Sarepta Therapeutics, Inc. · NASDAQ:SRPT
Sarepta Therapeutics — Investor Presentation (August 2026)
86 slides from Sarepta Therapeutics's investor presentation, August 2026
Slide 1: Patients can't wait for the next breakthrough in medical research
Patients can’t wait for the next breakthrough in medical research. So neither will we. DILLON Living with Duchenne muscular dystrophy August 2026 ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 1
Slide 2: Forward-looking statements
Forward-looking statements This presentation contains "forward-looking statements." Any statements that are not statements of historical fact may be deemed to be forward-looking statements. Words such as “believe,” “anticipate,” “plan,” “expect,” “will,” “may,” “intend,” “prepare,” “look,” “potentia
Slide 3: ~10,000 rare diseases, 80%+ single gene mutations
~10,000 rare diseases 80%+ are single gene mutations And only a few hundred rare diseases currently have treatments https://ncats.nih.gov/trnd/projects/gene-therapy Accessed June 2023. ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 3
Slide 4: Sarepta Therapeutics is a biopharmaceutical company
Sarepta Therapeutics, Inc. (Nasdaq: SRPT) is a biopharmaceutical company that discovers, develops and commercializes medicines intended to treat rare, genetic-based diseases. DARREN Living with Duchenne muscular dystrophy ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 4
Slide 5: Company profile
Company profile 3 3 1 technology platforms RNA-based therapies st gene therapy FDA approved on market1 siRNA to treat Duchenne2 for certain patients with Duchenne RNA Gene Therapy Advancing Pipeline siRNA GENE THERAPY Facioscapulohumerol Spinocerebellar ataxia Spinocerebellar ataxia Idiopathic pulmo
Slide 6: Three distinct, proprietary scientific platforms
Three distinct, proprietary scientific platforms siRNA RNA GENE THERAPY Knockdown Skipping Replacement Suppresses Bypasses an error in the Adds a functional copy overexpression RNA, allowing the body (a transgene) of a missing or of mutations to skip the mutation malfunctioning gene ©SAREPTA THERAPE
Slide 7: Duchenne muscular dystrophy (Duchenne)
Duchenne muscular dystrophy (Duchenne) Duchenne affects approximately 1 in 3,500 - 5,000 newborn males worldwide1 • Duchenne is a rare, fatal neuromuscular genetic disease inherited in an X-linked recessive pattern2 • Muscle weakness becomes increasingly noticeable by 3 to 5 years of age, and most p
Slide 8: Disease progression in Duchenne
Disease progression in Duchenne1-3 5 TO 7 8 TO 11 EARLY TEENS TEENS TO YEARS YEARS TEENS TWENTIES • Motor delay • Increasing loss of • Loss of ambulation • Increasing • Increasing cardiac walking ability respiratory dysfunction • Enlarged calves • Full-time impairment • Toe walking • Part-time wheel
Slide 9: Muscle biopsies of patients with Duchenne show continued damage at early ages
Muscle biopsies of patients with Duchenne show continued damage at early ages Biopsies showed fiber size variation, and progressive loss of muscle structure and integritya,b DMD Quadricep 1 Year DMD Quadricep 3 Years Control Quadricep 4 Years Blue arrows represent necrotic fibers DMD Quadricep 5 Yea
Slide 10: Physical function typically peaks around age 6-7
Physical function typically peaks around age 6 in individuals with Duchenne1-3 At the time of their last assessment, mean age of Part 1- treated patients is 9 years old Maximum score Slowed development Limited peak performance Physical function as measured by NSAA* Typically age 6–72 Eventual loss o
Slide 11: Potential outcomes based on timing of therapeutic intervention
Potential outcomes based on timing of therapeutic intervention when attempting to stabilize Duchenne progression Healthy children usually reach peak NSAA score of" 34 after age 41 Interventions Increased score/higher peak2,3 aim to slow or stabilize Stabilization / underlying slowed decline2,3 patho
Slide 12: Patients living with Duchenne today: 250,000-300,000
EUROPE Patients can’t wait for the next breakthrough in medicalNORTH research. AMERICA So neither will we. MIDDLE EAST ASIA PACIFIC AFRICA SOUTH AMERICA PATIENTS LIVING WITH DUCHENNE TODAY*: 250,000 – 300,000 ZYLER Living with Duchenne muscular dystrophy globally * Estimated global prevalence. ©SARE
Slide 13: Serving approximately 30% of the Duchenne community with RNA-based therapies
Serving approximately 30% of the Duchenne community with RNA-based therapies September 2016 December 2019 February 2021 Approved to treat patients with a Approved to treat patients with a Approved to treat patients with a confirmed genetic mutation that is confirmed genetic mutation that is confirme
Slide 14: Net product revenue from 2016 through 2025
Net product revenue from 2016 through 2025 2000 $1.86B $1.79B ELEVIDYS $899M $821M PMOs 1500 $ Millions $1.15B $200M 1000 $945M $967M $966M $844M 500 $612M $456M $155M $381M $301M $5.4M 0 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 14
Slide 15: Largest and most comprehensive clinical program in Duchenne
Largest and most comprehensive clinical program in Duchenne Clinical trial participants have ranged in age from 2 to 24 years old, with body weights ranging from 12 kg to close to 90 kg STUDY 101 STUDY 102 Ages 4-7, ambulatory Ages 4-7, ambulatory Ages 3+, ambulatory and Ages 4-7, ambulatory Open-La
Slide 16: SRP-9001-301
SRP-9001-301 CONFIDENTIAL. FOR INTERNAL USE ONLY. ©SAREPTA THERAPEUTICS, ©SAREPTA INC. INC. THERAPEUTICS, 2026. ALLALL 2024. 2026. RIGHTS RESERVED. RIGHTS RESERVED. 16 16 16
Slide 17: SRP-9001-301 study design
SRP-9001-301 study design A completed Phase 3, multinational, double-blind, randomized, placebo-controlled study evaluating the safety and efficacy of ELEVIDYS (delandistrogene moxeparvovec-rokl), in boys with Duchenne aged 4–7 years old Key functional inclusion criteria: • NSAA score 17-28 (inclusi
Slide 18: One-year follow-up: functional outcomes of patients treated at ≥8 years of age
One-year Follow-up: Functional outcomes of patients treated at ≥8 years of age At one-year post-gene therapy, patients treated at ≥8 years of age demonstrated statistically significant and clinically meaningful functional benefit versus a propensity-score-weighted EC cohort NSAA ∆ 4.75 points; P=0.0
Slide 19: EMBARK NSAA Total Score: Baseline to Year 2
EMBARK NSAA* Total Score: Baseline to Year 2, blinded study results 27 Part 1 Treated 26 Part 1 Placebo Crossover Treated NSAA Total Score 25 24 23 22 0 26 52 76 104 Time in Weeks *North Star Ambulatory Assessment ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 19
Slide 20: NSAA increases in crossover treated patients following ELEVIDYS dosing
NSAA increases in crossover treated patients following ELEVIDYS dosing Part 1 Treated 2 Crossover Treated Change from Part 1 W52 NSAA Total Score 1 0 -1 52 78 104 Time in Weeks ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 20
Slide 21: 2-Year Results: Musculoskeletal MRI - fat fraction
2-Year Results: Musculoskelatal MRI - fat fraction (FF) Vastus Lateralis 5 FF (%) Change From BL Part 1 Treated 4 Part 1 Placebo 3 2 1 0 0 52 104 Weeks Post Dosing Placebo N=16 N=14 N=17 N=15 Treated N=15 N=14 N=14 N=16 N=16 N=15 Stabilization in MRI muscle FF in 9001 treatment group with two years
Slide 22: 2-Year Results: Musculoskeletal MRI - T2
2-Year Results: Musculoskeletal MRI - T2 Placebo N=18 N=15 N=17 N=15 Treated N=13 N=12 N=12 N=15 N=15 N=14 Stable muscle T2 in most muscle groups over 2 years with lower T2 2 years after ELEVIDYS treatment than at 1 year in placebo cohort 1. Naarding KJ, Reyngoudt H, van Zwet EW, etal. MRI vastus la
Slide 23: EMBARK Part 2 Results: Crossover-treated vs external control, 1-year data
EMBARK Part 2 Results: Crossover-treated patients compared to external control, 1-year data ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 23
Slide 24: EMBARK statistical analysis plan and external control
EMBARK statistical analysis plan and external control • In the absence of a placebo arm after Part 1, the EMBARK study protocol and statistical analysis plan (SAP) are used to create a pre-specified, propensity-weighted external control to contextualize study level results • External control cohorts
Slide 25: Balanced baseline characteristics for crossover-treated patients and EC
Balanced baseline characteristics for crossover-treated patients and external control (EC) Baseline Characteristics (Weighted) Full Analysis Set SRP-9001 (n=59) External Control (n=276) Baseline Mean (Min, Max) Mean (Min, Max) Age 7.11 (5.07, 9.07) 7.07 (5.05, 9.98) NSAA 25.0 (12, 34) 25.0 (12, 34)
Slide 26: Significant improvements in functional outcomes one year after treatment vs EC
Statistically significant and clinically meaningful improvements in functional outcomes one year after treatment compared to EC NSAA TTR* TTR velocity 10MWR time* 10MWR velocity Diff in Means (of change from baseline) and confidence intervals are standardized by dividing by the standard error (SE).
Slide 27: Significant increase in NSAA one year after treatment vs EC
Statistically significant increase in NSAA one year after treatment compared to EC NSAA NSAA verall 2 .000 .2 S hange From aseline 0 ∆:2.34 2. 4 (p: <.0001) . 2 aseline ear SRP 00 2 2 reatment SRP 00 Source t f mrm nsaat t f mrm nsaat age ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 27
Slide 28: Significant improvements in time-to-rise one year after treatment vs EC
Statistically significant improvements in time-to-rise from floor one year after treatment compared to EC RFF time TTR verall 4 .000 2.4 S hange From aseline 2 ∆:-2.7 2. (p: <.0001) 0 0.2 aseline ear SRP 00 2 2 4 reatment SRP 00 Source t f mrm rfft t f mrm rfft age Mendell, J.R., et al. Neurol Ther
Slide 29: Significant improvement in 10m walk/run times one year after treatment vs EC
Statistically significant improvement in 10m walk/run times one year after treatment compared to EC 0 R time 10MWR time verall 2 0.000 S 0.8 hange From aseline ∆:-1.07 .0 (p: <.0001) 0 0.2 aseline ear SRP 00 2 2 reatment SRP 00 Source t f mrm tmwrt t f mrm tmwrt age ©SAREPTA THERAPEUTICS, INC. 2026.
Slide 30: EMBARK Part 2 Results: Year 2 expression and functional outcomes
EMBARK Part 2 Results: Year 2 expression and functional outcomes in Part-1 treated patients ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 30
Slide 31: Expression is consistent and sustained from week 12 to week 64
Expression is consistent and sustained from week 12 to week 64 Western Blot Part 1 SRP-treated Week-12 Week-64 n = 17 n = 16 Mean (SD) 34.29 (41.04) 45.68 (39.75) ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 31
Slide 32: Balanced baseline characteristics for Part 1 treated and EC
Balanced baseline characteristics for Part 1 treated and EC Baseline Characteristics (Weighted) Full Analysis Set SRP-9001 (n=64) External Control (n=143) Baseline Mean (Min, Max) Mean (Min, Max) Age 5.98 (4.07, 7.87) 6.24 (4.24, 7.99) NSAA 23.3 (14, 32) 23.5 (15, 32) Time to Rise from Floor 3.51 (1
Slide 33: Significant differences after treatment at Year 2 compared to EC
Statistically significant and clinically meaningful differences after treatment at Year 2 compared to EC NSAA TTR* TTR velocity 10MWR time* 10MWR velocity Diff in Means (of change from baseline) and confidence intervals are standardized by dividing by the standard error (SE). The half width of the f
Slide 34: NSAA improvements sustained two years after treatment
NSAA improvements were sustained two years after treatment, showing a widening divergence from natural history NSAA NSAA verall 4 .000 0.000 2. 4 2. 2 S hange From aseline 2.2 ∆:2.88 2.88 (p: 0.0001) 0. 0 0.2 2 aseline ear ear 2 SRP 00 4 4 4 4 4 reatment SRP 00 Source t f2 mrm nsaat t f2 mrm nsaat a
Slide 35: Time-to-rise over two years shows widening divergence
Time-to-rise over two years also demonstrates a widening divergence over time RFF time TTR verall 4 .000 0.00 2. S hange From aseline 2 ∆:-2.06 2.0 (p: 0.0033) 0. 0. 0. 4 0 0.2 aseline ear ear 2 SRP 00 4 4 4 40 reatment SRP 00 Source t f2 mrm rfft t f2 mrm rfft age Mendell, J.R., et al. Neurol Ther
Slide 36: 10MWR remains stable two years after treatment
10MWR remains stable two years after treatment, with a widening divergence from natural history over time 0 R time 10MWR time verall 2 0.0 00 0.0028 . 2 S hange From aseline ∆:-1.36 . (p: 0.0028) 0. 0 0.04 0.4 0. aseline ear ear 2 SRP 00 4 4 4 40 reatment SRP 00 Source t f2 mrm tmwrt t f2 mrm tmwrt
Slide 37: Cardiac MRI shows patients remain in normal range over 2 years
Cardiac MRI shows patients remain in normal range over 2 years of follow-up No statistical or clinical differences in these groups Part 1 Treated: Year 1 post- Year 2 post- Crossover Year 1 post- Year 1 post- Baseline treatment treatment Treated: placebo treatment Baseline Subjects (N) 16 16 14 19 1
Slide 38: Results from EMBARK: 3-Year Topline Data, Part 1-treated vs EC
Results from EMBARK: 3-Year Topline Data, Part 1-treated vs EC (Analysis Using LS-Mean by MMRM) CONFIDENTIAL. FOR INTERNAL USE ONLY. ©SAREPTA THERAPEUTICS, ©SAREPTA INC. INC. THERAPEUTICS, 2026. ALLALL 2024. 2026. RIGHTS RESERVED. RIGHTS RESERVED. 38 38 38
Slide 39: 3-year topline functional results from part 1 of EMBARK
3-year topline functional results from part 1 of EMBARK (Study 9001-301) • On average, ELEVIDYS-treated patients remain above their baseline three years after treatment as measured by NSAA • Statistically significant 73% slowing of disease progression as measured by TTR (time to rise) • Statisticall
Slide 40: Background on the external control (EC)
Background on the external control (EC) • In the absence of a placebo arm after Part 1, the EMBARK study protocol and statistical analysis plan (SAP) are used to create a pre-specified, propensity-weighted external control to contextualize study level results • External control cohorts chosen throug
Slide 41: Baseline characteristics balanced for part 1-treated and external control
Baseline characteristics balanced for part 1- treated and external control Baseline Characteristics (Weighted) Full Analysis Set EMBARK Part 1 Standardized mean Characteristic, Delandistrogene EC cohort difference after propensity- Mean (min, max) moxeparvovec (N=143)† score weighting* (N=64) Age, y
Slide 42: NSAA outcomes at Year 2 and Year 3 vs EC
ELEVIDYS-treated patients (n=52) achieved a significantly higher NSAA total score compared to the external control group, with a p-value of 0.0002 NSAA Outcomes at Year 2 & Year 3 vs EC Results Mean age of patients 9 years old at time of last assessment Year 2 Year 3 Key Observations: 2.63 NSAA tota
Slide 43: 73% slowing of disease progression on TTR
ELEVIDYS-treated patients demonstrated a highly significant 73% slowing of disease progression on TTR, with a p-value of < 0.0001 EMBARK Part 1: Time to Rise (TTR) Outcomes vs EC at Year 3 Results Mean age of patients 9 years old at time of last assessment Key Observations: TTRFF Change From Baselin
Slide 44: 70% slowing of disease progression on 10MWR
ELEVIDYS-treated patients achieved a statistically significant 70% slowing of disease progression on 10MWR, with a p-value of 0.0039 EMBARK Part 1: 10-meter walk/run (10MWR) Outcomes vs EC at Year 3 Results Mean age of patients 9 years old at time of last assessment 5 Key Observations: 10MWR Change
Slide 45: Three-year safety for part 1-treated patients
Three-year safety for part 1-treated patients Year 1 Year 2 Year 3 (EMBARK Y1) (EMBARK Y2)* (EXPEDITION Y1)^ Patients with any SAEs 14 5 4 Patients with treatment- 7 1 0 related SAEs Treatment-related 0 0 0Ŧ deaths • No new safety signals were observed • The safety profile of ELEVIDYS as observed i
Slide 46: Long-term results from EMBARK demonstrate significant and growing functional benefit
Long-term results from EMBARK demonstrate significant and growing functional benefit compared to EC • At the time of their last assessment, mean age of patients treated in EMBARK is 9 years old, corresponding to a nearly universal period of functional decline in Duchenne • On average, ELEVIDYS-treat
Slide 47: SRP-9001-103 Results
SRP-9001-103 Results CONFIDENTIAL. FOR INTERNAL USE ONLY. ©SAREPTA THERAPEUTICS, ©SAREPTA INC. INC. THERAPEUTICS, 2026. ALLALL 2024. 2026. RIGHTS RESERVED. RIGHTS RESERVED. 47 47 47
Slide 48: ENDEAVOR (Study 9001-103): expression and safety in 2-year-old participants
ENDEAVOR (Study 9001-103): Protein expression and safety results in 2-year-old participants at time of treatment • Clinical Results (cohort 6; n=6) – 93.87% mean expression as measured by western blot – 79.9% dystrophin positive fibers (PDPF) as measured by immunofluorescence • Safety – Safety in co
Slide 49: SRP-9001-101 Year 5 Results
SRP-9001-101 Year 5 Results ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 49
Slide 50: Study 9001-101 year 5 results demonstrate durable response
Study 9001-101 year 5 results demonstrate durable response 9.8-point difference on mean NSAA in patients receiving SRP-9001 compared to external control group EC cohort 17 17 17 17 17 17 SRP-9001 treated patients showed a sustained increase in NSAA total score over 5 years, with a statistically sign
Slide 51: ELEVIDYS Safety Data
ELEVIDYS Safety Data ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 51
Slide 52: Safety profile in EMBARK is consistent with previous studies
Safety profile in EMBARK is consistent with previous studies Part 1 Treated, Year 1 Part 1 Treated, Year 2 Crossover Treated, Year 1 Total SRP-9001 post-treatment post-treatment** post-treatment Treated* N=63 N=63 N=60 N=123 n (%) n (%) n (%) n (%) TEAE 62 ( 98.4) 0 56 ( 93.3) 118 ( 95.9) SAEs 14 (
Slide 53: No safety concerns on cardiac MRI over 2 years
No safety concerns on cardiac MRI over 2 years of follow-up • Values within normal range • No statistical or clinical differences in these groups Part 1 Treated: Year 1 post- Year 2 post- Crossover Year 1 post- Year 1 post- Baseline treatment treatment Treated: placebo treatment Baseline Subjects (N
Slide 54: Key siRNA Programs
Key siRNA Programs • Facioscapulohumeral muscular dystrophy type 1 (FSHD1) • Myotonic dystrophy type 1 (DM1) • Spinocerebellar ataxia type 2 (SCA2) • Huntington’s disease (HD) ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 54
Slide 55: Advancing pipeline
Advancing pipeline DISCOVERY/PRECLINICAL CLINICAL MUSCLE U.S. patient prevalence αv 6 integrin SRP-1001 Facioscapulohumeral muscular dystrophy, type 1 (FSHD1) ~16,0001 peptide SRP-1003 Myotonic dystrophy, type 1 (DM1) ~40,0002 LUNG SRP-1002 Idiopathic pulmonary fibrosis (IPF) ~60,0003 CNS SRP-1004
Slide 56: Components of TRiM and the science that enables our pipeline
Components of TRiM and the science that enables our pipeline TM Linker Delivery Designed to provide Tissue-specific ligands stability/orientation. Linker is (peptide, small molecule, Ab) selected to optimize efficacy, designed to deliver siRNA to reduce tox, and CMC Liver, CNS, Muscle, Heart etc. co
Slide 57: siRNA-mediated mRNA degradation designed to enable specific target knockdown
A Biology-First Approach: siRNA-mediated mRNA Degradation Designed to Enable Specific Target Knockdown 2 siRNA has been modified to preferentially load the guide strand for enhanced specificity 3 Complementary pairing 4 Catalytically active RISC cleaves multiple target mRNAs, with the goal of superi
Slide 58: Targeting αvβ6 integrin over TfR1 for greater muscle uptake
Targeting αv6 Integrin over TfR1 for Greater Muscle Uptake High expression and surface availability of αv6 in muscle make it a preferred receptor for targeted siRNA delivery TfR1 s : 5%1 of receptors available for binding on surface at any one time; majority are intracellular IV Delivery αv6: ~40
Slide 59: Potential advantages of siRNA integrin approach for FSHD1 and DM1
Potential advantages of siRNA integrin approach and best-in-class therapies to treat FSHD1 and DM1 Better delivery to muscle with integrin αv6 Optimal clinical impact αv6 siRNA TfR1mAb TfR1fAb siRNA ASO Potency Better muscle penetration (e.g., delivers more Rx to muscle) Safety and lack of dose li
Slide 60: SRP-1001: In clinical development for FSHD1
SRP-1001: In clinical development for Facioscapulohumeral muscular dystrophy type 1 (FSHD1) SRP-1001 is an RNA interference (RNAi) conjugate designed to specifically target the STAGE: gene that encodes human double Phase 1/2 homeobox 4 (DUX4) protein. ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RES
Slide 61: FSHD: Multiple skeletal muscles affected, beginning with the face
FSHD: Multiple skeletal muscles affected, beginning with the face Facial Muscles Scapular Girdle Muscles Upper Limb Muscles Abdominal Muscles Pelvic Girdle Muscles Muscle Weakness and Mobility • ~50% of FSHD patients will progress to becoming dependent on a wheelchair after ~20 years • >50% of FSHD
Slide 62: FSHD is caused by contraction of the D4Z4 repeat
FSHD is caused by the contraction of the D4Z4 repeat, leading to the abnormal expression of DUX4, which is typically silenced early in life DUX4 Gene Expression A DUX4 Transcription Factor B FSHD genotype leads to aberrant DUX4 expression C Downstream Cellular Consequences ©SAREPTA THERAPEUTICS, INC
Slide 63: Study SRP-1001-101: Phase 1/2 trial in FSHD1
Study SRP-1001-101: A phase 1/2 randomized, placebo-controlled trial in participants aged 16-70 with FSHD1 Part 1: SAD Part 2: MAD D1 Day 42 Day 90 D1 3M 6M 9M 12M Biopsy (Bx) Bx EOS Bx Bx EOS Cohort Design Endpoints SAD MAD C1-4: n=6, 2:1 C5-7: n up to 12, 3:1 Primary: • Functional: RWS, 6MWT, Coho
Slide 64: Baseline characteristics
Baseline characteristics SAD MAD Overall Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 Pooled Placebo Treated Total (1.02 mg/kg) (2.04 mg/kg) (4.08 mg/kg) (8.17 mg/kg) (4.08 mg/kg) (8.17 mg/kg) N=16 N=40 N=56 N=5 N=4 N=4 N=5 N=11 N=11 Age (years) 36.2 (14.15) 49.0 (6.00) 42.8 (9.29) 34.4 (11
Slide 65: SRP-1001 shows dose-dependent increase in plasma exposure
SRP-1001 shows consistent dose-dependent increase in plasma exposure up to the highest dose cohort tested so far Plasma Exposure by Dose Level Dose-dependent increase in plasma AUC up to 8 mg/kg, representing the highest siRNA dose evaluated to date for FSHD SRP-1001 siRNA dose AUC = area under the
Slide 66: Single dose of SRP-1001 delivers 6-fold greater siRNA muscle concentration
Single dose of SRP-1001 delivers 6-fold greater siRNA muscle concentration than multiple doses of transferrin-targeting ligand SRP-1001 Muscle Concentration by Dose Level • Dose-dependent increase in muscle concentration up to 4.08 mg/kg, representing the highest siRNA 28.4 nM dose with muscle PK da
Slide 67: SRP-1001 suppresses DUX4-regulated genes after a single dose
SRP-1001 suppresses DUX4-regulated genes after a single dose -90% -90% -93% SRP-1001 treatment cohorts pooled from siRNA dose cohort 1 (1.02 mg/kg), cohort 2 (2.04 mg/kg), and cohort 3 (4.08 mg/kg). • *qPCR composite scores for CS4 (MBD3L2, TRIM43, KHDC1L, LEUTX), CS6 (MBD3L2, KHDC1L, CCNA1, PRAMEF5
Slide 68: SRP-1001 drives rapid reduction in serum creatine kinase
SRP-1001 drives rapid reduction in serum creatine kinase (CK) with a single dose of SRP-1001 SRP-1001 achieved a 33% reduction in CK vs placebo at Day 42 SRP-1001 -33% SRP-1001 0 15 30 42 60 75 90 Days Data represent mean percent change from baseline ± SEM. Placebo (n = 16) and SRP-1001 treatment co
Slide 69: SRP-1001-101: Reassuring safety profile to date
SRP-1001-101: Reassuring safety profile to date with no serious related TEAEs SAD (Active and Placebo) MAD (Active and Placebo) Overall Cohort 1 Majority of TEAEs were mild to moderate Cohort 2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 in severity (1.02 Total (2.04 mg/kg) (4.08 mg/kg) (8.17 mg/kg) (4.08 m
Slide 70: SRP-1003: In clinical development for DM1
SRP-1003: In clinical development for myotonic dystrophy type 1 (DM1) SRP-1003 is an RNAi conjugate designed STAGE: to specifically silence DMPK mRNA in Phase 1/2 skeletal muscle. ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 70
Slide 71: DM1: A multi-system disorder
DM1: A multi-system disorder impacting skeletal and smooth muscle along with other organs Fatigue, apathy, cognitive impairment Frontal balding Cataracts Facial muscle weakness; TMJ dysfunction Respiratory failure (skeletal muscle weakness Cardiac conduction abnormalities (bradyarrythmias and CNS dy
Slide 72: DM1: Expanded DMPK repeat, leading to multi-system impact
DM1: Expanded DMPK Repeat, Leading to Multi-System Impact Targeting and knockdown of DMPK leads to therapeutic benefit DM1 Genetic Cause DMPK DNA Expanded tri-nucleotide repeat in the DMPK gene (CTG)n (50 – 1000 repeats) ’ AP AAAAA RNA Repeats accumulate in the nucleus and create 3D structures that
Slide 73: Study SRP-1003-101: Phase 1/2 trial in DM1
Study SRP-1003-101: A phase 1/2 randomized, placebo-controlled trial in participants aged 18-65 with DM1 Part 1: SAD Part 2: MAD D1 D30 Day 90 D1 D30 D90/71 D120/100 D180/140 Biopsy (Bx) Bx Bx/EOS Bx Bx Bx EOS Cohort Design Endpoints SAD MAD Primary: • Functional (secondary in Cohort 1 Cohort 3 • Sa
Slide 74: Baseline characteristics
Baseline characteristics SAD MAD Cohort 1 Cohort 2 Cohort 3 Cohort 4 Placebo Total (1.02 mpkg) (2.04 mpkg) (<=3.07 mpkg) (<=4.10 mpkg) N=11 N=36 N=10 N=6 N=5 N=4 Mean (sd) or Freq (%) Age (years) 39.2 (11.84) 36.0 (9.06) 47.0 (12.04) 41.8 (7.09) 36.3 (9.16) 39.1 (10.32) Female, n (%) 6 (60.0) 1 (16.
Slide 75: SRP-1003 shows dose-dependent increase in plasma exposure
SRP-1003 shows dose-dependent increase in plasma exposure, reinforcing cross-program consistency in the TRiM platform Plasma Exposure by Dose Level Dose-dependent increase in plasma AUC up to 3.07 mg/kg, representing the highest SRP-1003 dose cohort with data to date SRP-1003 siRNA dose AUC = area u
Slide 76: Superior muscle delivery with a single low dose of SRP-1003
Superior muscle delivery with a single low dose of SRP-1003 SRP-1003 Muscle Concentration • SRP-1003 in the lowest dose cohort SRP-1003 (1.02 siRNA mg/kg) mediates robust 12.2 nM siRNA delivery into the muscle (single lowest dose) • A single low dose of SRP-1003 significantly outperforms repeated Tf
Slide 77: SRP-1003-101: Reassuring safety profile with no serious related TEAEs
SRP-1003-101: Reassuring safety profile with no serious related TEAEs to date SAD (Active and Placebo) MAD (Active and Placebo) Overall Majority of TEAEs were mild to moderate in severity Cohort 1 Cohort 2 Cohort 3 Cohort 6 • Three serious TEAEs in 2 subjects Total (1.02 mg/kg) (2.04 mg/kg) (≤3.07 m
Slide 78: Summary: Conclusions from clinical data for FSHD1 and DM1
Summary: Conclusions from clinical data to date for FSHD1 and DM1 • Well-tolerated with no dose-limiting toxicity allowing us to continue dose escalating and the potential to drive differentiated efficacy • Superior muscle concentration • Successful target engagement with emerging biomarker evidence
Slide 79: Spinocerebellar ataxia type 2 (SCA2)
Spinocerebellar ataxia type 2 (SCA2) Spinocerebrellar ataxia (SCA) is a group of rare, genetic neurodegenerative disorders leading to severe disability and premature death.1 • In SCA, the nerve fibers carrying messages to and from the brain are affected, resulting in degeneration of the cerebellum (
Slide 80: SRP-1004 reduces ATXN2 in a mouse brain
SRP-1004 reduces ATXN2 in a mouse brain Mouse model engineered to express human ATXN2 SRP-1004 delivered ICV reduces ATXN2 SRP-1004 delivered ICV reduces ATXN2 mRNA 2 weeks after delivery protein 2 weeks after delivery ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 80
Slide 81: SRP-1004 lowers ATXN2 in NHP brain regions
SRP-1004 lowers ATXN2 in NHP brain regions important in disease >80% reduction in key brain regions (i.e. cerebellum) involved in SCA2 pathology SRP-1004 delivered IT reduces ATXN2 protein 1 month after delivery ©SAREPTA THERAPEUTICS, INC. 2026. ALL RIGHTS RESERVED. 81
Slide 82: SRP-1004: Spinocerebellar ataxia type 2 (SCA2)
SRP-1004: Spinocerebellar ataxia type 2 (SCA2) POC and confirmation of registrational dose • Development Status: Phase 1 • Design: • Randomized placebo-controlled single ascending dose • Multiple ascending dose Part 2 being added • Participants: Cohort 1 fully enrolled • Primary endpoint: Safety • S
Slide 83: Huntington's disease (HD)
Huntington’s disease (HD) A fatal genetic disorder that causes brain cells to gradually break down and die. HD deteriorates a person’s physical and mental abilities, and a person with HD is described as having ALS, Parkinson’s and Alzheimer’s disease simultaneously. 1 • HD is caused by a mutation in
Slide 84: TfR1-binding designed to optimize CNS delivery in Huntington's disease
TfR1-Binding Designed to Optimize CNS Delivery in Huntington’s Disease CNS-SC platform demonstrates improved delivery to deep brain in NHP compared to direct CSF injection CSF delivery via Systemic delivery via SRP-1005 in NHP IT injection SC injection SRP-1005 HD program employs a subcutaneous rout
Slide 85: Bolstering pipeline with preclinical programs and up to 6 discovery targets
Bolstering pipeline with preclinical programs and up to 6 discovery targets in muscle (skeletal and cardiac) or CNS PRECLINICAL PROGRAMS DISCOVERY TARGETS • Preclinical CNS leverages TfR1-binding for • Up to 6 targets in muscle (skeletal and optimal CNS delivery cardiac) or CNS • Subcutaneous delive
Slide 86: Dragging tomorrow into today
Dragging tomorrow into today #DraggingTomorrowIntoToday SAREPTA, SAREPTA THERAPEUTICS, the SAREPTA Helix Logo, DRAG TOMORROW INTO TODAY, DRAGGING TOMORROW INTO TODAY, ELEVIDYS, AMONDYS, AMONDYS 45, the AMONDYS 45 Logo, VYONDYS, VYONDYS 53, the VYONDYS 53 Logo, EXONDYS, EXONDYS 51, EXONDYS 51 Logo, a
Sarepta Therapeutics — Investor Presentation (August 2026) on 6ix