Mineralys Therapeutics (MLYS) 2024 Wells Fargo Healthcare Conference summary

Company overview and investment case

• Mineralys was founded in 2020, centered on lorundrostat, a licensed aldosterone synthase inhibitor (ASI) targeting cardiorenal metabolic diseases, especially hypertension.

• Hypertension remains a major unmet need globally, with over a billion affected and only a fraction achieving treatment goals.

• Current treatments inadequately address aldosterone-driven hypertension, with limited use of MRAs like spironolactone.

• Lorundrostat offers a selective approach to reducing aldosterone, potentially improving outcomes for a significant patient subset.

Mechanism of action and differentiation

• ASIs inhibit aldosterone synthesis at the source, while MRAs block its receptor, often causing compensatory aldosterone increases.

• Lorundrostat demonstrates high selectivity, reducing aldosterone without affecting cortisol, and shows robust efficacy and safety in early studies.

• MRAs can increase aldosterone and have off-target effects, while ASIs like lorundrostat directly lower aldosterone levels.

Clinical trial design and execution

• Advance-HTN trial uses a standardized background regimen and smartphone compliance monitoring to ensure rigorous patient selection and data quality.

• Patients are optimized on high-dose ARB, diuretic, and calcium channel blocker before randomization, enriching for aldosterone-dependent hypertension.

• The primary endpoint is 24-hour ambulatory blood pressure, with extensive subgroup and biomarker analyses planned.

• Launch-HTN trial features a six-week primary endpoint, pooling 50 mg arms for statistical power, with titration to 100 mg for non-responders.

• Both trials are designed for high statistical power and robust subset analyses, aiming to identify responders and inform guidelines.