Slide 1: Sevasemten: Topline Results from the CANYON Phase 2 Trial in Becker
1 ©2024 Edgewise Therapeutics. All rights reserved. Sevasemten: Topline Results from the CANYON Phase 2 Trial in Becker December 16, 2024
Slide 2: Forward-looking statements
2 This presentation contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this presentation that are not purely historical are forward-looking statements. Such forward-looking sta
Slide 3: Agenda
Agenda 1. Introduction 2. Becker muscular dystrophy and sevasemten 3. Topline results: Phase 2 CANYON trial in Becker 4. Sevasemten future development plans 5. Clinical perspectives on the results 6. Closing remarks 7. Q & A Distinguished Professor and Chair at the UC Davis Health Department of Phys
Slide 4: Focused on muscle science
Focused on muscle science ● Global leader in muscle disease therapeutic development ● Deep knowledge of integrated muscle physiology ● Novel & holistic therapeutic approach to protect muscle Rapidly advancing portfolio ● Sevasemten pivotal program in muscular dystrophies including potential first tr
Slide 5: The Evolution of Edgewise
5 The Evolution of Edgewise 2017 2020 2022 2023 2025 Founded as a muscle platform company targeting genetically driven muscle diseases EWTX completes IPO, expands development programs First program targeting muscular dystrophies Sevasemten, a fast skeletal myosin inhibitor, enters P1 in HVs and Beck
Slide 6: ARCH, CANYON and the Evolution to GRAND CANYON
6 ARCH, CANYON and the Evolution to GRAND CANYON Expedited the Development Timeline for Sevasemten in Becker • The Phase 2 CANYON study was originally designed as a dose-finding study to evaluate the effect of sevasemten on safety, pharmacokinetics, biomarkers, and function in individuals with Beck
Slide 7: Becker Muscular Dystrophy and Sevasemten
Becker Muscular Dystrophy and Sevasemten Dr. Joanne Donovan
Slide 8: Our goal is to positively impact the course of Becker muscular dystrophy
8 I was told, ‘You’re lucky you don’t have Duchenne.’ It’s frustrating that you live longer, but you are constantly going downhill” – Individual living with Becker Our goal is to positively impact the course of Becker muscular dystrophy ● Becker is a rare, genetic, life-shortening, debilitating and
Slide 9: Sevasemten: A First-in-Class Fast Myofiber Myosin Inhibitor
9 Sevasemten is an investigational therapy that has not been approved for use in muscular dystrophies by any regulatory agency, as its safety and effectiveness have not been established for the treatment of these diseases. Abbreviations: CK, creatine kinase Sevasemten: A First-in-Class Fast Myofiber
Slide 10: Muscle Injury Biomarkers Indicate Ongoing Muscle Damage
Abbreviations: CK, Creatine Kinase; TNNI2, Fast Skeletal Muscle Troponin I 10 Elevated Circulating Levels of Muscle Injury Biomarkers, including CK and TNNI2, Indicate Ongoing Muscle Damage in Muscular Dystrophies Contraction-Induced Muscle Injury in Muscular Dystrophies Contraction induced muscle d
Slide 11: Our Commitment to Becker: Completed and Ongoing Clinical Trials
11 PK, biomarkers and longer-term safety OLE Complete Function (NSAA), PK, biomarkers and longer-term safety OLE Recruiting GRASP Recruiting -01-002 24-Month, observational study Abbreviations: LGMD, limb-girdle muscular dystrophy; NSAA, North Star ambulatory assessment; PK, pharmacokinetics Our Com
Slide 12: CANYON Topline Results
THERAPEUTICS «J CANYON Topline Results
Slide 13: CANYON Phase 2 Study Design
13 A Phase 2 Multi-Center Study to Assess Sevasemten Safety and Effect on Biomarkers in Adults with Becker * Adolescents were not selected based on NSAA Reference: NCT05160415 Abbreviations: CK, creatine kinase 5 mg or 12.5 mg PO daily Study design - 12 months Key Secondary: North Star Ambulatory As
Slide 14: Summary of Key Study Metrics
14 Summary of Key Study Metrics * Trial sites in the US, UK and the Netherlands 16 sites 3 countries Enrollment: Largest Becker study to date Total of 80 patients screened and 69 patients enrolled: • Adults: 40 • Adolescents: 29 Low discontinuation rate • 4% overall • 2.5% in adult cohort (1 out of
Slide 15: Becker Mutation Overview
15 Becker Mutation Overview: Slow Progressor Genotypes were Largely Excluded with Functional Cut-Off Criteria Mutation type Adults (N=40) Adolescents (N=29) Becker mutations associated with progression 39 26 45-x 20 11 Other 19 15 None/very slow progression Becker mutations 1 3 X-51 1 (sevasemten) 2
Slide 16: Overview of Baseline Function in Safety Population
16 Overview of Baseline Function in Safety Population *At baseline, 1 placebo and 9 sevasemten treated participants were unable to rise from floor Functional test Adults Sevasemten (n=28) Adults Placebo (n=12) ARCH (N=12) Mean total NSAA score, points (SD) 18.4 (7.66) 24.2 (8.19) 15.1 (8.4) Mean 4SC
Slide 17: Functional Measures Not Well Matched at Baseline
17 Functional Measures Not Well Matched at Baseline; Patients in Sevasemten Group had Lower Baseline NSAA *At baseline, 1 placebo and 9 sevasemten treated participants were unable to rise from floor Functional test Adults Sevasemten (n=28) Adults Placebo (n=12) Difference (from placebo) P-value vs.
Slide 18: Sevasemten Well Tolerated: Overview of TEAEs
18 Sevasemten was Well Tolerated: Overview of Treatment Emergent Adverse Events (TEAE) * A treatment emergent adverse event (TEAE) is any adverse event (AE) that starts during or after the first dose of investigational product through the end of the safety follow-up period Functional test Sevasemten
Slide 19: TEAEs Occurring in ≥5% of Total
19 Sevasemten was Well Tolerated: TEAEs Occurring in ≥5% of Total System Organ Class/Preferred Term Sevasemten (n=28) n (%) Placebo (n=12) n (%) Total (N=40) n (%) Any TEAE 26 (92.9%) 10 (83.3%) 36 (90%) Eye disorders Vision blurred 1 (3.6%) 2 (17%) 3 (8%) Gastrointestinal disorders Abdominal pain 1
Slide 20: Statistically Significant Decrease in Primary Endpoint of CK
20 Statistically Significant Decrease in the Primary Endpoint of CK: 28% Reduction vs Placebo Note: CK values are log-transformed. LS (least squares) means, LS mean differences and CIs were back-transformed to percent scale Abbreviations: CFB, change from baseline, CI, confidence interval, CK, creat
Slide 21: TNNI2 Decreased 77% from Baseline vs Placebo
21 TNNI2 Decreased 77% from Baseline in the Sevasemten Treatment Group vs Placebo TNNI2 between-group difference LSMean: -77% (95% CI -89% to 51%); p-value < 0.001 Average 6 -12 months Sevasemten Placebo 0 3 6 9 12 -100 0 100 200 Time (months) % CFB in TNNI2 Placebo Sevasemten -100 -50 0 50 100 150
Slide 22: Key Secondary Endpoint: NSAA Remained Stable
22 Key Secondary Endpoint: NSAA Remained Stable Over Time in Sevasemten Group 0 3 6 9 12 -3 -2 -1 0 1 2 Time (months) CFB Total NSAA Score NSAA between-group difference LSMean: 1.12 (95% CI -0.4 to 2.7); p-value = 0.16 Sevasemten Placebo Positive trends in NSAA favoring sevasemten with placebo decli
Slide 23: 63% of Patients Showed Stable or Improved Function After 12 Months
23 63% of Patients Treated with Sevasemten Showed Stable or Improved Function After 12 Months Sevasemten NSAA Responder Analysis -6 -4 -2 2 4 6 -6 -4 -2 2 4 6 Placebo (n=12) Sevasemten (n=27) 63% 33% 67% 37% Stability or Improvement Odds Ratio: 3.4 (p=0.16) Abbreviations: NSAA, North Star Ambulatory
Slide 24: Trends in Other Functional Measures Favor Sevasemten
24 Trends in Other Functional Measures Favor Sevasemten Treatment Arm -4 -2 0 2 4 RFF Velocity 4SC Velocity 100MTT Velocity 10MWR Velocity NSAA Standardized Statistics (95% CI) 1.12 0.075 0.055 0.024 -0.005 LSMean Difference * At baseline, 9 sevasemten and 1 placebo treated participants were unable
Slide 25: Summary of Trial Results
25 Summary of Trial Results • Sevasemten treated patients showed stabilization of NSAA with trends toward improvement • Placebo group (n=12) declined in line with natural history • Primary endpoint achieved: 28% average decrease in CK versus placebo (p=0.02) • Plasma TNNI2 decreased 77% from baselin
Slide 26: Sevasemten Future Development Plans
Sevasemten Future Development Plans
Slide 27: GRAND CANYON Pivotal Cohort Design
27 9 15 Global, Multi-Center, Placebo-Controlled Pivotal Cohort Assessing Efficacy & Safety of Sevasemten in Becker Abbreviations: PO, by mouth; NSAA, North Star Ambulatory Assessment PRIMARY ENDPOINT NSAA at 18 months KEY INCLUSION CRITERIA Adult individuals with Becker with NSAA 5-32, not taking c
Slide 28: GRAND CANYON Powered at 96% to Show 1.68 Point NSAA Difference
28 GRAND CANYON Powered at 96% to Show a 1.68 Point NSAA Difference at 18 Months p<0.05 Treatment Difference Power Calculation Assumptions: • N=120 patients with 2:1 randomization • Month 12 CANYON treatment difference = 1.12 • Assumed 50% increase in NSAA treatment effect at month 18 vs month 12 (
Slide 29: Sevasemten for Becker Next Steps
29 Sevasemten for Becker Next Steps *European sites include the UK, Netherlands, Belgium, Denmark, Spain, France, Germany and Italy Increased confidence in GRAND CANYON future success based on sevasemten clinical experience to date, Becker natural history data, and internal modeling CANYON results s
Slide 30: CANYON Clinical Implications and Sevasemten's Potential Role in Becker
CANYON Clinical Implications and Sevasemten’s Potential Role in Becker Dr. Craig M. McDonald
Slide 31: Natural History Data in Becker Support Predictable Functional Decline
31 Reference: 1. Bello L, et al. 2016. 2. De Wel B, et al. Eur J Neurol. 2024. 3. Van de Velde NM, et al. Neurology. 2021.;4. Bello L et al 2024 WMS; 95% CI shown Natural History Data in Becker Support that Functional Decline, Measured by NSAA, is Consistent and Predictable 0 1 2 3 4 5 -10 -8 -6 -4
Slide 32: A Clinician's Perspective on Interpreting a 1-point NSAA Change
32 A Clinician’s Perspective on How to Interpret a 1-point NSAA Change in Becker From using the toilet independently… …to asking for help to get up from the toilet. …to requiring assistance from another person or mobility device. …to requiring someone else’s help to get back up. From using stairs or
Slide 33: Closing Remarks
Closing Remarks Kevin Koch, CEO
Slide 34: We Aim to Change the Lives of Individuals with Becker
We Aim to Change the Lives of Individuals with Becker ~12,000 PEOPLE WITH BECKER IN US, EU-5 & JAPAN ~16 AGE PEOPLE WITH BECKER CAN BECOME MOBILITY DEVICE DEPENDENT • Source: Parent Project Muscular Dystrophy: Fifteen Year Registry Report; Edgewise Therapeutics independent quantitative and qualitati
Slide 35: Edgewise Upcoming Value-Generating Milestones
35 Abbreviations: HV, healthy volunteers; oHCM, obstructive hypertrophic cardiomyopathy; nHCM, non-obstructive hypertrophic cardiomyopathy; CV, cardiovascular; IND, Investigational New Drug application; POC, proof of concept Edgewise Upcoming Value-Generating Milestones H2 2024 H1 2025 H2 2025 Becke
Slide 36: Well-Capitalized to Execute Important Milestones
36 As of September 30, 2024 Well-Capitalized to Execute Important Milestones Across Both EDG-7500 & Sevasemten (1) DEBT (1) $0 CASH, CASH EQUIVALENTS & MARKETABLE SECURITIES ~$493M COMMON SHARES OUTSTANDING (NASDAQ: EWTX) ~94M CASH RUNWAY THROUGH 2027
Slide 37: Q&A
THERAPEUTICS Q&A