WALTHAM, Mass. — Affinia Therapeutics presented new preclinical and translational data for its lead gene therapy program, AFTX-201, along with the design of a Phase 1/2 clinical trial in patients with BAG3-associated dilated cardiomyopathy.
The Waltham-based clinical-stage gene therapy company presented the research at the 29th American Society of Gene & Cell Therapy Annual Meeting, held May 11-15 in Boston and virtually. The presentations also included updates on Affinia’s blood-brain-barrier-penetrant AAV capsids and proprietary manufacturing process.
AFTX-201 is an investigational genetic medicine designed to treat BAG3-associated dilated cardiomyopathy, a form of heart disease linked to mutations in the BAG3 gene. The therapy is designed to deliver a fully human, full-length BAG3 transgene using Affinia’s proprietary capsid, which the company said enables efficient cardiac delivery at doses five to 10 times lower than those associated with conventional capsids such as AAV9 or AAVrh74.
Affinia said AFTX-201 is being evaluated in the Phase 1/2 UPBEAT clinical trial as a potential one-time intravenous treatment for people living with BAG3-associated dilated cardiomyopathy. In animal models, the therapy increased BAG3 protein levels in the heart and fully restored cardiac function, the company said.
The U.S. Food and Drug Administration accepted Affinia’s Investigational New Drug application for AFTX-201 and granted the program Fast Track designation in the first quarter of 2026. The European Medicines Agency also granted Orphan Drug designation, and Health Canada approved the company’s Clinical Trial Application to advance the UPBEAT trial in Canada.
New data presented at the meeting showed that a single intravenous dose of AFTX-201 corrected cardiac function and structure eight weeks after dosing in BAG3 haploinsufficient mice with established disease. Affinia said the therapy also showed durable transgene expression in the heart from 14 days to 140 days after dosing in mice, as well as durability of gene transfer and expression for up to six months in non-human primates.
The company said toxicology studies showed AFTX-201 was generally well tolerated, with no treatment-related mortality or significant adverse effects in mice or non-human primates. Affinia also said there were no elevations in liver function tests and no signs of complement activation in non-human primates, even without prophylactic immunosuppressants.
In a head-to-head study, Affinia said AFTX-201 restored cardiac function in BAG3 haploinsufficient mice at the tested dose, while a matched gene construct using the conventional AAVrh74 capsid did not show the same effect.
“AFTX-201 aims to be a transformative, one-time treatment to restore cardiac function and reverse heart failure in BAG3 DCM,” said Hideo Makimura, M.D., Ph.D., Chief Medical Officer at Affinia. “In preclinical studies, AFTX-201 has shown differentiated efficacy and improved safety as compared with a gene therapy construct using a conventional AAV capsid. The preclinical data presented at ASGCT support the safety and efficacy of the AFTX-201 doses being advanced into our first-in-human Phase 1/2 clinical trial (UPBEAT trial), using doses that are 5-10 times lower than those of investigational cardiac gene therapies employing traditional AAV capsids. We are delighted to announce advanced discussions with 10 potential trial sites across the U.S. and Canada for the UPBEAT trial, with the first site planned for Houston Methodist Hospital.”
“BAG3 DCM represents a significant unmet medical need as patients experience a rapidly progressive cardiac dysfunction and there is no treatment that exists which targets the underlying mechanism of disease,” said Arvind Bhimaraj, M.D., M.P.H., FACC, FHFSDA, Advanced Heart Failure Cardiologist and Physician Scientist, Houston Methodist Hospital. “AFTX-201 is designed to address the genetic root cause of BAG3 DCM and we look forward to participating in the UPBEAT clinical trial.”
