Multi-center, Open-label, Single-ascending Dose Study of Safety and Tolerability of TN-201 in Adults With Symptomatic MYBPC3 Mutation-associated HCM

TN-201 is an investigational gene therapy designed to treat Hypertrophic Cardiomyopathy (HCM) caused by mutations in the MYBPC3 gene — the most common genetic cause of HCM. HCM is a condition where the heart muscle becomes abnormally thick, making it harder for the heart to pump blood and increasing the risk of sudden cardiac death, heart failure, and the need for major interventions. TN-201 works by delivering a functional copy of the MYBPC3 gene directly into heart muscle cells using a viral carrier. Adults aged 18 to 75 with a confirmed MYBPC3 mutation, either obstructive or non-obstructive HCM, a preserved ejection fraction (≥45%), moderate-to-severe symptoms (NYHA Class II or III), and an elevated NT-proBNP level indicating cardiac stress are eligible. Those with high levels of neutralizing antibodies against the viral delivery system (AAV9) are excluded, as these antibodies would prevent the therapy from working. HCM affects approximately 1 in 500 people worldwide and is the most common cause of sudden cardiac death in young athletes. While medications and procedures can manage symptoms, there is currently no treatment that addresses the underlying genetic defect. A successful gene therapy would represent a fundamental shift from symptom management to disease modification — potentially halting or reversing the progression of a lifelong condition.