibrillator and elevated arrhythmia risk based on PVC counts during screening. Tenaya expects to provide additional clinical data from RIDGE-1 and an update on regulatory discussions during the fourth quarter of 2026, potentially informing plans for the next stage of development.

TN-401 Targets Genetic Cause of ARVC

TN-401 is designed to address the underlying genetic cause of PKP2-associated ARVC rather than primarily managing its cardiac manifestations. The investigational therapy uses an AAV9-based vector to deliver the PKP2 gene, with Tenaya selecting AAV9 based on its clinical and commercial safety record and its ability to target cardiac muscle cells. PKP2 mutations are estimated to account for approximately 40% of the overall ARVC population, with more than 70,000 people in the United States estimated to have PKP2-associated disease. Mutations can result in insufficient plakophilin-2 protein, disrupting the desmosomal structures that maintain connections and electrical signaling between heart muscle cells. Current management approaches include anti-arrhythmic medicines, implantable cardioverter-defibrillators and ablation procedures, but these interventions do not correct the underlying genetic defect. TN-401 is therefore being developed as a potential disease-modifying gene therapy approach for this rare inherited cardiomyopathy.

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Tenaya Advances Gene Therapy Toward Pivotal Development

The RMAT designation strengthens Tenaya’s regulatory position as it prepares for potential pivotal development of TN-401. The FDA program is intended for regenerative medicine therapies addressing serious conditions where preliminary clinical evidence indicates potential to meet an unmet medical need, providing opportunities for enhanced regulatory interaction and guidance covering clinical development, manufacturing and potential review pathways. Tenaya is also conducting the RIDGE natural history study, designed to characterize PKP2-associated ARVC and support the broader TN-401 development program. Beyond TN-401, Tenaya’s pipeline includes TN-201, a gene therapy candidate for MYBPC3-associated hypertrophic cardiomyopathy, and TN-301, an HDAC6 inhibitor being evaluated for potential applications including heart failure with preserved ejection fraction and Duchenne muscular dystrophy. With RMAT, Fast Track and Orphan Drug designations supporting TN-401, Tenaya is positioning its gene therapy platform for a potentially pivotal development program in genetically driven heart disease.

Source: Tenaya Therapeutics press release