Tenaya Therapeutics has secured a significant boost for its innovative gene therapy program with an $8 million CLIN2 grant from the California Institute for Regenerative Medicine (CIRM). The funding will support the ongoing RIDGE-1 clinical trial investigating TN-401, a potential breakthrough treatment for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC).
The Phase 1b RIDGE-1 trial is currently enrolling symptomatic adult patients diagnosed with PKP2-associated ARVC at leading medical centers. The open-label, dose-escalation study will evaluate the safety, tolerability, and preliminary clinical efficacy of a single intravenous infusion of TN-401.
"This substantial grant validates our innovative approach and strengthens our collaboration with CIRM," said Faraz Ali, Chief Executive Officer of Tenaya Therapeutics. "The funding will accelerate our efforts to develop what could be a best-in-class gene therapy for PKP2-associated ARVC, a severe progressive disease affecting approximately 70,000 people in the United States."
Understanding PKP2-Associated ARVC
PKP2-associated ARVC represents approximately 40% of all ARVC cases and results from mutations in the plakophilin-2 (PKP2) gene. These mutations lead to insufficient protein levels crucial for maintaining heart muscle cell structure and communication. The condition typically manifests before age 40 and can result in life-threatening arrhythmias, with sudden cardiac arrest often being the first sign of disease.
Current treatment options, including anti-arrhythmic medications, implantable cardioverter-defibrillators, and ablation procedures, only address symptoms without targeting the underlying genetic cause.
Innovative Gene Therapy Approach
TN-401 employs an AAV9 viral vector to deliver functional PKP2 genes directly to heart muscle cells. The therapy has shown promising results in preclinical studies, where a single dose:
- Restored healthy PKP2 protein levels
- Normalized heart rhythms
- Improved ventricular size and function
- Extended survival in test subjects
The FDA has granted both Orphan Drug and Fast Track Designations to TN-401, recognizing its potential importance in addressing this unmet medical need.
Clinical Development Progress
The RIDGE-1 trial represents a crucial step in evaluating TN-401's potential. To support the therapy's development, Tenaya is simultaneously conducting a global non-interventional study collecting natural history and AAV9 antibody data from ARVC patients with PKP2 mutations.
Initial data from the low-dose cohort of the RIDGE-1 trial is anticipated in the second half of 2025, marking a significant milestone in the development of this potentially transformative therapy.
