Sarepta Therapeutics, Inc. · NASDAQ:SRPT
Sarepta Therapeutics — 2025 American Society of Gene & Cell Therapy Conference
17 slides from Sarepta Therapeutics's conference presentation, 2025
Slide 1: Cardiovascular Investigation of SRP-9005 in Non-Human Primates
Cardiovascular Investigation of SRP-9005 (AAVrh74.MHCK7.hSGCG) in Non-Human Primates: SCAN THE QR CODE The QR code is intended to provide scientific information for individual A Gene Therapy for Limb-Girdle reference, and the information should not be altered or reproduced in any way. Muscular Dystr
Slide 2: Disclosures and acknowledgments
Disclosures and acknowledgments • SB, LL, KH, RS, WX, MG, AA, LR-K, RP: • This study and editorial support were funded All authors are employees of by Sarepta Therapeutics, Inc. Editorial support Sarepta Therapeutics, Inc., and may own was provided by Eloquent Scientific Solutions stock/options in t
Slide 3: Introduction (1/2)
Introduction (1/2) • LGMD2C/R5 is a rare and progressive neuromuscular disorder caused by pathogenic variants in the γ-sarcoglycan gene that leads to SGCG deficiency with consequent muscle weakness and atrophy1 • LGMD2C/R5 is often associated with cardiac impairment or cardiomyopathy that may presen
Slide 4: Introduction (2/2)
Introduction (2/2) • SRP-9005, an investigational gene therapy, utilizes an AAVrh74 vector delivering a codon-optimized full-length human SGCG transgene to restore functional SGCG SRP-9005: Self-complementary AAV vector expression and reduce LGMD2C/R5 pathogenesis1 rAAVrh74 MHCK7 promoter hSGCG cDNA
Slide 5: Study design, methods, and objective
Study design, methods, and objective • ECHO was performed at baseline, Weeks 6 and 12 to evaluate cardiac systolic and diastolic function • ECG was performed at baseline and Week 12 to determine Saline IV electrophysiological response to SRP-9005 • The effect of SRP-9005 on the cardiac injury biomar
Slide 6: Echocardiography (1/3)
RESULTS Echocardiography (1/3) From baseline to Week 12, SRP-9005 had no effect on cardiac systolic function compared with saline- treated animals Ejection fraction Fractional shortening Strain short-axis 80 45 Baseline Week 6 Week 12 -15 Strain SAX, mean (SEM), % FS, mean (SEM), % EF, mean (SEM), %
Slide 7: Echocardiography (2/3)
RESULTS Echocardiography (2/3) From baseline to Week 12, SRP-9005 treatment did not lead to systolic/diastolic volume changes compared with saline-treated animals End diastolic volume End systolic volume 10 End systolic volume, mean (SEM), End systolic volume, mean (SEM), 2.8 mL(SEM), mL mL(SEM), mL
Slide 8: Echocardiography (3/3)
RESULTS Echocardiography (3/3) From baseline to Week 12, SRP-9005 treatment did not lead to abnormalities in left ventricular dimensions compared with the saline-treated animals Left ventricular posterior wall thickness in diastole Left ventricular area in systole 0.7 LVPWd, mean (SEM), cm LVAs, mea
Slide 9: Electrocardiography
RESULTS Electrocardiography From baseline to Week 12, SRP-9005 had no effect on RR, PR, QRS and QTc intervals compared with the saline-treated animals ECG values at Baseline and Week 12 400 Saline (n=4) 300 SRP-9005 7x1012 Time, mean (SEM), ms (n=4) 200 SRP-9005 2x1013 (n=4) 100 SRP-9005 7.41x1013 (
Slide 10: Cardiac histopathology
RESULTS Cardiac histopathology Histopathology analysis in the heart revealed no evidence of cardiac remodeling or degeneration with SRP-9005 at all doses tested SRP-9005 7x1012 Saline 200 μm 200 μm SRP-9005 7.41x1013 SRP-9005 2x1013 200 μm 200 μm Representative images of cardiac tissue from wild-typ
Slide 11: Anatomic and clinical pathology in non-human primates
RESULTS Anatomic and clinical pathology in non-human primates Anatomic pathology Clinical pathology • No SRP-9005‒related effects on heart • SRP-9005 had no effects on histopathology, organs weight, gross pathology – Hematology including liver were observed – Coagulation – Serum chemistry Summary of
Slide 12: Immune response (AAVrh74 capsid)
RESULTS Immune response From baseline to Week 12 (Day 78), A humoral response was seen by SRP-9005 did not elicit a Week 12 (Day 85) cellular immune response to the AAVrh74 capsid across all dose groups Anti-AAVrh74 ELISpot Anti-AAVrh74 ELISA titer 60 IFN-γ SFC/106 PBMC 1 06 50 1 40 05 Titer (1:X) 1
Slide 13: Immune response (human SGCG transgene)
RESULTS Immune response From baseline to Week 12 (Day 78), SRP-9005 did A humoral response was seen by not elicit a cellular immune response Week 12 (Day 85) to the human SGCG transgene across all dose groups Anti-hSGCG ELISpot Anti-hSGCG ELISA titer 80 105 IFN-γ SFC/106 PBMC γ-SGCG ELISpot results
Slide 14: Vector biodistribution at Week 12
RESULTS Vector biodistribution at Week 12 In all SRP-9005 treatment groups, quantifiable vector genome copies were observed in the heart and skeletal muscles Heart left ventricle Left biceps femoris 3.10 20 4 Copies/nucleus, mean (SEM) Copies/nucleus, mean (SEM) 14.96 15 3 3 1.76 1 0.46 0.39 0.14 0
Slide 15: SGCG expression at Week 12
RESULTS SGCG expression at Week 12 A dose-dependent increase in SRP-9005 SGCG expression was observed in the heart and skeletal musclesa Cardiac apex Right biceps femoris 250 50.00 42.7 37.0 188.4 mean (SEM), ng/mg 35.9 33.4 mean (SEM), ng/mg SGCG expression, SGCG expression, 200 40.00 32.5 32.9 30.
Slide 16: Key takeaways
Key takeaways • SRP-9005 was well tolerated at all tested doses in non-human primates, showing no adverse effects or cardiotoxicity at doses up to 7.41x1013 vg/kg • There were no SRP-9005–related effects on cardiovascular anatomic or clinical pathology parameters including cardiac biomarker troponin
Slide 17: Thank You
Thank You
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