Tenaya Therapeutics’ TN-201 demonstrates tolerability and protein expression in early HCM trial

Tenaya Therapeutics, a clinical-stage biotechnology company, has released promising interim results from its MyPEAK-1 Phase 1b/2 clinical trial evaluating TN-201 gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM). The company’s findings signal early evidence that this innovative treatment could stabilise or potentially reverse the progression of this genetic heart condition.

The MyPEAK-1 clinical trial is a dose-escalating, multi-centre study investigating the safety and efficacy of TN-201 gene therapy. Designed for symptomatic adults with MYBPC3 mutations, the trial uses an AAV9-based gene therapy platform to deliver a functional MYBPC3 gene directly to heart muscle cells. This one-time intravenous infusion aims to restore healthy myosin-binding protein C (MyBP-C) levels, addressing the underlying genetic cause of the disease.

Why Does MYBPC3-Associated Hypertrophic Cardiomyopathy Need New Treatments?

Hypertrophic cardiomyopathy (HCM) is a progressive genetic heart disease often caused by MYBPC3 mutations. This leads to insufficient levels of myosin-binding protein C, a key structural protein in heart muscle cells. Patients experience thickening of the heart walls, which can reduce cardiac function and cause severe symptoms, including fatigue, shortness of breath, and chest pain.

For those with MYBPC3-associated HCM, conventional treatments like beta blockers or surgical interventions provide symptomatic relief but fail to target the root cause of the disease. TN-201 gene therapy, however, focuses on correcting this underlying deficiency, offering a potentially curative approach.

Key Findings from the MyPEAK-1 Clinical Trial

The first cohort of the MyPEAK-1 clinical trial involved three patients receiving a low dose of TN-201 (3E13 vg/kg). Preliminary data suggest that TN-201 was well tolerated, with encouraging signs of efficacy:

Safety Profile:

TN-201 demonstrated a manageable safety profile. No cardiac toxicities, complement activation, or thrombotic microangiopathy were observed. While some isolated liver enzyme elevations occurred—common with AAV9-based gene therapies—they were successfully managed with corticosteroids.

Cardiac Transduction and Gene Expression:

Biopsies revealed robust uptake of the gene therapy into heart muscle cells, a critical step for restoring myosin-binding protein C. Over time, patients showed measurable increases in both transgene RNA and MyBP-C protein levels, suggesting durable gene expression.

Clinical Improvements:

Biomarkers of cardiac strain, including NT-proBNP, remained stable overall. Cardiac troponin I, a marker of heart injury, normalised in one patient. Clinical measures such as New York Heart Association (NYHA) classifications showed stability or improvement, indicating early signs of disease control.

At Week 52, Patient 1 demonstrated a 3% increase in MyBP-C protein levels, combined with growing transgene RNA expression—key indicators that the therapy is active and reaching target cells.

The Potential Impact of TN-201 Gene Therapy

The positive interim results from the MyPEAK-1 clinical trial offer hope to patients struggling with MYBPC3-associated hypertrophic cardiomyopathy. For many, the disease progresses despite current treatment options, leading to an increased risk of complications like arrhythmias, heart failure, and sudden cardiac death.

Dr Milind Desai, a lead investigator at the Cleveland Clinic, emphasised the significance of these findings. He highlighted the therapy’s potential to “halt or even reverse the steady decline” seen in HCM patients by directly addressing its genetic root cause.

Tenaya Therapeutics’ Chief Medical Officer, Dr Whit Tingley, reinforced the company’s confidence in TN-201, noting that the emerging data support further investigation at higher doses. With robust cardiac transgene expression and increasing MyBP-C protein levels, TN-201 could revolutionise the hypertrophic cardiomyopathy treatment landscape.

What Comes Next for TN-201 and the MyPEAK-1 Trial?

Following the successful results of Cohort 1, Tenaya Therapeutics will expand the study to test a higher dose of TN-201 (6E13 vg/kg). Data from this next cohort, expected in 2025, will provide deeper insights into TN-201’s safety, efficacy, and long-term potential for stabilising or reversing disease progression.

As TN-201 continues to advance, it benefits from significant regulatory support. The therapy has received Fast Track, Orphan Drug, and Rare Pediatric Disease Designations from the U.S. Food and Drug Administration (FDA), alongside orphan medicinal product designation from the European Commission. These designations underscore TN-201’s potential as a game-changing treatment for MYBPC3-associated HCM.

A Transformative Step Toward Curative HCM Treatments

The promising early results of the MyPEAK-1 clinical trial position TN-201 as a breakthrough therapy for patients with MYBPC3-associated hypertrophic cardiomyopathy. By targeting the genetic root cause and restoring healthy MyBP-C levels, TN-201 gene therapy could redefine treatment outcomes for a condition long considered difficult to manage.

With further data on the horizon, Tenaya Therapeutics remains committed to advancing TN-201 and improving the lives of those affected by this debilitating heart disease.