Edgewise Therapeutics, Inc. · NASDAQ:EWTX

Edgewise Therapeutics — Technical Presentation (April 2025)

50 slides from Edgewise Therapeutics's technical presentation, Apr 2, 2025

  1. Slide 1: EDG-7500: Phase 2 CIRRUS-HCM Development Program Update

    EDG-7500: Phase 2 CIRRUS-HCM Development Program Update April 2, 2025 1

  2. 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.

  3. Slide 3: Agenda

    Agenda Dr. Kevin Koch Chief Executive Officer 1. Introduction to Edgewise Therapeutics Dr. Ahmad Masri 2. The continued unmet need in HCM Director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University and CIRRUS-HCM Investigator 3. Topline results: Phase 2 CIRRUS-HCM tria

  4. Slide 4: Focused on muscle science

    Focused on muscle science ● Global leader in muscle disease therapeutic development ● Deep knowledge of integrated muscle physiology ● Combined expertise in muscle biology and small molecule drug discovery to build our novel and differentiated muscle-focused platform Rapidly advancing portfolio ● Ad

  5. Slide 5: Our Pipeline

    Our Pipeline Pivotal / Regulatory Preclinical Phase 1 Phase 2 Phase 3 submission Cardiovascular EDG-7500 Undisclosed cardiac Hypertrophic cardiomyopathy (HCM) sarcomeric target Undisclosed cardiac sarcomeric Diseases of diastolic dysfunction target EDG-003 Cardiometabolic Undisclosed target Muscular

  6. Slide 6: Treatments for HCM Have Key Limitations Leaving Substantial Unmet Need for Patients

    Treatments for HCM Have Key Limitations Leaving Substantial Unmet Need for Patients LIMITED BENEFIT ACROSS SAFETY RISKS WORSEN RISK OF HEART FAILURE1,2 THE SPECTRUM OF HCM PATIENT EXPERIENCE Efficacy & safety Mavacamten Frequent limitations with black box echo interventions in warning for monitoring

  7. Slide 7: The Unmet Need in Hypertrophic Cardiomyopathy

    The Unmet Need in Hypertrophic Cardiomyopathy Ahmad Masri, MD MS Cardiomyopathy Section Head Director, Hypertrophic Cardiomyopathy Center Associate Professor of Medicine Oregon Health & Science University Disclosures: research grants from Pfizer, Ionis, Attralus, and Cytokinetics and consulting fees

  8. Slide 8: The Continuum in Hypertrophic Cardiomyopathy

    The Continuum in Hypertrophic Cardiomyopathy Myocyte hypertrophy, interstitial fibrosis, diastolic dysfunction underlie the continuum of HCM

  9. Slide 9: HCM Disease Complexity Requires Thorough Evaluation

    HCM Disease Complexity Requires Thorough Evaluation These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited.

  10. Slide 10: Burden of HCM is Substantial

    Burden of HCM is Substantial Data from the SHaRe Registry Ho CY et al. Circulation 2018

  11. Slide 11: Goals of Therapies in HCM Unmet Need

    Goals of Therapies in HCM Unmet Need • Rapid and consistent relief of • Non-obstructive HCM symptoms • No approved therapies • Improvement in quality of life • Obstructive HCM • Improvement in exercise capacity • Non responders • Mild obstruction • Favorable remodeling and in turn, • Diastolic dysfu

  12. Slide 12: Principles of Therapy: Improvement in Quality of Life

    Principles of Therapy → Improvement in Quality of Life* Validated tool in heart Beyond directionality, KCCQ is a robust Prognostic tool in heart failure failure and in HCM measure of magnitude of benefit Joseph et al. Circ HF 2013 Spertus et al. JACC 2020 Green et al. JACC 2000 *ACC/AHA Guidelines,

  13. Slide 13: Phase 2 CIRRUS-HCM Trial Part B (oHCM) and Part C (nHCM)

    Phase 2 CIRRUS-HCM Trial Part B (oHCM) and Part C (nHCM) Dr. Anjali Owens Medical Director, Center for Inherited Cardiac Disease Associate Professor of Medicine (Cardiovascular Medicine) at the Hospital of the University of Pennsylvania Disclosures: Consulting/advisory boards for Alexion, Avidity, B

  14. Slide 14: Single Dose Study in oHCM Highlighted the Potential for EDG-7500

    Single Dose Study in oHCM Highlighted the Potential for EDG- 7500 as a Novel Therapy for Patients with HCM Observations from CIRRUS-HCM Single Dose Study Highlighted EDG-7500’s Potentially Differentiated Profile in HCM Resting LVOT-G (N=7) LVEF Reduction (N=11) ● EDG-7500 was well tolerated across a

  15. Slide 15: EDG-7500 Fixed Daily Dosing 28-Days in oHCM and nHCM Study Design

    EDG-7500 Fixed Daily Dosing 28-Days in oHCM (Part B) and nHCM (Part C) Study Design KEY INCLUSION TOTAL CIRRUS TARGET ENROLLMENT KEY OUTCOME PRIMARY OBJECTIVE CRITERIA MEASURES Safety & tolerability in adults with HCM Male and female patients ≥18 yrs of age with HCM LVEF ≥60% ~70 Cardiovascular PD,

  16. Slide 16: CIRRUS-HCM Part B and C: Baseline Demographic and Clinical Characteristics

    CIRRUS-HCM Part B and C: Baseline Demographic and Clinical Characteristics Baseline Characteristics CIRRUS oHCM (Safety; n=17) CIRRUS nHCM (Safety; n=12) Age (yrs.) 61 54 Sex, % females 71% 58% BMI (kg/m2) 28 27 History of AF 6% 8% ICD 12% 50% Prior SRT 6% 0% Hypertension 65% 17% Diabetes 6% 17% NYH

  17. Slide 17: Prespecified oHCM Efficacy Evaluable Population for LVOT-G

    Prespecified oHCM Efficacy Evaluable Population for LVOT-G 1. Received at least 1 dose of EDG-7500 2. Baseline LVOT peak gradient ≥ 30 mmHg measured at rest and ≥ 50 mmHg measured during the Valsalva maneuver as determined by echocardiography 3. A good acoustic window and ability to obtain a high-qu

  18. Slide 18: Part B - Obstructive HCM

    CIRRUS @icw Part B - Obstructive HCM

  19. Slide 19: Cohort B (oHCM): Patients in Safety Population; Efficacy Evaluable

    Cohort B (oHCM): 17 Patients Assessed as Part of the Safety Population; 12 Patients Met the Efficacy Evaluable Criteria Pooled Safety Population Safety population assessed for LVEF, N=17 NT-proBNP, KCCQ, NYHA and e’ 50 mg 100 mg Safety Population Safety Population Baseline LVOT-G: N=8 N=9 Baseline L

  20. Slide 20: EDG-7500 Led to Meaningful Reductions in LVOT-G at Rest & Post Valsalva

    EDG-7500 Led to Meaningful Reductions in LVOT-G at Rest & Post Valsalva Even at 50 mg, with Greater Reduction at 100 mg Efficacy Evaluable Strong LVOT-G Responses Even in the Absence of Intra-Patient Dose-Optimization (N=12) Absolute Value % Change from Baseline %* Reaching LVOT <30 mmHg 100 (Week 4

  21. Slide 21: ~80% of oHCM Patients in Safety Population Showed Complete LVOT-G Response

    After Only 4 Weeks of Treatment, ~80% of oHCM Patients in the Safety Population Showed a Complete LVOT-G Response Safety Population Strong LVOT-G Responses Even in the Absence of Intra-Patient Dose-Optimization (N=17**) Absolute Value % Change from Baseline %* Reaching LVOT <30 mmHg 100 (Week 4) 100

  22. Slide 22: Rapid and Robust Reductions in NT-proBNP in oHCM

    EDG-7500 Resulted in Rapid and Robust Reductions in NT-proBNP, a Key Marker of Heart Failure in oHCM1 Safety Population 5/9 (56%) Patients at 100 mg Achieved <150 pg/ml NT-proBNP, the Threshold for Normal 10000 20 % Change from Baseline 0 NT-proBNP (pg/ml) -20 1000 -40 -60 100 -80 -62% p ≤ 0.05 at W

  23. Slide 23: Rapid and Sustained Increase in Early Diastolic Mitral Annulus Velocity

    Rapid and Sustained Increase in Early Diastolic Mitral Annulus Velocity (e') Suggesting an Improvement in Diastolic Function Safety Population Rapid Dose Responsive Improvements in Mean e’ Observed as Early as 1 Week After Initiation of Treatment with EDG-7500 40 8 +21% % Change from Baseline e' mea

  24. Slide 24: EDG-7500 Led to Improvements in Left Ventricular Diastolic Function in oHCM

    EDG-7500 Led to Improvements in Left Ventricular Diastolic Function in Patients with oHCM More Patients Achieving Normal Diastolic Function Across a Number of Parameters Safety Population Baseline 18% 82% e’ Septal Week 4 47% 53% Baseline 6% 94% e’ Lateral Week 4 19% 81% Baseline 19% 81% Average E/e

  25. Slide 25: 89% of Participants on 100 mg had Improvements in Patient Reported Outcomes

    89% of Participants on 100 mg had Improvements in Patient Reported Outcomes; Mean Increase in KCCQ-OSS of 23 points Safety Population KCCQ Changes with EDG-7500 in oHCM after 4 Weeks vs. Baseline 50mg Dose Group (N=8*) 100mg Dose Group (N=9) Baseline Week 4 D=20 ** 100 D=4 * D=23 ** D=3 * 100 88 75

  26. Slide 26: Positive KCCQ-OSS Changes Compelling Relative to CMIs

    The Positive KCCQ-OSS Changes with EDG-7500 in oHCM are Compelling Relative to What CMIs have Reported Safety Population KCCQ-OSS Changes with Mavacamten in EXPLORER- KCCQ-OSS Changes with Aficamten in 100 mg EDG-7500 KCCQ (N=9; 4 Weeks) HCM (6 Months) SEQUOIA-HCM (6 Months) D=23 100 83 80 KCCQ Summ

  27. Slide 27: 78% of oHCM Patients Treated with 100 mg Experienced Very Large KCCQ-OSS Improvements

    78% of oHCM Patients Treated with 100 mg EDG-7500 Experienced Very Large Improvements in KCCQ-OSS Safety Population KCCQ-OSS Changes with EDG-7500 in oHCM after 4 Weeks (100 mg) vs. Baseline Very Large Improvements of 89% ≥20 Points with Clinical 78% Improvements of ≥10 points 11% 11% Worsened Large

  28. Slide 28: 100 mg EDG-7500 Led to 78% Achieving Improvement of ≥1 NYHA Class

    100 mg EDG-7500 Led to 78% of Patients Achieving Improvements of ≥ 1 NYHA Class; 67% Achieved NYHA Class I Safety Population NYHA Functional Class Improvements with EDG-7500 in oHCM at 4 Weeks % Patients with ≥ 1 NYHA Class 50mg Dose Group (N=8*) 100mg Dose Group (N=9) Improvement at Week 4 100 100%

  29. Slide 29: Part C – Nonobstructive HCM

    Part C – Nonobstructive HCM 29

  30. Slide 30: Cohort C (nHCM): Patients Evaluated as Part of the Safety Population

    Cohort C (nHCM): 12 Patients Evaluated as Part of the Safety Population; 8 Patients Completed All 4 Weeks of Treatment Pooled Safety Population N=12 50 mg 100 mg Safety Population Safety Population N=7 N=5 50 mg 100 mg Assessed for LVEF, Completed 2 Weeks Completed 2 Weeks NT-proBNP and e’ N=7 N=5 5

  31. Slide 31: Rapid and Robust Reductions in NT-proBNP in Patients with nHCM

    Like oHCM Patients, EDG-7500 Resulted in Rapid and Robust Reductions in NT-proBNP in Patients with nHCM NT-proBNP 50 % Change from Baseline 0 -50 -42% -50% -100 Day 1 Wk1 Wk2 Wk4 EOS Study Visit 50 mg (N=7) 100 mg (N=5*) Wk2 vs Day 1: 50 mg p = NS; 100 mg p ≤ 0.05 Wk4 vs Day 1: 50 mg p ≤ 0.05; 100 m

  32. Slide 32: Early and Rapid Signs of Diastolic Improvements in nHCM

    EDG-7500 Led to Early and Rapid Signs of Diastolic Improvements in nHCM Participants after Only 4 Weeks Treatment with EDG-7500 Led to Mean e’ Changes in nHCM Patients as Early as One Week Following Initiation of Dosing 80 % Change from Baseline 60 40 20 0 -20 -40 Day 1 Wk1 Wk2 Wk4 EOS Study Visit W

  33. Slide 33: Preliminary KCCQ Observations with EDG-7500 in nHCM

    Preliminary KCCQ Observations with EDG-7500 in nHCM Suggest Improvements Beyond Those Observed with CMIs KCCQ Changes with EDG-7500 in nHCM after 4 Weeks vs. Baseline 50mg Dose Group (N=6) 100mg Dose Group (N=2) D=16 100 100 D=22 D=9 Baseline Week 4 78 D=17 73 80 68 80 Wk4 vs Day 1: p = NS at both d

  34. Slide 34: EDG-7500 Safety in Parts B and C

    EDG-7500 Safety in Parts B and C 34

  35. Slide 35: No Meaningful Reductions in LVEF; No Participants had LVEF Drops <50%

    EDG-7500 Continues to Demonstrate No Meaningful Reductions in LVEF; No Participants had LVEF Drops <50% No Correlation Between EDG-7500 Plasma Concentration and LVEF Change LVEF Changes in oHCM LVEF Changes in nHCM LVEF Change from Baseline (%) LVEF Change from Baseline (%) 20 20 15 15 10 10 5 5 0 0

  36. Slide 36: EDG-7500 was Generally Well Tolerated in oHCM and nHCM Participants

    EDG-7500 was Generally Well Tolerated in oHCM Participants in Part B and nHCM Participants in Part C Safety Summary for EDG-7500 in CIRRUS Parts B (oHCM) and C (nHCM) Treatment Emergent Adverse Events (TEAE) N=29 Dizziness (mostly mild and transient in duration) 8 (27.6%) Upper respiratory tract inf

  37. Slide 37: Atrial Fibrillation Rates Similar to Rates Observed in CMI Trials

    Atrial Fibrillation Rates Observed in the HCM Patients in CIRRUS are Similar to Rates Observed in CMI Trials Summary of Atrial Fibrillation Rates in HCM Clinical Trials PIONEER1 EXPLORER2 VALOR3 VALOR BL-128w4 MAVERICK (nHCM)16 MAVA-LTE (oHCM)11 Integrated Safety - Mavacamten PIONEER, EXPLORER, Coh

  38. Slide 38: Summary Remarks

    Summary Remarks • EDG-7500 is emerging as an exciting potential new therapeutic option for both oHCM and nHCM • The prospect of using EDG-7500 to improve LVOT-G, NT-proBNP, e’, KCCQ and NYHA without reductions in LVEF could allow treatment of a broader pool of HCM patients without the need for safet

  39. Slide 39: EDG-7500 Future Development Plans

    EDG-7500 Future Development Plans Dr. Robert Blaustein Chief Development Officer 39

  40. Slide 40: CIRRUS-HCM Part D: Updated Design on Path to Phase 3 Start in 1H2026

    CIRRUS-HCM Part D: Updated Design in oHCM and nHCM on Path to Phase 3 Start in 1H2026 Positive Observations from CIRRUS Part B and C Inform Intra-Patient Dose Optimization in CIRRUS Part D Optimize dose based on: NT-proBNP, KCCQ, NYHA and LVOT-G (oHCM only) Up to 200 mg 100 mg Long-term Extension 50

  41. Slide 41: Closing Remarks

    Closing Remarks Kevin Koch, CEO 41 ©2024 Edgewise Therapeutics. All rights reserved.

  42. Slide 42: No Meaningful Reductions in LVEF Across a Broad Exposure Range

    EDG-7500 Continues to Show No Meaningful Reductions in LVEF or LVEF Drops <50% Across a Broad Exposure Range Pooled Healthy Volunteer and CIRRUS Data 30 LVEF Change from Baseline (%) 20 10 0 -10 -20 Placebo SAD/MAD HV oHCM nHCM -30 -100 0 100 200 300 400 500 600 700 800 900 1000 1100 1200 EDG-7500 P

  43. Slide 43: Aficamten in REDWOOD Demonstrated an Exposure Dependent Decrease in LVEF

    Conversely, Treatment with Aficamten in REDWOOD Demonstrated an Exposure Dependent Decrease in LVEF REDWOOD Phase 2 Studies of Aficamten: As much as a 25% Absolute LVEF Reduction Observed with Aficamten Even at Low Plasma Exposures REDWOOD Cohorts 1 and 2 (oHCM) REDWOOD Cohort 1-4 Abbreviations: LVE

  44. Slide 44: EDG-7500 KCCQ Improvements Compare Favorably to CMIs

    EDG-7500 Led to KCCQ Improvements that Compare Favorably to Efficacy-Optimized oHCM Patients on CMIs Despite Being Medically More Complex, oHCM Patients Treated with 100 mg EDG-7500 Demonstrated a 23 Point KCCQ-OSS Improvement, Greater than That Observed in Any CMI Trial to Date KCCQ Mean Difference

  45. Slide 45: CIRRUS Outcomes Impressive Considering More Medically Complex Patients

    CIRRUS Part B and Part C Outcomes are Especially Impressive Considering More Medically Complex Patients were Enrolled Observations from CIRRUS Part A Demonstrating EDG-7500’s Lack of Reductions in Systolic Performance Allowed Us to Also Treat More Medically Complex oHCM Patients CIRRUS nHCM CIRRUS o

  46. Slide 46: EDG-7500 has the Potential to Revolutionize HCM Care

    EDG-7500 has the Potential to Revolutionize HCM Care, Where Unmet Needs and Persistent Challenges Remain EDG-7500 CMI Improved filling pressure Improved filling pressure Diastolic function Improved NT-proBNP Improved NT-proBNP Improved early relaxation Systolic effects % LVEF % LVEF Systolic functio

  47. Slide 47: Committed to Delivering a Novel and Differentiated Therapy for HCM

    Edgewise is Committed to Delivering a Novel and Differentiated Therapy for Patients with HCM Aspirational Target Product Profile for EDG-7500 in the Treatment of HCM Based on Observations to Date, No Concerns Safety of LVEF Drops; Potential to Eliminate Safety Echoes Ability to Deepen Functional, Sy

  48. Slide 48: Edgewise Upcoming Value-Generating Milestones

    Edgewise Upcoming Value-Generating Milestones H1 2025 H2 2025 H1 2026 P2 LYNX & FOX P3 trial Duchenne Controlled dose-ranging data Initiation Muscular Dystrophy CANYON EOP2 Feedback Path to Sevasemten Approval Sevasemten Becker GRAND CANYON GRAND CANYON ✓ Recruitment complete Results 4Q2026 Hypertro

  49. Slide 49: Well-Capitalized to Execute Important Milestones

    Well-Capitalized to Execute Important Milestones Across Both Sevasemten and EDG-7500 CASH, CASH EQUIVALENTS & DEBT COMMON (1) SHARES OUTSTANDING MARKETABLE SECURITIES* (NASDAQ: EWTX) ~$660M $0 ~105M CASH RUNWAY THROUGH 2028* * Takes into account the expected proceeds from the recently announced regi

  50. Slide 50: Thank You

    Thank You THERAPEUTICS

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