China-based Chengdu Origen Biotechnology and Vanotech - a US subsidiary of Chengdu Kanghong Pharmaceutical Group - have received US FDA clearance to proceed with a Phase I/II clinical trial of KHN921, an AAV9-based gene therapy targeting MYBPC3 mutation-associated hypertrophic cardiomyopathy (HCM). As per the firms' press release, the US FDA clearance means KHN921 will enter first-in-human testing in adults with symptomatic disease caused by pathogenic MYBPC3 variants.
The proposed Phase I/II study is a multicenter, open-label, dose-escalation and expansion trial evaluating the safety, tolerability, and efficacy of a single intracoronary administration of KHN921 in adults with symptomatic MYBPC3 mutation-associated HCM. No trial registry identifier has been publicly disclosed at the time of the announcement.
KHN921 and HCM
Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiovascular disorder, affecting approximately 1 in 500 individuals worldwide. The condition is characterized by unexplained left ventricular hypertrophy and carries risks of heart failure, arrhythmias, and sudden cardiac death, particularly in younger patients. Mutations in MYBPC3, which encodes cardiac myosin-binding protein C, a regulator of sarcomere structure and cardiac contraction, represent one of the most prevalent genetic causes of HCM. Pathogenic MYBPC3 variants typically lead to haploinsufficiency, disrupting normal cardiac function and driving the pathological remodeling that defines the disease.
KHN921 is a recombinant, replication-deficient adeno-associated virus vector of serotype AAV9 encoding a functional copy of the MYBPC3 gene. The intended mechanism is restoration of myosin-binding protein C expression in cardiomyocytes, directly addressing the protein deficit that results from pathogenic MYBPC3 variants. The construct is administered via a single intracoronary infusion, a route selected to promote cardiac tissue retention.
The current approved treatment landscape for HCM addresses symptoms and hemodynamics but does not modify the underlying genetic defect. Bristol Myers Squibb's mavacamten (Camzyos), a selective cardiac myosin ATPase inhibitor approved by the US FDA in 2022, and Cytokinetics' aficamten (Myqorzo), a next-generation myosin inhibitor approved in December 2025, both reduce left ventricular outflow tract obstruction in symptomatic obstructive HCM. Neither is approved for the non-obstructive phenotype, which accounts for roughly 30%–40% of HCM cases, and neither addresses the genetic root cause of disease in MYBPC3 carriers. Older agents including beta-blockers, verapamil, and disopyramide remain guideline-directed options for symptomatic control across phenotypes, but similarly offer no disease-modifying effect. No approved therapy corrects or compensates for MYBPC3 haploinsufficiency.