Slide 1: Clinical Update: Results from 30 mg/kg Cohort of MOMENTUM Study of SRP-5051
Doug Ingram President and CEO May 3, 2021 8:30 a.m. ET Clinical Update: Results from 30 mg/kg Cohort of MOMENTUM Study of SRP-5051 for Duchenne Muscular Dystrophy Gilmore o’neill, mb, mmsc Executive Vice President, R&D and Chief Medical Officer EXHIBIT 99.2 Sarepta therapeutics inc 2021 all rights r
Slide 2: Welcome and Introduction
Welcome and Introduction Doug Ingram President and CEO Sarepta therapeutics inc 2021 all rights reserved 2 logo
Slide 3: Forward-Looking Statements
Forward-Looking Statements This presentation contains "forward-looking statements." Any statements contained in this presentation that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends,"
Slide 4: Clinical Update: MOMENTUM Multiple-Ascending Dose Study of SRP-5051 for Duchenne
Clinical Update: MOMENTUM Multiple- Ascending Dose Study of SRP-5051 for Duchenne Muscular Dystrophy Gilmore O’Neill, MB, MMSC Executive Vice President, R&D and Chief Medical Officer Sarepta therapeutics inc 2021 all rights reserved 4 logo
Slide 5: Duchenne Muscular Dystrophy (DMD)
Duchenne Muscular Dystrophy (DMD) DMD affects approximately 1 in 3,500-5,000 males worldwide1 DMD is a rare, fatal neuromuscular genetic disease inherited in an X-linked recessive pattern2 Muscle weakness becomes increasingly noticeable by age 3 to 5, and most patients use a wheelchair by the time t
Slide 6: Sarepta's Proprietary PMO Technology
Sarepta’s Proprietary PMO Technology Phosphorodiamidate morpholino oligomer (PMO) technology Specificity: Enhanced affinity for targeting pre-mRNA for precise binding to the selected RNA target Stability: Highly resistant to degradation by enzymes Versatility: Ability to rapidly design and construct
Slide 7: Sarepta's Proprietary PMO Technology
Sarepta’s Proprietary PMO Technology Phosphorodiamidate morpholino oligomer (PMO) technology Specificity: Enhanced affinity for targeting pre-mRNA for precise binding to the selected RNA target Stability: Highly resistant to degradation by enzymes Versatility: Ability to rapidly design and construct
Slide 8: Natural History Genotype/Phenotype Correlations Predict Low Dystrophin Can Mitigate Phenotype
Natural History Genotype/Phenotype Correlations Predict that Even Low Dystrophin Quantities can Significantly Mitigate Duchenne Phenotype Integrated study of 100 patients with Xp21 linked muscular dystrophy using clinical, genetic, immunochemical, and histopathological data. Part 1. Trends across th
Slide 9: Peptide-conjugated PMO (PPMO): Next-generation Technology for Enhanced PMO Tissue Penetration
Enhances PMO Conjugated peptide greatly increases cell penetration Could potentially lead to more efficient dosing and greater benefit for patients Non-clinical data demonstrates delivery of PPMOs to unique muscle types (e.g., heart) Peptide-conjugated PMO (PPMO): Next-generation Technology for Enha
Slide 10: Clinical Update: SRP-5051 MOMENTUM Results from 30 mg/kg Cohort
Clinical Update: SRP-5051 MOMENTUM Multiple-Ascending Dose Study, Results from 30 mg/kg Cohort Sarepta therapeutics inc 2021 all rights reserved 10
Slide 11: MOMENTUM Part A: Designed to Assess Safety and PK/PD of Multiple Doses of SRP-5051
SRP-5051-201 MOMENTUM PART A: Designed to Assess Safety and PK/PD of Multiple Doses of SRP-5051 in Plasma and Muscle of Duchenne Patients Primary Outcome Measure Safety Secondary Outcome Measures Including: PK plasma concentration of SRP-5051 Change from baseline at 12 weeks: Muscle concentration of
Slide 12: MOMENTUM: 30 mg/kg Patient Demographics at Baseline
SRP-5051-201 MOMENTUM: 30 mg/kg Patient Demographics at Baseline Sarepta therapeuticncs inc 2021 all rights reserved 12 chart 30 mgkgmonth x4 age years weight kg doses at the time of biopsypatient 1patient 2patient 3patient 4 18 7 15 1 6 57 9 25 51 52 5 5 3 3 3
Slide 13: SRP-5051 30 mg/kg Drove 18x Increase in Exon Skipping vs. Eteplirsen
SRP-5051-201 MOMENTUM: SRP-5051 30 mg/kg Arm at 12 Weeks Drove 18x Increase in Exon Skipping vs. Eteplirsen at 24 Weeks1 Eteplirsen 30 mg/kg >4x increase in exon skipping in the 30mg/kg arm vs. 20 mg/kg at 12 weeks N=16 NA2 N=16 1.Comparative data produced with the same analytical methods using biop
Slide 14: SRP-5051 30 mg/kg Drove 8x Increase of Dystrophin vs. Eteplirsen
SRP-5051-201 MOMENTUM: SRP-5051 30 mg/kg Arm at 12 Weeks Drove 8x Increase of Dystrophin vs. Eteplirsen at 24 Weeks1 ~2x increase in dystrophin in the 30 mg/kg arm vs. 20 mg/kg at 12 weeks N=16 NA2 N=16 Eteplirsen 30 mg/kg Dystrophin (%), mean + se Western Blot 1.Comparative data produced with the s
Slide 15: Exon Skipping and Dystrophin Increase Over Time, as Seen in PROMOVI with Eteplirsen
Strong Evidence that Exon Skipping and Dystrophin Increase Over Time, as Seen in PROMOVI with Eteplirsen Exon Skipping Dystrophin** N=16 N=32 N=14 N=16 N=16 N=31 N=14 N=16 Mean % Normal Dystrophin Change from Baseline (Mean + SE) Time (Weeks) Time (Weeks) Mean Exon 51 (% Skipping) ddPCR* Change from
Slide 16: Model Assumes PPMO Trajectory Similar to Dystrophin Increase in PROMOVI
Model assumes that trajectory of PPMO will be similar to the increase of dystrophin that we observed in PROMOVI longitudinal study Predictions are based on dystrophin turnover model using PROMOVI and SRP-5051 data at 30 mg/kg and predicting dystrophin production over time Predicted Dystrophin Trajec
Slide 17: Predicted Dystrophin Trajectory of >10% Expression Achievable with Monthly Dosing
Predicted Dystrophin Trajectory of >10% Expression is Achievable Over Time with Monthly Dosing of SRP-5051 Dystrophin levels from 30mg/kg 5051-201 data Red numbers are predicted values Reference: Dystrophin estimated half life in the turnover model 136 days based on PROMOVI data 60 days in skeletal
Slide 18: Safety and Clinical Summary
Safety and Clinical Summary Sarepta therapeutics inc 2021 all rights reserved 18
Slide 19: MOMENTUM: Safety Experience Adverse Event Summary
SRP-5051-201 MOMENTUM: Safety Experience Adverse Event Summary Severe and serious TEAEs in the 30 mg/kg cohort are summarized in the next slide Sarepta therapeutics inc 2021 all rights reserved 19 chart Subjects with at least one4 mg kg N3 10 mg kg N3 20 mg kg N5 30 mg kg N7 Overall N18 Treatment-em
Slide 20: MOMENTUM: Serious TEAEs at 30 mg/kg
SRP-5051-201 momentum: Serious TEAEs at 30 mg/kg * Severity is based on CTCAE laboratory value. None of the SAEs were life-threatening, and both patients remained asymptomatic Onset day: interval (days) from last dose Sarepta therapeutics inc 2021 all rights reserved 20 Patient Preferred Term Severi
Slide 21: MOMENTUM: Safety Summary
SRP-5051-201 MOMENTUM: Safety Summary Hypomagnesemia is a newly identified risk in the SRP-5051 program Most cases were mild and asymptomatic with some serious cases occurring prior to the implementation of serum monitoring and magnesium repletion Analysis of clinical and nonclinical studies (serum
Slide 22: MOMENTUM: Clinical Summary
SRP-5051-201 MOMENTUM: Clinical Summary 30 mg/kg arm at 12 weeks dosing drove 18x increase in exon skipping vs. eteplirsen at 24 weeks dosing >4x increase in exon skipping in the 30 mg/kg arm vs. 20 mg/kg at 12 weeks 30mg/kg arm at 12 weeks dosing drove 8x increase in dystrophin vs. eteplirsen at 24
Slide 23: Next Steps for SRP-5051 Program
Next Steps for SRP-5051 Program Sarepta therapeutics inc 2021 all rights reserved 23
Slide 24: Next Steps
Next Steps Part A of 5051-201(MOMENTUM) is now complete Part B of MOMENTUM is intended to be the pivotal trial in the US Protocol is being amended to mitigate the hypomagnesemia risk Implementation of magnesium supplementation with appropriate monitoring Will engage FDA prior to the initiation of Pa
Slide 25: Question and Answer
Question and Answer Sarepta therapeutics inc 2021 all rights reserved 25
Slide 26: logo
Sarepta therapeutics inc 2021 all rights reserved 26 logo