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, highlighting a significant treatment gap.

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

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

• New guidelines emphasize tighter blood pressure control, targeting 120/70 mmHg due to increased cardiovascular risk at even modestly elevated pressures.

Market Opportunity and Unmet Need

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

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

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

Lorundrostat Mechanism and Early Clinical Data

• Lorundrostat is a selective aldosterone synthase inhibitor with a favorable pharmacokinetic profile, enabling once-daily dosing and about 70% reduction in aldosterone.

• Demonstrates best-in-class selectivity (374X) among ASIs, with a 10-12 hour half-life and no adrenal insufficiency.

• Phase II data (Target-HTN) showed significant, dose-dependent reductions in blood pressure, especially in obese patients, with a good safety profile and no effect on cortisol.

• Blood pressure reductions of 12-16 mmHg were observed in obese patients, and the drug was well tolerated with low rates of hyperkalemia.

• Adverse events included modest increases in serum potassium, decreased eGFR, urinary tract infection, and one serious case of hyponatremia.