Tenaya Therapeutics reports interim MyClimb study data on pediatric HCM patients.

Tenaya Therapeutics has presented interim data from its ongoing MyClimb natural history study of pediatric participants with MYBPC3-associated hypertrophic cardiomyopathy (HCM). The study found that 93% of participants had the nonobstructive form of HCM, for which there are no approved therapeutics. Genotypic status was identified as a significant predictor of risk and left ventricular mass index may serve as a surrogate marker for poor long-term outcomes.

Tenaya Therapeutics, a clinical-stage biotechnology company, has presented interim data from its ongoing MyClimb natural history study of pediatric participants with MYBPC3-associated hypertrophic cardiomyopathy (HCM) at the European Society of Cardiology Congress (ESC). The study, which is believed to be the largest of its kind, found that 93% of participants had the nonobstructive form of HCM, for which there are currently no approved treatment options [1].

Key findings from the MyClimb study include the identification of genotypic status as a significant predictor of risk. Participants were stratified based on three genetic inheritance patterns: homozygous, compound heterozygous, and heterozygous. Among the homozygous group, nearly all participants died or required heart transplant before age one. Compound heterozygous participants had a median age of diagnosis of 2.9 years and experienced severe cardiomyopathy with significant arrhythmia burden and high prevalence of heart-failure related hospitalization (63%), transplant or death (27%). Heterozygous children had a median age of diagnosis of 6.5 years, with 27% experiencing heart failure-related hospitalizations and 13% having arrhythmia-related symptoms [1].

The study also found that Left Ventricular Mass Index (LVMI) was a significant predictor of risk in compound heterozygous and heterozygous groups, with every 10-unit (g/m2) increase associated with a 10% higher hazard of a serious event. These findings suggest that LVMI may serve as an appropriate surrogate marker to evaluate the early effectiveness of gene therapy in potential future pivotal studies [1].

The MyClimb study aims to characterize the association between genotype, structural, and functional cardiac measures over time. The study has enrolled more than 200 individuals at 29 sites worldwide and is believed to be the largest study of pediatric individuals with MYBPC3-associated HCM ever conducted. Mutations in MYBPC3, the gene that encodes cardiac myosin-binding protein C, are among the most common genetic causes of HCM [1].

Tenaya Therapeutics is developing TN-201, an adeno-associated virus serotype 9 (AAV9)-based gene therapy designed to deliver a working MYBPC3 gene to heart muscle cells via a single intravenous infusion. The therapy aims to increase MyBP-C protein levels to address the underlying cause of MYBPC3-associated HCM. Encouraging initial data from the first three patients to receive TN-201 at the 3E13 vg/kg dose level (Cohort 1) were presented at the American College of Cardiology meeting. The U.S. Food and Drug Administration has granted TN-201 Fast Track, Orphan Drug and Rare Pediatric Drug Designations [1].

The MyClimb data offer actionable information for predicting those severe MYBPC3-associated HCM pediatric patients who may be at higher risk of death or severe complications. These new insights into predictive risk factors can inform clinicians’ thinking on risk stratification and interventions and offer important clues for endpoints and eligibility criteria as we consider advancing genetic medicines such as TN-201 in clinical trials for pediatric patients where there is high unmet need [1].

References:
[1] https://www.globenewswire.com/news-release/2025/08/31/3141920/0/en/Tenaya-Therapeutics-Presents-Interim-Data-from-MyClimb-Natural-History-Study-of-MYBPC3-associated-HCM-Pediatric-Patients-at-European-Society-of-Cardiology-Congress-2025.html