Affinia Therapeutics has announced that the US Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application for AFTX-201, an investigational gene therapy for the treatment of BAG3-associated Dilated Cardiomyopathy (DCM).

The company plans to initiate the UPBEAT clinical trial in the first half of 2026. The Phase I/II, multicentre, open-label study will evaluate the safety, tolerability, pharmacodynamics and preliminary efficacy of AFTX-201 in adults with genetically confirmed BAG3 DCM.

AFTX-201 is designed to deliver a fully functional BAG3 transgene using Affinia’s proprietary Adeno-Associated Virus (AAV) capsid engineered for efficient cardiac transduction. The therapy is intended to achieve therapeutic benefit at doses five to ten times lower than conventional AAV-based gene therapies such as AAV9 or AAVrh74. It is administered as a one-time intravenous infusion.

Preclinical studies demonstrated that AFTX-201 increased BAG3 protein levels in the heart and restored cardiac function to normal levels in animal models. The upcoming UPBEAT trial will include a dose-exploration phase followed by a dose-expansion phase, with safety and tolerability over 52 weeks as the primary endpoint. Secondary and exploratory objectives include pharmacodynamic measures and early signals of efficacy. The study incorporates protocol-defined stopping rules, centralised safety review and oversight by an independent Data Safety Monitoring Board.

Hideo Makimura, Chief Medical Officer at Affinia Therapeutics, said the company looks forward to initiating the trial and advancing a potential new treatment option for patients and families affected by this severe inherited heart disease.

BAG3 DCM is a rare genetic condition caused by mutations in the BAG3 gene, which encodes a protein critical to heart muscle structure and function. The disease affects more than 70,000 patients across the US, Canada, the EU and the UK, and is associated with early-onset heart failure and high mortality. Despite standard treatment, nearly 25 per cent of patients eventually require a heart transplant.

Affinia’s broader pipeline focuses on first-in-class or best-in-class AAV gene therapies for cardiovascular diseases, leveraging its proprietary capsid engineering and manufacturing platforms.