8-K: Mineralys Therapeutics Reports Positive Phase 2 Data for Lorundrostat in Hypertension and Chronic Kidney Disease

Mineralys Therapeutics announced positive topline results from its Phase 2 Explore-CKD trial, demonstrating lorundrostat's efficacy in reducing blood pressure and albuminuria in patients with hypertension and comorbid chronic kidney disease, alongside a favorable safety profile.

Summary

• Mineralys Therapeutics announced positive topline data from its Phase 2 Explore-CKD trial for lorundrostat (25 mg once daily) in subjects with hypertension and comorbid chronic kidney disease (CKD).
• The trial was a randomized, double-blind, placebo-controlled, crossover study involving 59 subjects (N=59).
• Lorundrostat achieved a highly statistically significant and clinically meaningful reduction in the primary endpoint: a placebo-adjusted change in systolic blood pressure (BP) of -7.5 mmHg (p=0.0024).
• It also showed a clinically meaningful reduction in the pre-defined exploratory endpoint of spot urine albumin-to-creatinine ratio (UACR) of -25.60% placebo-adjusted (p=0.0015), indicating potential renal protective effects.
• An anticipated, modest decrease in mean eGFR was observed (-6.8% lorundrostat, -4.6% mL/min/1.73m2 placebo-adjusted, p=0.0362), which is consistent with other renin-angiotensin-aldosterone pathway inhibitors.
• The drug demonstrated a favorable safety and tolerability profile, with Treatment Emergent Adverse Events (TEAEs) leading to discontinuation in 3% of lorundrostat subjects versus 2% in placebo, and confirmed hyperkalemia in 5% of lorundrostat subjects versus 0% in placebo.

Sentiment

Score: 9

Explanation: The document reports highly positive and statistically significant topline results from a Phase 2 trial, meeting its primary endpoint and showing clinically meaningful benefits. The safety profile is described as favorable, and the results are stated to be part of the core package for a planned NDA submission, indicating significant progress towards commercialization. The identified negatives (hyperkalemia, SAEs, discontinuations) are acknowledged but presented within the context of an overall favorable profile and anticipated effects for the drug class.

Positives

• Lorundrostat 25 mg once daily achieved a highly statistically significant and clinically meaningful placebo-adjusted reduction of -7.5 mmHg in systolic blood pressure (p=0.0024), meeting the primary endpoint.
• The trial showed a clinically meaningful placebo-adjusted reduction of -25.60% in spot urine albumin-to-creatinine ratio (UACR) (p=0.0015), consistent with potential renal protective effects.
• Lorundrostat demonstrated a favorable safety and tolerability profile.
• This is the fourth trial showing clinically meaningful effects of lorundrostat for hypertension, adding to data from Phase 3 Launch-HTN, Phase 2 Advance-HTN, and Phase 2 Target-HTN trials.
• The positive results from Explore-CKD, along with prior successful trials, comprise the core package for the company's planned New Drug Application (NDA) submission.

Negatives

• Confirmed hyperkalemia (K+ >6.0 mmol/L) occurred in 3 out of 58 subjects (5%) during lorundrostat treatment, compared to 0% in the placebo group.
• Serious Adverse Events were reported in two subjects (3%) during the lorundrostat treatment period, and none during the placebo treatment period.
• Two subjects (3%) discontinued treatment during the lorundrostat period due to Treatment Emergent Adverse Events (TEAEs), one due to elevated potassium associated with reduced eGFR and one due to reduced eGFR alone.
• An anticipated, modest decrease in mean eGFR was observed (-6.8% lorundrostat, -4.6% mL/min/1.73m2 placebo-adjusted), though this is noted as consistent with other drugs in its class.

Risks

• Topline results are based on preliminary analysis and such data may change following a more comprehensive review, potentially not accurately reflecting the complete results of a clinical trial.
• The company's future performance is entirely dependent on the success of lorundrostat.
• Potential delays in the commencement, enrollment, and completion of clinical trials and nonclinical studies.
• Later developments with the FDA may be inconsistent with prior feedback, including whether the proposed pivotal program will support registration of lorundrostat upon NDA submission.
• The results of clinical trials, including Advance-HTN and Launch-HTN, may not be deemed sufficient by the FDA to serve as the basis for an NDA submission or regulatory approval of lorundrostat.
• Dependence on third parties in connection with manufacturing, research, and clinical and nonclinical testing.
• Unexpected adverse side effects or inadequate efficacy of lorundrostat that may limit its development, regulatory approval, and/or commercialization.
• Results of prior clinical trials and studies of lorundrostat are not necessarily predictive of future results.
• Macroeconomic trends and uncertainty with regard to high interest rates, elevated inflation, tariffs, and the potential for a local and/or global economic recession.
• The company's ability to maintain undisrupted business operations due to any pandemic or future public health concerns.
• Regulatory developments in the United States and foreign countries.
• Reliance on an exclusive license with Mitsubishi Tanabe Pharma for intellectual property rights to develop and commercialize lorundrostat.
• Other risks described in the company's filings with the Securities and Exchange Commission (SEC), including under the heading Risk Factors in its annual report on Form 10-K, and any subsequent filings with the SEC.

Future Outlook

Mineralys Therapeutics plans to use the Explore-CKD trial data, along with successful pivotal trials Launch-HTN and Advance-HTN, as part of the core package for its planned New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA). The company continues to study lorundrostat in the ongoing, open-label Transform-HTN extension trial for long-term efficacy, safety, and tolerability, and the Explore-OSA trial, initiated in Q1 2025, is continuing to enroll subjects with obstructive sleep apnea and uncontrolled hypertension. The company expects that aldosterone synthase inhibitors (ASIs) with an SGLT2 inhibitor may provide additive clinical benefits to patients.

Management Comments

• "In a renally compromised hypertensive population, this trial demonstrated the benefit of lorundrostat in safely reducing both systolic blood pressure and proteinuria — a surrogate of kidney protection." Jon Congleton, Chief Executive Officer of Mineralys.
• "Explore-CKD established that lorundrostat 25 mg once daily has a favorable clinical profile for this patient population. Along with the successful pivotal trials, Launch-HTN and Advance-HTN, and the ongoing open-label extension trial, these results comprise the core package for our planned NDA submission." Jon Congleton, Chief Executive Officer of Mineralys.
• "The evidence generated from this trial demonstrates the unique mechanism of action and benefit of lorundrostat in lowering systolic blood pressure and UACR. Lorundrostat shows significant potential in the management of hypertension and related kidney disease." Dr. Matthew Weir, Director of the Division of Nephrology at the University of Maryland Medical Center and Professor of Medicine at the University of Maryland School of Medicine.

Industry Context

Chronic Kidney Disease (CKD) affects over 10% of the global population, with approximately 37 million U.S. adults having CKD and 22 million living with both hypertension and CKD. Sustained hypertension contributes to impaired kidney function, and worsening kidney function can lead to poorer blood pressure control, significantly increasing cardiovascular disease and mortality risk. Less than 50% of hypertension patients achieve their blood pressure goals with current medications. Dysregulated aldosterone, which lorundrostat targets by inhibiting CYP11B2, is a key factor in approximately 30% of all hypertensive patients and is increasingly recognized as a driver of both hypertension and CKD. Existing therapies leave a significant proportion of patients uncontrolled or undertreated, highlighting the need for new interventions like lorundrostat that address underlying mechanisms.

Comparison to Industry Standards

• The document notes that a reduction in eGFR, as observed with lorundrostat, is also seen with other renin-angiotensin-aldosterone pathway inhibitors, including ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists (MRAs). This is attributed to a reduction in deleterious over-perfusion of glomeruli.
• It highlights that less than 50% of hypertension patients achieve their blood pressure goal with currently available medications, suggesting a significant unmet need that lorundrostat aims to address.
• The document states that dysregulated aldosterone levels are a key factor in driving hypertension in approximately 30% of all hypertensive patients, positioning lorundrostat as a targeted therapy for this specific patient subgroup.

Stakeholder Impact

• Shareholders: Positive trial results are highly likely to increase investor confidence and potentially the company's stock value, as it significantly de-risks the development pathway towards NDA submission and potential commercialization.
• Patients (Hypertension & CKD): The positive data suggests a promising new therapeutic option for patients with hypertension and comorbid chronic kidney disease, especially those with dysregulated aldosterone, potentially offering better blood pressure control and renal protection.
• Healthcare Providers: The data provides evidence for a new mechanism of action (aldosterone synthase inhibition) that could be integrated into treatment paradigms for complex hypertensive and CKD patients.

Next Steps

• Planned New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) using data from Explore-CKD, Launch-HTN, and Advance-HTN trials.
• Continued study of lorundrostat in the ongoing, open-label Transform-HTN extension trial to evaluate long-term efficacy, safety, and tolerability.
• Continued enrollment of subjects in the Explore-OSA trial, initiated in Q1 2025, for obstructive sleep apnea and uncontrolled hypertension.
• Company management team to host a conference call on June 17, 2025, at 8:00 a.m. ET.

Key Dates

Recommendation

Keywords

Hypertension, Chronic Kidney Disease, CKD, Lorundrostat, Aldosterone Synthase Inhibitor, Mineralys Therapeutics, MLYS, Phase 2, Clinical Trial, Explore-CKD, Blood Pressure, Albuminuria, Renal Protection, Cardiovascular Disease, Obstructive Sleep Apnea, OSA, Biopharmaceutical