Affinia Therapeutics Presents New Data on its Lead AFTX-201 Program in BAG3 Dilated Cardiomyopathy, BBB-Penetrant AAV Capsids, and Proprietary Manufacturing Technology at the 28 th American Society of Gene & Cell Therapy 2025 Annual Meeting

Business Wire

13-05-2025

WALTHAM, Mass.--(BUSINESS WIRE)--Affinia Therapeutics ('Affinia'), an innovative gene therapy company with a pipeline of first-in-class and/or best-in-class adeno-associated virus (AAV) gene therapies for devastating cardiovascular and neurological diseases, today announced the presentation of new preclinical data on AFTX-201, its lead program for BAG3 dilated cardiomyopathy (DCM), as well as its novel AAV capsids for diseases of the central nervous system (CNS), and the company's high-yield manufacturing process. This research will be presented in several oral and poster sessions at the 28 th American Society of Gene and Cell Therapy (ASGCT) 2025 Annual Meeting, being held May 13-17, 2025 in New Orleans, LA and virtually.
Affinia has rationally designed novel capsids and gene therapies with increased tropism for cardiac muscle, skeletal muscle, or CNS and more uniform tissue distribution than AAV9. This improved biodistribution is attained at doses that are greater than 10-fold lower than those used with conventional capsids such as AAV9 while detargeting the liver and dorsal root ganglia, both potential sites of toxicity. Furthermore, Affinia has developed a proprietary plasmid design system that results in multi-fold improvement in manufacturing yields across a range of novel and conventional capsids and payloads.
New AFTX-201 data featured at ASGCT 2025
AFTX-201, a potential first-in-class and best-in-class investigational gene therapy intended to be given as a simple one-time intravenous administration, is designed to treat BAG3-associated dilated cardiomyopathy (DCM) using a novel cardiotropic capsid engineered for efficient and selective cardiac transduction at low doses. New data show that in BAG3 haploinsufficient mice, AFTX-201 restored cardiac function and showed a favorable safety profile, and in nonhuman primates (NHPs), achieved robust cardiomyocyte BAG3 expression with a favorable safety profile. These data will be featured in a poster entitled, 'A Novel Investigational AAV Gene Therapy for Treatment of BAG3 Dilated Cardiomyopathy,' being presented by Giri Murlidharan, Ph.D., Senior Director, Vector Translational Biology at Affinia, on Wednesday, May 14, 2025, 5:30-7:00 pm CT (Poster Hall 12; abstract AMA1161).
'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 is a potential first-in-class and best-in-class investigational gene therapy using a novel cardiotropic capsid. 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. These findings support clinical advancement of AFTX-201, with a Phase 1/2 trial, the UPBEAT trial, planned to assess safety, tolerability, and pharmacodynamics in patients with BAG3 DCM. Endpoints that have demonstrated efficacy in as early as one-to-three months post dose in prior studies for other cardiovascular drugs and diseases will be explored in the upcoming study.'
AFTX-201 is undergoing investigational new drug (IND)-enabling studies. Affinia has completed a successful pre-IND meeting with the U.S. Food and Drug Administration (FDA) and plans to file an IND in the fourth quarter of 2025 with potential initial readouts of clinical trial safety and efficacy in the first half of 2026.
Data on Affinia's high-yield manufacturing and CNS capsids at ASGCT
Affinia's flexible, high-yielding, and scalable process developed for the production of AFTX-201 will be featured in an oral presentation. Using Design of Experiment (DoE) optimization, the upstream process achieved a yield exceeding 3e15 vg/L at 50L scale, supported by a streamlined downstream process including single-use clarification, affinity purification, and CsCl ultracentrifugation resulting in a high-quality product with more than 90% full capsid enrichment. The process was successfully transferred to Affinia's Contract Development and Manufacturing Organization (CDMO) partner with results replicated. The product has shown stability for more than six months, with ongoing monitoring for extended time points. Additionally, the high yields enabled a reduction in Toxicology and Clinical lot production scale from 250L to 50L, resulting in significant cost savings. The presentation, 'Development of a Flexible High Yielding, High Performing Process for Manufacturing of AFTX-201, a Novel Investigational AAV Gene Therapy for Treatment of BAG3 Dilated Cardiomyopathy,' will be presented by Matt Edwards, MBA, Vice President of Process Science at Affinia, on Friday, May 16, 2025 at 4:45-5:00 pm CT (Room 288-290; abstract AMA1147).
Rob May, Affinia's Chief Technical Operations Officer, said, 'We are pleased with the successful technology transfer to our CDMO partner and are progressing toward the manufacture of GMP lots. 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.'
New data will be presented on Affinia's proprietary plasmid design system that significantly improves adeno-associated virus (AAV) manufacturing yields and packaging efficiency 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 burden. Implementation within Affinia's Vector Core in 2024 resulted in a 740% increase in R&D vector titers and yields exceeding 5e15 vg/L for programs, offering substantial cost and efficiency gains for both discovery and clinical manufacturing. These data will be featured in a poster entitled, 'High-Yield, Pan-Serotype Plasmid System for Manufacturing Adeno-Associated Virus Gene Therapies: Cost and Efficiency Benefits for R&D and Commercial Processes,' being presented today, Tuesday, May 13, 2025, at 6:00-7:30 pm CT by Mr. Edwards (Poster Hall 12; abstract 1150).
Affinia will also present data on its engineered capsids that target receptor-Y, a novel human brain receptor, to enable AAV crossing of the blood-brain barrier. Capsids were identified with the ability to bind both human and nonhuman primate (NHP) orthologs of this receptor in vitro. An initial screen of 13,000 Gen1 in vitro hits in NHPs using intravenous dosing revealed that a minority of capsids that bind the receptor protein in vivo actually have in vivo functionality. Affinia reports the results of screening in NHPs a Gen2 library of 50,000 capsids that built upon the Gen1 in vivo hits in a poster entitled, 'Engineered AAV Capsids That Target a Novel Human Brain Endothelial Receptor Achieve Robust Transduction in Nonhuman Primate Central Nervous System After Intravenous Dosing.' The poster is being presented by John Reece-Hoyes, Ph.D., Senior Director, Head of Vector Biology at Affinia, on Thursday, May 15, 2025, 5:30-7:00 pm CT (Poster Hall 12; abstract AMA1256).
'Compared to AAV9, the leading Gen2 hits achieved several orders of magnitude higher mRNA expression across NHP cortical and deep brain regions,' said Charles Albright, Ph.D., Affinia's Chief Scientific Officer. 'Affinia's capsids that target receptor-Y are highly differentiated from conventional AAVs being used in CNS programs currently in clinical trials. Studies generating clonal biodistribution and mechanistic data for Gen2 leads are currently underway."
Abstracts can be found at https://annualmeeting.asgct.org/.
About Affinia Therapeutics
Affinia Therapeutics is pioneering a new class of rationally designed gene therapies that treat rare and prevalent diseases. Affinia Therapeutics' pipeline of first-in-class or best-in-class product candidates in cardiovascular and neurological diseases leverages its proprietary next-generation capsids, payloads, or manufacturing approaches and have shown efficacy, safety, and differentiation in relevant animal models. For more information, visit https://www.affiniatx.com.