RBM20

— Received Rare Pediatric Disease and Orphan Drug Designation for Duchenne muscular dystrophy (Duchenne) gene therapy candidate SGT-003 with patient dosing in Phase 1/2 trial expected Q2 2024 — — Company entered into non-exclusive licensing agreement for use of its proprietary, muscle- targeted AAV-SLB101 capsid — — Company ends first quarter 2024 with approximately $206.1 million in cash and investments. Solid has anticipated cash runway into 2026 — CHARLESTOWN, Mass., May 15, 2024 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (Nasdaq: SLDB), a life sciences company developing precision genetic medicines for neuromuscular and cardiac diseases, today reported financial results for the first quarter ended March 31, 2024, and provided a business update. “In the first quarter of 2024, we continued our focus on executing across our pipeline and we remain on track to initiate patient dosing in our SGT-003 trial in the second quarter of 2024. We anticipate providing a topline readout of safety, microdystrophin expression and functional benefit by year end,” said Bo Cumbo, President and CEO, Solid Biosciences. “Supported by the $108.9 million capital raise completed in January 2024, our strong cash position of $206.1 million provides us with both anticipated runway into 2026 and the resources to execute across our portfolio, including bringing SGT-003 for Duchenne muscular dystrophy into the clinic, advancing SGT-501 for catecholaminergic polymorphic ventricular tachycardia (CPVT) towards IND submission and continuing to progress the rest of our diversified pipeline of neuromuscular and cardiac gene therapy candidates.” Company Updates Solid expects to initiate dosing in the Phase 1/2 trial of SGT-003 in pediatric patients with Duchenne in the second quarter of 2024. Initial safety, microdystrophin expression and functional benefit data from the first 3-4 patients enrolled in the trial is expected by the fourth quarter of 2024. Solid expects to Investigational New Drug Application (IND) for its first cardiac gene therapy candidate, SGT-501 for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), in the first quarter of 2025. Solid continues to advance the rest of its therapeutics portfolio with ongoing preclinical studies in BAG3, mouse studies in TNNT2 and preclinical work in RBM20. Platform enabling work in both capsids (NHP, mouse and pig studies) and portfolio wide CMC process development work is ongoing. Recent Company Highlights On April 1, 2024, Solid announced that the FDA granted Rare Pediatric Disease Designation for its Duchenne gene therapy candidate SGT-003. This designation encourages development of new drugs for the prevention and treatment of rare pediatric diseases. If a new biologics license application (BLA) is approved for SGT-003, the Company may be eligible to receive a priority review voucher. This voucher could be redeemed to obtain priority review for any subsequent marketing application for a different product and may be sold or transferred. On March 7, 2024, Solid announced that it entered into a non-exclusive licensing agreement for use of its proprietary, muscle-targeted AAV-SLB101 capsid in the development of an RNAi therapy to treat FSHD (Facioscapulohumeral muscular dystrophy). The Company aims to license AAV-SLB101 broadly to both companies and academic institutions pursuing treatments for rare diseases. On January 16, 2024, Solid announced that the FDA granted Orphan Drug Designation for SGT-003. This designation provides certain benefits, including specified financial incentives, to support clinical development and the potential for up to seven years of market exclusivity in the U.S. upon regulatory approval. On January 8, 2024, Solid announced a $108.9 million private placement with new and existing investors. The Company expects to use net proceeds of approximately $103.7 million from the private placement to fund ongoing pipeline development programs, business development activities, working capital and other general corporate purposes. First Quarter 2024 Financial Highlights There were no collaboration revenues for the first quarters of 2024 or 2023. Research and development expenses for the three months ended March 31, 2024, were $18.9 million, compared to $24.6 million for the three months ended March 31, 2023. The decrease of $5.8 million in research and development expenses was primarily due to a $7.2 million decrease in manufacturing and research related costs for SGT-003 and $2.3 million decrease in costs for SGT-001 primarily related to our decision to prioritize SGT-003, partially offset by a $3.8 million increase in manufacturing and research related costs for SGT-501. General and administrative expenses for the three months ended March 31, 2024, were $8.0 million, compared to $7.4 million for the three months ended March 31, 2023. The increase of $0.6 million was primarily related to a $0.4 million increase in legal fees, and a $0.2 million increase in corporate and business development costs. Net loss for the first quarter of 2024 was $24.3 million, compared to $30.1 million for the first quarter of 2023. The decrease in net loss was the result of lower research and development costs and an increase in yields on cash, cash equivalents, and available-for-sale securities. Solid had $206.1 million in cash, cash equivalents, and available-for-sale securities as of March 31, 2024, compared to $123.6 million as of December 31, 2023. The Company expects that its cash, cash equivalents, and available-for-sale securities as of March 31, 2024, will enable it to fund key strategic priorities into 2026. About Solid Biosciences Solid Biosciences is a life sciences company focused on advancing a portfolio of gene therapy candidates including SGT-003 for the treatment of Duchenne muscular dystrophy (Duchenne), SGT-501 for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), AVB-401 for the treatment of BAG3-mediated dilated cardiomyopathy, and additional assets for the treatment of fatal cardiac diseases. Solid is advancing its diverse pipeline across rare neuromuscular and cardiac diseases, bringing together experts in science, technology, disease management, and care. Patient-focused and founded by those directly impacted, Solid’s mandate is to improve the daily lives of patients living with these devastating diseases. For more information, please visit . 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 priorities and achieve key clinical milestones; the company’s SGT-003 program, including expectations for initiating dosing and availability of clinical trial data; the company’s expectations for submission of an IND for SGT-501; Solid’s plans to license AAV-SLB101 broadly to both companies and academic institutions; the anticipated use of proceeds from the January 2024 private placement; the potential benefits of Rare Pediatric Disease Designation and Orphan Drug Designation; the cash runway of the company and the sufficiency of the Company’s cash, cash equivalents, and available-for-sale securities to fund its operations; 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 ability to recognize the anticipated benefits of Solid’s acquisition of AavantiBio; the company’s ability to advance SGT-003, SGT-501, AVB-401 and other preclinical programs and capsid libraries on the timelines expected or at all; obtain and maintain necessary approvals from the FDA and other regulatory authorities; replicate in clinical trials positive results found in preclinical studies of the company’s product candidates; obtain, maintain or protect intellectual property rights related to its product candidates; compete successfully with other companies that are seeking to develop Duchenne 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-501, AVB-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: investors@solidbio.com Media Contact: Glenn Silver FINN Partners glenn.silver@finnpartners.com

Cardiomyopathy is not a uniform disease. Rather, individual genetic defects lead to heart failure in different ways, an international consortium reports. Cardiomyopathy is not a uniform disease. Rather, individual genetic defects lead to heart failure in different ways, an international consortium reports in Science. The molecular and cellular mechanisms that lead to heart failure in people with cardiomyopathy are determined by the specific gene variant that each patient carries, according to newly published research based on the first comprehensive single-cell analysis of cardiac cells from healthy and failing hearts. The work, reported in the journal Science, was conducted by 53 scientists from six countries in North America, Europe, and Asia. The study shows that cell type compositions and gene activation profiles change according to the genetic variants. The investigators say the findings can inform the design of targeted therapies that take into account each patient's underlying gene defect responsible for their particular form of cardiomyopathy. The team studied 880,000 single heart cells Examining the genes activated in about 880,000 single cells from 61 failing hearts and 18 healthy donor hearts as reference was a complex endeavor which required an interdisciplinary team. The organs were procured by the Brigham and Woman's Hospital in Boston, USA, University of Alberta in Canada, the Heart and Diabetes Center North Rhine-Westphalia in Bad Oeynhausen, Ruhr University Bochum in Germany and Imperial College London, UK. Senior authors who spearheaded the project are Christine Seidman, professor of medicine and genetics at Harvard Medical School and a cardiologist at Brigham and Women's Hospital; Jonathan Seidman, professor of genetics at Harvard Medical School; Norbert Hübner, professor of cardiovascular and metabolic sciences at the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC) and Charité -- Universitätsmedizin Berlin as well as Dr. Gavin Oudit, University of Alberta, Canada; Professor Hendrik Milting, Heart and Diabetes Center NRW, Bad Oeynhausen, Ruhr University Bochum, Germany; Dr. Matthias Heinig, Helmholtz Munich, Germany; Dr. Michela Noseda of the National Heart and Lung Institute at Imperial College London, UK and Professor Sarah Teichmann, Wellcome Sanger Institute in Cambridge, UK. Joint first authors are Dr. Daniel Reichart (Harvard), Eric Lindberg and Dr. Henrike Maatz (both MDC). A disease with many causes The scientists focused on dilated cardiomyopathy (DCM), the most common form of heart failure that leads to heart transplantations. It involves an expansion (dilation) of walls of the heart chamber, especially in the left ventricle, the heart's main pumping chamber. The muscles of the heart become weakened, compromising its ability to contract and pump blood, which ultimately leads to heart failure. The consortium studied tissues from patients with different genetic mutations that commonly lead to cardiomyopathies. These mutations occurred in proteins with different functions in the heart and the analyses indicate that these triggered different responses. "We investigated pathogenic gene variants in heart tissue at the single-cell level, which allowed us to map precisely how specific pathogenic variants drive cardiac dysfunction," says co-senior author Norbert Hübner. "To our knowledge, this is the first such analysis conducted in cardiac tissue, and we hope this approach can be used to study other types of genetic heart diseases." The scientists precisely characterized the various mutations in each of the hearts and compared them with each other, as well as with healthy hearts and with hearts in which the causes of dilation and dysfunction were unknown. Each cardiac cell type and the numerous subtypes were analyzed one by one, using single-cell sequencing methods. No lab on its own could deal with the massive amount of data generated, but close collaboration among specialists from different disciplines made it possible to assemble a coherent picture out of each individual piece of the puzzle. This study is also part of the efforts of the international Human Cell Atlas (HCA) consortium, which is aiming to map every cell type in the human body as a basis for both understanding human health and for diagnosing, monitoring, and treating disease. "Only this level of resolution allows us to see that cardiomyopathies do not uniformly trigger the same pathological pathways," says co-senior author Christine Seidman. "Rather, different mutations evoked specific and some shared responses that lead to heart failure. These genotype-specific responses point to therapeutic opportunities that may inform the development of precision-targeted interventions," Seidman says. Hyperactive connective tissue cells "For example, we discovered that fibrosis -- the abnormal growth of connective tissue -- observed in DCM is not caused by an increased number of fibroblasts in the heart," says Matthias Heinig, who carried out computational analyses. "The number of these cells stays the same. But the existing cells become more active and produce more extracellular matrix, which fills in the space between the connective tissue cells," Eric Lindberg adds. Thus, rather than overproduction of fibrotic cells, the researchers observed only a shift in the proportion cell subtypes, marked by an increase in the number of fibroblasts specializing in the production of extracellular matrix. "The phenomenon was especially pronounced in the hearts of patients with a mutated RBM20 gene," Henrike Maatz explains. This observation was also reflected in the patients' medical histories. On average, patients with this specific mutation suffered heart failure and needed a transplant much earlier than people with other genetic forms of DCM. Single-cell sequencing revealed a whole series of such genotype-specific differences in dilated hearts. Specific patterns of change The analysis also showed that in the hearts of people with arrhythmogenic cardiomyopathies (ACM) -- those that cause dangerous heart rhythm disturbances -- muscle cells are increasingly replaced by fat and connective tissue cells, particularly in the right ventricle. Although this form of cardiomyopathy can also be caused by a mutation in several genes the team focused its analysis on the gene for the protein plakophilin-2, or PKP2 for short. They compared cell signaling pathways from cells obtained from the right and left ventricles. The findings identify the cause behind increased cell-fat production in the cardiac muscle of people with this type of cardiomyopathy. "The precise molecular signatures obtained for the highly specialized cells of the heart allowed us to predict cell-to-cell communication pathways," Michela Noseda says. The team found that different genetic causes of cardiomyopathies were associated with specific aberrations of the cellular communication networks. "This is clear evidence of specified mechanisms driving the disease." Finally, the scientists used artificial intelligence to develop a model from all these data. Based on the specific patterns of molecular changes in the various cell types, the algorithm can predict with high degree of confidence which mutation is present -- confirming that differences in gene and cell activation are associated with pathogenic variants of specific genes. Biomarkers for targeted therapies The ultimate goal is to develop individualized therapies for heart disease the researchers said, because genotype-specific treatment could be more effective and with fewer side effects. The consortium has made all of its results available to the scientific community online. Seidman hopes that this resource propels studies by other groups to define new treatments that prevent heart failure, which today is an incurable disease. "We investigated tissues of patients who needed a heart transplant; it was their last option," Hendrik Milting says. "We hope that future pharmacological treatments will at least slow down the progression of the disease -- and that the data from our study will help make this happen." Meanwhile, the research team has identified its next task. "The heart tissue that we studied came from people in the final stage of a disease," Daniel Reichart, one of the first authors, says. "We are excited to see what changes we discover in earlier stages of disease, for example based on endomyocardial biopsies." Perhaps biomarkers and pathways will be found that elucidate a very precise disease pathogenesis truly enabling personalized medicine, Gavin Oudit adds.