Affinia Therapeutics Announces Development Candidate for BAG3 DCM and Completion of Pre-IND Meeting with the FDA

BAG3 DCM is a devastating monogenic heart disease affecting more than 70,000 patients in the U.S., Europe, and U.K., with almost 25% of patients requiring a heart transplant

AFTX-201 is a potential best-in-class gene therapy using Affinia's cardiotropic capsid with preclinical data showing replenishment of the BAG3 protein in the heart and restoration of cardiac structure and function to normal

Successful pre-IND meeting completed in late 2024 with IND-enabling studies underway and IND submission planned for fourth quarter 2025

WALTHAM, Mass., Jan. 9, 2025 /PRNewswire/ -- Affinia Therapeutics ("Affinia"), an innovative gene therapy company with a pipeline of rationally designed adeno-associated virus (AAV) gene therapies for devastating cardiovascular and neurological diseases, today announced the nomination of AFTX-201 as the company's development candidate for the treatment of BAG3 dilated cardiomyopathy (DCM). A potential best-in-class gene therapy given as a simple one-time intravenous (IV) injection, AFTX-201 is currently undergoing investigational new drug (IND)-enabling studies. Affinia completed a successful pre-IND meeting with the U.S. Food and Drug Administration (FDA) in late 2024 and plans to file an IND in the fourth quarter of 2025.

BAG3 DCM is a devastating monogenic heart disease affecting more than 70,000 patients in the U.S., Europe, and U.K. regions alone. The BAG3 gene, or Bcl2-associated athanogene 3, encodes for a protein that is critical to the normal structure and function of heart cells. Patients affected by BAG3 DCM have a mutation in the BAG3 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.

"BAG3 DCM is a disease that greatly impairs both quality of life and survival. Although conventional treatments including guideline-directed medical therapies, cardiac resynchronization therapy, and implanted defibrillators can be used in patients with BAG3 DCM, there is no specific disease-modifying treatment available and patients still may progress to heart failure, die prematurely, or require advanced therapies like heart transplantation," said Barry Greenberg, M.D., an internationally recognized pioneer in the field of heart failure and Director of the Advanced Heart Failure Treatment Program at University of California San Diego Health. "Development of AFTX-201 as a one-time therapy that addresses the genetic root cause of BAG3 DCM could be transformative."

"Following our successful meeting with the FDA, we are excited to unveil AFTX-201 as our lead program with an IND submission planned for fourth quarter 2025," said Rick Modi, Affinia's Chief Executive Officer. "Our vision is to bring this potential treatment option to patients affected by BAG3 DCM and to build an industry-leading cardiovascular gene therapy franchise."

Affinia recently reported the efficacy, safety, and differentiation of AFTX-201 to treat BAG3 DCM in a genetic mouse model that mirrors human disease. In this study, AFTX-201 showed the desired two-fold increase in BAG3 protein levels in the heart, improvement in dilated cardiomyopathy pathophysiology, and restoration of cardiac function four weeks after a one-time IV dose of AFTX-201. In contrast, the same gene construct delivered using the conventional capsid AAV9 did not show adequate cardiac tropism or improvement in cardiac function in the same genetic mouse model. AFTX-201 was also studied in nonhuman primates where it was shown to be well tolerated, transduce more than 90% of heart muscle cells, and achieve the desired two-fold increase in BAG3 protein levels in the heart. 

Affinia's pipeline of rationally designed gene therapies incorporate the company's novel tissue-tropic AAV capsids validated in single-clone nonhuman primate studies and the company's proprietary plasmid design system validated across a range of novel and conventional capsids and payloads. These innovations confer unique properties that enable the targeted delivery of genetic payloads to tissues of interest, improving efficacy, safety, and cost of goods, as well as the potential treatment of prevalent diseases with first-in-class or best-in-class therapies. The company's initial programs are intended to help patients affected by devastating cardiovascular or neurological diseases. 

About Affinia Therapeutics
Affinia Therapeutics is pioneering a shift to 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.

SOURCE Affinia Therapeutics