Edgewise Therapeutics, Inc. · NASDAQ:EWTX

Edgewise Therapeutics — Conference Presentation (August 2024)

29 slides from Edgewise Therapeutics's conference presentation, August 2024

  1. Slide 1: Clinical Development of EDG-5506 in Duchenne and Becker Muscular Dystrophy

    Clinical Development of EDG-5506 in Duchenne and Becker Muscular Dystrophy Joanne Donovan, M.D., Ph.D. Chief Medical Officer Edgewise Therapeutics 1

  2. Slide 2: Disclosures

    Disclosures • This presentation contains forward-looking statements that involve substantial risks and uncertainties of Edgewise Therapeutics, Inc. (“Edgewise” or the “Company”). All statements other than statements of historical facts contained in this presentation, including statements regarding o

  3. Slide 3: BMD and DMD Represent Severe Dystrophinopathies

    BMD and Duchenne Muscular Dystrophy (DMD) Represent Severe Dystrophinopathies Spectrum of Severity Across Dystrophinopathies Functional Dystrophin Normal Levels No Dystrophin BMD DMD Severe No Damage Intensity of Muscle Damage BMD and DMD represent a continuum of the same disease; Edgewise’s approac

  4. Slide 4: Schematic of Clinical Development of EDG-5506 to Date

    Schematic of Clinical Development of EDG-5506 to Date Phase 1 in Healthy Adults and Adults with Becker Muscular Dystrophy Open-label Study in Becker Muscular Dystrophy Phase 2 in Adults and Phase 2 in Children with Adolescents with Becker Duchenne Muscular Muscular Dystrophy Dystrophy 4

  5. Slide 5: EDG-5506 Represents a Novel, Potentially Disease-Modifying MOA for DMD and BMD

    EDG-5506 Represents a Novel, Potentially Disease-Modifying MOA for DMD and BMD The Core Problem in Dystrophinopathies EDG-5506 • Increased muscle injury biomarkers in plasma Reduced muscle Daily mechanical stress on muscle • Replacement of muscle by fat and fibrosis function fibers results in muscle

  6. Slide 6: EDG-5506 Phase 1 Study in Healthy Volunteers and Participants with BMD

    EDG-5506 Phase 1 Study Conducted in Healthy Volunteers and Participants with Becker Muscular Dystrophy Ambulatory Subjects with Becker Muscular Healthy Volunteers Dystrophy (BMD) • Single Ascending Doses: up to 135 mg, • Multiple Doses: 20 mg/day, administered as solid administered as liquid formula

  7. Slide 7: Overview of Healthy Volunteers Phase 1a SAD/MAD with EDG-5506

    Overview of Healthy Volunteers (HVs) Phase 1a SAD/MAD with EDG-5506 EDG-5506 was generally well tolerated with no serious adverse events observed. Most common AEs were somnolence and dizziness, which were generally mild and transient Plasma PK showed good oral absorption with or without food, and an

  8. Slide 8: Participants in the BMD Phase 1b Had Significant Baseline Functional Impairment

    Participants in the BMD Phase 1b Had Significant Baseline Functional Impairment Characteristic BMD Participants (N=7) Age Normative Values Age 33.8 years Functional Measures (median) 10-meter walk/run 8.3 sec < 4 sec Rise from floor 20 sec < 3 sec Serum Creatinine (mean, mg/dL) 0.58 0.92 - 1.16 Seru

  9. Slide 9: EDG-5506 Concentrates in Healthy and Dystrophic Muscle

    EDG-5506 Concentrates in Healthy and Dystrophic Muscle, Demonstrating Delivery of Drug to the Target, Fast Myosin Daily Dose Muscle (ng/g)* Healthy Adults 5 mg* 980 Liquid Healthy Adults 10 mg* 2,740 Formulation Healthy Adults 20 mg 4,360 Healthy Adults 20 mg 6,140 Solid Dosage Form Healthy Adults 4

  10. Slide 10: A Proteomic Signature for BMD Was Identified Using SOMAscan

    Using SOMAscan 7,000 Analyte Set, A Proteomic Signature for BMD was Identified Baseline BMD vs. Healthy Biomarker Fingerprint Analysis PROTEINS LOWER IN BMD PROTEINS HIGHER IN BMD • Baseline plasma samples (n=7) were compared to samples from healthy volunteers (n=25) • Proteins filtered by magnitude

  11. Slide 11: The Majority of BMD Signature Proteins are Lowered by EDG-5506

    The Majority of BMD Signature Proteins are Lowered by EDG-5506 BMD Biomarkers Change From Baseline After 14 Days ✱✱✱✱ • BMD proteomic fingerprint unchanged in 3 ns ✱✱✱ control group following EDG-5506 treatment (Log2 Relative to Respective Baseline) 2 Plasma Concentration 1 • BMD participants treate

  12. Slide 12: Biomarkers Most Elevated in BMD are Decreased Most with EDG-5506

    Biomarkers Most Elevated in BMD are Decreased Most with EDG-5506 Change with 14 Days EDG-5506 Treatment Baseline BMD vs Placebo EDG-5506 Healthy (n=2) (n=5) Consistent response across Log2 Difference treated individuals with DD greatest decrease in the most elevated biomarkers Source: Data on file 1

  13. Slide 13: Elevated Biomarkers Decrease Most Following EDG-5506

    Elevated Biomarkers Decrease Most Following EDG-5506 2 • Close association of elevated BMD biomarkers with EDG-5506 response Decreased by EDG-5506 at 14 days treatment (Log2) 1 reveals a significant relationship to biomarker lowering 0 -1 • Overall, this suggests a broad -2 normalization of the BMD

  14. Slide 14: Consistent and Progressive EDG-5506 Effect on Exercise Responsive Markers

    Consistent and Progressive EDG-5506 Effect on Exercise Responsive Markers EDG-5506 (N=5) • In adults with BMD SOMAscan 3 ✱✱✱✱ samples from an exercise study were (Log2 Relative to Pre-Dose Baseline) used to define a proteomic signature 2 ✱✱✱✱ that was elevated compared to Plasma Concentration ✱✱✱✱ c

  15. Slide 15: One Year Open Label Study Design

    One Year Open Label Study Design • An open-label, single-center study of EDG-5506 to assess the safety and pharmacokinetics (PK) of EDG-5506 in adults with Becker muscular dystrophy (BMD) —12 patients enrolled, ambulatory with BMD, including all from Phase 1 study Screening After 6 months all EDG-55

  16. Slide 16: Participants in the BMD Open-Label Study Had Significant Baseline Functional Impairment

    Participants in the BMD Open-Label Study Had Significant Baseline Functional Impairment R ange of N S A A and N S A D BMD Participants Age Normative Characteristic (N=12) Values 54 Age 32.8 (8.1) years r2= 0.9595 Functional Measures (median) 40 10-meter walk/run 8.4 sec < 4 sec NSAD Rise from floor

  17. Slide 17: Functional Measures Correlate with Measures of Muscle Mass

    Functional Measures Correlate with Measures of Muscle Mass 100 m walk/run vs. NSAD 100 m walk/run vs. creatinine % Lean Body Mass vs. NSAD 200 0.8 80 DXA Lean Body Mass (percent) 100 m walk/run time (secs) 150 0.6 70 Creatinine (ng/ml) 100 0.4 60 50 0.2 50 0 0.0 40 0 10 20 30 40 50 60 0 50 100 150 2

  18. Slide 18: EDG-5506 Continued to be Well Tolerated After Four Months of Dosing

    EDG-5506 Continued to be Well Tolerated After Four Months of Dosing with the 15 mg Dose; Six Months Total Dosing 2-month (%); 4-month period (%); Total Treatment Emergent AEs 10 mg EDG-5506 15 mg EDG-5506 6 months Dizziness 2 (17%) 1 (8%) 3 (25%) Somnolence 2 (17%) 1 (8%) 3 (25%) Headache - 3 (25%)

  19. Slide 19: Target Plasma PK Achieved After Increasing Dose; Continued Activity After 6 Months

    Target Plasma PK Achieved After Increasing Dose to 15 mg/day; BMD Patients Showed Continued Activity After 6 Months of Dosing 150 EDG-5506 Plasma PK Patient Step Count 5,000 Legend Mean AUC24 (ng/ml): 2,293 1,454 2,299 2,400 • Exposure with 15 mg dose 4,000 reached the target exposures observed with

  20. Slide 20: EDG-5506 Led to Sustained Decrease in CK and Suppression of TNNI2

    EDG-5506 Led to a Sustained Decrease in CK and Profound Suppression of TNNI2 Demonstrating Target Engagement Creatine Kinase Fast Skeletal Muscle Troponin I (TNNI2) 3,000 2,000 150 50 ✱✱✱ ✱✱✱ 40 1,500 TNNI2 Concentration (ng/ml) TNNI2 Concentration (ng/ml) 2,000 100 CK Activity (U/L) CK Activity (U/

  21. Slide 21: SOMAscan Signature of Long-Term Response Emerging with Treatment?

    SOMAscan Signature of Long-Term Response Emerging with Treatment? 2.0 Normalized Protein Concentration 1.5 1.0 0.5 0.0 s s s s l th e tro th th th th lin on on on on on on se M M M M M C Ba 1 y 2 3 4 6 lth D BM ea H • Previous studies focused on rapidly-changing biomarkers of muscle injury with EDG-

  22. Slide 22: Natural History of BMD Provides Context for Interpreting Changes in NSAA

    The Natural History of BMD Provides Helpful Context for Interpreting Changes in NSAA in Response to EDG-5506 34 30 • Luca Bello’s BMD Natural History Study, the most comprehensive study of its kind to date, demonstrates that NSAA 25 decline is consistent in BMD patients who are already progressing 2

  23. Slide 23: NSAA and NSAD Durable Improvements Relative to Natural History

    NSAA and NSAD Durable Improvements Observed Over 6 Months of EDG-5506 Relative to Natural History NSAA change NSAD change 3 3 Change in NSAA Change in NSAD 2 2 1 1 0 0 Natural History -1 Average -1 -2 -2 0 2 4 6 0 2 4 6 Month of Treatment Month of Treatment NSAA Represents an Integrated Measure of F

  24. Slide 24: Diffuse Pain in Becker Muscular Dystrophy

    Diffuse Pain in Becker Muscular Dystrophy • Self-reported pain over the previous 3 months in Duchenne and Becker muscular dystrophy (DMD N=15, Age 24+/-6 yrs; BMD N=18, Age 42+/-14 yrs) • 10/18 BMD ambulant • BMD individuals report more diffuse pain, focus on spine and calves PLoS ONE 14(2): e021243

  25. Slide 25: Self-Reported Pain Scores Also Trended Better Following EDG-5506 Dosing

    Self-Reported Pain Scores Also Trended Better Following 6 Months of EDG-5506 Dosing 5 • While the ARCH study is not placebo controlled, a Self-Reported Pain Score (0-10) 4 positive trend in self-reported pain scores was 3 observed after 6 months of EDG-5506 dosing 2 • Additionally, other patient-rep

  26. Slide 26: Ongoing and Upcoming Clinical Studies with EDG-5506

    Ongoing and Upcoming Clinical Studies with EDG-5506 Status Phase 1 OL Study (BMD) (NCT05160415) Steady-state PK, biomarker response and longer-term safety Fully Enrolled Natural History Study in BMD (NCT05257473) Observational natural history study in BMD adults and adolescents Enrolling Conducted b

  27. Slide 27: Phase 2 Study in Adults and Adolescents with Becker

    Phase 2 Study in Adults and Adolescents with Becker • Population: —Age 12 to 50 years old, inclusive —Confirmed mutation in dystrophin gene with characteristic Becker phenotype —Ambulatory —Not on corticosteroids • Design: 12-month placebo-controlled • Endpoints: —Biomarker (CK) at 12 months —Safety

  28. Slide 28: Phase 2 Dose-Ranging Study in Boys with Duchenne

    Phase 2 Dose-Ranging Study in Boys with Duchenne • Planned to start in Q4 2022 • Population: —4 to 9 years old, inclusive —Confirmed mutation in dystrophin gene with characteristic phenotype —Ambulatory —On stable dose of corticosteroids; can be on approved exon-skipping rx • Design: 3-month placebo

  29. Slide 29: Acknowledgements: Study Participants and their families

    Acknowledgements: Study Participants and their families Rare Disease Research Atlanta GA Principal Investigator: Han Phan, MD Site Personnel: Emily Murray Alvin Nguyen Darwin Nguyen H 29

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