Tenaya Therapeutics (TNYA) Study result summary

Study background, objectives, and design

• MyPEAK-1 is a Phase 1b/2 open-label, multi-center, dose-escalation and expansion trial evaluating TN-201 gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), focusing on safety, tolerability, dose-finding, pharmacodynamics, and efficacy at two dose levels (3E13 and 6E13 vg/kg).

• The trial includes cardiac biopsies, biomarker analysis, structural and functional cardiac assessments, and symptom improvement endpoints.

• All enrolled patients to date have non-obstructive HCM, with most having severe disease and significant symptom burden at baseline; follow-up ranges from 26 to 104 weeks.

Interim clinical and biomarker results

• Consistent improvements in cardiac structure, including reductions in left ventricular mass index (LVMI) and wall thickness, were observed and sustained, especially at higher doses, with all six evaluable patients showing LVMI reductions.

• Four of six patients had ≥10% reductions in LVMI, with durable improvements up to two years in early-dosed patients and deeper, faster responses in higher-dose cohorts.

• Symptom burden reduced in all patients, with most achieving NYHA Class 1 and significant gains in KCCQ scores; 83% became asymptomatic and 67% had meaningful quality-of-life improvements.

• Functional capacity improved in most high-dose patients, as measured by six-minute walk and cardiopulmonary exercise tests, with three patients showing meaningful increases.

• Cardiac biomarkers (troponin I, NT-proBNP) improved or remained stable in most patients up to 104 weeks post-dosing, indicating reduced cardiac injury and strain.

Biopsy and molecular findings

• Biopsies confirmed TN-201 delivery and robust DNA transduction in heart muscle, with dose-dependent increases in TN-201 mRNA and MyBP-C protein levels, especially in higher dose cohorts.

• MyBP-C protein levels increased in both cohorts, with higher and earlier rises in Cohort 2 and a mean 4% rise overall.