Sarepta Therapeutics, Inc. · NASDAQ:SRPT
Sarepta Therapeutics — 23rd International Congress of the World Muscle Society 2018
27 slides from Sarepta Therapeutics's conference presentation, Oct 3, 2018
Slide 1: Precision Genetic Medicine for Neuromuscular Diseases
23rd International Congress of the World Muscle Society Mendoza, Argentina 4 October 2018 Precision Genetic Medicine for Neuromuscular Diseases Exhibit 99.2
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains "forward-looking statements." Any statements that are not statements of historical fact may be deemed to be forward-looking statements. Words such as “believe,” “anticipate,” “plan,” “expect,” “will,” “may,” “intend,” “prepare,” “look,” “potentia
Slide 3: Welcome and Introduction
Doug Ingram President and CEO Sarepta Therapeutics, Inc. Welcome and Introduction 23rd International Congress of the World Muscle Society
Slide 4: Clinical Update: AAVrh74.MHCK7.Micro-dystrophin Program
Jerry Mendell, MD The Ohio State University College of Medicine Paul D Wellstone Muscular Dystrophy Cooperative Research Center Nationwide Children’s Hospital Columbus, OH Clinical Update: AAVrh74.MHCK7.Micro-dystrophin Program 23rd International Congress of the World Muscle Society
Slide 5: Goal of Study was to Validate Pre-clinical Results
AAVrh74.MHCK7.Micro-dystrophin: Goal of Study 1 was to Validate Pre-clinical Results Expectations based on pre-clinical models AAVrh74 efficient transduction to all muscle types MHCK7 selective for cardiac and skeletal transgene muscle expression Widespread micro-dystrophin expression in all biopsie
Slide 6: Widespread Expression after Gene Delivery in mdx Mice
AAVrh74.MHCK7.Micro-dystrophin Widespread Expression after Gene Delivery in mdx Mice Dystrophin-positive Fibers (%) Wt 6 x 1014 vg/kg 2 x 1014 vg/kg 8 x 1013 vg/kg Fiber Expression (%) Sarepta Therapeutics Data on File. AAVrh74.MHCK7.Micro-dystrophin is investigational and not approved in Argentina.
Slide 7: Micro-dystrophin Clinical Trial Design
Micro-dystrophin Clinical Trial Design
Slide 8: Open-Label Trial Design
Open-Label Trial Design Cohort B 4 subjects 4-7 years of age Inclusion criteria Confirmed DMD mutation Negative for AAVrh74 antibodies ClinicalTrials.gov Identifier: NCT03375164. Sarepta Therapeutics Data on File. AAVrh74.MHCK7.Micro-dystrophin is investigational and not approved in Argentina.
Slide 9: Cohort B (4-7 Years of Age) Endpoints
Cohort B (4-7 Years of Age) Endpoints Primary endpoint Safety Secondary endpoints Change in micro-dystrophin expression pre- vs post-treatment Decrease in CK 100-meter timed test (100 m) North Star Ambulatory Assessment (NSAA; 10-meter timed test included) Timed up and go (TUG) Ascend and descend 4
Slide 10: Subject Demographics at Baseline
Subject Demographics at Baseline Subject Age (years) CK Levels at Baseline (U/L) 1 5 20,691 2 4 23,414 3 6 34,942 4 4 29,210 ClinicalTrials.gov Identifier: NCT03375164. Sarepta Therapeutics Data on File. AAVrh74.MHCK7.Micro-dystrophin is investigational and not approved in Argentina.
Slide 11: Subject 4: Micro-dystrophin Data
Subject 4: Micro-dystrophin Data
Slide 12: Robust Micro-dystrophin Expression in Gastrocnemius in Subject 4
Robust Micro-dystrophin Expression in Muscle Fibers From the Gastrocnemius in Subject 4 Subject Mean Intensity Percentage of Dystrophin-positive Fibers 4 160.0% 96.2% Normal Control Micro-dystrophin Expression (IHC) Subject 4 Post-treatment Pre-treatment ClinicalTrials.gov Identifier: NCT03375164. S
Slide 13: Micro-dystrophin Gene Therapy Upregulates DAPC Proteins in Subject 4
Normal Control Pre-treatment Expression of β-sarcoglycan in Muscle Fibers From the Gastrocnemius of Subject 4 (IHC) Post-treatment Micro-dystrophin Gene Therapy Upregulates DAPC Proteins in Subject 4 ClinicalTrials.gov Identifier: NCT03375164. Sarepta Therapeutics Data on File. AAVrh74.MHCK7.Micro-d
Slide 14: Detection of Micro-dystrophin by Western Blot in Subject 4
Detection of Micro-dystrophin Expression by Western Blot Post-treatment in Subject 4 Western Quantitation Method Mean Micro-dystrophin Expression vs Normal Sarepta 182.7% (not adjusted for fat and fibrotic tissue) Nationwide 222.0% (adjusted for fat and fibrotic tissue) *Samples diluted 1:4 as ULOQ
Slide 15: Micro-dystrophin Summary: All Subjects (n=4)
Micro-dystrophin Summary: All Subjects (n=4)
Slide 16: Robust Micro-dystrophin Expression in All 4 Subjects
Robust Micro-dystrophin Expression in Muscle Fibers from the Gastrocnemius in All 4 Subjects Intensity Percentage of Dystrophin-positive Fibers Mean (n=4) 96.0% 81.2% Normal Control Subject 2 Subject 1 Subject 3 Micro-dystrophin Expression (IHC) Subject 4 Post-treatment Pre-treatment ClinicalTrials.
Slide 17: Western Blot Detection in All 4 Subjects
Detection of Micro-dystrophin Expression by Western Blot Post-treatment in All 4 Subjects Western Quantitation Method Mean Micro-dystrophin Expression (N=4) vs Normal Sarepta 74.3% (not adjusted for fat and fibrotic tissue) Nationwide 95.8% (adjusted for fat and fibrotic tissue) * p-Tyr phosphotyros
Slide 18: Expression Supported by Vector Genome Count
Robust Micro-dystrophin Expression is Supported by Vector Genome Count Intensity Percentage of Dystrophin-positive Fibers Mean (n=4) 96.0% 81.2% Sarepta (not adjusted for fat/fibrosis) Nationwide (adjusted for fat/fibrosis) Mean (n=4) 74.3% 95.8% Vector Copies/μg DNA Copies per Nucleus Mean (n=4) >1
Slide 19: Clinical Data Summary (n=4)
AAVrh74.MHCK7.Micro-dystrophin: Clinical Data Summary (n=4)
Slide 20: Summary of Clinical Data: Change from Baseline
ClinicalTrials.gov Identifier: NCT03375164. Sarepta Therapeutics Data on File. AAVrh74.MHCK7.Micro-dystrophin is investigational and not approved in Argentina. Summary of Clinical Data Change from Baseline to Last Assessment Subject Assessment NSAA (∆) Time to Rise (sec) 4 Stairs Up (sec) 100 m (sec
Slide 21: Patient Video: Rise From Floor
Patient Video: Rise From Floor — Subject 4 Baseline 90 days post-treatment 23° INTERNATIONAL CONGRESS OF THE WORLD MUSCLE SOCIETY
Slide 22: Patient Video: 4-stair Climb
Patient Video: 4-stair Climb — Subject 1 Baseline 270 days post-treatment 23° INTERNATIONAL CONGRESS OF THE WORLD MUSCLE SOCIETY
Slide 23: Safety (n=4)
Safety (n=4) No serious adverse events in this study 3 subjects had elevated γ‐glutamyl transpeptidase, which resolved with steroid treatment within a week No other clinically significant laboratory findings Subjects had transient nausea generally within the first week coincident with increased ster
Slide 24: Summary
Summary All 4 treated subjects are doing well Biomarkers show large magnitude of effect within 3 months (CK and dystrophin) “Very early days" but initial functional data show improvement consistent with biomarker data Early results show these boys performing in a manner unexpected for the typical bo
Slide 25: Patient Home Videos: Activities of Daily Living
Patient Home Videos: Activities of Daily Living 60 days post-treatment (Pt 1) 30 days post-treatment (Pt 2) 60 days post-treatment (Pt 3) 75 days post-treatment (Pt 4) 23° INTERNATIONAL CONGRESS OF THE WORLD MUSCLE SOCIETY 25
Slide 26: Question and Answer
Question and Answer
Slide 27: Thank You
Thank You o 3 < = < KH Qa lw [aa < YN §
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