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2025 Solid Biosciences
Cautionary Note Regarding Forward Looking Statements 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. 2 2025
1-4 Duchenne is a Disease of Impaired Muscle Integrity & Dysfunction
1-3 Muscle integrity is the ability of muscle tissue to remain structurally and functionally whole 1-3 Muscle integrity underlies strength and mobility Preservation of muscle integrity is critical for Decreased heart function 1-3
Cardiomyopathy normal muscle function HEART FAILURE Early signals of muscle integrity decline predict negative 5-7 outcomes in certain organs, such as the heart Weak diaphragm RESPIRATORY FAILURE In Duchenne, muscle fiber regeneration
becomes Loss of muscle mass impaired, leading to deterioration of muscle integrity Inflammation Fibrosis resulting in difficulties with mobility, thoracic scoliosis, 4 LOSS OF AMBULATION respiratory failure, and cardiac
failure 4 The impact of treatments on muscle integrity for patients with Duchenne is key to determining efficacy 1. Michele DE. FEBS J. 2022;289(21):6460-6462. 2. Coronado-Zarco R, de Le n 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. 3 Biomark Med. 2021;15(15):1389-1396. 2025 Solid Biosciences
SGT-003: Optimized to Robustly Transduce and Preserve Muscle SGT-003
MICRODYSTROPHIN TRANSGENE SGT-003 AAV-SLB101 CAPSID Dystroglycan Binding Domain COOH NH3 Actin Binding nNOS Binding Domain Domain Unique inclusion of nNOS-binding domain Rationally designed capsid targeting designed with the goal of preventing
activity-induced ischemia multiple integrin receptors which are upregulated 1 2 and associated muscle injury in dystrophic muscle SGT-003's optimized transgene and next-generation capsid were designed with the aim to de-target the liver, 1
deliver therapeutic benefit to skeletal muscle, and improve cardiac and pulmonary function SYN=alpha-syntrophin; ABD1=actin-binding domain 1; DGBD=dystroglycan binding domain; H=hinge; R=repeat. 4 1. Data on file. Solid Biosciences. 2024. 2.
Hong A.V., et al. Nature Communications. 2024;15:7965. 2025 Solid Biosciences
Solid's Microdystrophin Gene Therapy Demonstrated nNOS
Co-Localization and Activity in DMD Patients 1 42% of muscle fibers showed appropriately localized nNOS expression/activity at Day 90 (mean: N=3 patients) 2,3 nNOS Plays an Important Role in Muscle Health, Adaptation, and Performance + Prevents
Protects Protects Supports Promotes Supports Improves Improves Regulates 1 2,3 muscle against against muscle anti-inflammatory cellular blood flow stamina muscle 2 4 2 5 2 wasting fibrosis oxidative stress repair and effects repair and contraction 2
6 recovery regeneration Restoring properly localized nNOS activity is essential to more fully protect cardiac 4 and skeletal muscle Loss of nNOS at the sarcolemma leads to impaired NO-mediated vasodilation, 1,2 functional ischemia, and muscle
fatigue and breakdown 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. 5 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 Age at Dosing Weight Approx. Time Elapsed Participant Race/Ethnicity 1 (years) (kg) Post-Dose (Months) White/Not Hispanic or Latino 1 5 19.6 8 White/Not
Hispanic or Latino 2 5 26.4 7 Day 90 data White/Not Hispanic or Latino 3 7 27.8 5 available White/Not Hispanic or Latino 4 6 22.0 <3 White/Not Hispanic or Latino 5 7 23.2 <3 Asian/Not Hispanic or Latino 6 7 18.9 <3 SAFETY N=6: 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 TMA=thrombotic
microangiopathy; aHUS=atypical hemolytic uremic syndrome 6 Data on file as of February 11, 2025. Solid Biosciences. 2025 Solid Biosciences
Delivering on the Promise of Next Generation Gene Therapy for Duchenne
Muscular Dystrophy 6 participants have been dosed as of 135% 150 Day 90 112% 110% February 11, 2025 MICRODYSTROPHIN 84% 100 EXPRESSION (WB) >10 participants total projected to be 50 1 N=3, MEAN 110% : dosed by early Q2 2025 0 Participant
Participant Participant Mean 1 2 3 Approximately 20 participants total projected to be dosed by Q4 2025 Baseline Day 90 Day 90 DYSTROPHIN POSITIVE In first 3 participants dosed (Day 90), FIBERS (IF) SGT-003 showed: 1 N=3, MEAN 78% :
Significant microdystrophin expression Comprehensive improvements in SERUM TROPONIN SERUM TITIN eMHC on Histology muscle integrity/resilience MUSCLE INTEGRITY SERUM CK SERUM LDH EJECTION FRACTION 1 Early signs of cardiac benefit
BIOMARKER DATA : SERUM AST SERUM ALT 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 normal 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, 7 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. 2025 Solid Biosciences Microdystrophin protein, Mean %
Significant Next Generation Microdystrophin Expression at Day 90 1
Comprehensive orthogonal measurements showed significant microdystrophin expression 1 1 Microdystrophin Expression Measured by Western Blot Microdystrophin Expression Measured by MS 200 135% 150 152% 112% 110% 150 119% 108% 84% 100 100 53% 50 50 0 0
Participant 1 Participant 2 Participant 3 Participant 1 Participant 2 Participant 3 Mean Mean 1 Dystrophin Positive Fibers Measured by IF 88% 100 78% 77% 70% 75 50 25 0 Participant 1 Participant 2 Participant 3 Mean 1 Mean microdystrophin expression
(n=3) measured by western blot was observed to be >2x greater for SGT-003 (Day 2-4 90) than approved first-generation Duchenne gene therapy (Weeks 12 & 64) 1. Data on file as of February 11, 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. 2. Mendell JR, et al. Nat Med.
2025 Jan;31(1):332-341. 3. Sarepta Therapeutics EMBARK 8 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. 2025 Solid
Biosciences Microdystrophin Microdystrophin protein, Mean % protein, Mean % Microdystrophin protein, Mean %
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 Next-generation microdystrophin FDA approved first-generation 1 2 gene therapy candidate, SGT-003
microdystrophin gene therapy Patient Dose Copies/Nucleus Dose Copies/Nucleus 14 1 19.8 1.33 10 vg/kg 2.91 - 3.44 copies per nucleus 2 28.6 14 1.0 x 10 vg/kg 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 1-3 (N=3) when compared to approved first generation microdystrophin gene therapy 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 represent 9 cross-trial comparisons and do not involve data from a head-to-head clinical trial. 2025 Solid Biosciences
SGT-003 Microdystrophin was Observed to Bind and Restore Key Elements
of Dystrophin-Associated Protein Complex % Positive Fibers (IF) - Microdystrophin % Positive Fibers - Beta Sarcoglycan % Positive Fibers - nNOS activity Patient 1 2 3 Mean Patient 1 2 3 Mean Patient 1 2 3 Mean Day 90 Values Day 90 Values 77%
88% 70% 78% Day 90 Values 48% 53% 25% 42% 60% 88% 63% 70% Baseline Values Baseline Values 0.8% 2.3% 1.3% 1.5% Baseline Values 0% 1.5% 0.5% 0.7% 0% 2.5% 1.5% 1.3% Change From Baseline Change From Baseline Change From Baseline 96x 38x 53x 54x 34x 41x
53x 34x 49x 59x (Fold Change) (Fold Change) (Fold Change) 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. 2025 Solid
Biosciences Baseline Day 90 Day 90 Baseline Day 90 Baseline
Comprehensive Assessment of Muscle Integrity, Resilience, &
Preservation ALT leakage is caused by skeletal 8 muscle injury eMHC is expressed in newly generated 12 dystrophic muscle AST leakage is 3,4,6,7 caused by skeletal Heart 8 CK is released DAMAGED DUCHENNE MUSCLE muscle injury from muscle fibers CK as
a result of Troponin 9 muscle damage Titin Titin fragments are decomposed and 3-7 Cardiac troponin I Skeletal Muscle released into serum and LDH is released into the is released during urine when muscle is CK, AST, ALT, bloodstream from cells
myocardial 9 damaged LDH, Titin, eMHC 5 1 upon tissue damage cell injury 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. 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. 2025 Solid Biosciences
Reductions in Biomarkers of Muscle Breakdown Showed Comprehensive 1-3
Improvements in Muscle Health & Increased Potential of SGT-003 Clinical Benefit 7 simultaneous biomarker reductions observed at Day 90 (mean: N=3 patients) suggest SGT-003 1-4 enhanced muscle integrity and resilience Muscle Integrity 5 Serum CK
(-57%) Improved muscle integrity, as indicated by a coordinated biomarker profile, may support 5 Serum LDH (-60%) a slowing of disease progression and 1-3 better long-term clinical outcomes 5 Serum AST (-45%) 5 Serum ALT (-54%) Monitoring of
multiple Duchenne biomarkers 5 Serum Titin (-42%) offers a powerful approach for assessing disease trajectory, with long-term assessment 5 Histologic eMHC (-59%) 4 to establish treatment effectiveness a,5 Serum Troponin (-36%) a Serum 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. 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- 12 other-Tools-Resource.pdf. 5. Data on file as of February 11, 2025. Solid Biosciences. 2025 Solid Biosciences
In Children With DMD, eMHC is Elevated Primarily Due to Muscle
Breakdown 1-3 and Regeneration As muscle fibers deteriorate, muscle stem cells are activated to replace damaged fibers. During this 3,4 regenerative process, newly formed muscle fibers express embryonic myosin heavy chain (eMHC) 3,5 Model of
Skeletal Muscle Healing Degeneration Inflammation Regeneration Maturation Functional Recovery 0 to 2 days 1 to 4 days 2 to 7 days 4 to >14 days ~7 to >2 weeks During this regenerative process, the newly formed muscle fibers
Muscle fibers often remain in an immature state, leading 1,5 express eMHC to persistent eMHC expression, due to constant muscle 2-4 injury and incomplete repair in DMD High eMHC protein levels in muscle biopsies indicate active muscle 6
regeneration in DMD, muscle regeneration cannot keep up with muscle breakdown, leading to progressive weakness despite ongoing repair 2,4,5 attempts eMHC expression is significantly upregulated in dystrophic muscle fibers, making it 1-3 a
biomarker for disease progression and response to therapies 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 13 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. 2025 Solid Biosciences
SGT-003 was Observed to Reduce Muscle Breakdown & Increase Muscle
Preservation Robust microdystrophin expression and nNOS co-localization lead to reduced markers of muscle loss and dystrophic regeneration at Day 90 (mean: N=3 patients) MICRODYSTROPHIN EXPRESSION REDUCTION IN MUSCLE BREAKDOWN INCREASED MUSCLE
PRESERVATION & nNOS ACTIVITY 1 1 1 SERUM Titin (pmol/L) Histologic eMHC eMHC Positive Fibers Microdystrophin nNOS 800 %* 42 25% %* 59 20% 15% 400 10% 5% 0 0% Baseline Day 90 Baseline Day 90 Titin fragments are decomposed and SGT-003 demonstrated
robust microdystrophin eMHC is expressed in newly generated released into serum and urine when muscle is 2 expression and localized nNOS appropriately to dystrophic muscle. A decrease suggests 3 damaged. A decrease suggests reduction in the
sarcolemma muscle preservation and resilience muscle breakdown Reduced titin combined with reduced eMHC suggests that SGT-003 has interrupted muscle breakdown and preserved muscle fibers 14 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. 2025 Solid Biosciences Day 90 Baseline Absolute Concentrations Day 90 Baseline eMHC, %
1 Loss of Dystrophin Leads to Progressive Degeneration of Cardiac
Muscle 2 Cardiomyopathy is a leading cause of death in Duchenne muscular dystrophy 3 INCIDENCE OF DUCHENNE-RELATED CARDIOMYOPATHY OCCURS EARLY IN LIFE Cardiac tissue has limited regenerative AGE 0 AGE 10 AGE 18 AGE 6 capacity: by age 25, only ~1% of
cardiomyocytes will 5 turn over annually Cardiac disease 25% 59% 98% 40% is underway long evidence of evidence of evidence of of these patients before overt cardiac 4 cardiomyopathy cardiomyopathy cardiomyopathy will progress to dysfunction appears
3 3 3 3 by age 6 years by age 10 years by age 18 years heart failure Early troponin elevation is predictive of severe 6-9 Early detection of changes in the heart using troponin inform cardiac disease in neuromuscular diseases interventions to slow
disease progression, improve quality of life, A hs-cTnI level >7.6 ng/L is correlated with 11 and lower the risk of severe cardiomyopathy 10 a 3-fold increased risk of cardiac disease 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. 15 Circulation.