Cardiomyopathy, Dilated

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.

CHARLESTOWN, Mass., April 29, 2025 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (Nasdaq: SLDB), a life sciences company developing precision genetic medicines for neuromuscular and cardiac diseases, will present data from the Phase 1/2 INSPIRE DUCHENNE trial evaluating SGT-003, a next-generation gene therapy product candidate intended for the treatment of Duchenne muscular dystrophy (Duchenne), at the 28th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), from May 13-17, 2025, in New Orleans, LA. “The data we will present at this year’s ASGCT Annual Meeting reflect Solid’s significant advances in next-generation capsid design and therapeutic approach for Duchenne, including the encouraging initial safety, expression, and biomarker data in the INSPIRE DUCHENNE clinical trial,” said Bo Cumbo, President and CEO of Solid. “We are committed to accelerating safe and effective precision genetic medicines for individuals living with rare neuromuscular and cardiac diseases, and look forward to engaging with the medical and scientific community to advance the field of genetic medicine.” Oral Presentations 1. Title: Initial Experience from the INSPIRE DUCHENNE Phase I/II Study of SGT-003 Microdystrophin Gene Therapy for Duchenne Muscular Dystrophy Session Title: Late-Breaking Abstracts II Date/Time: May 17, 9:15 – 9:30am CT Location/Room: Room 391-392 Presenter: Kevin Flanigan, MD, Advisor Consultant & Researcher, Nationwide Children’s Hospital and investigator in the INSPIRE DUCHENNE clinical trial 2. Title: Insight into the Mechanism of Action of AAV-SLB101, a Novel Muscle-Tropic Capsid for Neuromuscular and Cardiac indications Session Title: AAV Gene Transfer (C): Antibody Evasion, Cardiac & Neuromuscular Targets Date/Time: May 17, 11:30 – 11:45am CT Location/Room: New Orleans Theater A Presenter: Jessica Boehler, PhD, Principal Scientist, Solid Biosciences 3. Title: Potential for AAV-SLB101-Mediated Gene Transfer Treatment in the Context of Natural Seropositivity and After an AAVrh74 Treatment Session Type: Oral presentation Session Title: Modulation of Humoral Immune Responses in AAV Gene Transfer Date/Time: May 16, 1:30 – 3:15pm CT Location/Room: Room 291-292 Presenter: Jessica Boehler, PhD, Principal Scientist, Solid Biosciences Poster Presentations 4. Title: AAV-SLB101, a Novel Muscle-Tropic Capsid, Increases Gene Delivery and Expression Versus AAV9 and AAVrh74 in Mouse Models of DMD and FSHD Muscle Disease Date/Time: May 14, 5:30 – 7:00pm CT Location/Room: Poster Hall I2 Presenter: Prushti Bhavsar, Senior Associate Scientist II, Solid Biosciences 5. Title: Full Length Transgene Quantification Utilizing NanoMosaic Tessie Technology Date/Time: May 13, 6:00 – 7:30pm CT Location/Room: Poster Hall I2 Presenter: Isabella Pajevic, Senior Associate Scientist II, Solid Biosciences 6. Title: Capillary Isoelectric Focusing (cIEF) Platform for Characterization of Charge Variants of Adeno-Associated Virus (AAV) Capsids and Impact on Their Transduction Efficiency Date/Time: May 13, 6:00 – 7:30pm CT Location/Room: Poster Hall I2 Presenter: Brandon Hoyle, Principal Associate Scientist, Solid Biosciences 7. Title: Automation of AAV Capsid ELISA on Tecan Fluent Date/Time: May 14, 5:30 – 7:00pm CT Location/Room: Poster Hall I2 Presenter: Sarah Tong, Associate Scientist, Solid Biosciences Following completion of the conference, presentations will be available on the Scientific Publications & Presentations page of the Our Science section of the Company website, or by clicking here. About Duchenne Duchenne is a genetic muscle-wasting disease predominantly affecting boys, with symptoms usually appearing between three and five years of age. Duchenne is a progressive, irreversible, and ultimately fatal disease that affects approximately one in every 3,500 to 5,000 live male births and has an estimated prevalence of 5,000 to 15,000 cases in the United States alone. About SGT-003 SGT-003 is an investigational gene therapy containing a differentiated microdystrophin construct and a proprietary, next-generation capsid, AAV-SLB101, which was rationally designed to target integrin receptors, and has shown enhanced cardiac and skeletal muscle transduction with decreased liver targeting in nonclinical studies. SGT-003’s microdystrophin construct uniquely includes the R16/17 domains, which localize nNOS to the muscle. Nonclinical studies have shown that nNOS can improve blood flow to the muscle thereby reducing muscle breakdown from ischemia and muscle fatigue. Together, these design features suggest that SGT-003 could be a potential best-in-class investigational gene therapy for the treatment of Duchenne. About INSPIRE DUCHENNE INSPIRE DUCHENNE is a first-in-human, open-label, single-dose, multicenter Phase 1/2 clinical trial to evaluate the safety, tolerability and efficacy of SGT-003 in pediatric participants with a genetically confirmed Duchenne diagnosis with a documented dystrophin gene mutation. INSPIRE DUCHENNE is a multinational trial designed to enroll participants in the United States, Canada, the United Kingdom and Italy. About Solid Biosciences Solid Biosciences is a precision genetic medicine company focused on advancing a portfolio of gene therapy candidates targeting rare neuromuscular and cardiac diseases, including Duchenne muscular dystrophy (Duchenne), Friedreich’s ataxia (FA), catecholaminergic polymorphic ventricular tachycardia (CPVT), TNNT2-mediated dilated cardiomyopathy, BAG3-mediated dilated cardiomyopathy, and additional fatal, genetic cardiac diseases. The Company is also focused on developing innovative libraries of genetic regulators and other enabling technologies with promising potential to significantly impact gene therapy delivery cross-industry. Solid is advancing its diverse pipeline and delivery platform in the pursuit of uniting experts in science, technology, disease management, and care. Patient-focused and founded by those directly impacted by Duchenne, Solid’s mission is to improve the daily lives of patients living with devastating rare diseases. For more information, please visit www.solidbio.com. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding future expectations, plans and prospects for the Company; the ability to successfully achieve and execute on the Company’s goals, priorities and achieve key clinical milestones; the anticipated benefits of SGT-003; the Company’s SGT-003 clinical program, including planned enrollment and site activations in the INSPIRE DUCHENNE trial, planned regulatory interactions and the potential accelerated approval pathway; and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” “working” and similar expressions. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with the Company’s ability to advance SGT-003, SGT-212, SGT-501, SGT-601, SGT-401 and other preclinical programs and capsid libraries on the timelines expected or at all; obtain and maintain necessary approvals and designations from the FDA and other regulatory authorities; replicate in clinical trials positive results found in preclinical studies and early-stage clinical trials of the Company’s product candidates; replicate preliminary or interim data from early-stage clinicals trials in the final data of such trials; obtain, maintain or protect intellectual property rights related to its product candidates; compete successfully with other companies that are seeking to develop Duchenne, Friedreich’s ataxia and other neuromuscular and cardiac treatments and gene therapies; manage expenses; and raise the substantial additional capital needed, on the timeline necessary, to continue development of SGT-003, SGT-212, SGT-501, SGT-601, SGT-401 and other candidates, achieve its other business objectives and continue as a going concern. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties and other important factors, in the Company’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date hereof and should not be relied upon as representing the Company’s views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. Solid Biosciences Investor Contact: Nicole Anderson Director, Investor Relations and Corporate Communications Solid Biosciences Inc. investors@solidbio.com Media Contact: Glenn Silver FINN Partners glenn.silver@finnpartners.com Source: Solid Biosciences Inc.

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.