Affinia Advances Gene Therapy for BAG3 DCM with FDA IND Acceptance

Affinia Therapeutics, on 4 February, said the U.S. Food and Drug Administration accepted its IND for AFTX-201, enabling initiation of the UPBEAT clinical trial in adults with genetically confirmed BAG3-associated dilated cardiomyopathy. The company said it expects to start the multicenter, open-label Phase 1/2 study in the first half of 2026, with site initiation expected during that period.

AFTX-201 is designed to deliver a fully human, full-length functional BAG3 transgene via Affinia’s proprietary AAV capsid, with the company stating efficient cardiac transduction at doses 5 to 10-fold lower than gene therapies using conventional capsids such as AAV9 or AAVrh74. The product is intended as a one-time intravenous administration. Commercially, the program targets a population Affinia estimates at more than 70,000 patients across Canada, the EU, the US, and the UK. The company has stated that nearly 25% of patients with BAG3-associated DCM ultimately require a heart transplant.

UPBEAT’s primary objective is safety and tolerability through 52 weeks, with secondary and exploratory objectives covering pharmacodynamics and preliminary efficacy. The protocol includes dose exploration followed by dose expansion. In a November 2025 Onyx interview, CEO Rick Modi described planned assessments including echocardiography, NYHA class, exercise capacity, and said lower dosing may mitigate side effects observed at higher doses with conventional capsids. The interview also described a manufacturing relationship with Forge Biologics, with Modi stating that a 50-liter GMP run is expected to be sufficient to supply more than 100 patients for the UPBEAT study, based on Affinia’s reported yield, purity, and full-capsid metrics.

Affinia also cited a prior partnership with Vertex Pharmaceuticals that ended following reprioritization, after which the company continued development independently. The company said it raised $40 million in a Series C financing that brought Eli Lilly in as a new strategic investor, and said the financing was raised to support clinical advancement of its BAG3-DCM program.

You can read our previous interviews with Affinia Therapeutics' CEO, Rick Modi, from November 2025 and November 2024.