Solid Biosciences Inc. · NASDAQ:SLDB

Solid Biosciences — 42nd Annual J.P. Morgan Healthcare Conference 2024

30 slides from Solid Biosciences's conference presentation, Jan 8, 2024

  1. Slide 1: 42nd Annual J.P. Morgan Healthcare Conference January 2024

    42nd Annual J.P. Morgan Healthcare Conference January 2024 Exhibit 99.1

  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: Industry Leading Platform, Partners, Pipeline, Management, and Strong Balance Sheet

    Diversified Pipeline Strategic Pipeline Across Multiple Therapeutic Areas Leading Collaborators Leading Edge CMC Capabilities Next Generation DMD Program New Management Team Industry Leading Platform, Partners, Pipeline, Management, and Strong Balance Sheet $123.9M* as of 12/31/23 & $100.0M+ In anti

  4. Slide 4: Clinical Stage Company With Additional Cardiac IND in Early 2025

    Program Indication Research / Discovery Preclinical Phase 1/2 Milestone (anticipated) Worldwide Rights Neuromuscular SGT-003 Duchenne Initial FIH Data Q3 2024 AVB-202 – TT Friedreich’s Ataxia Cardiac SGT-501 RYR2-Mediated CPVT IND Q1 2025 CASQ2-Mediated CPVT AVB-401 BAG3-Mediated DCM SGT-601 TNNT2 D

  5. Slide 5: Lead Programs (DMD & CPVT)

    (DMD & CPVT) Lead Programs

  6. Slide 6: SGT-003 Utilizes an Optimized Transgene, Next Generation Capsid and Improved Manufacturing Process

    Next-generation Construct Has Shown Promising Results in Preclinical Testing Capsid Rational design approach used to engineer capsid candidates with the goal of improving skeletal muscle tropism Fold Change μDys Expression vs. AAV9 AAV9 AAV-SLB101 3.0 2.0 1.0 0.0 Robust μDys Expression in mdx Mouse

  7. Slide 7: Rapid AAV-SLB101 Transduction and Expression in mdx Mouse Model by Day 4

    Quadriceps – Day 4 h-uD5+ Myofibers (%) 0 50 150 100 Vehicle SGT-003 3.0E13 SGT-003 1.0E14 SGT-003 3.0E14 Heart – Day 4 h-uD5+ Myofibers (%) 0 50 100 150 Vehicle SGT-003 3.0E13 SGT-003 1.0E14 SGT-003 3.0E14 Diaphragm – Day 4 h-uD5+ Myofibers (%) 0 50 100 150 Vehicle SGT-003 3.0E13 SGT-003 1.0E14 SGT

  8. Slide 8: SGT-003 Showed Sustained Microdystrophin Expression in mdx Mouse Muscle

    SGT-003 Showed Sustained Microdystrophin Expression in mdx Mouse Muscle Vehicle 3.0E13 vg/kg 1.0E14 vg/kg 3.0E14 vg/kg % uDys5 Positive Fibers % uDys5 Positive Fibers Diaphragm 0 29 92 4 0 50 100 Days Post Dosing % uDys5 Positive Fibers Gastrocnemius 0 29 92 4 0 50 100 Days Post Dosing % uDys5 Posit

  9. Slide 9: High Microdystrophin Expression and nNOS Activity in Multiple Tissues at Low Doses in mdx Mouse Model

    High Microdystrophin Expression and nNOS Activity in Multiple Tissues at Low Doses in mdx Mouse Model N=10 per group Microdystrophin Diaphragm % Positive Fibers 0 50 100 Quadriceps % Positive Fibers 0 50 100 Heart % Positive Fibers 0 50 100 WT Vehicle mdx Vehicle mdx SGT-003 (2.0E12) mdx SGT-003 (6.

  10. Slide 10: SGT-003 With AAV-SLB101 Capsid Demonstrated Superior Muscle Tropism vs AAV9

    Robust μDys Expression in mdx Mouse Reduced CK Levels in mdx Mouse Tissue Specific Biodistribution in mdx Mouse 0 2 4 6 8 10 Quad Diaphragm Liver AAV9 Fold Change μDys vg/μg DNA vs. AAV9 Fold Change μDys Expression vs. AAV9 CK Level (U/L) 1 AAV9 AAV-SLB101 0 1000 mdx Vehicle mdx AAV9 mdx AAV-SLB101

  11. Slide 11: Significant Microdystrophin Expression and Functional Efficacy Observed in mdx Mouse Model at Low Doses

    Significant Microdystrophin Expression and Functional Efficacy Observed in mdx Mouse Model at Low Doses (3E13) **p<0.005, ***p<0.0005, ****p<0.00005 N=10 per group Mass Spectrometry - % Normal Dystrophin Grip Strength (11 weeks) 0 1 2 3 4 5 Normalized Forelimb (KgF/kg) ** *** ** WT Vehicle mdx Vehic

  12. Slide 12: NHP IV Administration of AAV-SLB101 with Constitutive Promoter and Reporter Gene

    NHP IV Administration of AAV-SLB101 with Constitutive Promoter and Reporter Gene BIODISTRIBUTION NHPs Administered AAV-SLB101 Showed Improved Biodistribution in Cardiac and Skeletal Muscle With Decreased Hepatic Transduction as Compared to AAV9 *Average fold differences calculated from the five skel

  13. Slide 13: GLP Toxicology NHP Study Showed SGT-003 Was Well Tolerated

    GLP Toxicology NHP Study Showed SGT-003 Was Well Tolerated NHP GLP TOX Study 3-month study 2 treatment groups (1E14 vg/kg & 3E14 vg/kg) n = 3/group > 60 tissues evaluated including skeletal muscle, liver, brain Well tolerated in both groups throughout the study No early mortality events, no unschedu

  14. Slide 14: FDA Cleared SGT-003 Phase 1/2 Trial Design

    To investigate the safety and tolerability of a single intravenous 1E14vg/kg dose of SGT-003 To investigate the efficacy of a single intravenous dose of SGT-003 Objective Design Endpoint First-in-human Open-label, Single-dose Study to Enroll a Minimum of 3 Patients From Two Sites Primary Objective S

  15. Slide 15: FDA Cleared SGT-003 Phase 1/2 Trial Design: Cohorts

    Study will include 2 cohorts based on age, weight, and North Star Ambulatory Assessment (NSAA) at the time of signing the informed consent: Cohort 1: Participants 4 to < 6 years of age, <18 kg, NSAA total score 17 to <27 Cohort 2: Participants 6 to < 8 years of age, <30 kg, NSAA total score 20 to <2

  16. Slide 16: FDA Cleared SGT-003 Phase 1/2 Trial Design: Endpoints

    Primary Endpoint Secondary Endpoint Incidence of treatment-emergent adverse events (AEs) through Day 360 Change from baseline of microdystrophin protein levels at Day 90 and 360 Change from baseline in the NSAA score at Day 360 Change from baseline in 6‑minute walk test (6MWT) distance at Day 360 Ob

  17. Slide 17: CASQ2 & RYR2 Proteins Regulate Cardiac Calcium: Clinical Presentation and Unmet Need

    CASQ2 & RYR2 proteins regulate cardiac calcium (Ca2+ ), important for electrical conduction and cardiac contraction / relaxation Postulated Mechanism: Mutations in RYR2 or CASQ2 genes disrupt Ca2+ release into the cytoplasm triggering abnormal contraction and relaxation leading to arrythmias Cause A

  18. Slide 18: Rationale for CASQ2 Overexpression in RYR2 CPVT

    Rationale for CASQ2 Overexpression in RYR2 CPVT CASQ2 Overexpression Leads to Increased Ca2+ Buffering to Counteract Ca2+ Sensitivity of RYR2 Mutant RYR2 Mutation-related CPVT Mutations in RYR2 make the channel more sensitive to SR Ca2+ levels, resulting in early release of Ca2+ into the cytoplasm a

  19. Slide 19: Rationale for CASQ2 Overexpression in RYR2 CPVT (cont.)

    Rationale for CASQ2 Overexpression in RYR2 CPVT (cont.) CASQ2 Overexpression Leads to Increased Ca2+ Buffering to Counteract Ca2+ Sensitivity of RYR2 Mutant RyR, Ryanodine Receptor; SR, sarcoplasmic reticulum; AP, action potential; Ca2+, calcium Sources: Proprietary data from Priori Lab RYR2 Mutatio

  20. Slide 20: Elimination of Arrythmias in Multiple Disease State Models: RYR2 Mouse

    Elimination of Arrythmias in Multiple Disease State Models Data Suggests CASQ2 Augmentation Was Well Tolerated & Highly Protective CASQ2 & RYR2 CPVT Arrhythmias ***P<0.001, AAVa-CASQ2–treated vs untreated and AAVa-CASQ2–treated vs AAVa-GFP–treated 1. Priori Lab, unpublished data. RYR2mut Animals Wit

  21. Slide 21: Elimination of Arrythmias in Multiple Disease State Models: CASQ2 Mouse

    Elimination of Arrythmias in Multiple Disease State Models Data Suggests CASQ2 Augmentation Was Well Tolerated & Highly Protective CASQ2 & RYR2 CPVT Arrhythmias ***P<0.001, AAVa-CASQ2–treated vs untreated and AAVa-CASQ2–treated vs AAVa-GFP–treated 1. Denegri, et al. 2014 CASQ2 Mouse Significantly fe

  22. Slide 22: CPVT IND Planned for Q1 2025, Potentially Followed by Multiple Ex-US CTAs

    CPVT IND Planned for Q1 2025, Potentially Followed by Multiple Ex-US CTAs Regulatory interactions intended to shed light on regulators’ thinking for addressing multiple genetic mutations (RYR2 & CASQ2) with single gene replacement therapy UK, NL, IT sites planned in addition to US as part of develop

  23. Slide 23: BAG3 Mutations Lead to Reduced BAG3 Protein Leading to Dilated Cardiomyopathy

    BAG3 mutations lead to reduced BAG3 protein leading to dilated cardiomyopathy (DCM)​ Postulated mechanism: Decreased BAG3 protein leads to heat shock protein dysfunction, and a build-up of dysfunctional proteins in the sarcomere, causing myofilament damage and heart failure. Cause Affected Populatio

  24. Slide 24: Cardiac-selective Expression of Human BAG3 Transgene Protein in Wild Type Mouse Heart

    30 20 10 0 Cardiac-selective Expression of Human BAG3 Transgene Protein in Wild Type Mouse Heart 2000 1500 1000 500 0 Human BAG3 (ng/mg) AAVrh74 AAV9 Liver 100 75 50 25 0 225 200 125 175 Human BAG3 (ng/mg) AAVrh74 AAV9 Gastrocnemius 200 150 100 Human BAG3 (ng/mg) AAVrh74 AAV9 Transgene expression us

  25. Slide 25: Cardiac-selective Expression of Human BAG3 Transgene Protein in Wild Type Mouse (cont.)

    Vehicle AAVrh74 + Cardiac promoter Transgene expression using a cardiac promoter and AAVrh74 was higher in target tissue (heart) and lower in off-target tissues (e.g. liver) Human BAG3 expression in off-target tissues lower than endogenous BAG3 Cardiac-selective Expression of Human BAG3 Transgene Pr

  26. Slide 26: Early Data Showed the Ability of AVB-401 to Rescue Cardiac Function in BAG3 cKO Mouse Model

    Early Data Showed the Ability of AVB-401 to Rescue Cardiac Function in BAG3 cKO Mouse Model 2E13 vg/kg Rescues Cardiac Function at 24 WOA Time-dependent Decrease in Cardiac Function *p =0.01; ** p<0.008, Mixed effects analysis, Sidaks multiple comparisons test N=13 *p <0.05 One way ANOVA, Tukey’s mu

  27. Slide 27: Platform Technologies

    Platform Technologies

  28. Slide 28: Novel Capsid AAV-SLB134, Modified for Cardiac Tropism and Liver De-targeting

    Mice Received 5 Different Treatments Novel Capsid AAV-SLB134, Modified for Cardiac Tropism and Liver De-targeting High Level of Heart Transduction with ~1000-fold Decrease In Liver Transduction in Wild Type Mice Parental Capsid Data on File, Wild Type Mice Heart VCN 100 1 2 3 4 5 10-1 Fold Changes N

  29. Slide 29: Solid's Manufacturing Platform Has Potential to Challenge Industry Yields and Empty/Full Purity

    *Currently at 2L scale in PD, DMD currently at 1000L Solid's Manufacturing Platform Has Potential to Challenge Industry Yields and Empty/Full Purity Significant Increase in Yields and Continued Improvements in Empty/Full Ratios Seen at Research Scales* Yield & Quality Performance Pre-enrichment caps

  30. Slide 30: Anticipated Near Term Milestones

    Program Milestone (anticipated) Milestone (anticipated) Timing Neuromuscular SGT-003 for Duchenne First Patient Dosing FIH Data Q3 2024 Mid-Late Q1 2024 Phase 1/2 cohort 1 completion of dosing Mid-2024 Submit multiple CTAs for global trial 1H 2024 Phase 1/2 cohort 1 data (microdystrophin expression

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