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© 2025 Solid Biosciences SGT-003 INSPIRE DUCHENNE DATA UPDATE February 2025
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© 2025 Solid Biosciences This presentation 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 presentation 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. This presentation contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data and estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Cautionary Note Regarding Forward Looking Statements 2
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© 2025 Solid Biosciences The impact of treatments on muscle integrity for patients with Duchenne is key to determining efficacy 4 3 1. Michele DE. FEBS J. 2022;289(21):6460-6462. 2. Coronado-Zarco R, de León AO. J Frailty Sarcopenia Falls. 2023;8(4):254-260. 3. Collins KH, et al. Front Physiol. 2018;9:112. 4. Escobar-Huertas JF, et al. Cytoskeleton (Hoboken). 2024;81(6-7):269-286. 5. Sheybani A, et al. Pediatr Res. 2022;92(6):1613-1620. 6. Voleti S, et al. Pediatr Cardiol. 2020;41(6):1173-1179. 7. Wagner KR, et al. Biomark Med. 2021;15(15):1389-1396. Duchenne is a Disease of Impaired Muscle Integrity & Dysfunction1-4 Muscle integrity is the ability of muscle tissue to remain structurally and functionally whole1-3 Muscle integrity underlies strength and mobility1-3 Preservation of muscle integrity is critical for normal muscle function1-3 Early signals of muscle integrity decline predict negative outcomes in certain organs, such as the heart5-7 In Duchenne, muscle fiber regeneration becomes impaired, leading to deterioration of muscle integrity resulting in difficulties with mobility, thoracic scoliosis, respiratory failure, and cardiac failure 4 • Decreased heart function • Cardiomyopathy HEART FAILURE • Loss of muscle mass • Inflammation • Fibrosis LOSS OF AMBULATION • Weak diaphragm RESPIRATORY FAILURE
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© 2025 Solid Biosciences 4 αSYN=alpha-syntrophin; ABD1=actin-binding domain 1; DGBD=dystroglycan binding domain; H=hinge; R=repeat. 1. Data on file. Solid Biosciences. 2024. 2. Hong A.V., et al. Nature Communications. 2024;15:7965. SGT-003: Optimized to Robustly Transduce and Preserve Muscle SGT-003’s optimized transgene and next-generation capsid were designed with the aim to de-target the liver, deliver therapeutic benefit to skeletal muscle, and improve cardiac and pulmonary function1 Unique inclusion of nNOS-binding domain designed with the goal of preventing activity-induced ischemia and associated muscle injury1 Rationally designed capsid targeting multiple integrin receptors which are upregulated in dystrophic muscle2 SGT-003 AAV-SLB101 CAPSID Dystroglycan Binding Domain SGT-003 MICRODYSTROPHIN TRANSGENE Actin Binding Domain nNOS Binding Domain COOH NH3
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© 2025 Solid Biosciences 5 NO=nitric oxide; SR=sarcoplasmic reticulum. 1. Data on file as of February 11, 2025. Solid Biosciences. 2. Zhao J, et al. Mol Med. 2019;25(1):31. 3. Kobayashi YM, et al. Nature. 2008;456(7221):511-515. 4. Wehling-Henricks M, Tidball JG. PLoS One. 2011;6(10):e25071. 5. Nguyen HX, Tidball JG. J Physiol. 2003;550(Pt 2):347-356. 6. Buono R, et al. Stem Cells. 2012; 30(2):197-209. Solid’s Microdystrophin Gene Therapy Demonstrated nNOS Co-Localization and Activity in DMD Patients Restoring properly localized nNOS activity is essential to more fully protect cardiac and skeletal muscle4 Improves blood flow1 Improves stamina2,3 Supports muscle repair and recovery2 Protects against oxidative stress2 Prevents muscle wasting2 Promotes anti-inflammatory effects5 Supports cellular repair and regeneration6 Protects against fibrosis4 Regulates muscle contraction2 + Loss of nNOS at the sarcolemma leads to impaired NO-mediated vasodilation, functional ischemia, and muscle fatigue and breakdown1,2 nNOS Plays an Important Role in Muscle Health, Adaptation, and Performance2,3 42% of muscle fibers showed appropriately localized nNOS expression/activity at Day 90 (mean: N=3 patients)1
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© 2025 Solid Biosciences Participant Age at Dosing (years) Race/Ethnicity Weight (kg) Approx. Time Elapsed Post-Dose (Months)1 1 5 White/Not Hispanic or Latino 19.6 8 2 5 White/Not Hispanic or Latino 26.4 7 3 7 White/Not Hispanic or Latino 27.8 5 4 6 White/Not Hispanic or Latino 22.0 <3 5 7 White/Not Hispanic or Latino 23.2 <3 6 7 Asian/Not Hispanic or Latino 18.9 <3 • 6 participants have been dosed as of February 11, 2025 • Dosing has been well tolerated in all participants as of February 11, 2025 • No serious adverse events (SAEs) and no SUSARs observed • No TMA/aHUS observed SAFETY N=6: 6 Day 90 data available TMA=thrombotic microangiopathy; aHUS=atypical hemolytic uremic syndrome Data on file as of February 11, 2025. Solid Biosciences. Demographics and Early Safety Experience for First 6 Participants 3 participants have reached 90-day follow up and 2 participants have reached 180-day follow up
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© 2025 Solid Biosciences 7 ALT=alanine transaminase; AST=aspartate aminotransferase; CK=creatinine kinase; eMHC =embryonic myosin heavy chain; LDH=lactate dehydrogenase; nNOS=neuronal nitric oxide synthase; WT=wild type. 1. Data on file as of February 11, 2025. Solid Biosciences. Baseline Western Blot and Mass Spectrometry were both 0% mean nor mal dystrophin. Dystrophin positive fibers are not adjusted for fat and fibrosis; these are absolute numbers. 2. Kim EY, et al. Ann Rehabil Med. 2017;41(2):306-312. 3. Voleti S, et al. Pediatr Cardiol. 2020;41(6):1173-1179. 4. Farhana A, et al. StatPearls [Internet]. 2024. 5. Aulbach AD, Amuzie CJ. A Comprehensive Guide to Toxicology in Nonclinical Drug Development (Second Edition). 2017. 6. Oshida N, et al. Sci Rep. 2019;9(1):19498. Delivering on the Promise of Next Generation Gene Therapy for Duchenne Muscular Dystrophy MUSCLE INTEGRITY BIOMARKER DATA1: SERUM TROPONIN SERUM CK SERUM AST SERUM TITIN SERUM LDH SERUM ALT eMHC on Histology DYSTROPHIN POSITIVE FIBERS (IF) N=3, MEAN 78%1: 6 participants have been dosed as of February 11, 2025 • >10 participants total projected to be dosed by early Q2 2025 • Approximately 20 participants total projected to be dosed by Q4 2025 In first 3 participants dosed (Day 90), SGT-003 showed: • Significant microdystrophin expression • Comprehensive improvements in muscle integrity/resilience • Early signs of cardiac benefit Participant 1 Participant 2 Participant 3 Mean Baseline Day 90 EJECTION FRACTION MICRODYSTROPHIN EXPRESSION (WB) N=3, MEAN 110%1: Microdystrophin protein, Mean % Day 90 Day 90 135% 112% 84% 110% 0 50 100 150
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© 2025 Solid Biosciences 1. Data on file as of February 11, 2025. Solid Biosciences. Baseline Western Blot and Mass Spectrometry were both 0% mean nor mal dystrophin. Baseline mean dystrophin positive fibers were 1.5% measured by IF. Dystrophin positive fibers are not adjusted for fat and fibrosis; these are absolute numbers. 2. Mendell JR, et al. Nat Med. 2025 Jan;31(1):332-341. 3. Sarepta Therapeutics EMBARK Part 2 conference call, January 27, 2025. 4. The comparison presented represent cross-trial comparisons and do not involve data from a head-to-head clinical trial. Significant Next Generation Microdystrophin Expression at Day 90 Microdystrophin Expression Measured by MS1 Microdystrophin protein, Mean % Participant 1 Participant 2 Participant 3 Mean Participant 1 Participant 2 Participant 3 Mean Participant 1 Participant 2 Participant 3 Mean Microdystrophin Expression Measured by Western Blot1 Dystrophin Positive Fibers Measured by IF1 Mean microdystrophin expression (n=3) measured by western blot1 was observed to be >2x greater for SGT-003 (Day 90) than approved first-generation Duchenne gene therapy (Weeks 12 & 64)2-4 8 77% 88% 70% 78% 0 25 50 75 100 Microdystrophin protein, Mean % Microdystrophin protein, Mean % Comprehensive orthogonal measurements showed significant microdystrophin expression1 135% 112% 84% 110% 0 50 100 150 119% 152% 53% 108% 0 50 100 150 200
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© 2025 Solid Biosciences 1. Data on file as of February 11, 2025. Solid Biosciences. 2. ELEVIDYS prescribing information. Sarepta Therapeutics, Inc; Cambridge, MA. August 2024. 3. The comparison presented repres ent cross-trial comparisons and do not involve data from a head-to-head clinical trial. Patient Dose Copies/Nucleus 1 1.0 x 1014 vg/kg 19.8 2 28.6 3 7.6 Mean 18.7 SGT-003 had a 25% lower dose and was observed to have greater than 5x mean skeletal muscle transduction (N=3) when compared to approved first generation microdystrophin gene therapy1-3 Dose Copies/Nucleus 1.33 × 1014 vg/kg 2.91 - 3.44 copies per nucleus Next-generation microdystrophin gene therapy candidate, SGT-0031 FDA approved first-generation microdystrophin gene therapy2 9 Greater Than 5x Transduction vs. Approved First-Generation Microdystrophin Gene Therapy Lower dose than approved first generation therapy – no use of eculizumab or other intensive immunomodulation
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© 2025 Solid Biosciences BaselineDay 90 % Positive Fibers - Beta Sarcoglycan % Positive Fibers – nNOS activity% Positive Fibers (IF) - Microdystrophin Patient 1 2 3 Mean Day 90 Values 60% 88% 63% 70% Baseline Values 0% 2.5% 1.5% 1.3% Change From Baseline (Fold Change) ∞ 34x 41x 53x Patient 1 2 3 Mean Day 90 Values 48% 53% 25% 42% Baseline Values 0% 1.5% 0.5% 0.7% Change From Baseline (Fold Change) ∞ 34x 49x 59x Patient 1 2 3 Mean Day 90 Values 77% 88% 70% 78% Baseline Values 0.8% 2.3% 1.3% 1.5% Change From Baseline (Fold Change) 96x 38x 53x 54x SGT-003 Microdystrophin was Observed to Bind and Restore Key Elements of Dystrophin-Associated Protein Complex BaselineDay 90 BaselineDay 90 10 Dystrophin positive fibers are not adjusted for fat and fibrosis; these are absolute numbers. Data on file as of February 11, 2025. Solid Biosciences.
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© 2025 Solid Biosciences 1. Hiramuki Y, et al. Sci Rep. 2025;15(1):1778. 2. Siddique Ahmed Khan M, et al. Int J Sci Res. 2016;5(11):156-157. 3. Aujla RS, et al.StatPearls [Internet]. 2024. 4. US Department of Veterans Affairs. Accessed December 13, 2024. https://www.hepatitis.va.gov/hcv/patient/diagnosis/labtests-AST.asp 5. Farhana A, Lappin SL. StatPearls [Internet]. 2023. 6. Park KC, et al. Cardiovasc Res. 2017;113(14):1708-1718. 7. ElSaygh J, et al. Cardiol Rev. February 9, 2024. Online ahead of print. 8. Aulbach AD, Amuzie, CJ. A Comprehensive Guide to Toxicology in Nonclinical Drug Development (Second Edition). 2017. 9. Oshida N, et al. Sci Rep. 2019;9(1):19498. 10. Kim EY, et al. Ann Rehabil Med. 2017;41(2):306-312. 11. Voleti S, et al. Pediatr Cardiol. 2020;41(6):1173-1179. 12. Guiraud S, et al. Hum Mol Genet. 2019;28(2):307-319. DAMAGED DUCHENNE MUSCLE 11 LDH is released into the bloodstream from cells upon tissue damage5 Titin fragments are decomposed and released into serum and urine when muscle is damaged9 AST leakage is caused by skeletal muscle injury8 Skeletal Muscle3-7 CK, AST, ALT, LDH, Titin, eMHC Heart3,4,6,7 CK Troponin Titin Cardiac troponin I is released during myocardial cell injury1 CK is released from muscle fibers as a result of muscle damage9 ALT leakage is caused by skeletal muscle injury8 eMHC is expressed in newly generated dystrophic muscle12 Comprehensive Assessment of Muscle Integrity, Resilience, & Preservation
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© 2025 Solid Biosciences 12 aSerum troponin data only from Participant 3 at Day 90: Participant 3 had elevated troponin levels at baseline. Troponin level s for Participants 1 & 2 were 0 at baseline. 1. Siddique Ahmed Khan M, et al. Int J Sci Res. 2016;5(11):156-157. 2. Voleti S, et al. Pediatr Cardiol. 2020;41(6):1173-1179. 3. Oshida N, et al. Sci Rep. 2019;9(1):19498. 4. FDA-NIH Biomarker Working Group. Last updated January 25, 2021. Accessed December 12, 2024. https://health.uconn.edu/pepper -center/wp-content/uploads/sites/272/2023/12/BEST-Biomarkers-EndpointS-and- other-Tools-Resource.pdf. 5. Data on file as of February 11, 2025. Solid Biosciences. Muscle Integrity Monitoring of multiple Duchenne biomarkers offers a powerful approach for assessing disease trajectory, with long-term assessment to establish treatment effectiveness4 Improved muscle integrity, as indicated by a coordinated biomarker profile, may support a slowing of disease progression and better long-term clinical outcomes 1-3 Serum CK (-57%)5 Serum Titin (-42%)5 Serum LDH (-60%)5 Serum AST (-45%)5 Serum ALT (-54%)5 Histologic eMHC (-59%)5 Serum Troponin (-36%)a,5 Reductions in Biomarkers of Muscle Breakdown Showed Comprehensive Improvements in Muscle Health & Increased Potential of SGT-003 Clinical Benefit1-3 7 simultaneous biomarker reductions observed at Day 90 (mean: N=3 patients) suggest SGT-003 enhanced muscle integrity and resilience1-4
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© 2025 Solid Biosciences eMHC, embryonic myosin heavy chain. 1. Schiaffino S, et al. Skelet Muscle. 2015;5:22. 2. Guiraud S, et al. Hum Mol Genet. 2019;28(2):307-319. 3. Dubuisson N, et al. Int J Mol Sci. 2022;23(24):16080. 4. Cardone N, et al. Acta Neuropathol Commun. 2023;11(1):167. 5. Forcina L, et al. Cells. 2020;9(5):1297. 6. Sewry CA, et al. Neuromuscul Disord. 2021;31(5):371-384. In Children With DMD, eMHC is Elevated Primarily Due to Muscle Breakdown and Regeneration1-3 As muscle fibers deteriorate, muscle stem cells are activated toreplace damaged fibers. During this regenerative process, newly formed muscle fibers expressembryonic myosin heavy chain (eMHC)3,4 • During this regenerative process, the newly formed muscle fibers express eMHC1,5 • High eMHC protein levels in muscle biopsies indicate active muscle regeneration6 • in DMD, muscle regeneration cannot keep up with muscle breakdown, leading to progressive weakness despite ongoing repair attempts2,4,5 • Muscle fibers often remain in an immature state, leading to persistent eMHC expression, due to constant muscle injury and incomplete repair in DMD2-4 Degeneration 0 to 2 days Inflammation 1 to 4 days Regeneration 2 to 7 days Maturation 4 to >14 days Functional Recovery ~7 to >2 weeks Model of Skeletal Muscle Healing3,5 eMHC expression is significantly upregulated in dystrophic muscle fibers, making it a biomarker for disease progression and response to therapies1-3 13
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© 2025 Solid Biosciences 0% 5% 10% 15% 20% 25% Baseline Day 90 eMHC Positive Fibers1 1. Data on file as of February 11, 2025. Solid Biosciences. 2. Guiraud S, et al. Hum Mol Genet. 2019;28(2):307-319. 3. Oshida N, et al. Sci Rep. 2019;9(1):19498. 14 Reduced titin combined with reduced eMHC suggests that SGT-003 has interrupted muscle breakdown and preserved muscle fibers Titin fragments are decomposed and released into serum and urine when muscle is damaged.3 A decrease suggests reduction in muscle breakdown REDUCTION IN MUSCLE BREAKDOWN INCREASED MUSCLE PRESERVATION Histologic eMHC1 0 400 800 Baseline Day 90 Absolute Concentrations 42%* SERUM Titin (pmol/L)1 Microdystrophin BaselineDay 90 eMHC is expressed in newly generated dystrophic muscle.2 A decrease suggests muscle preservation and resilience eMHC, % 59%* MICRODYSTROPHIN EXPRESSION & nNOS ACTIVITY nNOS SGT-003 demonstrated robust microdystrophin expression and localized nNOS appropriately to the sarcolemma SGT-003 was Observed to Reduce Muscle Breakdown & Increase Muscle Preservation BaselineDay 90 Robust microdystrophin expression and nNOS co-localization lead to reduced markers of muscle loss and dystrophic regeneration at Day 90 (mean: N=3 patients)
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© 2025 Solid Biosciences 15 hs-cTnI=high-sensitivity cardiac troponin. 1. Schultz TI, et al. JACC Basic Transl Sci. 2022;7(6):608-625. 2. Meyers TA, et al. Int J Mol Sci. 2019;20(17):4098. 3. Gandhi S, et al. Cells. 2024;13(14):1168. 4. James J, et al. Neuromuscul Disord. 2011;21(7):462-467. 5. Parmacek MS, Epstein JA. N Engl J Med. 2009;361(1):86-88. 6. Sheybani A, et al. Pediatr Res. 2022;92(6):1613-1620. 7. Voleti S, et al. Pediatr Cardiol. 2020;41(6):1173-1179. 8. Wagner KR, et al. Biomark Med. 2021;15(15):1389-1396. 9. Saunders JT, et al. Circulation. 2011;123(13):1367-1376. 10. Spurney CF, et al. Open Heart. 2021;8(1):e001592. 11. D’Amario D, et al. Heart. 2017;103(22):1770-1779. Early troponin elevation is predictive of severe cardiac disease in neuromuscular diseases6-9 Cardiac tissue has limited regenerative capacity: by age 25, only ~1% of cardiomyocytes will turn over annually5 INCIDENCE OF DUCHENNE-RELATED CARDIOMYOPATHY OCCURS EARLY IN LIFE3 AGE 10 59% evidence of cardiomyopathy by age 10 years3 AGE 18 98% evidence of cardiomyopathy by age 18 years3 40% of these patients will progress to heart failure3 25% evidence of cardiomyopathy by age 6 years3 AGE 6 Early detection of changes in the heart using troponin inform interventions to slow disease progression, improve quality of life, and lower the risk of severe cardiomyopathy11 AGE 0 Cardiac disease is underway long before overt cardiac dysfunction appears4 A hs-cTnI level >7.6 ng/L is correlated with a 3-fold increased risk of cardiac disease10 Cardiomyopathy is a leading cause of death in Duchenne muscular dystrophy2 Loss of Dystrophin Leads to Progressive Degeneration of Cardiac Muscle 1
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© 2025 Solid Biosciences aParticipant 3 has yet to reach the Day 180 follow-up as of February 12, 2025. All three participants demonstrate LVEF above baseline at all follow up timepoints iCell Cardiomyocytes are derived from human, induced pluripotent stem cells (iPSCs); LVEF=left ventricular ejection fraction. 1. Data on file as of February 11, 2025. Solid Biosciences. 2. Soslow JH, et al. Circ Heart Fail. 2023;16(8):e010040. Lower LVEF correlates with a higher 5-year probability of death.2 Observed mean increase in LVEF is a promising sign of SGT-003’s potential cardiac benefit 45 55 65 75 85 Baseline Day 90 Day 180 SGT-003 Clinical Study LVEF(%)1,a Ejection Fraction, % In the 2 participants at Day 180, mean baseline cardiac function increased by 8% from a Baseline LVEF of 56% Participant #3 has 90 days of LVEF follow up. 16 Skeletal Muscle Heart Non-Clinical: Luciferase Expression in iCell Cardiomyocytes1 Fold Change (relative to AAV9) Participant 3 Participant 1 Participant 2 0 5 10 15 20 25 AAV9 AAV-SLB101 1 20.8x AAV-SLB101: an Observed 20.8x Greater Cardiomyocyte Transduction Than AAV9 SGT-003 Suggests Promising Early Signs of DMD Cardiac Benefit1
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© 2025 Solid Biosciences 0.00 0.05 0.10 0.15 0.20 Baseline Day 90 SERUM Troponin (ng/mL) Participant #3 (only)** Troponin Concentration *iCell Cardiomyocytes are derived from human, induced pluripotent stem cells (iPSCs). **aSerum troponin data only from Participant 3 at Day 90: Participant 3 had elevated troponin levels at baseline. Troponin levels for Participants 1 & 2 were 0 at baseline. 1. Data on file as of February 11, 2025. Solid Biosciences. 2. Soslow JH, et al. Circ Heart Fail. 2023;16(8):e010040. 3. James KA, et al. Cardiol Young. 2020;30(2):171-176. 4. James KA, et al. Cardiol Young. 2020;30(2): 171-176. 5. Renella P, Lai WW. Circ Cardiovasc Imaging. 2020;13(11):e012003. 6. Starnes JR, et al. Circ Cardiovasc Imaging. 2024;17(12):e017287. 7. Hiramuki Y, et al. Sci Rep. 2025;15(1):1778. Reducing troponin concentrations by >25% could result in 5-fold greater reduction in risk of cardiac events 2 Non-Clinical: Luciferase Expression in iCell Cardiomyocytes* Fold Change (relative to AAV9) Skeletal Muscle Heart Participant #3 17 Cardiac troponin I is released during myocardial cell injury7 ~36% Reduction 0 5 10 15 20 25 AAV9 AAV-SLB101 1 20.8x AAV-SLB101: an Observed 20.8x Greater Cardiomyocyte Transduction Than AAV9 SGT-003 Suggests Promising Early Signs of DMD Cardiac Benefit1
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© 2025 Solid Biosciences 18 Adverse Events expected and consistent with AAV gene therapy * Participant #6 Troponin I was elevated at baseline which increased during first week of therapy and returned to baseline wi thout intervention and is now in the normal range of troponin (below baseline). This represents 2 participants in total (N=6) with troponin reduced below initial baseline values post -dose. Overall Safety Summary - SGT-003 Well Tolerated in N=6 Participants Prophylactic glucocorticoids alone - no need for intensive immunomodulation • Most Common AEs • Nausea/vomiting • All have resolved • Thrombocytopenia observed • 1 CTCAE Grade 3 observed • All returned to within normal laboratory range with no clinical consequence (no bleeding) • No evidence of hemolysis (hemoglobin stable and no schistocytes on smears) • No eculizumab • No steroids or other agents used • No Hospitalizations or intervention required • Infusion Related Hypersensitivity Reaction • 1 CTCAE Grade 3 observed of prolonged fever • Resolved • Fever • All have resolved • No AEs of Hepatic Transaminitis • Consistent declines in AST and ALT • No GGT increases • All Treatment Related AEs Resolved With No Sequelae • Began in days following treatment • Resolved within weeks • Serious Adverse Events • No SAEs • No SUSARs • No TMA/aHUS observed • Adverse Events of Special Interest • Episode of mild transient hs-troponin I elevation • 1 CTCAE Grade 1 observed first week post dosing* • No clinical evidence of myocarditis • No EKG or Echocardiographic changes
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© 2025 Solid Biosciences Craig McDonald, M.D. Chair, Department of Physical Medicine & Rehabilitation, Distinguished Professor, Physical Medicine & Rehabilitation and Pediatrics, Director, Neuromuscular Disease Clinics, Director, Neuromuscular Research Laboratory, University of California Davis Health, Study Chair, CINRG Duchenne Natural History Study & Investigator, INSPIRE DUCHENNE Clinical Trial
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© 2025 Solid Biosciences aKey secondary endpoint (Stride Velocity 95%). AE=adverse event; NSAA=North Star Ambulatory Assessment; TTR=time to rise. 1. ClinicalTrials.gov. Accessed January 29, 2025. https://clinicaltrials.gov/study/NCT04281485 2. ClinicalTrials.gov. Accessed J anuary 29, 2025. https://clinicaltrials.gov/study/NCT05096221#participation- criteria 3. ClinicalTrials.gov. Accessed January 29, 2025. https://clinicaltrials.gov/study/NCT06138639?intr=SGT- 003&rank=1#participation-criteria ISSUES WITH PREVIOUS CLINICAL TRIAL DESIGNS1,2 Patient Population • Aged 4 to 7 years • <5 second TTR Functional Endpoint • NSAA Length of Trial • 12 months Previous studies of Duchenne gene therapies conducted by third parties chose young, healthy patients and used blunt functional evaluations at early time points after dosing POTENTIAL IMPROVEMENTS IN SOLID’S CLINICAL TRIAL DESIGN 3 Patient Population • Aged 4 to <12 years • Optimized TTR cutoff Functional Endpoint • Time to rise − SV95ca Length of Trial • 18 months 20 Solid is selecting a broader range of children with a more predictable level of disease-related decline, and will utilize more specific functional evaluations at later time points after dosing Clinical Trial Design Crafted to Demonstrate Potential Best-in-Class Clinical Benefit for Patients With Duchenne1-3
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© 2025 Solid Biosciences • Participant enrollment continues: >10 participants in total expected to be dosed by early Q2 2025 • Have identified a significant number of additional prescreened patients for enrollment • Patient #7 dosed on February 17, 2025 • 6 clinical sites in North America (5 in the U.S., 1 in Canada) have been activated • Global clinical site expansion underway: additional sites expected to be activated by year-end 2025 • U.K. & Italy CTAs approved • In mid-2025, Solid plans to request a meeting with the FDA to discuss Accelerated Approval ENROLLMENT: 21 REGULATORY: INSPIRE DUCHENNE Enrollment & Regulatory Update
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© 2025 Solid Biosciences Data on file. Solid Biosciences 2025. Findings indicate potential to redose with AAV-SLB101 after treatment with AAVrh74 capsid used in the approved first-generation microdystrophin gene therapy DAY 30 ASSESSMENT OF AAV-SLB101 NAbs n=6 NAb Titer NAb Titers 150,000 100,000 50,000 0 HUMANS DOSED WITH AAVrh74 (Sera Samples) n=3 Low cross-reactivity observed between AAVrh74 & AAV-SLB101 NAb titers combined with rapid transduction & expression observed with AAV-SLB101 provide a potential opportunity for redosing Duchenne patients treated with AAVrh74 22 Ongoing Preclinical Studies Showed Low Cross-Reactivity Between AAV- SLB101 & AAVrh74 Titers in Mice, NHPs & Human Sera Samples LONGITUDINAL ASSESSMENT OF AAV-SLB101 NAbs n=5 AAV-SLB101 NAb Titer AAVrh74 NAb Titer NAb Titer Days
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© 2025 Solid Biosciences SGT-003 INSPIRE DUCHENNE DATA UPDATE February 2025