Edgewise Therapeutics, Inc. · NASDAQ:EWTX
Edgewise Therapeutics — Corporate Update (September 2024)
43 slides from Edgewise Therapeutics's corporate update, Sep 19, 2024
Slide 1: EDG-7500: Phase 1 & Phase 2 CIRRUS-HCM Development Program Update
EDG-7500: Phase 1 & Phase 2 CIRRUS-HCM Development Program Update September 19, 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 to Edgewise Therapeutics Chief Executive Officer 2. The unmet need in HCM Marc Evanchik 3. EDG-7500, a novel sarcomere regulator for the Vice President of Discovery treatment of HCM Dr. Anjali Owens 4. Topline results: Phase 1 trial in healthy volunteers and Cen
Slide 4: Focused on muscle science, rapidly advancing portfolio
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 ● Advancing EDG-7500 in oHCM, nHCM, and other potential indications ● Pivotal tri
Slide 5: Edgewise Evolution into Cardiovascular Disease
Edgewise Evolution into Cardiovascular Disease Identified a unique set EDG-7500 EDG-7500 enters Initiated of CV molecules as characterized the clinic; CIRRUS-HCM, part of skeletal muscle as a selective continued EDG-7500 counter-screen EDG-7500 identified cardiac research on novel P2 program as lead
Slide 6: The Unmet Need in HCM
The Unmet Need in HCM Dr. Marc Semigran 6
Slide 7: The Significance of Hypertrophic Cardiomyopathy (HCM)
The Significance of Hypertrophic Cardiomyopathy (HCM) Can manifest at any age, Most common genetic important cause of sudden cardiovascular disease cardiac death, atrial fibrillation, impacting ~1 in 500 people1 stroke and of heart failure in all ages1,2 Prevalence of HCM gene carriers could be HCM
Slide 8: HCM: Abnormalities in Heart Muscle Structure and Function
HCM: Abnormalities in Heart Muscle Structure and Function Lead to Severe Abnormalities in Cardiac Performance HEALTHY HEART OBSTRUCTIVE HCM NON-OBSTRUCTIVE HCM (~65% OF PATIENT POPULATION) (~35% OF PATIENT POPULATION) Normal contraction Excessive contraction & impaired relaxation Abbreviations: LVOT
Slide 9: LVOT Obstruction and Diastolic Dysfunction Contribute to Heart Failure in HCM
LVOT Obstruction and Diastolic Dysfunction Contribute to the Development of Heart Failure in HCM1–3 oHCM1-3 nHCM4 Addressing LVOT obstruction alone will not LVOT resolve heart failure across the spectrum of HCM obstruction Unmet need to resolve diastolic Diastolic Diastolic dysfunction dysfunction d
Slide 10: Treatments for HCM Have Key Limitations Leaving Substantial Unmet Needs
Treatments for HCM Have Key Limitations Leaving Substantial Unmet Needs for Patients LIMITED BENEFIT ACROSS THE SUBOPTIMAL PATIENT RISK OF HEART FAILURE1,2 EXPERIENCE SPECTRUM OF HCM Efficacy and safety Safety-driven frequent Mavacamten black box limitations with echo monitoring1-3 warning for HF3 i
Slide 11: EDG-7500, a Novel Sarcomere Regulator for the Treatment of HCM
EDG-7500, a Novel Sarcomere Regulator for the Treatment of HCM Marc Evanchik 11
Slide 12: EDG-7500: Designed to Slow Acto-Myosin Engagement and Speed Disengagement
EDG-7500: Designed to Slow Rate of Acto-Myosin Engagement and Speed Disengagement Without Inactivating Myosin Heads The Sarcomere is the Molecular Unit in Cardiac Muscle Responsible for Heart Contraction and Relaxation Gene # of mutations to TNNI3 Protein Symbol cause HCM TNNT2 Cardiac -MyHC MYH7 1
Slide 13: A Compelling Preclinical Package Supported Initiation of Clinical Studies
A Compelling Preclinical Package Supported Initiation of Clinical Studies of EDG-7500 as a Novel Therapy for HCM Preclinical model Key result Preserves myosin head motor function In vitro: Myofibril systems1 More potent at low calcium In vivo: MYBPC3 A31P feline validated Potent LVOT gradient reduct
Slide 14: EDG-7500 is Positioned to Address Unmet Needs in HCM
EDG-7500 is Positioned to Address Unmet Needs in HCM Targeted MOA* Efficacy Potential ease of disassociated from administration changes in LVEF* EDG-7500 is targeted to EDG-7500 avoids EDG-7500’s novel MOA address both obstructive excessive drops in supports investigating and non-obstructive HCM sys
Slide 15: Phase 1 Trial in Healthy Subjects
Phase 1 Trial in Healthy Subjects 15
Slide 16: Study Overview of EDG-7500 in Healthy Adults
Study Overview of EDG-7500 in Healthy Adults PRIMARY OBJECTIVE KEY INCLUSION CRITERIA ENROLLMENT KEY OUTCOME MEASURES 72 Safety & tolerability in Healthy male, PK, LVEF healthy volunteers non-pregnant female 18 to <60 years of age Part A (n=48) Single Ascending Dose (SAD) 5 mg 15 mg 50 mg 100 mg 200
Slide 17: EDG-7500 Well Tolerated Across All Doses in SAD and MAD Cohorts
EDG-7500 was Well Tolerated Across All Doses in Both the SAD and MAD HV Cohorts TEAEs by body system and treatment after single ascending doses of EDG-7500 (n=6 per cohort on active) Pooled EDG-7500 System Organ Class Placebo Overall 5 mg 15 mg 50 mg 100 mg 200 mg 300 mg (N=12) (N=36) Any TEAE 3 (25
Slide 18: EDG-7500 Well Tolerated Across All Doses (continued)
EDG-7500 was Well Tolerated Across All Doses in Both the SAD and MAD HV Cohorts (continued) Across both the SAD and MAD cohorts: ● No significant changes in vital signs were observed ● Well-tolerated with no clinically significant changes or trends in clinical chemistry, hematology, or ECGs ● Incide
Slide 19: SAD: Mean Plasma Elimination Half-Life Ranged from 25 to 39 Hours
SAD: EDG-7500 Mean Plasma Elimination Half-Life (T1/2) Ranged from 25 to 39 Hours SAD: EDG-7500 Plasma Concentration Over Time (mean ± SD) 700 5 mg 15 mg 50 mg Cmax T1/2 AUC0-24h AUCINF EDG-7500 Dose 100 mg 200 mg 300 mg (ng/mL) (h) (h*ng/mL) (h*ng/mL) 600 22.7 ± 6.41 27.4 ± 9.07 168 ± 28.3 363 ± 14
Slide 20: MAD: Consistent Observations to SAD with 2-Fold Accumulation Ratio
MAD: Consistent Observations to SAD with a 2-Fold Accumulation Ratio Consistent with a ~30 Hour T1/2 MAD: EDG-7500 Plasma Concentration Over Time (mean ± SD) 800 25 mg QD 50 mg QD 100 mg QD Cmax T1/2 AUC0-24h 700 EDG-7500 Dose AUC0-24h AR (ng/mL) (h) (h*ng/mL) Concentration (ng/mL) 600 EDG-7500 Plas
Slide 21: Steady-State Achieved ~4 Days After Start of Once-Daily Dosing
Steady-State was Achieved ~4 Days After Start of Once-Daily Dosing with EDG-7500 Plasma Concentration Over Time (mean ± SD) After 3 Ascending Doses of Daily EDG-7500 for 14 Days Concentration (ng/mL) 400 300 EDG-7500 Plasma 200 100 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Days Post-Dose 25 mg QD 50 mg Q
Slide 22: CMIs Show a Decrease in LVEF as a Mechanistic Component
Data with CMIs, Both Approved and in Development, Show a Decrease in LVEF as a Mechanistic Component PD Active Doses of CMIs Decreased LVEF in a Concentration Dependent Manner EWTX prioritized candidates that preserved LVEF as part of the clinical candidate selection criteria 22
Slide 23: No Change in Contractility Versus Placebo and Baseline
There Was No Change in Contractility Versus Placebo and Baseline With Increasing Doses of EDG-7500 20 SAD MAD Placebo (N=12) EDG-7500 (N=36) Placebo (N=6) EDG-7500 (N=18) Mean Baseline LVEF (SD) 63.7 (2.0) 61.4 (3.7) 60.9 (2.3) 61.2 (2.2) 10 from Baseline (%) LVEF Change 0 -10 -20 Pooled Placebo Poo
Slide 24: Observations Highlight a Potentially Unique Mechanism to Target HCM
Observations with EDG-7500 Highlight a Potentially Unique Mechanism to Target HCM without Risk of Reducing LVEF • EDG-7500 was well-tolerated with no clinically significant changes or trends in clinical chemistry, hematology or ECGs • EDG-7500 showed optimal PK properties supporting once-daily fixed
Slide 25: Phase 2 CIRRUS-HCM Trial in oHCM
Phase 2 CIRRUS-HCM Trial in oHCM Dr. Semigran and Dr. Owens 25
Slide 26: Results of Mavacamten Single Dose Administration in oHCM Patients
Results of Mavacamten Single Dose Administration in oHCM Patients Treatment of 2 oHCM patients with a single dose of mavacamten (MYK-461), a cardiac myosin inhibitor, led to relief of LVOT obstruction at expense of a reduction in contractility (LVEF drops) Conclusions • Both patients’ gradients redu
Slide 27: CIRRUS-HCM: Clinical Trial Design
CIRRUS-HCM: Clinical Trial Design PRIMARY OBJECTIVE KEY INCLUSION CRITERIA TARGET ENROLLMENT KEY OUTCOME MEASURES ~55 Safety & tolerability Male and female patients Cardiovascular PD, LVEF, in adults with HCM ≥ 18 years of age with HCM Biomarkers, PK LVEF ≥ 60% PART A (oHCM): Single Dose Administrat
Slide 28: Focus on CIRRUS Part A Cohort of oHCM Patients
Today’s Focus will be on the CIRRUS Part A Cohort of oHCM Patients Treated with a Single Dose of EDG-7500 PRIMARY OBJECTIVE KEY INCLUSION CRITERIA ENROLLMENT KEY OUTCOME MEASURES Safety & tolerability in • Healthy male, non-pregnant female ≥ 18 diagnosed with oHCM • Safety and tolerability 11 adults
Slide 29: Pre-Specified Efficacy Evaluable Population
Pre-Specified Efficacy Evaluable Population • 11 patients were eligible at screening and constituted the safety population • 7 patients met the following criteria at baseline qualifying for efficacy evaluation: – Resting left ventricular outflow tract gradient (LVOT-G) ≥ 30 mmHg and Valsalva LVOT-G
Slide 30: CIRRUS-HCM Part A: Baseline oHCM Patient Demographics and Characteristics
CIRRUS-HCM Part A: Baseline oHCM Patient Demographics and Characteristics CHARACTERISTIC oHCM PARTICIPANTS (n=11) Age (Years), Mean (SD) 59 (15) Sex – Female (%) 73 Race – Black/White (%) 9 / 91 BMI (kg/m2) 28 (4) NYHA Class (%) Class I 27 Class II 45 Class III 27 Time from HCM Diagnosis (years), Me
Slide 31: Single Doses of EDG-7500 Well Tolerated Across All Doses in oHCM
Single Doses of EDG-7500 Were Well Tolerated Across All 3 Doses Studied in oHCM Patients • EDG-7500 was well-tolerated by all oHCM patients • No treatment emergent abnormalities in clinical hematology or chemistry laboratories • No patients experienced a decrease in LVEF <50% Summary of AEs Dose Ter
Slide 32: EDG-7500 Led to Reduction in Resting LVOT-G of 67%
EDG-7500 Led to a Meaningful Reduction in Resting LVOT-G of 67% for the Combined 100/200 mg Cohorts Group Mean Values (n=7)* Percent Change from Baseline (n=7)* 120 80 60 Change from Baseline (%) Resting LVOT-G (mmHg) 100 40 80 20 60 0 -20 40 30 -40 Clinically significant 20 gradient -60 0 -80 Pre 2
Slide 33: EDG-7500 Led to Reduction of Valsalva LVOT-G of 55%
EDG-7500 Led to a Meaningful Reduction of Valsalva LVOT-G of 55% for the Combined 100/200 mg Cohorts Group Mean Values (n=7)* Percent Change from Baseline (n=7)* 180 80 160 60 Change from Baseline (%) Valsalva LVOT-G (mmHg) 140 40 120 20 100 0 80 -20 60 50 Clinically significant -40 40 gradient 20 -
Slide 34: Gradient Relief Achieved Without Meaningful Reduction in LVEF
Gradient Relief in oHCM Patients was Achieved Without a Meaningful Reduction in LVEF Group Mean Values (n=11) 80 -0.2% +2.4% 70 -2.0% +0.8% -3.2% -1.2% 60 50 LVEF (%) Safety threshold 40 30 20 10 50 mg (n=3) 100 mg (n=4) 200mg (n=4) 0 Pre 2 hr. 24 hr. There was No Correlation Between EDG-7500 Plasma
Slide 35: Robust Reductions in NT-proBNP
EDG-7500 Administration Resulted in Robust Reductions in NT-proBNP, a Key Marker of Heart Failure in HCM1 Mean Relative Change from Baseline (n=7)* 10 Relative Change from Baseline (%) 0 -10 -17% -20 NTpro-BNP -30 -31% -40 -50 Baseline NT-proBNP levels ranged from 279-11,408 pg/ml for the efficacy e
Slide 36: EDG-7500 in oHCM Relieved LVOT-G Without Reductions in LVEF
EDG-7500 in oHCM patients Relieved LVOT-G Without Reductions in LVEF • EDG-7500 was well tolerated across all doses studied in oHCM patients • EDG-7500 administration led to a reduction in resting LVOT-G of 67% for the 100/200 mg cohorts combined with multiple individuals achieving gradients <30 mmH
Slide 37: EDG-7500 Future Development Plans
EDG-7500 Future Development Plans Dr. Marc Semigran 37
Slide 38: Positive Data from Part A Supported Initiation of Parts B and C
Positive Data from CIRRUS-HCM Part A Supported the Initiation of Parts B and C in oHCM and nHCM, respectively ● Edgewise has initiated enrollment of patients in the 28 Day study of EDG-7500 for both obstructive and non-obstructive HCM ○ Part B: designed to demonstrate continued safety and deepening
Slide 39: Closing Remarks
Closing Remarks Kevin Koch, CEO 39
Slide 40: Early Observations Highlight EDG-7500's Potentially Differentiated Profile in HCM
Early Observations from the CIRRUS-HCM Single Dose Study Highlight EDG-7500’s Potentially Differentiated Profile in HCM Aspirational Target Product Profile for EDG-7500 in the Treatment of HCM Based on Observations to Date, No Concerns Safety of LVEF Drops Ability to Deepen Functional, Symptom and Q
Slide 41: What's Next? Edgewise Upcoming Value-Generating Milestones
What’s Next? Edgewise Upcoming Value-Generating Milestones H1 2024 H2 2024 H1 2025 Phase 2 CIRRUS-HCM Phase 1/Phase 2 Initiation ✓ EDG-7500 data in HVs & oHCM** ✓ Cardiac Hypertrophic Cardiomyopathy EDG-7500 Phase 2 28-day study Phase 2 28-day study Initiate in oHCM & nHCM** ✓ Initial Data readout A
Slide 42: Well-Capitalized to Execute Important Milestones Across Both Programs
Well-Capitalized to Execute Important Milestones Across Both EDG-7500 and Sevasemten CASH, CASH EQUIVALENTS & DEBT (1) COMMON (1) SHARES OUTSTANDING MARKETABLE SECURITIES (NASDAQ: EWTX) ~$512M $0 ~94M CASH RUNWAY THROUGH 2027 As o June 30, 2024 42
Slide 43: Q&A
THERAPEUTICS, Q&A
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