May 14, 2026 —
Affinia Therapeutics presented new preclinical, translational, clinical trial design, manufacturing, and capsid engineering data at the 29th American Society of Gene & Cell Therapy Annual Meeting, highlighting progress across its AAV gene therapy platform. The company’s lead program, AFTX-201, is an investigational AAV gene therapy being developed for BAG3-associated dilated cardiomyopathy, a serious inherited heart disease with high unmet medical need.
AFTX-201 is designed to deliver a fully human, full-length BAG3 transgene using Affinia’s proprietary cardiac-targeted AAV capsid. According to Affinia, this engineered capsid enables efficient cardiac transduction at doses 5- to 10-fold lower than those associated with conventional capsids such as AAV9 or AAVrh74. The therapy is intended as a one-time intravenous administration to restore BAG3 protein expression and improve cardiac function in patients with BAG3-associated DCM.
New preclinical data showed that a single IV dose of AFTX-201 at 9e11 vg/kg fully corrected cardiac function and structural abnormalities in BAG3 haploinsufficient mice with established disease eight weeks after dosing. Durable transgene expression was observed in mouse hearts from 14 days to 140 days post-dose, and non-human primate studies showed durable gene transfer and transgene expression up to six months. Toxicology studies indicated that AFTX-201 was generally well tolerated in mice and NHPs, with no treatment-related mortality, no significant adverse effects, no liver function test elevations, and no complement activation in NHPs even without prophylactic immunosuppressants.
Affinia also presented the design of the Phase 1/2 UPBEAT clinical trial, a multicenter, single-arm, open-label study evaluating AFTX-201 in adults with genetically confirmed BAG3-associated DCM. The trial includes a dose-exploration phase followed by dose expansion, with safety and tolerability through 52 weeks as the primary objective. The FDA accepted Affinia’s IND application for AFTX-201 and granted Fast Track designation in Q1 2026, while the EMA granted Orphan Drug designation and Health Canada approved the company’s Clinical Trial Application to advance UPBEAT in Canada.
Beyond clinical translation, Affinia highlighted its high-yield AAV manufacturing process for AFTX-201. The company reported that its GMP manufacturing run, transferred to Forge Biologics, achieved harvest titers above 6e15 vg/L, supporting confidence in potential commercial-scale supply. Affinia also presented analytical method development and qualification work for AFTX-201, establishing a product-specific analytical panel to support clinical product quality.
Affinia further showcased progress in AAV capsid engineering, including BBB-penetrant and myotropic capsids. Its ATC-134 capsid achieved broad CNS transduction in non-human primates after low-dose systemic administration, with reported transduction of more than 90% of neurons across cortical, deep brain, and spinal cord regions at 3e13 vg/kg IV. The company also presented work pairing its myotropic capsid ATC-187 with Modalis Therapeutics’ epigenetic editing payload for a potential gene therapy approach in myotonic dystrophy type 1.
Together, the ASGCT data highlight Affinia’s broader strategy to develop next-generation AAV gene therapies through engineered tissue-targeted capsids, lower-dose delivery, scalable manufacturing, and disease-specific clinical translation. For BAG3-associated DCM, AFTX-201 represents a potentially important one-time therapeutic approach aimed at addressing the genetic root cause of inherited heart failure.
