Edgewise Therapeutics (EWTX) 3rd Annual Guggenheim Healthcare Innovation Conference summary

EDG-7500 mechanism and differentiation

• EDG-7500 targets a regulatory protein on the sarcomere lever arm to regulate contraction rate, unlike cardiac myosin inhibitors that bind the ATPase directly.

• June data showed no ejection-fraction decrease and no PK/PD relationship with ejection fraction across more than 1,000 measures.

• Cardiac myosin inhibitors have dose- and concentration-related ejection-fraction decreases, linked to REMS, a boxed heart-failure warning and constrained community use.

• Estimated the cardiac myosin inhibitor market at $2B-$3B; 200,000 symptomatic HCM patients represent a broader opportunity if treatment reaches community cardiologists.

Phase III design and execution

• FDA accepted a design without echo monitoring to reach the 150 mg target dose; physicians will select each patient's dose based on tolerability.

• One umbrella protocol includes separately powered obstructive and non-obstructive HCM trials, each designed for statistical significance; peak VO2 is primary, with KCCQ, VE/VCO2 and other functional measures secondary.

• Adaptive design may expand enrollment, particularly in non-obstructive HCM, using trial results to reassess sample size; favorable results could save six months.

• Primary endpoint is at 24 weeks; patients may receive the maximum dose for 16 weeks, which management expects to be sufficient to show changes in KCCQ and peak VO2.

Safety and clinical rationale

• Dose escalation starts low and proceeds to the highest well-tolerated dose, encouraged even if patients feel better at a lower dose; echoes are scheduled at baseline, 12 weeks and 24 weeks, but do not guide titration.

• HCM trial inclusion requires LVEF of 60%; management expects placebo comparison to be more informative than an absolute 50% threshold.

• A REMS-free label is plausible if trial data support safety without titration echoes; the FDA will make the final determination.

• EDG-7500 is four to five times more potent on ventricular diastolic relaxation, which management views as central to non-obstructive HCM and HFpEF.

• Placebo control is needed to interpret AFib rates because AFib is part of the HCM phenotype and cross-trial comparisons are difficult.