Tenaya Therapeutics (TNYA) Study Update summary

Study overview and patient characteristics

• 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), targeting the underlying genetic cause using AAV9 to deliver a functional MYBPC3 gene.

• The study aims to assess safety, tolerability, pharmacodynamics, and clinical endpoints over a 52-week period with extended follow-up.

• Cohort one included three young, severely affected patients with prior myectomy and ICDs, all symptomatic with elevated biomarkers and significant LV mass index; dose escalation to cohort two (6E13 vg/kg) is underway.

• Endpoints include safety, cardiac biopsy (DNA, mRNA, protein), biomarkers, imaging, functional capacity, and patient-reported outcomes.

• Up to 24 patients may be enrolled in expansion cohorts, with additional data from higher-dose cohorts expected in 2025.

Safety and tolerability

• TN-201 was generally well tolerated at the 3E13 vg/kg dose, with a safety profile consistent with other AAV gene therapies and immunosuppressive regimens.

• All patients experienced reversible elevated liver enzymes, managed with steroids; no cardiac toxicities, myocarditis, arrhythmia, or TMA-related events were observed.

• Most adverse events were mild, transient, or reversible; two unrelated serious adverse events occurred.

• DSMB reviewed all data and cleared dose escalation to 6E13 vg/kg for cohort two; all patients remain on study.

• Patients 1 and 2 tapered off immunosuppressives.

Cardiac delivery, expression, and biomarker data

• Robust cardiac transduction was observed, with vector copy number exceeding preclinical expectations and favorable compared to peer programs.

• TN-201 mRNA expression increased over time, with patient one showing a 50% rise from week 8 to week 52; levels were comparable to other clinical gene therapies.

• MyBP-C protein levels in patient one rose from 56% to 59% of normal over one year, with patient two at 62% at week 8; protein restoration was modest but aligns with benefits seen in other cardiac gene therapy trials.

• Baseline and post-dose biopsies are now protocol for all patients to better track protein changes.

• Modest protein increases are considered meaningful, as even small rises have shown clinical benefit in other gene therapy programs.