Mineralys Therapeutics (MLYS) Status Update summary

Unmet Need and Disease Background

• Hypertension is the leading cause of morbidity and mortality globally, with suboptimal control rates and increasing prevalence, especially among patients with comorbidities like obesity and diabetes.

• Only 10-15% of treated hypertensive patients achieve guideline-recommended blood pressure targets, and less than 50% reach blood pressure goals with current medications, highlighting a significant treatment gap.

• Resistant hypertension, often linked to excess aldosterone production and obesity, is becoming more prevalent and represents a major therapeutic challenge.

• Aldosterone's effects extend beyond the kidney, contributing to cardiovascular, renal, and metabolic complications, particularly in obese individuals.

• Aldosterone dysregulation affects about 25% of hypertension patients.

Disease Focus and Therapeutic Approach

• Obesity-driven aldosterone elevation contributes to hypertension, CKD, and heart failure.

• Elevated aldosterone is a key driver in multiple cardiorenal diseases, including resistant hypertension and heart failure.

• About 50% of hypertension and CKD patients are obese, highlighting a large target population.

• 115M people in the US have hypertension, with 30M uncontrolled cases; 35M have CKD, with significant overlap.

• Hypertension contributes to over 670,000 U.S. deaths in 2020 and an annual economic cost of $130 billion.

Lorundrostat and Clinical Development

• Lorundrostat is a selective aldosterone synthase inhibitor with best-in-class selectivity (374X), a 10-12 hour half-life, and once-daily dosing, showing significant blood pressure reductions in early trials.

• Lorundrostat reduces aldosterone by about 70% without significant off-target effects or adrenal insufficiency, offering rapid reversibility for at-risk patients.

• Phase II Target-HTN demonstrated placebo-adjusted systolic blood pressure reductions of 12-16 mmHg in obese patients, with no effect on cortisol and low incidence of side effects.

• Enhanced BP reduction observed in obese patients and those on thiazide diuretics; 24-hour, central, and nighttime BP reductions support cardiovascular benefit.

• Lorundrostat was well-tolerated; hyperkalemia events were infrequent and mostly mild or unrelated, with modest increases in serum potassium and rare serious adverse events.