Chengdu Origen Biotechnology has announced that the US Food and Drug Administration has granted ‘study may proceed’ status to the Investigational New Drug (IND) application for KHN921, an investigational gene therapy being developed for Hypertrophic Cardiomyopathy (HCM) associated with MYBPC3 mutations.

The clearance enables the initiation of a multi-centre, open-label, dose-escalation and expansion Phase 1/2 clinical study to assess the safety, tolerability and efficacy of a single intracoronary administration of KHN921 in adults with symptomatic MYBPC3 mutation-associated HCM.

KHN921 is a recombinant replication-deficient adeno-associated virus vector of serotype AAV9 engineered to deliver a functional MYBPC3 gene encoding cardiac myosin-binding protein C. The therapy is designed to directly address the underlying genetic cause of HCM by restoring normal protein expression in cardiomyocytes.

According to the company, preclinical studies in HCM disease models demonstrated that intracoronary infusion of KHN921 resulted in prolonged retention of the transgene product in cardiac tissues and prevented disease-related symptoms. These findings suggest the therapy may offer a potential one-time treatment option for patients carrying MYBPC3 mutations.

Avner Ingerman, Chief Medical Officer, Vanotech, said KHN921 has been designed to address the root genetic cause of hypertrophic cardiomyopathy by restoring normal cardiac protein function. He added that the FDA’s IND clearance marks an important step toward bringing a potentially transformative therapy to patients with limited long-term treatment options for the life-threatening disease.

Hypertrophic cardiomyopathy is the most common monogenic cardiovascular disorder, affecting approximately one in 500 individuals globally. The condition is characterised by unexplained thickening of the heart muscle, which can lead to heart failure, arrhythmias and sudden cardiac death, particularly among young adults and athletes.

Mutations in the MYBPC3 gene are among the leading genetic causes of HCM. These mutations disrupt the production of cardiac myosin-binding protein C, a critical regulator of heart muscle structure and contraction, resulting in abnormal cardiac remodelling and impaired heart function. Currently, no approved disease-modifying therapies specifically target the underlying genetic mechanisms of MYBPC3-associated HCM, highlighting a significant unmet medical need.

Chengdu Origen Biotechnology is a clinical-stage gene therapy company focused on developing treatments for genetic and chronic diseases while also maintaining viral vector manufacturing capabilities.

Vanotech is serving as sponsor-representative for the US clinical development programme of KHN921. The company is also conducting additional gene therapy studies, including VAN-2201 and VAN-2401, focused on treatments for neovascular age-related macular degeneration.