Edgewise Therapeutics (EWTX) Study result summary

Study design and patient population

• CIRRUS-HCM Part D was a 12-week, open-label, goal-directed dose escalation study of EDG-7500 in 53 patients with obstructive (n=20) and non-obstructive (n=33) hypertrophic cardiomyopathy (HCM) at over 20 U.S. sites.

• Dose titration was subtype-specific: LVOT gradient for obstructive HCM, NT-proBNP for non-obstructive HCM.

• Most patients reached 100 mg or higher by week 12, with doses ranging from 25 mg to 150 mg and higher doses more common in non-obstructive HCM.

• Baseline characteristics were comparable to pivotal CMI trials, with preserved ejection fraction and significant symptom burden.

• After 12 weeks, patients transitioned to a long-term extension with flexible dosing up to 200 mg.

Safety and tolerability

• No clinically significant changes in LVEF or reductions below 50% were observed across all dose levels, with no heart failure events or hospitalizations due to LVEF drop.

• No dose-dependent or unexpected declines in systolic function by LVEF, global longitudinal strain, or global circumferential strain.

• Most adverse events were mild to moderate (fatigue, upper respiratory infection, rash); two new-onset atrial fibrillation cases were deemed unrelated to the drug.

• Five serious adverse events occurred, all considered unrelated to the study drug.

• No new safety signals were identified in over 700 echos and >240 individuals exposed.

Efficacy in obstructive HCM (oHCM)

• Resting LVOT gradient reduced by over 50% (from 40 to 18 mmHg); Valsalva gradient also dropped by over 50%.

• 90% of patients showed clinically meaningful gradient improvement; 74% achieved NT-proBNP normalization or ≥50% reduction.

• NT-proBNP decreased by ~60%, troponin by ~40%, with early biomarker improvements seen by week 4.

• KCCQ-OSS improved by 24 points at week 12; 85% achieved ≥5-point improvement, 75% ≥10 points.

• 55% became asymptomatic (NYHA Class 1) by week 12, with 70% improving by at least one class.