Mineralys Therapeutics (MLYS) Study Result summary

Study design and patient population

• Explorer-CKD/Explore-CKD was a randomized, double-blind, placebo-controlled, crossover phase 2 trial evaluating lorundrostat in patients with uncontrolled hypertension and CKD, with eGFR as low as 30 and albuminuria between 200–5,000 mg/g, all on ACEI/ARB and SGLT2 inhibitor therapy.

• The primary endpoint was placebo-adjusted change in systolic blood pressure at week four; exploratory endpoints included changes in UACR and eGFR.

• Inclusion criteria included eGFR ≥30 mL/min/1.73m², AOBP SBP ≥135 mmHg, and serum potassium <5.0 mmol/L.

• The study population had a mean age of 65, 69% male, 66% white, 17% Black or African American, 76% diabetic, and mean BMI of 33 kg/m².

• Mean baseline eGFR was 54.6 mL/min/1.73m², mean spot urine UACR was 516 mg/g, and mean systolic AOBP was 149 mmHg.

Efficacy results

• Lorundrostat 25 mg once daily led to a placebo-adjusted reduction in systolic blood pressure of 7.5 mmHg at week four (p=0.002 to p=0.0024).

• There was a 31% reduction in urine albumin-to-creatinine ratio (UACR) at week four (p<0.0001), indicating potential renal protection.

• Placebo-adjusted reduction in eGFR was -4.6% to -6.8% at four weeks, consistent with other RAAS pathway inhibitors.

• Efficacy results were consistent with prior lorundrostat trials and comparable to other aldosterone synthase inhibitors and MRAs.

• Most subjects rolled over into an open-label extension to assess long-term durability of response.

Safety and tolerability

• No new safety signals were observed; adverse events of special interest included hyperkalemia, hyponatremia, and reduced eGFR.

• Hyperkalemia (>5.5 mmol/L) occurred in 12.1% of subjects; 1.7% had >6.5 mmol/L, all reversible; confirmed hyperkalemia in 5% of subjects.

• Mean serum potassium increased by 0.5 mmol/L, consistent with other RAS pathway inhibitors.

• Discontinuation rate due to adverse events was low (3–3.4%).

• Modest, anticipated decrease in eGFR observed, similar to other aldosterone pathway inhibitors, and stabilized over time.