Mineralys Therapeutics, Inc. presented final results from the Target-HTN Phase 2 trial of lorundrostat, a highly selective aldosterone synthase inhibitor, in individuals with uncontrolled hypertension (uHTN) and resistant hypertension (rHTN). The data were presented during a late-breaking science session at the 2023 American Heart Association (AHA) Hypertension Scientific Sessions, which is being held in Boston from September 7?10, and simultaneously published in the Journal of the American Medical Association. Target-HTN trial results demonstrate treatment with lorundrostat at doses of 50mg and 100mg once daily (QD) led to a statistically and clinically significant reduction of systolic blood pressure (BP) in inadequately controlled hypertensive individuals on at least two background antihypertensive medications.

The reduction in BP was particularly evident among participants with hypertension and concomitant obesity. Key clinical data from Target-HTN suggest robust BP reductions in the treatment of patients with uHTN and rHTN: Target-HTN successfully met its primary endpoint, demonstrating a statistically significant change from baseline in systolic automated office BP (AOBP) with lorundrostat 50mg (n=28) and 100mg (n=25) QD doses versus placebo (n=29): -13.7 mmHg systolic AOBP change at 50mg QD, or -9.6 mmHg placebo-adjusted change (p=0.01) -11.9 mmHg systolic AOBP change at 100mg QD, or -7.8 mmHg placebo-adjusted change (p=0.04) Key secondary endpoint results demonstrated a change in diastolic AOBP of -7.1 mmHg with 50mg QD (or -5.5 mmHg placebo-adjusted change; p=0.02) and -5.8 mmHg with 100mg QD (or -4.1 mmHg placebo-adjusted change; p=0.09) Other secondary endpoints, including assessment of 24-hour average BP, supported the efficacy of the QD dosing regimen. A pre-specified analysis examined the impact of body mass index (BMI) on the degree of BP lowering with lorundrostat, testing the hypothesis that aldosterone-dependent hypertension may be more significant in obese individuals: With 50mg QD, changes in systolic AOBP were 2.2 mmHg in subjects with a BMI 25-30 kg/m2, versus -16.7 in subjects with a BMI =30 kg/m2 (placebo-adjusted; p<0.01) With 100mg QD, changes in systolic AOBP were -4.5 mmHg in subjects with a BMI 25-30 kg/m2, versus -12.3 in subjects with a BMI =30 kg/m2 (placebo-adjusted; p=0.03) Key safety and tolerability findings from Target-HTN suggest lorundrostat was well-tolerated with a favorable safety profile, particularly with 50mg lorundrostat QD: Lorundrostat was well tolerated at all dose levels There was a modest, dose-dependent increase in mean serum potassium (0.25-0.29 mmol/L) and low incidence of elevated serum potassium (3.6% subjects with serum potassium levels above 6.0 mmol/L) Three serious adverse events occurred, only one (worsening of pre-existing hyponatremia with 100mg lorundrostat QD) was deemed treatment-related Target-HTN trial results support the transition to late-stage development of lorundrostat as a treatment for inadequately controlled hypertension.

The Company?s ongoing pivotal development program for lorundrostat to treat uHTN and rHTN is currently enrolling subjects in the Advance-HTN trial, and the Phase 3 Launch-HTN trial is expected to be initiated in the second half of the year, with topline data expected in the first half of 2024 and mid-2025, respectively. The Target-HTN (NCT05001945) Phase 2 proof-of-concept trial was a randomized, double-blind, placebo-controlled, dose-ranging, multicenter trial conducted in the U.S. The trial was designed to evaluate the safety, efficacy, tolerability and dose response of orally administered lorundrostat on BP for the treatment of uncontrolled and resistant hypertension when used as add-on therapy to stable background treatment of two or more antihypertensive agents in 200 male and female subjects 18 years of age or older. Five active doses of lorundrostat (12.5mg QD, 50mg QD, 100mg QD, 12.5mg twice daily [BID], and 25mg BID) were compared to placebo in hypertensive subjects.

Adverse events observed were a modest increase in serum potassium, decrease in estimated glomerular filtration rate, urinary tract infection and hypertension with one serious adverse event possibly related to study drug being hyponatremia. Having sustained, elevated blood pressure (or hypertension) increases the risk of heart disease, heart attack and stroke, which are leading causes of death in the U.S. In 2020, more than 670,000 deaths in the U.S. included hypertension as a primary or contributing cause. Hypertension and related health issues resulted in an average annual economic burden of about $130 billion each year in the U.S., averaged over 12 years from 2003 to 2014.

Less than 50% of hypertension patients achieve their blood pressure goal with currently available medications. Abnormally elevated aldosterone levels are a key factor in driving hypertension in up to 25% of all hypertensive patients.