Tenaya Therapeutics (TNYA) Study update summary

Study background, objectives, and design

• RIDGE-1 is a multi-center, open-label, Phase 1b/2 trial evaluating TN-401 gene therapy for PKP2-associated ARVC, a severe genetic heart disease with high unmet need.

• The study aims to assess safety, pharmacodynamics, and exploratory clinical endpoints at two dose levels (3E13 and 6E13 vg/kg), with sequential dosing, cardiac biopsies, and a 52-week primary period plus four-year follow-up.

• Both cohorts have completed enrollment, with an expansion cohort ongoing at the higher dose.

• The study population includes adults with severe disease, many diagnosed young, with ICDs and prior interventions.

• Endpoints include changes in PVC and NSVT counts, ICD shock/VT frequency, structural changes, biomarkers, and patient-reported outcomes.

Patient population and unmet need

• PKP2-associated ARVC affects over 70,000 people in the U.S., is severe, progressive, and lacks approved therapies.

• ARVC is responsible for over 15% of heart-related deaths in patients under 35, with 40% of cases linked to PKP2 mutations.

• Most patients have high PVC burden despite standard care, leading to significant quality-of-life impacts.

Key clinical efficacy results

• All treated patients showed consistent, deep, and sustained reductions in arrhythmia burden, including PVCs and NSVT, with mean PVC reductions of 60% in cohort 1 and 67% in cohort 2.

• NSVT episodes dropped dramatically in high-burden patients, with some going from dozens per day to near zero by Week 52.

• Clinical measures such as QRS duration, T-wave inversions, and NYHA class remained stable or normal during follow-up.

• Reductions in arrhythmia burden were associated with lower odds of severe ventricular arrhythmias and are considered highly clinically meaningful.