Edgewise Therapeutics, Inc. · NASDAQ:EWTX
Edgewise Therapeutics — Technical Presentation (December 2024)
38 slides from Edgewise Therapeutics's technical presentation, Dec 16, 2024
Slide 1: Sevasemten: Topline Results from the CANYON Phase 2 Trial in Becker
Sevasemten: Topline Results from the CANYON Phase 2 Trial in Becker December 16, 2024 1 ©2024 Edgewise Therapeutics. All rights reserved.
Slide 2: Forward Looking Statement
Forward Looking Statement 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.
Slide 3: Agenda
Agenda Dr. Kevin Koch 1. Introduction Chief Executive Officer 2. Becker muscular dystrophy and sevasemten 3. Topline results: Phase 2 CANYON trial in Becker Dr. Joanne Donovan Chief Medical Officer 4. Sevasemten future development plans 5. Clinical perspectives on the results Dr. Craig M. McDonald D
Slide 4: Focused on muscle science, rapidly advancing portfolio, unwavering patient commitment
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
Sevasemten, The Evolution of Edgewise P2 CANYON 12-month results in Becker Initiated Initiated Becker GRAND CANYON Sevasemten First program Sevasemten, a fast ARCH open label pivotal cohort ARCH open label targeting skeletal myosin study with Sevasemten sevasemten in 24-month results muscular inhibi
Slide 6: ARCH, CANYON and the Evolution to GRAND CANYON Expedited the Development Timeline
ARCH, CANYON and the Evolution to GRAND CANYON Expedited the Development Timeline for Sevasemten in Becker Original CANYON Design Expanded CANYON/GRAND CANYON Design 10 mg PO daily 10 mg PO daily (12 mos.) N=40 15 mg PO daily Placebo 20 mg PO daily PIVOTAL Cohort 10 mg PO daily (18 mos.) Placebo N=
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
Our goal is to positively impact the course of Becker muscular dystrophy ● Becker is a rare, genetic, life-shortening, debilitating and degenerative neuromuscular disorder ● The disease predominately affects males and imposes significant physical, emotional, financial and social impacts on the indiv
Slide 9: Sevasemten: A First-in-Class Fast Myofiber (Type II) Myosin Inhibitor
Sevasemten: A First-in-Class Fast Myofiber (Type II) Myosin Inhibitor Designed to Protect Against Contraction-Induced Muscle Injury Sevasemten Therapeutic Hypothesis Protected sarcomere Prevention of Sevasemten contraction-induced muscle injury Duchenne Excessive contraction induced muscle damage Co
Slide 10: Elevated Circulating Muscle Injury Biomarkers Indicate Ongoing Muscle Damage
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 damage Fast fibers are subsequently injured leading to release of muscle causes
Slide 11: Our Commitment to Becker: Completed and Ongoing Clinical Trials
Our Commitment to Becker: Completed and Ongoing Clinical Trials Phase 1 Becker Open-label, safety, PK, function OLE Complete Phase 2 Becker, Complete Exercise challenge study OLE LGMD2i, & McArdle Phase 2 Becker PK, biomarkers and longer-term safety OLE Complete Pivotal Cohort Becker Function (NSAA)
Slide 12: Topline Results
THERAPEUTICS «J CANYON Topline Results
Slide 13: A Phase 2 Multi-Center Study to Assess Sevasemten Safety and Effect on Biomarkers
A Phase 2 Multi-Center Study to Assess Sevasemten Safety and Effect on Biomarkers in Adults with Becker ADULT PRIMARY EFFICACY KEY INCLUSION CRITERIA PATIENTS ENROLLED ENDPOINT Change from baseline in CK Ambulatory males aged 12 to 50 years with a dystrophin mutation Adults: 40 averaged across Month
Slide 14: Summary of Key Study Metrics
Summary of Key Study Metrics Enrollment: Largest Becker study to date Total of 80 patients screened and 69 patients enrolled: • Adults: 40 3 * • Adolescents: 29 countries Low discontinuation rate • 4% overall 16 • 2.5% in adult cohort (1 out of 40 enrolled) sites 99% of eligible participants enrolle
Slide 15: Becker Mutation Overview
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 (s
Slide 16: Overview of Baseline Function in Safety Population
Overview of Baseline Function in Safety Population Adults Sevasemten Adults Placebo ARCH Functional test (n=28) (n=12) (N=12) Mean total NSAA score, points (SD) 18.4 (7.66) 24.2 (8.19) 15.1 (8.4) Mean 4SC velocity, 1/seconds (SD) 0.22 (0.128) 0.34 (0.173) 0.19 (0.164) Mean RFF velocity, 1/seconds (S
Slide 17: Functional Measures Not Well Matched at Baseline
Functional Measures Not Well Matched at Baseline; Patients in Sevasemten Group had Lower Baseline NSAA Adults Sevasemten Adults Placebo Difference P-value vs. Functional test (n=28) (n=12) (from placebo) Placebo Mean total NSAA score, points (SD) 18.4 (7.66) 24.2 (8.19) -5.8 0.04 Mean 4SC velocity,
Slide 18: Sevasemten was Well Tolerated: Overview of TEAEs
Sevasemten was Well Tolerated: Overview of Treatment Emergent Adverse Events (TEAE) Sevasemten (n=28) Placebo (n=12) Total (N=40) Functional test n (%) n (%) n (%) Any TEAE* 26 (92.9) 10 (83.3) 36 (90) Severe TEAE 0 (0) 0 (0) 0 (0) Serious Adverse Events 1 (3.6) 0 (0) 1 (2.5) Any drug related TEAE 1
Slide 19: Sevasemten was Well Tolerated: TEAEs Occurring in ≥5% of Total
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 (4
Slide 20: Statistically Significant Decrease in CK: 28% Reduction vs Placebo
Statistically Significant Decrease in the Primary Endpoint of CK: 28% Reduction vs Placebo CK between-group difference LSMean: -28% (95% CI -44% to -6%); p-value = 0.02 100 40 % CFB CK (Avg 6-12 mo) Average 6 -12 months 20 % CFB in CK 50 Placebo Sevasemten 0 0 -20 -50 -40 0 3 6 9 12 Placebo Sevasemt
Slide 21: TNNI2 Decreased 77% from Baseline vs Placebo
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 % CFB TNNI2 (Avg 6-12 mo) Average 6 -12 months 200 150 % CFB in TNNI2 100 100 Placebo Sevasemten 50 0 0 -50 -100 -100 0 3 6 9 12 Placebo Se
Slide 22: Key Secondary Endpoint: NSAA Remained Stable Over Time
Key Secondary Endpoint: NSAA Remained Stable Over Time in Sevasemten Group NSAA between-group difference LSMean: 1.12 (95% CI -0.4 to 2.7); p-value = 0.16 CFB Total NSAA Score 2 1 0 -1 -2 Placebo Sevasemten -3 0 3 6 9 12 Time (months) Positive trends in NSAA favoring sevasemten with placebo declinin
Slide 23: 63% of Patients 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 6 37% 4 2 63% Sevasemten (n=27) -2 Odds Ratio: 3.4 (p=0.16) -4 -6 Stability or Improvement 6 67% 4 2 33% Placebo (n=12) -2 -4 -6 23 Abbreviations: NSAA, North Star Ambulatory
Slide 24: Trends in Other Functional Measures Favor Sevasemten
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 tr
Slide 25: Summary of Trial Results
Summary of Trial Results • Well-tolerated, at all doses, in adults and adolescents Safety • No safety concerns identified • Primary endpoint achieved: 28% average decrease in CK versus Biomarkers placebo (p=0.02) • Plasma TNNI2 decreased 77% from baseline versus placebo (p<0.001) • Sevasemten treate
Slide 26: Sevasemten Future Development Plans
Sevasemten Future Development Plans
Slide 27: Global, Multi-Center, Placebo-Controlled Pivotal Cohort
Global, Multi-Center, Placebo-Controlled Pivotal Cohort Assessing Efficacy & Safety of Sevasemten in Becker POTENTIAL REGISTRATIONAL COHORT PRIMARY ENDPOINT KEY INCLUSION ENROLLMENT POWERED AT CRITERIA NSAA at 18 months Adult individuals with Becker with NSAA 5-32, not taking corticosteroids >120 >9
Slide 28: GRAND CANYON Powered at 96% to Show a 1.68 Point NSAA Difference
GRAND CANYON Powered at 96% to Show a 1.68 Point NSAA Difference at 18 Months Power Calculation Assumptions: • N=120 patients with 2:1 randomization Power: 96% • Month 12 CANYON treatment difference = 1.12 • Assumed 50% increase in NSAA treatment effect at month 18 vs month 12 ( = 1.68) • 10% dro
Slide 29: Sevasemten for Becker Next Steps
Sevasemten for Becker Next Steps 1 2 3 4 CANYON results GRAND CANYON is To date, 99% of Increased support near full eligible Becker confidence in engagement with enrollment participants GRAND CANYON FDA & EMA in 51 sites across the who have completed future success about marketing United States, Eur
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 Consistent, Predictable Functional Decline
Natural History Data in Becker Support that Functional Decline, Measured by NSAA, is Consistent and Predictable Natural history of Becker muscular dystrophy • NSAA is utilized in muscular 0 dystrophy natural history studies to longitudinally assess function -2 Change in NSAA • Multiple natural histo
Slide 32: A Clinician's Perspective on Interpreting a 1-point NSAA Change
A Clinician’s Perspective on How to Interpret a 1-point NSAA Change in Becker For individuals living with Becker, this decline could look like: …to requiring assistance from another person or From using stairs mobility device. or steps… …to asking for help From using to get up from the the toilet to
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 0 APPROVED THERAPIES • Source: Parent Project Muscular Dystrophy: Fifteen Year Registry Report; Edgewise Therapeutics independent quant
Slide 35: Edgewise Upcoming Value-Generating Milestones
Edgewise Upcoming Value-Generating Milestones H2 2024 H1 2025 H2 2025 Becker Phase 2 CANYON GRAND CANYON 1-year placebo-controlled data ✓ Recruitment complete (Q1) Skeletal Sevasemten Duchenne Phase 2 LYNX & FOX Phase 3 trial Controlled dose-ranging data Initiation Phase 1/Phase 2 Phase 2 28-day stu
Slide 36: Well-Capitalized to Execute Important Milestones
Well-Capitalized to Execute Important Milestones Across Both EDG-7500 & Sevasemten CASH, CASH EQUIVALENTS & DEBT (1) COMMON (1) SHARES OUTSTANDING MARKETABLE SECURITIES (NASDAQ: EWTX) ~$493M $0 ~94M CASH RUNWAY THROUGH 2027 As of September 30, 2024 36
Slide 37: Q&A
THERAPEUTICS, Q&A
Slide 38: Edgewise Therapeutics
=>Edgewise THERAPEUTICS,
Edgewise Therapeutics — Technical Presentation (December 2024) on 6ix