Slide 1: Potential for AAV-SLB101–Mediated Gene Transfer Treatment in the Context of Natural Seropositivity and After an AAVrh74 Treatment
Potential for AAV-SLB101–Mediated Gene Transfer Treatment in the Context of Natural Seropositivity and After an AAVrh74 Treatment Jessica F Boehler, PhD Principal Scientist – DMD Scientific Lead Solid Biosciences © 2025 Solid Biosciences - Nonconfidential
Slide 2: Forward-Looking Statements
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 t
Slide 3: Disclosures
Disclosures • I am a full-time employee at Solid Biosciences Inc. and hold equity in the company 3 © 2025 Solid Biosciences - Nonconfidential
Slide 4: Overcoming Anti-AAV Antibody Barriers Can Improve Gene Therapy Availability
Overcoming Anti-AAV Antibody Barriers Can Improve Gene Therapy Availability • Pre-existing or treatment-induced anti-AAV antibodies can Prevent Transduction limit efficacy of AAV gene therapies ‒ NAbs may prevent effective transduction, particularly with systemic delivery Decrease Patient Enrollment
Slide 5: Assays for Anti-AAV Antibodies Inform Inclusion Criteria and Dosing Strategy
Assays for Anti-AAV Antibodies Inform Inclusion Criteria and Dosing Strategy AAV-SLB101 NAb-TAb Correlation AAV Seropositivity 105 r=0.94 P<0.001 AAV-SLB101 NAb Titer 104 • Pre-existing anti-AAV antibodies in serum arise from natural exposure to wild-type AAV and vary by 103 serotype, geography, and
Slide 6: Assays for Anti-AAV Antibodies Inform Inclusion Criteria and Dosing Strategy
Assays for Anti-AAV Antibodies Inform Inclusion Criteria and Dosing Strategy AAV-SLB101 NAb-TAb Correlation AAV Seropositivity 105 r=0.94 P<0.001 AAV-SLB101 NAb Titer 104 • Pre-existing anti-AAV antibodies in serum arise from natural exposure to wild-type AAV and vary by 103 serotype, geography, and
Slide 7: Understanding the Relationship Between TAb and Transduction Neutralization Is Important in Gene Therapy Trials
Understanding the Relationship Between TAb and Transduction Neutralization Is Important in Gene Therapy Trials Why does this matter? Inform patient eligibility, Optimize dosing strategy, Estimate treatment success Study Design Question: Can we define a titer “threshold” Day -1 0 14 that negatively i
Slide 8: AAV TAb Titer Generally Correlated With In Vivo Transduction
AAV TAb Titer Generally Correlated With In Vivo Transduction Assessment of In Vivo Transduction Correlation to AAV TAb Titer Total Body Luciferase Activity (Flux, p/s) Total Body Luciferase Activity (Flux, p/s) 8×1010 8×1010 6×1010 6×1010 R2=0.7199 4×1010 4×1010 2×1010 2×1010 0 0 <1:5 Low Low-Mid Mi
Slide 9: Tissue Dependent Impact of AAV TAb Titer on Transduction
Tissue Dependent Impact of AAV TAb Titer on Transduction Skeletal Muscle Cardiac Muscle 1,000,000 1,000,000 800,000 800,000 RLUs in Quadriceps RLUs in Heart 600,000 600,000 400,000 400,000 200,000 200,000 0 0 <1:5 Low Low-Mid Mid Mid-High High IVIg <1:5 Low Low-Mid Mid Mid-High High IVIg Titer Titer
Slide 10: Opportunity for Dosing With AAV-SLB101 Following Treatment With AAVrh74
Opportunity for Dosing With AAV-SLB101 Following Treatment With AAVrh74 1200 AAV2 AAV1 AAV2.5 Redosing remains a major barrier to broader 800 NAb titer1 use of AAV-based therapies1: 400 • High systemic AAV doses induce robust and persistent NAb responses 0 AAV2 AAV1 AAV2.5 • Current immunomodulatory
Slide 11: Low AAV-SLB101 NAb Titers Detected in AAVrh74-Dosed Mice, Enabling Potential for Redosing
Low AAV-SLB101 NAb Titers Detected in AAVrh74-Dosed Mice, Enabling Potential for Redosing With AAV-SLB101 Low Anti-AAV-SLB101 Titers in AAVrh74 Dosed Mice Longitudinal Assessment of AAV-SLB101 NAbs Support the Opportunity For Redosing With AAV- rh74 NAb Titer AAV-SLB101 NAb Titer SLB101 15,000 AAV-S
Slide 12: Low Anti-AAV-SLB101 Titers Detected in NHPs and Patients With Duchenne Dosed With AAVrh74
Low Anti-AAV-SLB101 Titers Detected in NHPs and Patients With Duchenne Dosed With AAVrh74 Exploring if current immunomodulation strategies support redosing with AAV-SLB101 Day 30 Assessment Humans Dosed With of AAV-SLB101 NAbs AAVrh74 (Sera Samples) n=6 n=3 150,000 12,000 12000 9000 100,000 NAb Tite
Slide 13: Conclusions
Conclusions TAb and NAb assays for anti-AAV antibodies can be useful for defining patient eligibility and optimizing dosing strategies1 Understanding the strengths and limitations of anti-AAV antibody assays is critical for informing clinical trial patient selection, redosing feasibility, and interp
Slide 14: Acknowledgements
Acknowledgements Deborah Miller Kruti Patel Heather Medlin Marla Bazile Individuals with DMD and their Sharon McGonigle families & caregivers Sury Somanathan Nicolas Christoforou Prusthi Bhavsar If you would like to discuss opportunities to use AAV-SLB101, please contact Solid’s BD team at businessd