MyPeak-1: A Phase 1b Study to Evaluate Safety and Efficacy of TN-201, an Adeno-Associated Virus Serotype 9 (AAV9) Investigational Gene Therapy, in Adults with MYBPC3-Associated Hypertrophic Cardiomyopathy (HCM)

Background Mutations in the MYBPC3 gene are the leading genetic cause of HCM, representing nearly half of all pathogenic/likely pathogenic HCM variants. The majority of MYBPC3-associated HCM patients have a nonobstructive phenotype (nHCM), which is progressive, lacks an approved therapy, and cannot be addressed through surgical intervention. MyPeak-1 is the first clinical trial of a gene therapy for the treatment of MYBPC3-associated HCM and will initially enroll adult nHCM patients. Methods TN-201 is an AAV9-based gene therapy designed to deliver the MYBPC3 transgene to cardiomyocytes to restore MyBP-C protein levels to ameliorate disease following a single infusion. Efficacy of TN-201 has been demonstrated in preclinical models in which cardiac function, hypertrophy and survival improved at clinically relevant doses. Initiation of a first-in-human clinical trial of TN-201 in adult nHCM patients has been cleared by the FDA. Results MyPeak-1 is an open-label, dose escalation study to evaluate the safety, tolerability, and pharmacodynamics of TN-201. Measures of gene expression, cardiac biomarkers and function, as well as patient symptoms, exercise capacity and quality of life will also be assessed. Up to 15 adults with MYBPC3-associated nHCM will be enrolled in two dose cohorts, starting at 3E13 vg/kg. To optimize patient safety, participants will be monitored closely and required to take immunosuppressive medication pre-dose and for a limited time following administration of TN-201. Conclusion Upon establishing positive safety, tolerability and efficacy results in nHCM adults, Tenaya Therapeutics plans to enroll obstructive HCM and younger participants in future studies. Mutations in the MYBPC3 gene are the leading genetic cause of HCM, representing nearly half of all pathogenic/likely pathogenic HCM variants. The majority of MYBPC3-associated HCM patients have a nonobstructive phenotype (nHCM), which is progressive, lacks an approved therapy, and cannot be addressed through surgical intervention. MyPeak-1 is the first clinical trial of a gene therapy for the treatment of MYBPC3-associated HCM and will initially enroll adult nHCM patients. TN-201 is an AAV9-based gene therapy designed to deliver the MYBPC3 transgene to cardiomyocytes to restore MyBP-C protein levels to ameliorate disease following a single infusion. Efficacy of TN-201 has been demonstrated in preclinical models in which cardiac function, hypertrophy and survival improved at clinically relevant doses. Initiation of a first-in-human clinical trial of TN-201 in adult nHCM patients has been cleared by the FDA. MyPeak-1 is an open-label, dose escalation study to evaluate the safety, tolerability, and pharmacodynamics of TN-201. Measures of gene expression, cardiac biomarkers and function, as well as patient symptoms, exercise capacity and quality of life will also be assessed. Up to 15 adults with MYBPC3-associated nHCM will be enrolled in two dose cohorts, starting at 3E13 vg/kg. To optimize patient safety, participants will be monitored closely and required to take immunosuppressive medication pre-dose and for a limited time following administration of TN-201. Upon establishing positive safety, tolerability and efficacy results in nHCM adults, Tenaya Therapeutics plans to enroll obstructive HCM and younger participants in future studies.