Slide 1: CIRRUS-HCM: 12-Week Evaluation of EDG-7500 in Nonobstructive and Obstructive HCM
CIRRUS-HCM: 12-Week Evaluation of the Safety and Efficacy of the Novel Cardiac Sarcomere Modulator EDG-7500 in Nonobstructive and Obstructive Hypertrophic Cardiomyopathy Anjali T Owens1, Theodore P Abraham2, Michael Nassif3, Scott Solomon4, Christopher Dufton5, Jeffrey A Silverman5, Michael P Ayers5
Slide 2: Disclosures
Disclosures • Dr. Owens has received payments as a consultant to Alexion, Avidity, Biomarin, Bayer, Bristol Myers Squibb, Braveheart, BridgeBio, Cytokinetics, Lexeo, Stealth, Tenaya, Imbria, and Edgewise Therapeutics.
Slide 3: Background
Background • EDG-7500 is a novel cardiac sarcomere modulator shown in preclinical models to: • Increase early diastolic relaxation while maintaining myosin availability • Reduce LVOT gradients by slowing early systolic pressure development • Preserve net systolic function • Once-daily dosing with st
Slide 4: CIRRUS-HCM: 12-Week Open-Label Study Design
CIRRUS-HCM: 12-Week Open-Label Study Design Adults LVOT-G Guided Dose Escalation (25-150 mg QD) with Dose to target: LVOT-G rest < 30 mmHg and Valsalva <50 mmHg Screening Washout oHCM Long-Term Extension Adults NT-proBNP Guided Dose Escalation (25-150 mg QD) with Dose to target: NT-proBNP < 200 pg/m
Slide 5: Baseline Characteristics
Baseline Characteristics Characteristic oHCM (n=20) nHCM (n=33) Characteristic oHCM (n=20) nHCM (n=33) Demographics Echocardiographic Parameters Age (yrs), mean (SD) 59 (13) 49 (16) LVEF (%), mean (SD) 67 (3) 63 (4) Female, n (%) 9 (45%) 15 (45%) LVOT-G Resting (mmHg), mean (SD) 40 (20) 7 (3) BMI (k
Slide 6: Left Ventricular Systolic Function
Left Ventricular Systolic Function
Slide 7: No Clinically Meaningful Change in LVEF Observed with EDG-7500
No Clinically Meaningful Change in LVEF Observed with EDG-7500 90 oHCM nHCM 80 70 • No reductions in LVEF to below 50% LVEF (%) 60 • No clinical heart failure or hospitalizations due to drops in LVEF 50 40 Day 1 Wk4 Wk8 Wk12 Mean±SEM HCM, hypertrophic cardiomyopathy; LVEF, left ventricular ejection
Slide 8: No Correlation Between EDG-7500 Exposure and LVEF Change
No Correlation Between EDG-7500 Exposure and LVEF Change 30 LVEF Absolute Change from Baseline (%) 20 10 0 -10 -20 Part D - oHCM Part D nHCM -30 0 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 1400 1500 EDG-7500 Plasma Concentration (ng/ml) Based on echo core lab reads. HCM, hypertrophic c
Slide 9: No Correlation Between EDG-7500 Exposure and LVEF Change
No Correlation Between EDG-7500 Exposure and LVEF Change 30 LVEF Absolute Change from Baseline (%) 20 10 0 -10 -20 HV Placebo SAD/MAD HV Part A & B - oHCM Part C - nHCM Part D - oHCM Part D nHCM -30 0 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 1400 1500 EDG-7500 Plasma Concentration (ng
Slide 10: No Correlation Between EDG-7500 Exposure and GLS or GCS Change
No Correlation Between EDG-7500 Exposure and GLS or GCS Change Global Longitudinal Strain (GLS) Global Circumferential Strain (GCS) 30 30 GCS Absolute Change from Baseline (%) GLS Absolute Change from Baseline (%) 20 20 10 10 0 0 -10 -10 -20 -20 HV Placebo CIRRUS Part D - oHCM CIRRUS Part D - nHCM H
Slide 11: oHCM Efficacy Results
CIRRUS HCM oHCM Efficacy Results ESC CONGRESS 2026 MUNICH
Slide 12: Clinically Meaningful Improvement in LVOT Gradient Observed in 90% of oHCM Participants
Clinically Meaningful Improvement in LVOT Gradient Observed in 90% of oHCM Particpants¹ oHCM 100 Valsalva Resting LVOT-G (mmHg) SRT eligibility Valsalva 50 51% vs baseline Resting 55% vs baseline 0 Baseline Wk4 Wk8 Wk12 Study Visit Mean±SEM; LVOT-G, left ventricular outflow tract gradient. 1Defined
Slide 13: Improvements in Cardiac Biomarkers (oHCM)
Improvements in Cardiac Biomarkers oHCM NT-proBNP (geometric mean) Hs-cTnI (geometric mean ratio) 56% decrease from baseline to Week 12 40% decrease from baseline to Week 12 600 1.0 500 NT-proBNP (pg/ml) Hs-cTnI (pg/ml) 400 0.8 300 0.6 200 100 0.4 Baseline Wk4 Wk8 Wk12 Baseline Wk4 Wk8 Wk12 Error ba
Slide 14: Very Large Increase in KCCQ-OSS at Week 12 (oHCM)
Very Large (≥20 points) Increase in KCCQ-OSS at Week 12 oHCM 90 80 KCCQ-OSS 70 +24 points at Week 12 60 50 Baseline Wk4 Wk8 Wk12 Study Visit Mean±SEM KCCQ, Kansas City Cardiomyopathy Questionnaire; oHCM, obstructive hypertrophic cardiomyopathy; OSS, overall summary score.
Slide 15: Rapid and Sustained Improvements in NYHA Class (oHCM)
Rapid and Sustained Improvements in NYHA Class oHCM 100 55% NYHA Class I by Week 12 75 70% Percent (%) 50 ≥1 NYHA class improvement at Week 12 25 50% NYHA Class III at baseline improved 0 to NYHA Class I at Week 12 Baseline Wk4 Wk8 Wk12 Study Visit NYHA Class III NYHA Class II NYHA Class I NYHA, New
Slide 16: Improvements in Echo Measures of Diastolic Function (oHCM)
Improvements in Echo Measures of Diastolic Function oHCM +1.2 cm/s +20% Improvement in e’ lateral at Week 12 Improvement in e’ lateral at Week 12 9.5 30 % Change from Baseline 25 e' Lateral (cm/s) 8.5 20 15 7.5 10 5 6.5 0 Baseline Wk4 Wk8 Wk12 Baseline Wk4 Wk8 Wk12 Study Visit Study Visit Mean±SEM e
Slide 17: nHCM Efficacy Results
CIRRUS HCM nHCM Efficacy Results ESC CONGRESS 2026 MUNICH
Slide 18: Improvements in Cardiac Biomarkers (nHCM)
Improvements in Cardiac Biomarkers nHCM NT-proBNP hs-cTnI 65% decrease from baseline to Week 12 33% decrease from baseline to Week 12 1000 1.0 800 NT-proBNP (pg/ml) Hs-cTnI (pg/ml) 0.8 600 400 0.6 200 100 0.4 Baseline Wk4 Wk8 Wk12 Baseline Wk4 Wk8 Wk12 NT-proBNP: geometric mean and 95% CI. Hs-cTnI:
Slide 19: Large Improvement in KCCQ-OSS at Week 12 (nHCM)
Large (≥10 points) Improvement in KCCQ-OSS at Week 12 nHCM 80 70 KCCQ-OSS 60 +13 points at Week 12 50 Baseline Wk4 Wk8 Wk12 Study Visit Mean±SEM KCCQ, Kansas City Cardiomyopathy Questionnaire; nHCM, nonobstructive hypertrophic cardiomyopathy; OSS, overall summary score.
Slide 20: Rapid and Sustained Improvements in NYHA Class (nHCM)
Rapid and Sustained Improvements in NYHA Class nHCM 100 52% NYHA Class I by Week 12 75 64% Percent (%) 50 ≥1 NYHA class improvement at Week 12 25 29% NYHA Class III at baseline improved to NYHA Class I at Week 12 0 Baseline Wk4 Wk8 Wk12 Study Visit NYHA Class III NYHA Class II NYHA Class I NYHA, New
Slide 21: Improvements in Echo Measures of Diastolic Function (nHCM)
Improvements in Echo Measures of Diastolic Function nHCM +1.6 cm/s +37% Improvement in e’ lateral at Week 12 Improvement in e’ lateral at Week 12 10.5 50 % Change from Baseline 10.0 40 e' Lateral (cm/s) 9.5 9.0 30 8.5 20 8.0 10 7.5 7.0 0 Baseline Wk4 Wk8 Wk12 Baseline Wk4 Wk8 Wk12 Study Visit Study
Slide 22: Safety Summary
CIRRUS HCM Safety Summary ESC CONGRESS 2026 MUNICH
Slide 23: 12-weeks of EDG-7500 was Well Tolerated with No LVEF < 50%
12-weeks of EDG-7500 was Well Tolerated with No LVEF < 50% Treatment Emergent Adverse Events (TEAEs) Participants with ≥1 TEAE, n (%) 34 (64%) Mild 23 (43%) Moderate 9 (17%) Severe 2 (3.8%) Serious Adverse Events (SAEs) Participants with ≥1 SAE – Related, n (%) 0 (0%) Participants with ≥1 SAE – Unre
Slide 24: EDG-7500: Summary and Next Steps
EDG-7500: Summary and Next Steps • Novel once-daily mechanism with potential for differentiated safety profile • >240 participants exposed to EDG-7500 to date (all studies) • No measurable change in global systolic performance • No observed LVEF <50% • No observed HF events • Clinical meaningful imp
Slide 25: Thank You!
Thank You! We would like to thank all the investigators, coordinators, site staff, and especially the patients who participated in this trial. The advancement of new therapies to patients can only happen with your incredible efforts and commitment to clinical research!