Sarepta Therapeutics : Oral P.107 Proud et al. One-year Data from ENDEAVOR Ph1B Trial of Del Mox in DMD pts

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One-year data from ENDEAVOR, a Phase 1b trial of delandistrogene moxeparvovec in patients with

DMD

Crystal M. Proud,1* Craig M. Zaidman,2 Craig M. McDonald,3 Stefanie Mason,4 Maitea Guridi,5 Shufang Wang,4 Carol Reid,6 Eddie Darton,4 Christoph Wandel,5 Sarah Lewis,4 Jyoti Malhotra,4 Danielle A. Griffin,4 Rachael A. Potter,4 Louise R. Rodino-Klapac,4 Jerry R. Mendell7,8

1Children's Hospital of the King's Daughters, Norfolk, VA, USA; 2Department of Neurology, WUSTL, Washington, MO, USA; 3UC Davis Health, Sacramento, CA, USA; 4Sarepta Therapeutics, Inc., Cambridge, MA, USA; 5F. Hoffmann-La Roche Ltd, Basel, Switzerland; 6Roche Products Ltd, Welwyn Garden City, UK; 7Center for Gene Therapy, Nationwide Children's Hospital, Columbus, OH, USA; 8The Ohio State University, Columbus, OH, USA

Acknowledgments and disclosures

Acknowledgments

• The authors would like to thank the patients and their families for their participation in ENDEAVOR, as well as the investigators and trial staff involved in ENDEAVOR
• This study was sponsored by Sarepta Therapeutics, Inc., Cambridge, MA, USA and funded by Sarepta Therapeutics, Inc., Cambridge, MA, USA and F. Hoffmann-La Roche Ltd, Basel, Switzerland
• Medical writing and editorial support were provided by Marketta Kachemov, PhD, of Nucleus Global, in accordance with Good Publication Practice (GPP) 2022 guidelines (https://www.ismpp.org/gpp-2022) and were funded by Sarepta Therapeutics, Inc., Cambridge, MA, USA and F. Hoffmann-La Roche Ltd, Basel, Switzerland
• These data are an encore of data first presented by CM Zaidman at 17th International Congress on Neuromuscular Diseases (ICNMD) 2022

Disclosures

• CMP participates on an advisory board and is a consultant for Biogen, Sarepta Therapeutics, AveXis/Novartis Gene Therapies, Genentech/Roche, and Scholar Rock; serves as a speaker for Biogen; is a principal investigator of studies sponsored by AveXis/Novartis Gene Therapies, AMO, Astellas, Biogen, CSL Behring, Fibrogen, PTC Therapeutics, Pfizer, Sarepta Therapeutics and Scholar Rock
• CMZ receives research support from and serves on an advisory board for Biogen, was a paid consultant for Optum, and has received research support from Novartis and speaker and consultant fees as well as support for attending meetings from Sarepta Therapeutics
• CMM served as a consultant on clinical trials of DMD for Astellas, Avidity Biosciences, Capricor Therapeutics, Catabasis, Edgewise Therapeutics, Entrada Therapeutics, Epirium Bio (formerly Cardero Therapeutics), FibroGen, Italfarmaco, Pfizer, PTC Therapeutics, Roche, Santhera Pharmaceuticals, and Sarepta Therapeutics. He reports honoraria for presentations from PTC Therapeutics, Sarepta Therapeutics, Solid Biosciences, Santhera Pharmaceuticals, Capricor Therapeutics, and Catabasis. He has received compensation for participation on advisory boards from PTC Therapeutics, Sarepta Therapeutics, Avidity Biosciences, Edgewise Therapeutics and Santhera Pharmaceuticals. He has received research support for clinical trials from Capricor Therapeutics, Catabasis, Italfarmaco, Pfizer, PTC Therapeutics, Santhera Pharmaceuticals and Sarepta Therapeutics, and reports grants from the U.S. Department of Defense, U.S. National Institutes of Health (NINDS), Parent Project Muscular Dystrophy and the National Institute on Disability, Independent Living, and Rehabilitation Research
• SM, SW, ED, SL, JM, DAG, and RAP are employees of Sarepta Therapeutics and may own stocks or have stock options
• MG and CW are employees of F. Hoffmann-La Roche Ltd. and have nothing to disclose
• CR is an employee of Roche Products Ltd and holds stock in F. Hoffman-La Roche Products Ltd
• LRRK is an employee of Sarepta Therapeutics, has received grant support from Sarepta Therapeutics and the Parent Project Muscular Dystrophy, and financial consideration from Sarepta Therapeutics and Myonexus Therapeutics (now acquired by Sarepta Therapeutics); in addition, she is a co-inventor of AAVrh74.MHCK7.SRP- 9001-dys technology
• JRM has received study funding from Sarepta Therapeutics and has a service agreement with Sarepta Therapeutics to provide training on ongoing studies. JRM is a co- inventor of AAVrh74.MHCK7.SRP-9001-dys technology

Objectives and overview

• ENDEAVOR (NCT04626674)1 is an open-label, Phase 1b study with a primary purpose to assess the expression and safety of intended commercial process delandistrogene moxeparvovec (SRP-9001) material in patients with DMD*
• We present safety, 1-year functional, and 12-week expression data from Cohort 1 of ENDEAVOR
• • A rigorous, well-matched,propensity-score-weighted EC cohort was developed as a pre-specified analysis for comparison with Cohort 1, prior to interim data extraction

*ENDEAVOR used a vector from a different source compared with prior delandistrogene moxeparvovec clinical trials. DMD, Duchenne muscular dystrophy; EC, external control.

1. ClinicalTrials.gov. NCT04626674 (Accessed March 2023).

What does this study

mean for the

DMD community?

Findings from Cohort 1 of ENDEAVOR suggest similar clinical benefit from the intended commercial process delandistrogene moxeparvovec material as has been observed in Phase 1 and 2 trials of clinical process material

Background

• Delandistrogene moxeparvovec is an investigational rAAV vector- based gene therapy, designed to compensate for missing dystrophin in DMD by delivering a transgene encoding SRP-9001 dystrophin, an engineered dystrophin protein that retains key functional domains of the wild-typeprotein1-3

*ITRs are required for genome replication and packaging. † PolyA signals the end of the transgene to the cellular machinery that transcribes (i.e. copies) it.

AAVrh74, adeno-associated virus rhesus isolate serotype 74; DMD, Duchenne muscular dystrophy; ITR, inverted terminal repeat; OH, hydroxide; polyA, polyadenylation; rAAV, recombinant adeno-associated virus; ssDNA, single-stranded DNA.

1. Asher DR, et al. Expert Opin Biol Ther. 2020; 20:263-274; 2. Zheng C and Baum BJ. Methods Mol Biol. 2008; 434:205-219; 3. Mendell JR, et al. JAMA Neurol. 2020; 77:1122-1131; 4. Chandler RJ and Venditti CP. Transl Sci Rare Dis. 2016; 1:73-89.

Study design

• ENDEAVOR is a two-part,open-label, Phase 1b study assessing the expression and safety of intended commercial process delandistrogene moxeparvovec material in five cohorts of male patients with DMD

Study design: Single IV infusion dose of 1.33x1014 vg/kg* of intended commercial process delandistrogene moxeparvovec material

Cohort 1† (ambulatory, ≥4 to

<8 years old)

Cohort 2†

(ambulatory,

≥8 to <18 years old)

Cohort 3†

(non-ambulatory)

Cohort 4† (ambulatory, ≥3 to

<4 years old)

Cohort 5a†

(ambulatory, ≥4 to

<9 years old)

Cohort 5b†

(non-ambulatory)

Screening:	Part 1:	Part 2:
Up to 31 days	12 weeks	Up to 5 years

				Long-termfollow-up period Week 260
Biopsy at	Biopsy at
baseline	Week 12

*Linear qPCR. † Only 1-year data for Cohort 1 are shown in this presentation; 1-year data for other cohorts are not yet available; genetic mutation criteria varied by cohort. DMD, Duchenne muscular dystrophy; IV, intravenous; qPCR, quantitative polymerase chain reaction.