Solid Biosciences Inc. · NASDAQ:SLDB
Solid Biosciences — Technical Presentation (February 2025)
23 slides from Solid Biosciences's technical presentation, Feb 18, 2025
Slide 1: SGT-003 INSPIRE DUCHENNE Data Update
Exhibit 99.1 February 2025 SGT-003 INSPIRE DUCHENNE DATA UPDATE © 2025 Solid Biosciences
Slide 2: Cautionary Note Regarding Forward Looking Statements
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 successfull
Slide 3: Duchenne is a Disease of Impaired Muscle Integrity & Dysfunction
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
Slide 4: SGT-003: Optimized to Robustly Transduce and Preserve Muscle
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 o
Slide 5: Microdystrophin Gene Therapy Demonstrated nNOS Co-Localization and Activity in DMD Patients
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
Slide 6: Demographics and Early Safety Experience for First Participants
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.
Slide 7: Delivering on the Promise of Next Generation Gene Therapy for Duchenne
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 P
Slide 8: Significant Next Generation Microdystrophin Expression at Day 90
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 1
Slide 9: Greater Than 5x Transduction vs. Approved First-Generation Microdystrophin Gene Therapy
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 micro
Slide 10: SGT-003 Microdystrophin Observed to Bind and Restore Dystrophin-Associated Protein Complex
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
Slide 11: Comprehensive Assessment of Muscle Integrity, Resilience, & Preservation
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 fibe
Slide 12: Reductions in Biomarkers of Muscle Breakdown Showed Comprehensive Improvements
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 Integr
Slide 13: In Children With DMD, eMHC is Elevated Primarily Due to Muscle Breakdown and Regeneration
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 Mode
Slide 14: SGT-003 was Observed to Reduce Muscle Breakdown & Increase Muscle Preservation
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 INCREAS
Slide 15: Loss of Dystrophin Leads to Progressive Degeneration of Cardiac Muscle
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
Slide 16: AAV-SLB101: Observed 20.8x Greater Cardiomyocyte Transduction Than AAV9
AAV-SLB101: an Observed 20.8x Greater Cardiomyocyte Transduction Than 1 AAV9 SGT-003 Suggests Promising Early Signs of DMD Cardiac Benefit In the 2 participants at Day 180, mean Non-Clinical: Luciferase Expression in SGT-003 Clinical Study 1 1,a baseline cardiac iCell Cardiomyocytes LVEF(%) function
Slide 17: AAV-SLB101: Observed 20.8x Greater Cardiomyocyte Transduction Than AAV9 (Troponin)
AAV-SLB101: an Observed 20.8x Greater Cardiomyocyte Transduction Than 1 AAV9 SGT-003 Suggests Promising Early Signs of DMD Cardiac Benefit Non-Clinical: Luciferase Expression in SERUM Troponin (ng/mL) Participant #3 * iCell Cardiomyocytes Participant #3 (only)** 0.20 % ~36 Reduction 20.8x 25 0.15 He
Slide 18: Overall Safety Summary - SGT-003 Well Tolerated in N=6 Participants
Overall Safety Summary - SGT-003 Well Tolerated in N=6 Participants Prophylactic glucocorticoids alone - no need for intensive immunomodulation • All Treatment Related AEs Resolved With No Sequelae • Most Common AEs • Nausea/vomiting • Began in days following treatment • All have resolved • Resolved
Slide 19: Craig McDonald, M.D.
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 Du
Slide 20: Clinical Trial Design Crafted to Demonstrate Potential Best-in-Class Clinical Benefit
Clinical Trial Design Crafted to Demonstrate Potential Best-in-Class Clinical 1-3 Benefit for Patients With Duchenne ISSUES WITH PREVIOUS POTENTIAL IMPROVEMENTS IN 1,2 3 CLINICAL TRIAL DESIGNS SOLID’S CLINICAL TRIAL DESIGN • Aged 4 to 7 years • Aged 4 to <12 years Patient Population Patient Populati
Slide 21: INSPIRE DUCHENNE Enrollment & Regulatory Update
INSPIRE DUCHENNE Enrollment & Regulatory Update ENROLLMENT: • 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 clinica
Slide 22: Low Cross-Reactivity Between AAV-SLB101 & AAVrh74 Titers
Ongoing Preclinical Studies Showed Low Cross-Reactivity Between AAV- SLB101 & AAVrh74 Titers in Mice, NHPs & Human Sera Samples Findings indicate potential to redose with AAV-SLB101 after treatment with AAVrh74 capsid used in the approved first-generation microdystrophin gene therapy LONGITUDINAL AS
Slide 23: SGT-003 INSPIRE DUCHENNE Data Update
February 2025 SGT-003 INSPIRE DUCHENNE DATA UPDATE © 2025 Solid Biosciences
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