Executive Summary / Key Takeaways

• Differentiated Therapeutic Approach: Mineralys Therapeutics is poised to disrupt the multi-billion dollar hypertension market with lorundrostat, a highly selective aldosterone synthase inhibitor (ASI) that directly targets dysregulated aldosterone, a key driver in approximately 30% of hypertensive patients.
• Robust Clinical Validation: Lorundrostat has demonstrated clinically meaningful and sustained systolic blood pressure reductions across four successful trials, including pivotal Phase 3 Launch-HTN and Phase 2 Advance-HTN studies, with a favorable safety and tolerability profile, particularly a modest impact on potassium levels.
• Expanding Therapeutic Horizons: Beyond hypertension, lorundrostat shows promise in related cardiorenal conditions, with positive Phase 2 data in chronic kidney disease (CKD) and an ongoing Phase 2 trial in obstructive sleep apnea (OSA), aiming to extend its clinical utility and market opportunity.
• Clear Regulatory Pathway & Strong Liquidity: Following positive pre-NDA feedback, Mineralys plans to submit its New Drug Application (NDA) for lorundrostat in late 2025 or Q1 2026, supported by a robust cash position of $593.6 million, projected to fund operations into 2028.
• Significant Market Opportunity: With over 20 million U.S. patients suffering from uncontrolled or resistant hypertension, and strong physician intent to prescribe, lorundrostat is positioned as a potential best-in-class treatment, particularly for third-line or later therapy.

The Unmet Need in Hypertension: A Foundation for Innovation

Mineralys Therapeutics ($MLYS) stands at the forefront of addressing a critical global health challenge: uncontrolled and resistant hypertension. This clinical-stage biopharmaceutical company is dedicated to developing lorundrostat, a proprietary, orally administered, highly selective aldosterone synthase inhibitor (ASI), for cardiorenal conditions driven by dysregulated aldosterone. Hypertension affects approximately 120 million patients in the United States, with over half failing to achieve their blood pressure goals of below 130/80 mmHg using currently available medications. A staggering 20 million of these treated patients have systolic blood pressure levels exceeding 140 mmHg, facing a 1.8 to 2.5 times greater mortality risk from cardiovascular disease or stroke. This pervasive issue contributes to an estimated annual economic burden of $219 billion in the U.S.

The company's strategic focus is rooted in the understanding that dysregulated aldosterone levels are a key factor in driving hypertension in about 30% of all hypertensive patients. Mineralys was incorporated in May 2019, quickly securing an exclusive worldwide license for lorundrostat from Mitsubishi Tanabe Pharmaceutical Company in July 2020. This foundational agreement, coupled with a successful Initial Public Offering in February 2023 and subsequent capital raises totaling approximately $1 billion, has fueled the rapid advancement of lorundrostat through its clinical development program.

Technological Differentiation: Lorundrostat's Precision Targeting

Lorundrostat represents a significant technological advancement in hypertension management. As a highly selective aldosterone synthase inhibitor, its core mechanism involves reducing aldosterone levels by specifically inhibiting CYP11B2, the enzyme responsible for its production. This direct approach contrasts with mineralocorticoid receptor antagonists (MRAs) like spironolactone, which block aldosterone's effects at the receptor level. The distinction is crucial for patient outcomes and tolerability.

A key quantifiable benefit of lorundrostat is its impressive 374-fold selectivity for aldosterone-synthase inhibition versus cortisol-synthase inhibition in vitro. This high selectivity minimizes off-target effects on cortisol, a critical steroid hormone. Furthermore, lorundrostat exhibits an observed half-life of 10-12 hours and has demonstrated a 40-70% reduction in plasma aldosterone concentration in hypertensive subjects. This half-life is considered ideal by the company, as it allows for 24-hour blood pressure control while also recapitulating the normal circadian rhythm of aldosterone, with some natural elevation pre-arousal.

For investors, this technological differentiation translates into a compelling competitive moat. By directly reducing aldosterone, lorundrostat avoids the androgenic side effects (e.g., gynecomastia, fertility issues) often associated with MRAs. Moreover, it offers a more modest and manageable impact on serum potassium levels compared to the "compromised trade-off" often seen with MRAs, where pushing for efficacy can invariably lead to hyperkalemia. This improved benefit-risk profile is critical for long-term patient adherence and broader physician acceptance, potentially leading to superior market penetration and sustained revenue streams.

Clinical Validation and Expanding Therapeutic Horizons

Mineralys has built a robust clinical data package for lorundrostat, validating its potential as a transformative therapy. The company's pivotal program for uncontrolled or resistant hypertension comprises two key trials: Launch-HTN and Advance-HTN.

The Phase 3 Launch-HTN trial, a large global study with 1,083 participants, was designed to reflect a real-world clinical setting. It demonstrated a clinically meaningful and statistically significant mean reduction in automated office systolic blood pressure (AOSBP) of 16.9 mmHg at Week 6 (-9.1 mmHg placebo-adjusted, p<0.0001), which was sustained at 19.0 mmHg at Week 12 (-11.6 mmHg placebo-adjusted, p<0.0001). Importantly, these reductions were consistent across diverse and high-risk subgroups, including Black or African American adults (29%), women (47%), and obese participants (63%). The Advance-HTN trial, a more rigorous Phase 2 study conducted in partnership with the Cleveland Clinic, enrolled 285 hard-to-treat participants with confirmed uncontrolled or resistant hypertension. In this population, lorundrostat achieved a significant 15.4 mmHg absolute reduction in systolic blood pressure (-7.9 mmHg placebo-adjusted) at Week 12, measured by 24-hour ambulatory blood pressure monitoring (ABPM). Over 50% of participants in Advance-HTN were Black or African American, demonstrating consistent efficacy in this high-risk group.

The safety and tolerability profile across both pivotal trials was favorable. The anticipated on-target increases in serum potassium were modest and manageable. In Launch-HTN, the confirmed incidence of hyperkalemia (>6 mmol/L) was 0.6% in the 50 mg arm, comparing favorably to prior reports of MRAs. In Advance-HTN, the confirmed incidence was 2.1% in the 50 mg arm, considered acceptable given the high-risk patient population and concomitant use of other potassium-elevating medications. These results underscore lorundrostat's potential to provide robust efficacy with a manageable safety profile.

Beyond hypertension, Mineralys is strategically expanding lorundrostat's profile into comorbid conditions driven by dysregulated aldosterone. The Phase 2 Explore-CKD trial evaluated 25 mg of lorundrostat in hypertensive participants with Stage 2 to 3b chronic kidney disease (eGFR 30-90 mL/min/1.73m²) and albuminuria, already on an SGLT2 inhibitor. This trial met its primary endpoint, demonstrating a clinically meaningful 9.3 mmHg reduction in systolic blood pressure (7.5 mmHg placebo-adjusted, p=0.0024) at four weeks. Crucially, it also showed a highly statistically significant and clinically meaningful 31% reduction in urinary albumin-to-creatinine ratio (UACR), an accepted surrogate for renal protection. These findings suggest lorundrostat's potential for renal protective effects, further enhancing its value proposition.

The company is also exploring obstructive sleep apnea (OSA) with the Phase 2 Explore-OSA trial, which completed enrollment in Q3 2025. This trial investigates lorundrostat 50 mg once daily, dosed in the evening, for overweight and obese participants with moderate-to-severe OSA and hypertension. The rationale is compelling: 60-85% of OSA patients have resistant hypertension, and nocturnal hypoxia drives aldosterone production, contributing to adverse cardiovascular events. By targeting this nighttime aldosterone surge, Mineralys aims to alleviate upper airway obstruction severity (primary endpoint: apnea-hypopnea episodes reduction) and reduce nocturnal hypertension, with topline results anticipated in Q1 2026.

Competitive Landscape and Market Positioning

Mineralys Therapeutics operates within a dynamic and competitive landscape, vying for market share against established pharmaceutical giants and other innovative biotechs. The company positions lorundrostat as a "best-in-class" aldosterone synthase inhibitor, differentiating itself from both older mineralocorticoid receptor antagonists (MRAs) and other emerging ASIs.

Compared to traditional MRAs like spironolactone, lorundrostat's mechanism of directly inhibiting aldosterone production offers a distinct advantage by avoiding the androgenic side effects that limit MRA use. While spironolactone is recognized for its value in resistant hypertension, it remains significantly underutilized, creating an opportunity for a better-tolerated alternative.

In the nascent ASI class, Mineralys highlights lorundrostat's robust and consistent efficacy, 24-hour blood pressure control, and favorable safety profile across diverse patient populations as key differentiators. The company's clinical program, particularly the Launch-HTN trial, is the largest ASI trial reported to date, providing extensive data on a broad patient base. Lorundrostat's 10-12 hour half-life is considered optimal, contrasting with competitors like AstraZeneca (AZN)'s baxdrostat (25-30 hours) and another ASI from Boehringer Ingelheim (4-6 hours), which may present different efficacy and safety profiles. Mineralys has also emphasized its commitment to diverse patient representation, with nearly 30% Black/African American participants in Launch-HTN and over 50% in Advance-HTN, addressing a critical need in a population often underrepresented in clinical trials.

The market opportunity for lorundrostat is substantial. Uncontrolled and resistant hypertension affects over 20 million people in the U.S. Market research indicates that nearly 9 million patients initiated new treatments in the third-line or later position in 2024, reflecting significant dissatisfaction with existing therapies. A survey of cardiologists and primary care physicians revealed that 95% would likely prescribe lorundrostat broadly for uncontrolled or resistant hypertension if approved, specifically for third-line or later treatment. This translates to an addressable market of roughly 15-20 million patients for third-line or later therapy.

Mineralys' commercial strategy focuses on market access and payer engagement, aiming for favorable coverage by demonstrating lorundrostat's differentiated value. The company anticipates that payers will likely require a step-through of two generic classes, but not spironolactone, facilitating access. Initial launch efforts are expected to target the fourth-line resistant hypertension population, where the unmet need is highest and existing treatments offer minimal benefit. Partnering is a key strategic component to maximize lorundrostat's commercial reach both in the U.S. and globally, and to explore co-development opportunities in additional indications.

Financial Performance and Liquidity

As a clinical-stage biopharmaceutical company, Mineralys Therapeutics has not yet generated product revenue and has incurred significant operating losses since its inception. For the nine months ended September 30, 2025, the company reported a net loss of $122.4 million, an improvement from $128.9 million in the same period of 2024. Quarterly net loss for Q3 2025 was $36.9 million, down from $56.3 million in Q3 2024.

Research and development (R&D) expenses, the primary driver of operating costs, decreased to $107.6 million for the nine months ended September 30, 2025, from $124.0 million in the prior year period. This reduction was largely due to the conclusion of the lorundrostat pivotal program in the second quarter of 2025, partially offset by increased compensation and manufacturing costs.

General and administrative (G&A) expenses, however, increased to $24.7 million for the nine months ended September 30, 2025, from $16.6 million in the same period of 2024, primarily due to higher personnel-related expenses and professional fees as the company scales for potential commercialization.

Mineralys maintains a strong liquidity position, crucial for its continued development and regulatory efforts. As of September 30, 2025, the company held $593.6 million in cash, cash equivalents, and investments. This robust cash balance is projected to fund operations into 2028. The company has successfully raised approximately $1 billion in aggregate gross proceeds since its inception, including significant public offerings in March 2025 ($188.7 million net proceeds) and September 2025 ($269.6 million net proceeds), and a private placement in February 2024 ($116.1 million net proceeds). Net cash used in operating activities for the nine months ended September 30, 2025, was $104.5 million, reflecting ongoing investment in lorundrostat's development.

Outlook and Risks

Despite the promising outlook, investors should consider several risks. Mineralys expects to incur substantial losses and negative cash flows for the foreseeable future, necessitating additional funding beyond its current runway. Failure to secure this capital could delay or terminate product development and commercialization.

Macroeconomic factors such as inflation, changes in trade policy, and global supply chain disruptions could increase operational costs and make future financing more challenging. Furthermore, disruptions at regulatory agencies, including potential government shutdowns like the one that began on October 1, 2025, could delay the FDA's review and approval processes for lorundrostat.

Conclusion

Mineralys Therapeutics is at a critical juncture, transitioning from a clinical-stage entity to a potential commercial enterprise with lorundrostat. The company's core investment thesis is firmly rooted in its differentiated ASI technology, which offers a targeted and potentially superior approach to managing hypertension, particularly in uncontrolled and resistant patient populations. The robust clinical data from its pivotal trials, demonstrating significant blood pressure reductions and a favorable safety profile, provides a strong foundation for its upcoming NDA submission.

The strategic expansion into comorbid conditions like CKD and OSA further enhances lorundrostat's market potential, positioning it as a versatile therapeutic with benefits extending beyond mere blood pressure control. With a clear regulatory path, strong liquidity to support operations into 2028, and a significant unmet medical need in its target markets, Mineralys is well-positioned to unlock substantial value. While challenges such as future funding requirements and regulatory uncertainties persist, the company's technological leadership and comprehensive clinical evidence suggest a compelling opportunity for investors seeking exposure to innovative solutions in cardiovascular medicine.