Tenaya Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has provided clearance of the company?s Investigational New Drug (IND) application to initiate clinical testing of TN-401. TN-401 is Tenaya?s adeno-associated virus serotype 9 (AAV9)-based investigational gene therapy product candidate for the treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by mutations in the plakophilin-2 (PKP2) gene. Based on this IND clearance, the company plans to initiate the RIDGE-1? Phase 1b clinical trial of TN-401, a multi-center, open-label study to assess the safety, tolerability and clinical efficacy of a one-time intravenous infusion of TN-401.

Tenaya is currently conducting the RIDGE? global non-interventional natural history and serotype study of PKP2-associated ARVC. ARVC, also known as arrhythmogenic cardiomyopathy (ACM), is a chronic, progressive, familial disease that typically presents before age 40.

People with ARVC experience symptoms related to ventricular arrhythmias, including palpitations, lightheadedness and fainting, and are at increased risk of sudden cardiac death. PKP2 mutations are the most common genetic cause of ARVC and result in a loss of key proteins needed to maintain the structural integrity and cell-to-cell signaling of heart muscle cells. TN-401 is designed to address the underlying cause of disease by delivering a fully functional PKP2 gene to restore normal PKP2 protein levels and thereby slow disease progression and reverse the course of disease after a single dose.

In preclinical studies in a knock-out mouse model of disease, Tenaya?s PKP2 gene therapy administered at a dose of 3E13 vg/kg restored normal levels of PKP2 protein expression and demonstrated durable efficacy in preventing disease development and slowing or reversing disease progression after onset leading to long-term survival. AAV9 was selected as the vector for delivery of Tenaya?s PKP2 gene therapy based on its extensive clinical and commercial safety record in thousands of patients globally and its demonstrated ability in clinical studies to broadly distribute around the human heart and robustly express in heart muscle cells. Tenaya has completed cGMP drug product manufacturing at the 1000-liter scale for TN-401 at the company?s Genetic Medicines Manufacturing Center, with sufficient drug product produced to support the entire Phase 1b study.