Solid Biosciences Inc. · NASDAQ:SLDB

Solid Biosciences — Cardiovascular Clinical Trialist (CVCT) Forum 2025

25 slides from Solid Biosciences's conference presentation, December 2025

1. Slide 1: Cardiovascular Clinical Trialist Forum: Cardiac Gene Treatment

   Cardiovascular Clinical Trialist Forum: Cardiac Gene Treatment An Industry Prospective: Drive to Inflection Point © 2025 Solid Biosciences - Nonconfidential

2. Slide 2: Forward Looking Statement

   Forward Looking Statement 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 th

3. Slide 3: Acknowledgments

   Acknowledgments CVCT and Overcome • Faiez Zannad, Patrick Wahby, Javed Butler, Silvia Priori, Roger Hajjar CPVT Community • SADS Foundation, The Canadian SADS Foundation, HiRO Solid Biosciences • Preclinical and clinical development departments ICS Maugeri • The Silvia Priori Lab CPVT=catecholaminer

4. Slide 4: Implications of Advanced Therapies for Drug Development Feasibility

   Implications of Advanced Therapies for Drug Development Feasibility Balancing “Time and Resources” vs “Probability of Clinical Success” Time Probability of and Resources Clinical Success • High CoGS • Clinical development efficiency • Delivery complexity • Biologic target engagement • Off target saf

5. Slide 5: Implications of Advanced Therapies for Drug Development Feasibility

   Implications of Advanced Therapies for Drug Development Feasibility Balancing “Time and Resources” vs “Probability of Clinical Success” Time Probability of and Resources Clinical Success • High CoGS • Clinical development efficiency • Delivery complexity • Biologic target engagement • Off target saf

6. Slide 6: Clinical Development Efficiency

   Clinical Development Efficiency Early infection point Early signal Lowest number of Fastest time to detection patients to demonstrate meaningful safety and efficacy clinical benefit 6 © 2025 Solid Biosciences - Nonconfidential

7. Slide 7: Meaningful Clinical Benefit: Challenges With Rare Disease

   Meaningful Clinical Benefit: Challenges With Rare Disease Meaningful clinical benefit = something that affects feel, function, and survival Optimizing signal detection with feel, function, and survival requires: Large treatment signal Frequent events and/or Or both large patient population 7 © 2025

8. Slide 8: Optimizing Feel, Function, and Survival Detection

   Optimizing Feel, Function, and Survival Detection Large Treatment Effect Large Available Patient Population • Rapidly progressive neuromuscular diseases • CHF (PARADIGM-HF – sacubitril and – SMA: onasemnogene abeparvovec-xioi valsartan (Entresto) (Zolgensma) • ASCVD (VESALIUS-CV – Evolocumab) • Aggr

9. Slide 9: Optimizing Feel, Function, and Survival Detection

   Optimizing Feel, Function, and Survival Detection Large Treatment Effect Large Available Patient Population • Rapidly progressive neuromuscular diseases • CHF (PARADIGM-HF – sacubitril and – SMA: onasemnogene abeparvovec-xioi valsartan (Entresto) (Zolgensma) • ASCVD (VESALIUS-CV – Evolocumab) • Aggr

10. Slide 10: Accelerated Approval Pathway

    Accelerated Approval Pathway In 2012, the US Congress passed the Food and Drug Administration Safety Innovations Act (FDASIA) A surrogate endpoint is generally a biomarker (eg, laboratory An intermediate clinical endpoint Section 901 of FDASIA allows measurement, radiographic image, is a measurement

11. Slide 11: Main Gene Therapy Trials for Cardiovascular Diseases

    Main Gene Therapy Trials for Cardiovascular Diseases Arrhythmogenic Cardiomyopathy Outcome Measure Categories Arrhythmia Imaging Clinical PRO Tissue Exercise Hospitalization Lab c c c LX2020 for RP-A601 for TN-401 for PKP2-Mediated PKP2-Mediated Arrhythmogenic PKP2-Mediated Arrhythmogenic Arrhythmog

12. Slide 12: Main Gene Therapy Trials for Cardiovascular Diseases

    Main Gene Therapy Trials for Cardiovascular Diseases Dilated Cardiomyopathy (DCM) Outcome Measure Categories Arrhythmia Imaging Clinical PRO Tissue Exercise Hospitalization Lab c c c c c c c SGT-003 for SGT-003 for RP-A701 for RGX-202 for GNT0004 for AAV1/SERCA2a Myocardial Duchenne Duchenne BAG3-Di

13. Slide 13: Main Gene Therapy Trials for Cardiovascular Diseases

    Main Gene Therapy Trials for Cardiovascular Diseases Hypertrophic Cardiomyopathy Outcome Measure Categories Arrhythmia Imaging Clinical PRO Tissue Exercise Hospitalization Lab c c c c c c c c c SGT-212 for ST-920 for Fabry RP-A501 for AAVrh.10hFXN rAAV1-CMV-GAA GC301 for AAV2/8-LSPhGAA EXG110 for TN

14. Slide 14: Main Gene Therapy Trials for Cardiovascular Diseases

    Main Gene Therapy Trials for Cardiovascular Diseases Inherited Arrhythmia Syndrome Outcome Measure Categories Arrhythmia Imaging Clinical PRO Tissue Exercise Hospitalization Lab c SGT-501 for CPVT (ARTEMIS Trial) (Phase I) 14 © 2025 Solid Biosciences - Nonconfidential

15. Slide 15: CPVT Represents a High Unmet Need With No Approved Therapies

    CPVT Represents a High Unmet Need With No Approved Therapies That Treat Underlying Cause of Disease Standard CPVT treatments are used off-label, require strict compliance, and have c c c challenging side effects that are life limiting8-13 • Beta blockers CPVT is a Mutations in the genes coding Alter

16. Slide 16: Rationale for CASQ2 Augmentation in RYR2 CPVT

    Rationale for CASQ2 Augmentation in RYR2 CPVT In RYR2 pathogenic mutations, normal CASQ2 levels are insufficient to maintain RYR2 in a closed conformation during diastole in high Ca2+ flux states (such as with adrenaline) RYR2 Mutation-Related CPVT Arrhythmia Mutations in RYR2 make the channel more

17. Slide 17: Rationale for CASQ2 Augmentation in RYR2 CPVT (cont'd)

    Rationale for CASQ2 Augmentation in RYR2 CPVT (cont’d) Cardiac delivery of SGT-501 is intended to increase CASQ2, thus enhancing Ca2+ buffering and counteracting Ca2+ sensitivity caused by RYR2 pathogenic mutations RYR2 Mutation-Related CPVT Normal Rhythm + Increased CASQ2 Expression Increased CASQ2

18. Slide 18: RYR2 CPVT Transgenic Mouse Model Used to Support Proof-of-Concept

    RYR2 CPVT Transgenic Mouse Model Used to Support Proof-of-Concept for AAV Gene Delivery of Human CASQ2 ECG response to β-adrenergic stimulation in 85 days post vehicle or SGT-501 treatment WT Mice Normal heart rhythm in Dosed With Vehicle WT background strain animals IP dose epinephrine and caffeine

19. Slide 19: ARTEMIS Clinical Trial Design: SGT-501 Phase 1b Study

    ARTEMIS Clinical Trial Design: SGT-501 Phase 1b Study First-in-human, open-label, multi-center study to enroll a minimum of 6 participants. Activation of first clinical trial site expected Q4 2025 c OBJECTIVE c DESIGN c ENDPOINTS Primary Objective Participants Primary Endpoint • To evaluate the safe

20. Slide 20: Study Schema

    Study Schema Screening period Enrolled in long-term COHORT 1 (n=3 to ≤6): Active treatment (1 year) (up to 47 days) follow-up study (4 years) Dose 1, aged ≥18 years DSMB review of safety after third participant’s Day-90 visit Optional Screening period Enrolled in long-term Active treatment (1 year)

21. Slide 21: Study Visits Schema

    Study Visits Schema Exercise Stress Test ECG ECG Patch Day 30 Day 90 Day 180 Day 270 Day 360 Enrolled in long-term Screening Active treatment follow-up study Period (1 year) (4 years)a Day 1: Administration of SGT-501 Immunosuppressive regimen Day -7 to Week 12 Continuous monitoring of ILR/ICD +Back

22. Slide 22: Backup

    Backup © 2025 Solid Biosciences - Nonconfidential

23. Slide 23: Main Gene Therapy Trials for Cardiovascular Diseases

    Main Gene Therapy Trials for Cardiovascular Diseases Heart Failure With Preserved Ejection Fraction (HFpEF) Outcome Measure Categories Arrhythmia Imaging Clinical PRO Tissue Exercise Hospitalization Lab c c c c c AAV1-CMV-Serca2a MYDICAR MYDICAR gene Therapy Trial AAV1/SERCA2a for AAV1/SERCA2a for (

24. Slide 24: Main Gene Therapy Trials for Cardiovascular Diseases

    Main Gene Therapy Trials for Cardiovascular Diseases Ischemic Cardiomyopathy Outcome Measure Categories Arrhythmia Imaging Clinical PRO Tissue Exercise Hospitalization Lab c c c c c AdvVEGF-D for YAP101 for VEGF-D for Severe XC001 for Epicardial XC001 Angina Pectoris Ischemic HFrEF Coronary Heart Ch

25. Slide 25: Main Gene Therapy Trials for Cardiovascular Diseases

    Main Gene Therapy Trials for Cardiovascular Diseases Non-Ischemic Cardiomyopathy Outcome Measure Categories Arrhythmia Imaging Clinical PRO Tissue Exercise Hospitalization Lab c Phosphatase Inhibition Gene Therapy for Non-Ischemic Heart Failure (Phase II) 25 © 2025 Solid Biosciences - Nonconfidentia

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