Tenaya’s AAV Gene Therapy TN-401 Shows Early Safety and Arrhythmia Reduction in ARVC Patients

SOUTH SAN FRANCISCO, CA – December 11, 2025 — Tenaya Therapeutics, Inc. (NASDAQ: TNYA), a clinical-stage biotechnology company, today announced positive interim data from the ongoing RIDGE™-1 Phase 1b/2 clinical trial of TN-401. The investigational AAV gene therapy is being developed as a potential one-time treatment for adults with arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by mutations in the PKP2 gene.

The initial results from the first three patients in the low-dose cohort (3x 10^13 vg/kg) demonstrated a promising safety profile, evidence of successful gene delivery, and clinically meaningful improvements in cardiac electrical stability.

Gene Delivery and Protein Expression Confirmed

ARVC is a form of arrhythmogenic cardiomyopathy (ACM) where mutations in the PKP2 gene lead to insufficient levels of the plakophilin-2 (PKP2) protein, compromising the structural integrity and electrical signaling of heart muscle cells (cardiomyocytes).

TN-401 is an AAV9-based gene replacement therapy designed to deliver a functional PKP2 gene into these heart muscle cells, addressing the underlying genetic cause of the disease.

Key findings from biopsies, with follow-up ranging from 20 to 40 weeks, confirm the AAV mechanism:

• Robust Transduction: Consistent TN-401 DNA and high mRNA expression were detected in all three patients, confirming the AAV vector successfully transduced the heart.

• Protein Increase: Post-treatment PKP2 protein levels increased significantly by a mean of 10% from baseline in two of the three patients with available data. This increase was confirmed using rigorous mass spectrometry methods.

Meaningful Reduction in Arrhythmia Burden

For patients with greater than six months of follow-up, the interim data showed a strong trend toward reduced electrical instability, a critical risk factor for sudden cardiac arrest in ARVC:

• PVC Reduction: Patient 1 experienced a 46% decrease in PVC (premature ventricular contraction) counts, while Patient 2 saw an 89% decrease.

• NSVT Elimination: Patient 2 had a substantial non-sustained ventricular tachycardia (NSVT) burden at baseline that dropped completely to zero by Week 32 and remained stable.

Dr. Whit Tingley, Tenaya’s Chief Medical Officer, noted the results indicate “consistent transduction of the AAV gene therapy in cardiomyocytes and RNA and protein expression, and meaningful reductions in PVCs and NSVTs, well-established risk factors for dangerous sustained arrhythmias.”

Favorable Safety Profile

The AAV therapy was reported to be well tolerated at the initial dose level, with no dose-limiting toxicities observed:

• Safety: Adverse events were generally mild and deemed unrelated to TN-401.

• Cardiotoxicity: No incidents of thrombotic microangiopathy (TMA) or cardiotoxicities were observed.

• ICD Events: No implantable cardioverter-defibrillator (ICD) shocks or arrhythmias associated with the AAV treatment have occurred to date.

Enrollment and dosing are now complete for the higher dose cohort (6 x 10^13  vg/kg), and monitoring of all patients continues in the RIDGE-1 trial.