Affinia Therapeutics presented promising new preclinical data for AFTX-201, its lead gene therapy program targeting BAG3 dilated cardiomyopathy (DCM), at the 28th Annual American Society of Gene and Cell Therapy (ASGCT) meeting in New Orleans. The data showcased the therapy's potential to address a significant unmet medical need in cardiovascular disease.
AFTX-201 is designed as a one-time intravenous administration using Affinia's novel cardiotropic capsid engineered for efficient and selective cardiac transduction at doses more than 10-fold lower than conventional AAV9 capsids. The therapy delivers a fully human, full-length BAG3 transgene to treat BAG3 DCM, a devastating monogenic heart disease affecting more than 70,000 patients in the U.S., Europe, and U.K.
Promising Preclinical Efficacy and Safety
In BAG3 haploinsufficient mice, AFTX-201 successfully restored cardiac function and demonstrated a favorable safety profile. Studies in non-human primates (NHPs) achieved robust cardiomyocyte BAG3 expression while maintaining safety.
"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 Hideo Makimura, M.D., Ph.D., Chief Medical Officer at Affinia. "AFTX-201 addresses the genetic root cause of BAG3 DCM and in preclinical studies has shown highly differentiated efficacy and an improved safety profile as compared with a gene therapy construct using a conventional AAV capsid."
The BAG3 gene encodes a protein critical to the normal structure and function of heart cells. Patients with BAG3 DCM have a mutation in this gene and a deficiency in functioning BAG3 protein, resulting in early-onset heart failure that progresses rapidly. Despite current standard of care, almost 25% of patients require a heart transplant.
Innovative Manufacturing Process
A key highlight from the ASGCT presentations was Affinia's flexible, high-yielding manufacturing process developed for AFTX-201 production. Using Design of Experiment optimization, the upstream process achieved yields exceeding 3e15 vg/L at 50L scale, supported by a streamlined downstream process that results in a high-quality product with more than 90% full capsid enrichment.
"We are pleased with the successful technology transfer to our CDMO partner and are progressing toward the manufacture of GMP lots," said Rob May, Affinia's Chief Technical Operations Officer. "We have demonstrated that Affinia's proprietary high-yield manufacturing process delivers high-quality, stable product and enables reduced production scale and significant cost efficiency."
The company also presented data on its proprietary plasmid design system that significantly improves AAV manufacturing yields across both wild-type and novel capsids. This system enables greater than 10-fold increase in vector genome yield and up to four-fold improvement in the percentage of full capsids at harvest, reducing upstream batch size and downstream purification requirements.
Novel CNS-Targeting Capsids
Beyond cardiovascular applications, Affinia showcased its engineered capsids that target receptor-Y, a novel human brain receptor, enabling AAV crossing of the blood-brain barrier. Compared to AAV9, the leading Gen2 hits achieved several orders of magnitude higher mRNA expression across NHP cortical and deep brain regions.
"Affinia's capsids that target receptor-Y are highly differentiated from conventional AAVs being used in CNS programs currently in clinical trials," noted Charles Albright, Ph.D., Affinia's Chief Scientific Officer. Studies generating clonal biodistribution and mechanistic data for Gen2 leads are currently underway.
Path to Clinical Development
AFTX-201 is currently undergoing investigational new drug (IND)-enabling studies. Following a successful pre-IND meeting with the U.S. Food and Drug Administration, Affinia plans to file an IND in the fourth quarter of 2025.
"We're focused on advancing our AFTX-201 investigational program into the clinic and evaluating multiple endpoints that have been shown, for other cardiovascular drugs and diseases, to demonstrate efficacy as early as one-to-three months post-dose," said Rick Modi, Affinia's Chief Executive Officer.
The planned Phase 1/2 UPBEAT trial will assess safety, tolerability, and pharmacodynamics in patients with BAG3 DCM, with potential initial readouts of clinical trial safety and efficacy expected in the first half of 2026.
About Affinia Therapeutics
Affinia Therapeutics is pioneering a new class of rationally designed gene therapies for rare and prevalent diseases. The company's pipeline focuses on first-in-class or best-in-class product candidates in cardiovascular and neurological diseases, leveraging proprietary next-generation capsids, payloads, and manufacturing approaches that have demonstrated efficacy, safety, and differentiation in relevant animal models.
