News|Articles|February 4, 2026

FDA Clears Affinia’s AFTX-201 for Phase I/II BAG3 Cardiomyopathy Trial

Listen

0:00 / 0:00

Key Takeaways

FDA IND clearance enables UPBEAT Phase I/II testing of AFTX-201 in BAG3-associated DCM, an inherited cardiomyopathy with early-onset heart failure and high transplant rates.
Loss-of-function BAG3 mutations disrupt cardiomyocyte structural homeostasis, driving rapid progression despite standard heart failure therapy that remains largely symptomatic rather than etiologic.
AFTX-201 uses a proprietary cardiotropic AAV capsid to deliver full-length human BAG3, targeting five- to ten-fold lower dosing than AAV9/AAVrh74-based approaches.
The trial employs single-dose IV administration with dose exploration/expansion, prioritizing 52-week safety and tolerability alongside pharmacodynamic readouts and preliminary efficacy endpoints.
Preclinical data showed increased cardiac BAG3 protein and functional rescue in an animal model, supporting translation of cardiac-targeted gene replacement for monogenic cardiomyopathies.

FDA’s acceptance of Affinia Therapeutics’ IND positions the company to test lower-dose, heart-targeted AAV gene therapy for BAG3 cardiomyopathy.

FDA has accepted an investigational new drug (IND) application from Affinia Therapeutics (Affinia), a US-based clinical-stage gene therapy company, for AFTX-201, an investigational genetic medicine. Affinia announced on Feb. 4, 2026 that the agency’s acceptance clears the way for a Phase I/II clinical trial (UPBEAT) in patients with Bcl2-associated athanogene 3 (BAG3)-associated dilated cardiomyopathy (DCM), a rare inherited heart disease with high morbidity and limited treatment options (1).

The candidate is designed to restore functional BAG3 protein expression using an adeno-associated virus (AAV) gene therapy that has been engineered for efficient cardiac delivery at substantially lower doses than conventional capsids. Affinia plans to initiate the trial in the first half of 2026.

“This newly accepted IND reflects extensive engagement with regulators and the clinical community,” said Hideo Makimura, MD, PhD, chief medical officer, Affinia, in a company press release (1). “We look forward to initiating the UPBEAT clinical trial at multiple trial sites in the coming weeks and bringing a much-needed treatment option for patients and families affected by this devastating disease.”

Why does BAG3-associated DCM remain an unmet clinical challenge?

BAG3 DCM is caused by mutations in the BAG3 gene, which encodes a protein essential for maintaining cardiac muscle structure and function. Loss of functional BAG3 leads to early-onset heart failure that often progresses rapidly despite standard therapies. The disease affects more than 70,000 patients across the United States, Canada, the European Union, and the United Kingdom, with nearly one-quarter of patients eventually requiring heart transplantation (1,2).

“BAG3 DCM is a genetic heart disease with significant medical need despite current standard of care. A gene therapy approach could make a real difference to patients living with BAG3 DCM.”

Current management focuses on symptom control and slowing disease progression rather than addressing the underlying genetic deficiency. As a result, BAG3 DCM has emerged as a compelling target for gene replacement strategies aimed at restoring protein expression in cardiomyocytes (1).

“BAG3 DCM is a genetic heart disease with significant medical need despite current standard of care,” said Matthew Wheeler, MD, PhD, a physician scientist in genetic cardiomyopathies and associate professor of cardiovascular medicine at Stanford Medicine, in the release (1). “A gene therapy approach could make a real difference to patients living with BAG3 DCM.”

How is AFTX-201 designed to improve cardiac gene delivery?

AFTX-201 delivers a fully human, full-length BAG3 transgene using Affinia’s proprietary AAV capsid, which has been engineered for enhanced cardiac transduction. According to the company, the capsid enables effective gene delivery at doses approximately five- to ten-fold lower than those typically required for therapies based on conventional AAV serotypes such as AAV9 or AAVrh74 (1).

In preclinical studies, the therapy increased BAG3 protein levels in the heart and restored cardiac function in an animal disease model, supporting advancement into clinical testing.

What will the trial evaluate in early clinical development?

The Phase I/II study is a multicenter, open-label trial enrolling adults with genetically confirmed BAG3-associated DCM. The study includes a dose-exploration phase followed by dose expansion, with all participants receiving a single intravenous administration of AFTX-201.

Primary endpoints focus on safety and tolerability through 52 weeks post-infusion, while secondary and exploratory endpoints assess pharmacodynamic effects and preliminary signals of efficacy. Trial design, dose selection, and monitoring strategies were informed by patient and clinician input, regulatory feedback, and completed nonclinical studies demonstrating correction of cardiac ejection fraction and acceptable safety margins.

If successful, AFTX-201 could help establish whether targeted cardiac gene delivery can modify disease course in inherited cardiomyopathies driven by single-gene defects (1).

References

Affinia Therapeutics. Affinia Therapeutics Announces FDA Acceptance of IND Application to Advance AFTX-201 to a Phase 1/2 Trial for the Treatment of BAG3-Associated Dilated Cardiomyopathy (DCM). Press Release. Feb. 4, 2026.
Knezevic, T.; Myers, V. D.; Gordon, J.; et al. BAG3: A New Player in the Heart Failure Paradigm. Heart Failure Rev. 2015, 20 (4), 423–434. DOI: 10.1007/s10741-015-9487-6

Stay at the forefront of biopharmaceutical innovation—subscribe to BioPharm International for expert insights on drug development, manufacturing, compliance, and more.

Subscribe Now!