Tenaya Therapeutics (TNYA) Study Result summary

Program and Study Overview

• RIDGE-1 is a Phase 1b/2, open-label, multi-center, dose escalation trial evaluating TN-401 gene therapy in adults with PKP2-associated ARVC, aiming to establish safety, dosing, and pharmacodynamic efficacy; both cohorts have been fully enrolled.

• Initial data from Cohort 1 focused on safety, biopsy, and early clinical results, with all patients having persistent electrical instability and arrhythmias despite standard of care.

• The MyPEAK-1 trial for TN-201 (MYBPC3-associated HCM) had its clinical hold lifted by the FDA after protocol amendments, and learnings are being applied to the RIDGE-1 protocol.

• The RIDGE natural history study, the largest for PKP2 disease, informs trial design, eligibility, and provides context for interpreting clinical trial results.

• PKP2-associated ARVC is a severe genetic heart disease affecting over 70,000 people in the U.S., with high risk of arrhythmias and sudden cardiac death, and limited treatment options.

Study Design and Patient Characteristics

• Cohort 1 received 3E13 vg/kg and Cohort 2 received 6E13 vg/kg, with sequential dosing and DSMB oversight.

• The study aims to enroll up to fifteen adults with PKP2-associated ARVC and increased arrhythmia risk.

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

• TN-401 has received Orphan Drug and Fast Track Designations from the FDA.

Safety and Tolerability Findings

• TN-401 at 3E13 vg/kg was well tolerated, with most adverse events mild, asymptomatic, and manageable; no dose-limiting toxicities, treatment-related arrhythmias, cardiotoxicities, or serious adverse events were observed.

• No evidence of cardiac inflammation, proarrhythmic effects, or clinical TMA events was observed; all Cohort 1 patients have tapered off immunosuppressants and remain on study.

• Immunosuppression regimens were refined to reduce prednisone exposure, and no complement inhibitors were needed.

• Safety monitoring protocols leverage experience from both TN-201 and TN-401 programs.