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© 2025 Solid Biosciences SGT-003 INSPIRE DUCHENNE DATA UPDATE November 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 key clinical and preclinical milestones; strategies and expectations for the company’s SGT-003 program; expectations for additional site activations, planned enrollment, planned regulatory interactions and the potential approval pathways for SGT-003; 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 and other preclinical programs, capsid libraries and other enabling technologies 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 and early-stage clinical trials of the company’s product candidates; obtain, maintain or protect intellectual property rights related to its product candidates; replicate preliminary or interim data from early-stage clinicals trials in the final data of such trials; compete successfully with other companies that are seeking to develop Duchenne, FA, CPVT 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 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. 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 αSYN=alpha-syntrophin; ABD1=actin-binding domain 1; ALT=alanine aminotransferase; AST=aspartate aminotransferase; DGBD=dystroglycan binding domain; H=hinge; LDH=lactate dehydrogenase; R=repeat. 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 DAMAGED DUCHENNE MUSCLE Decreased heart function Cardiomyopathy HEART FAILURE Loss of muscle mass Inflammation Fibrosis LOSS OF AMBULATION Weak diaphragm RESPIRATORY FAILURE 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 failure4 CK AST Troponin LDH ALT Histologic eMHC Muscle Integrity 3 The impact of treatments on muscle integrity for patients with Duchenne is key to determining efficacy4
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© 2025 Solid Biosciences nNOS=neuronal nitric oxide synthase. Data cutoff of September 29, 2025. Solid Biosciences. SGT-003 is Designed to Transduce and Preserve Muscle SGT-003 AAV-SLB101 CAPSID REPAIRED & RESCUED SGT-003 MUSCLE SGT-003 MICRODYSTROPHIN TRANSGENE Actin Binding Domain R16/R17 Binding Domain (nNOS) COOH NH3 CK AST Troponin LDH ALT Histologic eMHC Muscle Integrity 4 SGT-003’s optimized transgene and next-generation capsid were designed with the goal of enhancing cardiac and skeletal muscle transduction and reducing liver targeting
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© 2025 Solid Biosciences MICRODYSTROPHIN TRANSDUCTION DAPC=dystrophin-associated protein complex. LVEF=left ventricular ejection fraction. WB=Western blot. MS=mass spectrometry. IF=immunofluorescence. 1. Baseline western blot and mass spectrometry were both 0% mean normal dystrophin. 2. 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. Data cutoff of September 29, 2025. Solid Biosciences. INSPIRE DUCHENNE Clinical Progress 58% (WB)1 58% (MS)1 51% (IF)2 23 PARTICIPANTS DOSED AS OF OCTOBER 31, 2025 Dose Vector Copies/Nucleus Day 90 (N=10) Vector Copies/Nucleus Day 360 (N=2) 1.0E14 vg/kg 13 12 MICRODYSTROPHIN LOCALIZATION • All participants responded to SGT-003 treatment (n=10): Mean microdystrophin protein observed at consistent levels across three measures • Observed comprehensive DAPC & biomarker analysis suggest coordinated downstream effect of SGT-003 • Early data suggest potential cardiac benefit through observed troponin I reductions & improvements in systolic function (LVEF) • Early 2026: 30 participants dosed in total (anticipated) • Oct 2025: First clinical trial site activated & participant screening underway for IMPACT DUCHENNE, a Phase 3 randomized, placebo-controlled, ex-US trial of SGT-003 in pediatric participants 5 • 1H 2026: FDA meeting to discuss registrational pathways (anticipated) 107% (WB)1 100% (MS)1 67% (IF)2 Day 360 (Mean, N=2) Day 90 (Mean, N=10) REGULATORY UPDATE
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© 2025 Solid Biosciences Microdystrophin positive fibers are not adjusted for fat and fibrosis; this is an absolute number. Representative images are shown. 1. Data cutoff of September 29, 2025. Solid Biosciences. 2. Anastasi G, et al. Cells Tissues Organs. 2003;173(1):54-63. Compelling Microdystrophin Positive Fibers with Concordant DAPC Restoration Observed After SGT-003 Treatment Compelling levels of microdystrophin expression observed, which was strongly correlated with restoration of key elements of the DAPC, suggesting biologic evidence of therapeutic effect1 The DAPC stabilizes the sarcolemma of skeletal and cardiac muscle during contraction and relaxation and protects muscle fibers from damage2 PERCENT POSITIVE FIBERS AT DAY 90 (N=10)1 6 nNOS activity MEAN 26% Microdystrophin MEAN 51% β-sarcoglycan MEAN 50%
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© 2025 Solid Biosciences 7 CTCAE, common terminology criteria for adverse events. Safety cutoff of October 31, 2025. Solid Biosciences. INSPIRE DUCHENNE Interim Safety Summary for all Participants 23 participants have received SGT-003 at ages ranging from 1 to 10 years as of October 31, 2025 SGT-003 Treatment-Related Adverse Events as of October 31, 2025 (n=23) n (%) Serious Adverse Events (SAEs) 1 (4.3)1 Most Common Treatment-related Adverse Events (AEs) Nausea 17 (73.9) Vomiting 16 (69.6) Decreased Appetite 11 (47.8) Thrombocytopenia / Platelet Count Decreased 11 (47.8) Headache 6 (26.1) Cohort Eligible Age Range (years) Ages at Enrollment (years) Weights for Dosing (kg) Participants Enrolled (n) 1 4 to <7 4 to 6 ≤27.8 13 2 7 to <12 7 to 10 ≤39.7 8 3 0 to <3 1 to 3 ≤17.0 2 Total 0 to <12 1 to 10 ≤39.7 23 SGT-003 has been generally well tolerated as of October 31, 2025 1. One (n=1) CTCAE Grade 3 serious adverse event of immune-mediated myositis. The myositis was not associated with muscle pain or weakness. The participant responded promptly to steroid treatment, with all clinical symptoms noted at presentation resolving and with CK levels declining well below baseline.
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© 2025 Solid Biosciences ALT=alanine aminotransferase; AST=aspartate aminotransferase; GGT=gamma-glutamyl transferase. 1. Data cutoff of September 29, 2025. Solid Biosciences. 2. Steroid tapering begins at Day 30 per INSPIRE DUCHENNE trial protocol. Liver Enzymes Remained Stable After SGT-003 Administration High-dose steroid duration2 SGT-003 Clinical Trial Liver Biomarkers1 (n=14) Visit Day 0 150 300 450 600 750 0 30 60 90 120 150 -5 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 Mean GGT Levels, U/L Mean ALT/AST Levels, U/L GGT ALT AST 8
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© 2025 Solid Biosciences 9 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: only ~1% of cardiomyocytes 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 In muscular dystrophies, 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 BL, baseline; CFB, change from baseline. 1. Data cutoff of September 29, 2025. Solid Biosciences. 2. The mean ± SD normal LVEF range is 60% to 69% for this age-matched population. 3. Romanowicz J, et al. J Am Soc Echocardiogr. 2023;36(3):310-323. Stable-to-Improved Cardiac Function Observed After SGT-003 Dosing 0 6 12 18 BL 90 180 360 Mean Absolute Change From Baseline LVEF, % INSPIRE DUCHENNE Absolute Change From Baseline LVEF (%) N=5 N=5 N=3 N=2 Visit Day Low to Low-Normal Baseline LVEF Participants (n=5 at baseline) Early observations of improved cardiac function driven by participants with low to low-normal baseline left ventricular ejection fraction (LVEF)1 10 63 60 56 66 66 69 64 64 66 45 55 65 75 85 Participants who reached Day 90 Participants who reached Day 180 Participants who reached Day 360 Mean Absolute LVEF, % INSPIRE DUCHENNE Absolute LVEF Over Time (%) Visit Day N=14 N=8 N=2 Day 90 Day 180 Day 360 BL Day 90 Day 180 BL Day 90 BL 60-69% Normal Range of LVEF = Mean ± SD2,3 (n=14 at baseline)
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© 2025 Solid Biosciences 1. Sheybani A, et al. Pediatr Res. 2022;92(6):1613-1620. 2. Data cutoff of September 29, 2025. Solid Biosciences. Troponin Reductions May Indicate Early Signals of SGT-003 Cardiac Treatment Effect INSPIRE DUCHENNE Percent Change From Baseline Troponin2 Troponin, Mean % Change 11 Troponin I is released during myocardial cell injury, acting as a signal of muscle breakdown and a surrogate for cardiac myocyte damage1 -120 -80 -40 0 40 80 BL Day 90 Day 360 N=14 N=14 N=3 31% 70%
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© 2025 Solid Biosciences Wilson DGS, et al. Commun Biol. 2022 Sep 27;5(1):1022. Dystrophin Organizes Critical Skeletal and Cardiac Muscle Proteins Required for Muscle Health OVERVIEW OF THE SKELETAL DAPC OVERVIEW OF THE CARDIAC DAPC 12 The absence of dystrophin can cause dissolution, or significant downregulation, of the entire DAPC and many of the mechanoprotective and mechanotransductive features are subsequently lost
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© 2025 Solid Biosciences 13 1. Data cutoff of September 29, 2025. Solid Biosciences. Baseline Western Blot and Mass Spectrometry were both 0% mean normal 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. Representative ima ges are shown. Compelling Microdystrophin Expression Observed at Day 90 Post SGT-003 TreatmentComprehensive orthogonal measurements showed consistent microdystrophin expression EXAMPLE MICRODYSTROPHIN BIOPSY1 BaselineDay 90 SGT-003 MICRODYSTROPHIN EXPRESSION1 Microdystrophin protein, Mean % 0 40 80 120 160 Western Blot Mass Spectrometry Immunofluorescence Day 90 Day 360 n=2n=10 n=2n=10 n=2n=10 107% 100% 67%58% 58% 51%
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© 2025 Solid Biosciences α=alpha; β=beta; δ=delta; γ=gamma. 1. Gao QQ, McNally EM. Compr Physiol. 2015;5(3):1223-39. 2. Tarakci H, Berger J. Front Biosci (Landmark Ed). 2016;21(4):744-756. 3. Shi W, et al. Muscle Nerve. 2004;29(3):409-419. 4. Lai Y, et al. J Clin Invest. 2009;119(3):624-35. Staining captured after 8 days of intensive treadmill running (6- month-old male mice). 5. Buono R, et al. Stem Cells. 2012; 30(2):197-209. β-sarcoglycan and nNOS are Key Components of the DAPC 14 SARCOGLYCAN COMPLEX FORMATION1 β-sarcoglycan tightly associates with δ-sarcoglycan to form a functional core that recruits γ- and α-sarcoglycan2 Disruption of the β/δ core interferes with association of the sarcoglycan complex to the plasma membrane3 Lack of nNOS at the sarcolemma leads to impaired NO- mediated vasodilation, functional ischemia, muscle fatigue and breakdown 5 Restoration of properly localized nNOS helps prevent muscle wasting, regulate muscle contraction, protect against oxidative stress, and is essential to more fully protect cardiac and skeletal muscle 5 ∆H2-R15 (Contains R16/R17) ∆H2-R19 (Missing R16/R17) MICRODYSTROPHIN CONTRUCTS WITHOUT R16/R17 CANNOT RECRUIT nNOS4
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© 2025 Solid Biosciences 15 Restoration of Key Elements of the DAPC Observed After SGT-003 Treatment β-SG= β-sarcoglycan. Data cutoff of September 29, 2025. Solid Biosciences. β-SG was measured by immunofluorescence and nNOS was measured using an activity assay. Representative images from the same participant are shown. β-SARCOGLYCAN POSITIVE FIBERS MICRODYSTROPHIN POSITIVE FIBERS BaselineDay 90 26% 36% 0 20 40 60 Day 90 Day 360 nNOS, Mean % SGT-003 % Positive Fibers nNOS Activity 50% 70% 0 25 50 75 100 Day 90 Day 360 β-SG, Mean % SGT-003 % β-sarcoglycan Positive Fibers (r Pearson =0.95). nNOS ACTIVITYMICRODYSTROPHIN + β-SARCOGLYCAN n=10 n=2 n=10 n=2 SGT-003 microdystrophin positive fibers (%) achieved a statistical correlation with both β-sarcoglycan positive fibers (%) and nNOS activity positive fibers (%)
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© 2025 Solid Biosciences eMHC Expression Is Significantly Upregulated in Dystrophic Muscle Fibers1-3 Muscle stem cells (satellite cells) are activated to repair and replace damaged muscle fibers–during this process, newly formed muscle fibers transiently express embryonic myosin heavy chain (eMHC)3,4 Muscle fiber damage and degeneration3,4 Newly formed muscle fibers3,4 Continuous, incomplete muscle repair2,4,5 Satellite cell exhaustion6 Progressive fibrosis and muscle failure6 Muscle regeneration is futile: new fibers will be dystrophic CYCLE OF IMPAIRED MUSCLE REGENERATION IN DUCHENNE Over time, the chronic cycle of muscle damage and repair will exhaust satellite cells and lead to progressive muscle weakness Ultimately, muscle failure occurs when ineffective regeneration is unable to keep up with constant muscle breakdown & incomplete repair 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. Abdel-Sama E, et al. Acta Myol. 2009;28(3):94-100.16 Satellite cell activation and proliferation; eMHC is expressed 3,4
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© 2025 Solid Biosciences 17 Full Slide Scans of Muscle Biopsy Sections Showed Uniform Improvements in eMHC1,2 Data cutoff of September 29, 2025. Solid Biosciences. Representative images from the same participant are shown. eMHC, Mean % -49%-60 -40 -20 0 Day 90 SGT-003 % eMHC Positive Fibers1 % positive microdystrophin fibers & the reduction in eMHC positive fibers at Day 90 were negatively correlated (r Pearson = -0.51) eMHC POSITIVE FIBERS MICRODYSTROPHIN POSITIVE FIBERS BaselineDay 90 MICRODYSTROPHIN + eMHC n=10
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© 2025 Solid Biosciences 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. . Aulbach AD, Amuzie, CJ. A Comprehensive Guide to Toxicology in Nonclinical Drug Development (Second Edition). 2017. 5. Farhana A, Lappin SL. StatPearls [Internet]. 2023. 6. Data cutoff of September 29, 2025. Solid Biosciences. n=14 data collected at Day 90 for mean % reductions from baseline in CK, AST, ALT, troponin. N=12 data collected at Day 90 for mean % reductions from baseline in LDH; 2 LDH samples hemolyzed. N=11 data collected at Day 90 for mean % reductions from baseline in titin, which was batch analyzed at an earlier data cutoff date. Comprehensive Reductions in Muscle Injury Signals Suggest Improved Muscle Integrity After SGT-003 Treatment Improved muscle integrity may support slower disease progression and better long-term clinical outcomes1-3 DETERIORATION OF MUSCLE INTEGRITY IN DUCHENNE OBSERVED IMPROVEMENTS IN MUSCLE INTEGRITY WITH SGT-003 AST Leakage is caused by skeletal muscle injury4 CK Released from muscle fibers upon muscle damage3 LDH Released from cells upon tissue damage5 Titin Released into serum and urine upon muscle damage3 ALT 41% mean reduction at Day 906 AST CK LDH Titin 25% mean reduction at Day 906 34% mean reduction at Day 906 42% mean reduction at Day 906 22% mean reduction at Day 906 ALT Leakage is caused by skeletal muscle injury4 18
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© 2025 Solid Biosciences CK=creatinine kinase; LS=least squares. 1. Oshida N, et al. Sci Rep. 2019;9(1):19498. 2. Data cutoff of September 29, 2025. Solid Biosciences. Reductions in CK Levels Observed After SGT-003 Treatment 19 INSPIRE DUCHENNE Percent Change From Baseline CK2 CK, Mean % Change Reductions in CK are signals of improved muscle integrity; CK is released from muscle fibers as a result of muscle damage1 -80 -40 0 40 BL Day 90 Day 360 N=14 N=14 N=3 34% 42%
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© 2025 Solid Biosciences 20 1. Data cutoff of September 29, 2025. Solid Biosciences. 2. Titin was batch analyzed at an earlier data cutoff date. 3. Two LDH samples hemolyzed at day 90 and are not available for inclusion. Improvements in Measures of Muscle Integrity & Resilience Observed After SGT-003 Treatment Comprehensive and thorough assessment of muscle injury and metabolismMean % Change from Baseline SERUM ALT Percent Change From Baseline1 41% at Day 90 -45 -30 -15 0 BL Day 90 Day 360 29% at Day 360 SERUM AST Percent Change From Baseline1 -45 -30 -15 0 BL Day 90 Day 360 Mean % Change from Baseline 25% at Day 90 40% at Day 360 SERUM Titin Percent Change From Baseline1,2 -30 -15 0 BL Day 90 Day 360 Mean % Change from Baseline 22% at Day 90 25% at Day 360 SERUM LDH Percent Change From Baseline1,3 -60 -40 -20 0 BL Day 90 Day 360 Mean % Change from Baseline 42% at Day 90 46% at Day 360 N=14 N=14 N=3 N=14 N=14 N=3 N=11 N=11 N=2 N=14 N=12 N=3
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© 2025 Solid Biosciences Promising Clinical Profile Positions SGT-003 for Potential Functional Benefit 21 Vector genome copies/nucleus % Normal expression % Positive fibers (β-sarcoglycan, nNOS) % Change in biomarkers of muscle breakdown (CK, LDH, AST, ALT, titin, troponin, eMHC) Potential Functional Outcomes Time to rise 10-meter walk/run 4-stair climb North Star Ambulatory Assessment 6-minute walk test Stride velocity 95th %centile PCR Optimized Transduction Western blot Mass spec Microdystrophin Expression Immunofluorescence Serum/histologic biomarkers Enhanced Muscle Integrity + Restoration of the Dystrophin-Associated Protein Complex Data on file. Data cutoff of September 29, 2025. Solid Biosciences.
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