Slide 1: Solid Biosciences
Solid Biosciences Genevieve A. Laforet, MD, PhD Vice President, Clinical R&D 2019 ANNUAL 28 June 2019 CONFERENCE
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, which involve a number of risks and uncertainties. These forward-looking statements include all matters that are not historical facts and, wi
Slide 3: Presentation Overview
Presentation Overview • Introduction to Solid Biosciences • Background on dystrophin • Gene transfer for the treatment of Duchenne • Solid’s SGT-001 microdystrophin gene therapy program and the IGNITE DMD clinical trial • SGT-001 manufacturing © 2019 Solid Biosciences 3
Slide 4: Purpose-Built to Solve Duchenne Muscular Dystrophy (DMD)
Purpose-Built to Solve Duchenne Muscular Dystrophy (DMD) 360-Degree Differentiated Scalable Approach Lead Gene Manufacturing Address all Transfer Process facets of DMD Program Meet clinical and Data from second commercial needs dose cohort later this year © 2019 Solid Biosciences 4
Slide 5: Solid Is Addressing the Full Spectrum of Duchenne
Solid Is Addressing the Full Spectrum of Duchenne CORRECTIVE THERAPIES DISEASE-MODIFYING THERAPIES Gene therapy to address the Small molecules and biologics to genetic cause of DMD address disease mechanisms DISEASE UNDERSTANDING ASSISTIVE DEVICES Biomarkers and endpoints to Technology to improve de
Slide 6: The Importance of Dystrophin
The Importance of Dystrophin © 2019 Solid Biosciences 6
Slide 7: Dystrophin Function in Healthy Muscle
Dystrophin Function in Healthy Muscle HEALTHY MUSCLE • Dystrophin protects the muscle from damage and stabilizes Muscle Membrane critical dystrophin- associated proteins Dystrophin Myofibril Actin Visual representation only © 2019 Solid Biosciences 7
Slide 8: Dystrophin is Missing in DMD Muscle
Dystrophin is Missing in DMD Muscle DYSTROPHIC MUSCLE • In DMD, mutations in the dystrophin gene result in the absence of functional dystrophin protein Muscle Membrane • Muscle fibers become damaged, cannot be repaired or replaced and are taken over Myofibril by fat and scar tissue Actin Visual repr
Slide 9: Gene Transfer to Address the Genetic Cause of DMD
Gene Transfer to Address the Genetic Cause of DMD TREATED MUSCLE • Gene transfer brings instructions to the cell to make a new kind of dystrophin designed Muscle Membrane to replace the missing dystrophin protein Microdystrophin Myofibril Actin Visual representation only © 2019 Solid Biosciences 9
Slide 10: Microdystrophin Gene Transfer
Corrective Therapies Microdystrophin Gene Transfer © 2019 Solid Biosciences 10
Slide 11: What Is Gene Transfer For DMD?
What Is Gene Transfer For DMD? Gene transfer for DMD is made The combined product is then up of three essential elements: given to the patient 1 Gene 33 Vector Carries the gene 2 Promoter Controls expression © 2019 Solid Biosciences 11
Slide 12: Each Component of SGT-001 Was Carefully Selected
Each Component of SGT-001 Was Carefully Selected Restore key functions SGT-001 Transgene of a complex protein microdystrophin gene Expression in skeletal Promoter CK8 promoter and heart muscle Targets skeletal and Vector AAV9 vector heart muscle © 2019 Solid Biosciences 12
Slide 13: SGT-001 AAV-Mediated Microdystrophin Gene Therapy
SGT-001 AAV-Mediated Microdystrophin Gene Therapy Microdystrophin Microdystrophin Transgene Protein AAV9 . Visual representation only. © 2019 Solid Biosciences 13
Slide 14: Features of SGT-001 Microdystrophin
Features of SGT-001 Microdystrophin Full Length Dystrophin Protein SGT-001 Microdystrophin Protein • SGT-001 selection based on more than 30 years of research; confirmed through comparison experiments by Solid Visual representation only. © 2019 Solid Biosciences 14
Slide 15: Animal Studies Show SGT-001 Microdystrophin is Made Selectively in Muscle
Animal Studies Show SGT-001 Microdystrophin is Made Selectively in Muscle Target Tissue Non-target Tissue SGT-001 Treated SGT-001 Treated Diaphragm 100% 50% 25% 10% 0% Liver 100% 50% 25% 10% 0% Microdystrophin Microdystrophin Dystrophin Dystrophin Dose (vg/kg) Dose (vg/kg) 0 1E14 2E14 1E13 0 1E14 2E
Slide 16: SGT-001 Microdystrophin with nNOS Binding Domain Showed Greater Improvements in Muscle Strength
SGT-001 Microdystrophin with nNOS Binding Domain Showed Greater Improvements in Muscle Strength in a Mouse Model of DMD SGT-001 treament led to force generation levels comparable to those in wild-type mice Specific diaphragm force 6 months post-treatment. Data shown as mean ± SEM. n=5-7 per group. ©
Slide 17: Microdystrophin Expression Lasts at Least 2.5 years in an Animal Model of DMD
Microdystrophin Expression Lasts at Least 2.5 years in an Animal Model of DMD 1 Month 3 Months 24 Months 30 Months Hakim et al. American Society of Gene and Cell Therapy (ASGCT), 2018. © 2019 Solid Biosciences 17
Slide 18: IGNITE DMD
SGT-001 Clinical Program IGNITE DMD © 2019 Solid Biosciences 18
Slide 19: SGT-001 Phase I/II Clinical Study Ongoing
SGT-001 Phase I/II Clinical Study Ongoing 12 months primary endpoint Cohort 1 DSMB Cohort 2 DSMB Observation Started at 5E13 vg/kg Escalated to 2E14 vg/kg Screening, Baseline Ambulatory & children, Matched control group SGT-001 Randomization aged 4-11 1:1 and Non-ambulatory (n=16 to 32) adolescents,
Slide 20: IGNITE DMD: Study Status
IGNITE DMD: Study Status 2H MAY 2019 MAR 2019 FEB 2019 Data from second cohort 2019 Announced dosing of first expected later this year Necessary steps were patient in second cohort completed to dose escalate (2E14 vg/kg) and initiation Announced preliminary SGT-001 to 2E14 vg/kg in a of clinical tri
Slide 21: Producing SGT-001
Manufacturing Producing SGT-001 © 2019 Solid Biosciences 21
Slide 22: Addressing the DMD Gene Therapy Supply Challenge
Addressing the DMD Gene Therapy Supply Challenge ( )( HIGH PATIENT NEED HIGH ) ( ) AVERAGE PATIENT WEIGHT HIGH DOSES SIGNIFICANT SUPPLY NEEDS Solid Manufacturing Capability • Successfully scaled up to 250L in suspension and produced multiple batches • Each 250L batch can dose multiple patients • Cre
Slide 23: Thank you!
Thank you! @SolidBioDMD #TogetherWeAreSolid #PatientPowereed © 2019 Solid Biosciences 23