Sarepta Therapeutics, Inc. · NASDAQ:SRPT
Sarepta Therapeutics — Technical Presentation (2020)
10 slides from Sarepta Therapeutics's technical presentation, 2020
Slide 1: SRP-5051, a Peptide-conjugated PMO, Increases Exon Skipping, Dystrophin Production, and Grip Strength
OTS 2020 SRP-5051, a Peptide-conjugated PMO, Increases Exon Skipping, Dystrophin Production, and Grip Strength in a Humanized Mouse Model of Duchenne Muscular Dystrophy Leslie C.L. Wu, John R. Hadcock, Miralem Prijic, Jenna Wood, Kamela Bellovoda, Bryan Mastis, Jianbo Zhang, Sam Foley, Mohammad Shad
Slide 2: Disclosures
Disclosures • All authors are employees of Sarepta Therapeutics, Inc. and may own stock in the company • The study was funded by Sarepta Therapeutics, Inc. • Editorial support was provided by Eloquent Scientific Solutions and was funded by Sarepta Therapeutics, Inc. • Products are investigational on
Slide 3: Introduction
Introduction • Duchenne muscular dystrophy (DMD) is a severe, X-linked neuromuscular disease caused by mutations in the dystrophin gene1 − Dystrophin mutations leading to deletions flanking exon 51 account for 13% of all DMD patients2 • Phosphorodiamidate morpholino oligomers (PMOs) are an effective
Slide 4: Humanized DMD Transgenic Mouse Allows Assessment of SRP-5051 Pharmacology
Humanized DMD Transgenic Mouse Allows Assessment of SRP-5051 Pharmacology in a Preclinical Disease-Relevant Model of DMD hDMDdel52/mdx mice Treatment with SRP-5051 hDMD del52/mdx mouse Dystrophin 49 50 51 53 54 49 50 53 54 ɑ-actinin human DMD transgene with exon 52 deleted by gene editing SRP-5051 i
Slide 5: Single-dose SRP-5051 Increased Exon Skipping and Dystrophin Protein
Single-dose SRP-5051 Increased Exon Skipping and Dystrophin Protein in hDMDdel52/mdx Mice Dose response (single dose): 6-8 w/o male hDMDdel52/mdx mice were injected with SRP-5051 IV at indicated doses and analyzed 7 post dose HEART BICEPS QUADRICEPS Exon 51 skipping (%) 100 *** 100 100 **** 80 ****
Slide 6: Exon Skipping was Sustained Weeks After Single Dose SRP-5051
Exon Skipping was Sustained 4 Weeks After Single Dose SRP-5051 and Remained Detectable to 12 Weeks in hDMDdel52/mdx Mice Time course (single dose): 6-8 w/o male hDMDdel52/mdx mice were injected with SRP-5051 at 100 mg/kg IV; exon skipping and dystrophin were measured 4, 8, and 12 weeks post-dose HEA
Slide 7: Repeated SRP-5051 Dosing Resulted in Increased Exon Skipping and Accumulation of Dystrophin
Every 4 Weeks Repeated SRP-5051 Dosing Resulted in Increased Exon Skipping and Accumulation of Dystrophin in hDMDdel52/mdx Mice Time course (repeated doses): 6-8 w/o male hDMDdel52/mdx mice were injected with SRP-5051 100 mg/kg IV every 4 weeks and analyzed 4 weeks after 1 dose, 3 doses, or 5 doses
Slide 8: Single and Repeated SRP-5051 Dosing Restored Grip Strength to Wild Type Levels
Single and Repeated SRP-5051 Dosing Every 4 Weeks Restored Grip Strength in hDMDdel52/mdx Mice to Wild Type Levels Time course (repeated doses): hDMDdel52/mdx mice were injected with SRP-5051 100 mg/kg IV every 4 weeks and analyzed every 4 weeks GRIP STRENGTH P<0.0001 P<0.0001 P<0.0001 P=0.0003 P<0.
Slide 9: Conclusions
Conclusions • This is the first-time examination of the pharmacology of SRP-5051, a peptide conjugated PMO, in a disease- relevant, humanized mouse model of DMD • A single dose of SRP-5051 resulted in sustained exon 51 skipping and human dystrophin levels in muscle and heart, which was associated wi
Slide 10: Questions?
Questions? Please direct any questions you may have to the Sarepta Medical Information team at [email protected] 10