Edgewise Therapeutics, Inc. · NASDAQ:EWTX
Edgewise Therapeutics — World Muscle Society Conference 2025 Symposium
55 slides from Edgewise Therapeutics's conference presentation, Oct 8, 2025
Slide 1: Breakthroughs in Becker: Unveiling New Natural History Insights and a Novel Agent's Clinical Progress
Breakthroughs in Becker: Unveiling New Natural History Insights and a Novel Agent’s Clinical Progress Symposium at World Muscle Society Conference Vienna, Austria Wednesday 08 October 2025 ©2025 Edgewise Therapeutics. All rights reserved.
Slide 2: Disclosures
Disclosures Roxana Donisa Dreghici is an employee of Edgewise Therapeutics and holds stock. 2
Slide 3: Program Overview
Program Overview Introduction Roxana Donisa Dreghici, MD VP Clinical Development Roxana Donisa Dreghici, MD Edgewise Therapeutics Becker Muscular Dystrophy Natural History & Modeling Erik Niks, MD, PhD Erik Niks, MD, PhD Pediatric and adult neurologist Leiden University Medical Center Advancements w
Slide 4: Session Objectives
Session Objectives • Expand awareness of the most current Becker muscular dystrophy (Becker) natural history studies and how they support the severity of Becker. • Increase understanding of functional assessments, such as the North Star Ambulatory Assessment (NSAA), and their clinical meaningfulness
Slide 5: Becker Muscular Dystrophy Natural History & Modeling
Becker Muscular Dystrophy Natural History & Modeling Erik H. Niks, MD, PhD
Slide 6: Disclosures
Disclosures Participant in advisory boards for Edgewise Therapeutics, BioMarin, Entrada, Pfizer, Roche, Italfarmaco, Sarepta, and Solid Bioscience. Principal investigator at LUMC for clinical trials from Edgewise Therapeutics, Italfarmaco, Entrada, Sarepta, Solid Bioscience, Fibrogen, NS Pharma, Rev
Slide 7: Becker Muscular Dystrophy is a Serious, Progressive, and Debilitating Neuromuscular Disease
Becker Muscular Dystrophy is a Serious, Progressive, and Debilitating Neuromuscular Disease BMD is an X-linked recessive disease caused by mutations in the DMD gene, affecting approximately 1:18,000 male births. BMD is a multi-systemic disease that can lead to irreversible loss of muscle function an
Slide 8: Becker Muscular Dystrophy is Hallmarked by Variable Onset and Progression
Becker Muscular Dystrophy is Hallmarked by Variable Onset and Progression • Original publication on 14 male patients • Onset 12-25 years • Hypertrophic calves & waisting of quadriceps 8
Slide 9: Partial and Variable Expression of Dystrophin in Muscle Fibers
The picture can't be displayed. Partial and Variable Expression of Dystrophin in Muscle Fibers Normal BMD DMD BMD, Becker muscular dystrophy; CTRL, control; DMD, Duchenne muscular dystrophy. 9 Beekman et al. PloS One. 2018; 13(4):e0195850.
Slide 10: North Star Ambulatory Assessment: a Validated Measure of Ambulatory Function
North Star Ambulatory Assessment: a Validated Measure of Ambulatory Function that is Clinically Meaningful in a Real-World Context The NSAA Test Items Hop left leg Hop right leg Stand on heels Real-world implications for individuals with BMD Rise from floor Measure Activity Run Jump, hop, run Playin
Slide 11: NSAA Trajectories in a Recent 6-year Natural History Study
NSAA Trajectories in a Recent 6-year Natural History Study • Sample size: 107 BMD participants Overall Age Distribution of o Ambulatory Patients at Baseline o Includes patients already on corticosteroids or initiated during observation period • Ages: 31.4 ± 17.3 years old (range 3-69 years old) • Fo
Slide 12: NSAA Decline More Evident in Participants with Baseline Values ≤32
NSAA Decline More Evident in Participants with Baseline Values ≤32 All BMD BMD with Baseline NSAA ≤32 (n=100) (n=45) NSAA Score NSAA Score Age (years) Age (years) BMD, Becker muscular dystrophy; NSAA, North Star Ambulatory Assessment Bello L, et al. Neurol Genet. 2025;11(4):e200285. 12
Slide 13: NSAA Decline Highly Variable Across Genotypes
NSAA Decline Highly Variable Across Genotypes Deletions 45-47 Deletions 48 Deletions x-51 (n=14) (n=12) (n=15) NSAA Score NSAA Score NSAA Score Age (years) Age (years) Age (years) NSAA, North Star Ambulatory Assessment Bello L, et al. Neurol Genet. 2025;11(4):e200285. 13
Slide 14: NSAA Trajectories in a Recent 3-year Natural History Study
NSAA Trajectories in a Recent 3-year Natural History Study Characteristics of the Study Population • Sample size: 36 BMD participants o Ambulatory and non-ambulatory patients • Mean age: 41.8 years old (range 18.6-67.3) • Follow up: yearly visits at baseline up to 3 years 14 BMD, Becker Muscular Dys
Slide 15: NSAA Decline More Linear in Subpopulation with Baseline Values 10-32
NSAA Decline More Linear in Subpopulation with Baseline Values 10-32 NSAA, North Star Ambulatory Assessment; Sec, second Schrama E, et al. Neurology 2025;105(7):e214071 15
Slide 16: Phenotypical Variability within the del 45-47 Genotype
Phenotypical Variability within the del 45-47 Genotype NSAA, North Star Ambulatory Assessment; Sec, second Schrama E, et al. Neurology 2025;105(7):e214071 16
Slide 17: Combined Natural History Studies Show Mean Annual Rates of Decline in NSAA
Combined Natural History Studies Show Mean Annual Rates of Decline in NSAA between 1.0 and 1.7 Points Mean Annual Rates of NSAA Decline From Becker Natural History Studies 0 Change in NSAA -5 -10 de Wel B, et al. (ambulatory, n=21) Bello L, et al. (ambulatory, NSAA 10-32, n=45) Schrama EJ, et al. (a
Slide 18: Prediction Models
Prediction Models • Models to predict disease trajectories provide contextualization for clinical trial outcomes. • This is especially valuable over multi-year periods in Becker muscular dystrophy for which placebo controls are not feasible. • A prediction model for changes in the North Star Ambulat
Slide 19: A Predictive Model Based on Becker Natural History Data was Developed and Validated
A Predictive Model Based on Becker Natural History Data was Developed and Validated Input Data Set Predictive Model • Source: Leiden University Medical Center Becker natural history study • Baseline Predictors Applied: – Age • Data: Changes from base in NSAA – 4 Stair climb velocity total score – 10
Slide 20: Participant Baseline Characteristics
Participant Baseline Characteristics Baseline Characteristics LUMC Patients Ambulatory at Patient Characteristics, Baseline Mean ± SD n = 24 • A total of 24 ambulatory male patients with Becker Age, years 39.4 ± 12.6 were included NSAA total score 23.9 ± 10.6 10MWR velocity, meter/sec 2.0 ± 1.2 • Me
Slide 21: The Model was Validated Against Two Publications: Bello 2016 and De Wel 2024
The Model was Validated Against Two Publications: Bello L, et al. 2016 and De Wel B, et al. 2024. Baseline Functional Measures and Functional Changes at 1 year Bello L, et al. Sci Rep. 2016 n with n at Mean ± SD at Median (range) Mean Median Change Functional Measures longitudinal baseline Baseline
Slide 22: The Model was Validated Against Two Publications: Bello 2016 and De Wel 2024
The Model was Validated Against Two Publications: Bello L, et al. 2016 and De Wel B, et al. 2024. Baseline Characteristics and Changes at 9 and 18 Months of Follow-Up De Wel B, et al. 2024 Baseline Functional Measures Month 9 p-value Month 18 p-value Mean ± SD 6MWT distance, meters 433.2 ± 178.8 −15
Slide 23: The Model Performed Well, With Predicted Means Closely Matching Observed Values
The Model Performed Well, With Predicted Means Closely Matching Observed Values Δ Predicted NSAA over time with 95% CI Mean Δ NSAA (95% CI) Bello – predicted De Wel – predicted x Bello – observed x De Wel – observed Baseline Month 9 Month 12 Month 18 • Compared to Bello et al. 2016, the predicted me
Slide 24: Key Takeaways
Key Takeaways • Natural history is essential for understanding disease progression and severity. • Recent Becker muscular dystrophy natural history data helps to identify subpopulations in decline. • Prediction models for natural history trajectories can provide important benchmarks for the outcomes
Slide 25: Advancements with an Investigational Agent: Sevasemten Clinical Program Update
Advancements with an Investigational Agent: Sevasemten Clinical Program Update Craig McDonald, MD
Slide 26: Disclaimers
Disclaimers Dr. Craig McDonald has served on advisory boards, done consulting work on Becker and Duchenne muscular dystrophy clinical trials for Edgewise Therapeutics, and has received research funding for the conduct of clinical trials from Edgewise Therapeutics. 26
Slide 27: In Dystrophinopathy, Fast Muscle Fibers Are Disproportionately Injured By Contraction
In Dystrophinopathy, Fast Muscle Fibers Are Disproportionately Injured By Contraction Healthy muscle contraction Dystrophic muscle contraction mechanical stress fiber breakdown Dystrophin connects contractile proteins to the membrane Contraction-induced muscle injuries occur in the absence of full-
Slide 28: Becker Muscular Dystrophy Research at Edgewise Therapeutics
Becker Muscular Dystrophy Research at Edgewise Therapeutics Edgewise Approach: Edgewise Becker Research Program Protect Susceptible Muscle Fibers Phase 1 Becker In Becker, fast skeletal muscle fibers are more Open-label, safety, PK, function OLE Completed susceptible to damage due to the lack of fun
Slide 29: Sevasemten Overview
Sevasemten Overview • A novel, first-in-class, oral, fast myofiber (type II) myosin inhibitor that is designed to limit contraction of fast muscle fibers • Inactive against slow skeletal and cardiac myofiber (type I) myosin and so does not directly affect cardiac function • In pre-clinical models, l
Slide 30: Sevasemten Targets Fast Myosin To Protect Dystrophic Muscle in mdx Mice
Sevasemten Targets Fast Myosin To Protect Dystrophic Muscle Against Contraction-Induced Injury In mdx Mice Contracting at 100% without sevasemten Contracting at 85% with sevasemten In mdx mouse muscle, even a few contractions cause By minimally decreasing contraction, while preserving visible injury
Slide 31: Open-label, single-center study of sevasemten in adults with Becker (NCT05160415)
An open-label, single-center study to assess sevasemten safety and pharmacokinetics in adults with Becker NCT05160415
Slide 32: An Open-Label, Single-Center Study To Assess Sevasemten Safety and Pharmacokinetics
An Open-Label, Single-Center Study To Assess Sevasemten Safety and Pharmacokinetics In Adults With Becker • Primary objective: Safety and tolerability at 24 months • Key inclusion criteria: Ambulatory males aged 18 to 55 years with a dystrophin mutation and a Becker phenotype, not on corticosteroids
Slide 33: Open-Label Study To Assess Sevasemten Safety and PK In Adults With Becker
An Open-Label, Single-Center Study To Assess Sevasemten Safety and PK In Adults With Becker ARCH is a 24-month open-label study in 12 ambulatory adults with Becker muscular dystrophy NSAA change +3 -0.2 mean • Sevasemten was well-tolerated. change in Change in NSAA score +2 • Early and rapid reducti
Slide 34: Phase 2 randomized placebo-controlled study of sevasemten (NCT05291091)
A multi-center, randomized, double-blind, placebo-controlled, Phase 2 study to evaluate the safety, pharmacokinetics, biomarkers, and functional measures of sevasemten NCT05291091
Slide 35: A Phase 2 Multi-Center Study to Assess Sevasemten Safety and Effects on Biomarkers
A Phase 2 Multi-Center Study to Assess Sevasemten Safety and Effects on Biomarkers in Adults with Becker ADULT PRIMARY EFFICACY KEY INCLUSION CRITERIA PATIENTS ENROLLED ENDPOINT Change from baseline in CK averaged Ambulatory males aged 12 to 50 years with a dystrophin mutation and a Becker Adults: 4
Slide 36: Adult Participants Had Significant Functional Impairment at Baseline
Adult Participants Had Significant Functionally Impairment at Baseline Adolescents Adults Sevasemten Adults Placebo Adolescents Placebo Functional test Sevasemten (n=28) (n=12) (n=9) (n=20) Mean total NSAA score, points 18.4 (7.66) 24.2 (8.19) 31.3 (2.53) 29.3 (6.34) (SD) Mean 4SC velocity, 1/second
Slide 37: Sevasemten was Well Tolerated in Adults and Adolescents
Sevasemten was Well Tolerated in Adults and Adolescents Adults Adolescents Adolescents Adults Placebo (n=12) n Sevasemten (n=20) n Placebo (n=9) n Sevasemten (n=28) n (%) (%) (%) (%) Any TEAE in ≥5% of participants 26 (92.9%) 10 (83.3%) 19 (95%) 9 (100%) Eye disorders Vision blurred 1 (3.6%) 2 (17%)
Slide 38: Biomarkers of Muscle Damage Decreased Significantly
Biomarkers of Muscle Damage Decreased Significantly Primary Endpoint: TNNI2 % Change from Baseline CK % Change from Baseline -28% * -77% ** * p-value = 0.02 ** p-value < 0.001 *p-value < 0.05 **p-value < 0.001 Sevasemten Placebo LS Means, LS Mean differences and 95% CI shown for Safety Population. C
Slide 39: NSAA Trajectory on Sevasemten Diverged from Natural History
NSAA Trajectory on Sevasemten Diverged from Natural History NSAA Score Change from Baseline 12 Months in 2 1 +0.8 (change from baseline) vs baseline Natural history studies Total NSAA Score 0 +1.12* have shown that NSAA NSAA vs placebo at month 12 +0.2 decreased between an average of 1 to 1.7 -1 sin
Slide 40: 63% of Patients Treated with Sevasemten Showed Stable or Improved Function After 12 Months
63% of Patients Treated with Sevasemten Showed Stable or Improved Function After 12 Months Sevasemten NSAA Responder Analysis CFB NSAA Score 6 37% 4 63% 2 Individuals on sevasemten -2 Odds Ratio: 3.4 (p=0.16) -4 -6 Stability or Improvement 6 67% 4 33% 2 Individuals on placebo -2 -4 -6 CFB NSAA Score
Slide 41: Trends in Other Functional Measures Favor Sevasemten Treatment Arm
Trends in Other Functional Measures Favor Sevasemten Treatment Arm Favors Placebo Favors Sevasemten LSMean Difference NSAA 1.12 10MWR Velocity 0.075 100MTT Velocity 0.055 4SC Velocity 0.024 RFF Velocity* -0.005 -4 -2 0 2 4 Standardized Statistics (95% CI) *At baseline, 9 sevasemten and 1 placebo tre
Slide 42: Adolescents Treated with 12.5 mg Sevasemten had Significant Decreases in CK and TNNI2
Adolescents Treated with 12.5 mg Sevasemten had Significant Decreases in CK and TNNI2, Similar to Changes in Adults Primary Endpoint: TNNI2 % Change from Baseline CK % Change from Baseline * p-value = 0.02 ** p-value < 0.001 *p-value < 0.05 *p-value < 0.05 Placebo 5 mg 12.5 mg Placebo 5 mg 12.5 mg S
Slide 43: Summary of Trial Results
For more information on CANYON, Summary of Trial Results please see Poster #614P • Well-tolerated at all doses, in adults and adolescents Safety • No safety concerns identified • Primary endpoint achieved: 28% decrease in CK vs. placebo (p<0.05) in adults • TNNI2 decreased 77% from baseline vs. plac
Slide 44: An Open-Label Extension of Sevasemten in Participants with Becker Muscular Dystrophy
An Open-Label Extension of Sevasemten in Participants with Becker Muscular Dystrophy NCT06066580
Slide 45: Sevasemten Efficacy in Becker Continues to be Assessed in the MESA Open-Label Study
Sevasemten Efficacy in Becker Continues to be Assessed in the MESA Open-Label Study Phase 1: 24-month Open Label Study (N=12) COMPLETE Phase 2: 16-weeks Placebo Controlled Exercise Challenge Study (N=9) COMPLETE Phase 2: 12-month Placebo Controlled Study (N=40 Adults) COMPLETE Pivotal Cohort: 18-mon
Slide 46: After Transitioning To MESA, CANYON Participants Showed an Increase in NSAA After 18 Months
After Transitioning To MESA, CANYON Participants Showed an Increase in NSAA After 18 Months 2 12 Months in 6 Months in 1 +0.8 (change from baseline) vs baseline Total NSAA Score 0 -1 +0.2 since initiation of sevasemten Range from NHx -2 Studies -3 Participants remain blinded to initial Sevasemten Pl
Slide 47: CANYON Participants' NSAA Scores Diverge from Predicted Natural History
CANYON Participants' NSAA Scores Diverge from Predicted Natural History; 92% Improved vs their Predicted Scores NSAA Score Change from Baseline 2 12 Months in 6 Months in 1 +0.8 (change from baseline) Total NSAA Score 0 D= -1 +3.0 -2 Sevasemten -2.2 Predicted NSAA -3 Predicted NSAA trajectory based
Slide 48: ARCH Participants Remained Stable After 3 Years vs a Predicted Decline
ARCH Participants Remained Stable After 3 For more information on the application of the model to Years vs a Predicted -4.4 Point NSAA Decline; ARCH & CANYON, please 89% Achieved Higher NSAA Scores vs Predicted see poster #629P 4 NSAA Score Change from Baseline 24 Months in 12 Months in 2 (change fr
Slide 49: GRAND CANYON is Fully Enrolled and Ongoing
Sevasemten Continues to be Investigated in Becker; GRAND CANYON is Fully Enrolled and Ongoing An 18-month pivotal placebo-controlled trial to evaluate the effect of sevasemten on biomarkers of muscle damage and functional measures in individuals living with Becker Primary Endpoint is NSAA at 18 mont
Slide 50: Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy
Slide 51: Duchenne Clinical Program at Edgewise Therapeutics
Duchenne Clinical Program at Edgewise Therapeutics Duchenne Study Goals: Explore a Range of Doses to Assess Safety and Identify a Phase 2 trial of sevasemten in Potentially Beneficial Dose for Phase 3 children with Duchenne Status: Active, not recruiting • Determine the target patient population, ba
Slide 52: Sevasemten is Positioned as a Foundational Therapy and Continues to be Investigated in Duchenne
Sevasemten is Positioned as a Foundational Therapy For more information on LYNX, and Continues to be Investigated in Duchenne please see Poster #730LBP Functional observations support the 10 mg dose of sevasemten as the dose to move forward with to a pivotal-stage program. Phase 2 trial of sevasemte
Slide 53: Sevasemten is Currently Being Investigated in Becker, Duchenne, and Other Muscular Dystrophies
Sevasemten is Currently Being Investigated in Becker, Duchenne, and Other Muscular Dystrophies Phase 1 Becker Open-label, safety, PK, function OLE Completed Phase 2 Becker, Exercise challenge study OLE Completed LGMD2i, & McArdle Becker Phase 2 Becker Biomarkers, safety, function OLE Completed Pivot
Slide 54: Thank You For Your Attendance!
Thank You For Your Attendance! We wish to thank the patients, investigators, study site personnel, and all of those who are helping to facilitate clinical trials and to improve care! Talk to Edgewise at Booth #16 For questions about our clinical trials, please email: Learn more at posters 614P, 629P
Slide 55: Panel Discussion
Panel Discussion We now welcome both virtual and in person questions from the audience. For virtual viewers, please utilize the WMS app to ask your questions. ? For the in person audience, please use the microphone to ask your question. Thank you! 55
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