BAG3

Vertex is pulling back on its genetic medicine research, ending all work related to adeno-associated viruses, or AAVs — the viral vectors commonly used to deliver gene therapies into the body, the company confirmed to Endpoints News . The cuts impact Vertex’s collaborations with at least two biotech startups: the AAV design company Affinia Therapeutics and tRNA therapy company Tevard Biosciences, which uses AAVs. It also calls into question Vertex’s work on CRISPR therapies for genetic muscle diseases. Several bigger pharmaceutical companies, including Biogen , Pfizer , Roche and Takeda , have cut or pared back on AAV gene therapy research in recent years. And several gene therapy biotech companies have trimmed their pipelines and staff as private and public investors sour on the field. This change of fortune was seemingly unimaginable a few years ago. AAV technology ushered in a new era of gene therapy investment and led to several commercial products for diseases, including Roche’s Luxturna for childhood blindness, Sarepta Therapeutics’ Elevidys for Duchenne muscular dystrophy, and Novartis’ Zolgensma for an otherwise fatal neurodegenerative condition in infants. But a panoply of challenges — including costly manufacturing, multimillion-dollar drug prices, slow progress in improving targeted delivery and lingering safety issues — has raised questions about the future of AAV medicines. Vertex did not have any AAV gene therapies in clinical development, despite work on the technology stretching back to at least 2019 when it acquired Exonics Therapeutics for its early-stage CRISPR therapies for two muscle diseases: Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1). Exonics relied on AAV vectors to deliver its therapies to muscles. Vertex has shared few updates on the program since its acquisition. The approach was essentially a permanent version of the commercial exon-skipping therapies for DMD, meaning it wouldn’t fully restore the dystrophin protein that’s broken in people with the disease. A Chinese biotech called HuidaGene has developed a similar CRISPR therapy and has already treated two boys, Endpoints reported last month . The first patient had modest improvement in his walking ability three months after the treatment. It is unknown why Vertex’s own CRISPR therapy has seemingly lagged behind. It is possible that the company is holding out for a more curative approach. It may also have been spooked by multiple deaths in people who received the high doses of AAV needed to reach the body’s many muscles, including two from Pfizer’s experimental therapy , one from Sarepta’s approved drug and one from a custom CRISPR therapy . Heather Nichols, a spokesperson for Vertex, confirmed that the company has discontinued its AAV work, but in an email said that the company’s “commitment to cell and genetic therapies remains strong” and that other investments in DMD and DM1 continue. The company declined to provide further comment on its AAV cuts or make an executive available for an interview. The need for better AAVs, ones that could deliver more of the therapy at lower doses, has been clear for years. Vertex struck a partnership with Affinia in 2020 worth up to $1.6 billion for access to the startup’s viral vectors designed to better target the muscles for treating DMD and DM1 and target the lungs to treat cystic fibrosis, the disease responsible for most of the company’s $11 billion revenue last year. Affinia CEO Rick Modi told Endpoints in an email that his company regained the rights to its muscle-targeting viruses from Vertex in March. He said the earlier work on cystic fibrosis ended in 2022 and rights to those programs were returned then. The startup is currently focused on finishing preclinical studies and designing a clinical trial for its lead candidate, for a heart condition called BAG3 dilated cardiomyopathy. Modi said that Affinia received “the maximum amount of milestone payments” for the research phase of its DMD and DM1 collaboration with Vertex, but he wouldn’t specify the amount. He added that Affinia is looking to license its newly-regained muscle capsids to other companies. Vertex’s step back from AAVs also impacts Tevard Biosciences. The small startup, which is housed in Eli Lilly’s genetics-focused research center that opened in Boston last summer, struck a four-year partnership with Vertex in February 2023 to develop a new class of genetic medicines known as tRNA therapies. In nature, tRNA molecules are part of the machinery that cells use to translate genetic code into proteins. Tevard is one of a few companies developing synthetic versions of these molecules to help skip over genetic mutations that prevent cells from making fully functional proteins. Tevard believes its approach could help restore the vital dystrophin protein missing from the muscles of the 15% of people with DMD whose disease is caused by so-called nonsense mutations. While some companies are trying to package tRNA therapies in lipid nanoparticles, those delivery vessels are not readily taken up by the body’s many muscles, so Tevard planned to use AAVs to deliver its treatment. “We were doing great. The collaboration was going great. But in December, we were informed that they were realigning priorities, and multiple programs were being terminated, including this one,” Tevard CEO Daniel Fischer told Endpoints in an interview. “Two weeks ago, we got the rights back to this program.” Other tRNA companies have also struggled, including HC Bioscience, which shut down in March after “challenges in targeted delivery,” Endpoints previously reported . Fischer said the fate of the DMD program will depend on whether Tevard can find another drugmaker to partner with or raise enough money to move it forward on its own. The company is planning to present data showing that the DMD therapy works in mice at the upcoming American Society of Gene & Cell Therapy meeting later this month.

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 that 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, will be presented in several oral and poster sessions at the 28th Annual 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. AFTX-201, a potential best-in-class investigational gene therapy intended to be given as a simple one-time intravenous (IV) administration, 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. 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. AFTX-201 is designed to deliver a fully human, full-length BAG3 transgene using Affinia’s novel cardiotropic capsid. Preclinical studies with AFTX-201 have shown correction of BAG-3 protein levels in the heart and complete restoration of cardiac function, whereas such benefits were not achieved with the same gene construct using a conventional capsid at the same dose. “We look forward to unveiling data on AFTX-201, our lead program for BAG3 DCM, as well as our high-yield manufacturing process and our BBB-penetrant capsids,” said Rick Modi, Affinia’s Chief Executive Officer. “Affinia’s purpose is to bring potentially curative treatments to patients affected by devastating diseases. In the near-term, 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.” The oral and poster presentation details are provided below. Abstracts can be found at https://annualmeeting.asgct.org/. Updated data, new graphics, and follow up information to be presented are embargoed until 6:00 AM CT on the presentation day for oral abstracts and until 6:00 AM CT on May 13, 2025 for poster abstracts. Oral presentation Title: 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 Session: CMC for AAV Vectors Date/Time: Friday, May 16, 2025, 4:45-5:00 pm CT Location: Room 288-290 Abstract Number: AMA1147 Presenter: Matt Edwards, MBA, Vice President (VP), Process Science, Affinia Poster presentations Title: High-Yield, Pan-Serotype Plasmid System for Manufacturing Adeno-Associated Virus Gene Therapies: Cost and Efficiency Benefits for R&D and Commercial Processes Date/Time: Tuesday, May 13, 2025, 6:00-7:30 pm CT Location: Poster Hall 12 Abstract Number: AMA1150 Presenter: Matt Edwards, MBA, VP, Process Science, Affinia Title: A Novel Investigational AAV Gene Therapy for Treatment of BAG3 Dilated Cardiomyopathy Date/Time: Wednesday, May 14, 2025, 5:30-7:00 pm CT Location: Poster Hall 12 Abstract Number: AMA1161 Presenter: Giri Murlidharan, Ph.D., Senior Director, Vector Translational Biology, Affinia Title: Novel AAV Capsids That Bind Human Transferrin Receptor (TFRC) Demonstrate Widespread and Preferential CNS Tropism in TFRC-KI Mice After Low-dose Systemic Dosing Date/Time: Thursday, May 15, 2025, 5:30-7:00 pm CT Location: Poster Hall 12 Abstract Number: AMA877 Presenter: Giri Murlidharan, Ph.D., Senior Director, Vector Translational Biology, Affinia Title: Engineered AAV Capsids That Target a Novel Human Brain Endothelial Receptor Achieve Robust Transduction in Non-human Primate Central Nervous System After Intravenous Dosing Date/Time: Thursday, May 15, 2025, 5:30-7:00 pm CT Location: Poster Hall 12 Abstract Number: AMA1256 Presenter: John Reece-Hoyes, Ph.D., Senior Director, Head of Vector Biology, Affinia 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.

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 . SOURCE Affinia Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED