Sarepta Therapeutics, Inc. · NASDAQ:SRPT

Sarepta Therapeutics — Technical Presentation (February 2019)

21 slides from Sarepta Therapeutics's technical presentation, Feb 27, 2019

  1. Slide 1: Clinical update: MYO-101 for LGMD type 2e

    Cambridge, MA February 27, 2019 Clinical update: MYO-101 for LGMD type 2e Clinical update: MYO-101 for LGMD type 2e Cambridge, MA February 27, 2019 SAREPTA THERAPEUTICS Exhibit 99.4

  2. Slide 2: 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,"

  3. Slide 3: Clinical Update: MYO-101 Beta-Sarcoglycanopathy Gene Therapy program

    Louise Rodino-Klapac, Ph.D. Senior Vice President, Gene Therapy Sarepta Therapeutics, Inc. Clinical Update: MYO-101 Beta-Sarcoglycanopathy Gene Therapy program Limb-Girdle Muscular Dystrophy Type 2E Clinical Update: MYO-101 Beta-Sarcoglycanopathy Gene Therapy program Limb-Girdle Muscular Dystrophy T

  4. Slide 4: LGMDs Are Devastating Muscular Dystrophies

    LGMDs Are Devastating Muscular Dystrophies monogenic, rare neuromuscular diseases that affect hundreds of thousands globally LGMDs are progressive, debilitating muscle-wasting diseases with no therapies1,2 Affect males and females equally Affect skeletal muscle Affect cardiac muscle in some types El

  5. Slide 5: Each of the Myonexus LGMDs is Caused by a Monogenic Defect

    Each of the 5 Myonexus LGMDs is Caused by a monogenic defect resulting in the lack of one of the Proteins Comprising the Dystrophin-associated Protein Complex Sarcoglycans prevent muscle damage during contraction All 4 functional sarcoglycans must be present to form a functional sarcoglycan complex

  6. Slide 6: β-sarcoglycan Is the Fundamental Subunit of the Sarcoglycan Complex

    Each of the 5 Myonexus LGMDs is Caused by a monogenic defect resulting in the lack of one of the Proteins Comprising the Dystrophin-associated Protein Complex β-sarcoglycan (SGCB) Is the Fundamental Subunit of the Sarcoglycan Complex (SGC) Sarcoglycans prevent muscle damage during contraction All 4

  7. Slide 7: LGMD2E Phase I/II Study: Cohort 1 (n=3)

    LGMD2E Phase I/II Study: Cohort 1 (n=3) LGMD2E Phase I/II Study: Cohort 1 (n=3) SAREPTA THERAPEUTICS Up to 9 subjects with LGMD

  8. Slide 8: LGMD Type 2E Open-label Trial Design

    LGMD TYPE 2E Open-label Trial Design Up to 9 subjects with LGMD Cohort 1: 3 subjects; 4-15 years of age, 5x1013 vg/kg AAVrh74.MHCK7.SGCB Inclusion criteria A confirmed SGCB mutation in both alleles Negative for AAVrh74 antibodies >40% of Normal 100 meter walk test 60-day muscle biopsy Prednisone 1 d

  9. Slide 9: Endpoints in the LGMD2E Study

    Endpoints in the LGMD2E Study Primary endpoints Expression: ≥20% b-sarcoglycan positive fibers Safety Secondary endpoints, including: Decrease in CK Functional endpoints Endpoints in the LGMD2E Study Primary endpoints Expression: ≥20% b-sarcoglycan positive fibers Safety Secondary endpoints, includi

  10. Slide 10: Pre-clinical models correlated expression and function

    Pre-clinical models correlated expression and function ≥20 percent expression leads to increased function Pretreatment Post Treatment Function WT BSG KO AAVrh74.hSGCB 5x1012 vg/kg 300 200 100 0 Specific Force (mN/mm2) Pre-clinical models correlated expression and function ≥20 percent expression lead

  11. Slide 11: LGMD2E Study Results: Cohort 1 (n=3)

    LGMD2E Study RESULTS: Cohort 1 (n=3) LGMD2E Study RESULTS: Cohort 1 (n=3) SAREPTA THERAPEUTICS

  12. Slide 12: LGMD2E Subject Demographics at Baseline

    LGMD2E Subject Demographics at Baseline ClinicalTrials.gov Identifier: NCT03652259. Subject Age (years) Weight (kg) CK Levels at Baseline (U/L) 1 13 55 10,727 2 4 17 12,826 3 13 50 10,985 LGMD2E Subject Demographics at Baseline Subject Age (years) Weight (kg) CK Levels at Baseline (U/L) 1 2 3 13 4 1

  13. Slide 13: Robust b-Sarcoglycan Expression in Muscle Biopsies in All Subjects

    Robust b-Sarcoglycan Expression in Muscle Biopsies in All 3 Subjects at a dose of 5x1013 vg/kg Percentage of SGCB-positive Fibers Intensity Mean (n=3) 51% 47% Normal Control Subject 2 Subject 1 Subject 3 b-Sarcoglycan Expression (IHC) Post-treatment Pre-treatment Robust b-Sarcoglycan Expression in M

  14. Slide 14: Robust b-Sarcoglycan Expression in Muscle Biopsies in All Subjects

    Robust b-Sarcoglycan Expression in Muscle Biopsies in All 3 Subjects at a dose of 5x1013 vg/kg Subject Percentage of SGCB-Positive Fibers Mean Intensity 1 63% 47% 2 49% 57% 3 42% 38% Mean 51% 47% Robust b-Sarcoglycan Expression in Muscle Biopsies in All 3 Subjects at a dose of 5x1013 vg/kg SubjectPe

  15. Slide 15: Robust and Consistent b-Sarcoglycan Expression by Western Blot

    ROBUST AND CONSISTENT b-Sarcoglycan EXPRESSION in All 3 Subjects AS MEASURED by Western Blot Post-treatment Subject Mean Beta-Sarcoglycan Expression (N=3) vs Normal 1 34.7% 2 39.2% 3 34.5% Mean 36.1% The gene transfer delivers full length b-sarcoglycan ROBUST AND CONSISTENT b-Sarcoglycan EXPRESSION

  16. Slide 16: Optimized Vector and Promoter Provided Robust Expression at 5x10^13 vg/kg

    THE OPTIMIZED VECTOR AND PROMOTER PROVIDEd ROBUST EXPRESSION AT 5x1013 vg/kg Percentage of Beta-Sarcoglycan-positive Fibers Intensity Mean (n=3) 51% 47% Percent of Normal Mean (n=3) 36.1% Vector Copies/μg DNA Copies per Nucleus Mean (n=3) 8.4E04 0.60 Beta-Sarcoglycan Expression (IHC) Vector Genome N

  17. Slide 17: b-Sarcoglycan Expression Upregulated Sarcoglycan Complex

    Robust b-Sarcoglycan Expression significantly UpregulateD Sarcoglycan Complex at a dose of 5x1013 vg/kg Normal Control Subject 2 Subject 1 Subject 3 Alpha-Sarcoglycan Expression (IHC) Post-treatment Pre-treatment Robust b-Sarcoglycan Expression significantly UpregulateD Sarcoglycan Complex at a dose

  18. Slide 18: 90% Mean Reduction of Creatine Kinase Levels

    90% Mean reduction of Creatine Kinase (CK) Levels observed with b-Sarcoglycan GENE Therapy ClinicalTrials.gov Identifier: NCT03652259 Subject Age (years) CK Levels at Baseline (U/L) CK Levels at Last Visit (U/L) 1 13 10,727 1135 2 4 12,826 2159 3 13 10,985 320 90% Mean Reduction in CK 90% Mean reduc

  19. Slide 19: Steroids had no impact on CK Levels in prior LGMD 2d study

    Steroids had no impact on CK Levels in A PRIOR, LOWER DOSE, NON-SYSTEMIC LGMD 2d study ClinicalTrials.gov Identifier: NCT01976091 Subject Age (years) CK Levels at Baseline (U/L) CK Levels at Day 90 (U/L) 1* 49 440 336 2 11 5191 4680 3 15 4722 4709 4 10 16654 21740 5 13 2500 3912 6 9 5734 7547 Mean 1

  20. Slide 20: Safety (n=3)

    Safety (n=3) All patients doing well, patients 1,2: 90 days follow up, patient 3: 60 days follow up Two patients had elevated liver enzymes, one of which was designated a serious adverse event (SAE), as the patient had associated transient increase in bilirubin Both events occurred when the patients

  21. Slide 21: Clinical update: MYO-101 for LGMD type 2e

    Cambridge, MA February 27, 2019 Clinical update: MYO-101 for LGMD type 2e Clinical update: MYO-101 for LGMD type 2e Cambridge, MA February 27, 2019 SAREPTA THERAPEUTICS

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