Executive Summary / Key Takeaways

• Phase 3 Validation Establishes Best-in-Class Profile: Lorundrostat's Launch-HTN and Advance-HTN trials delivered placebo-adjusted systolic BP reductions of 11.6 mmHg and 7.9 mmHg respectively, with hyperkalemia rates of just 0.6-2.1%—a safety profile that distinguishes it from mineralocorticoid receptor antagonists and positions it for broad adoption in the 15-20 million patient U.S. market.

• Capital Efficiency Through Inflection: Despite being pre-revenue, Mineralys has amassed $593.6 million in cash as of September 2025, providing runway into 2028. This funding supports NDA submission in late Q4 2025 or Q1 2026, commercial infrastructure build-out, and multiple late-stage trials without near-term dilution risk.

• Differentiated Science with Real-World Relevance: Lorundrostat's 374-fold selectivity for aldosterone synthase versus cortisol synthase, combined with a 10-12 hour half-life that mirrors the diurnal rhythm of aldosterone, translates into consistent efficacy across diverse populations—including 30-50% Black/African-American enrollment where resistant hypertension prevalence is higher.

• Pipeline Expansion Beyond Hypertension: The Explore-CKD trial demonstrated not only 7.5 mmHg BP reduction but also a 25.6% reduction in urine albumin-to-creatinine ratio , suggesting renal protective effects. With Explore-OSA enrollment complete and data expected Q1 2026, Mineralys has created multiple shots on goal that extend the addressable market beyond hypertension alone.

• Commercial Strategy Built on Physician Demand: Market research indicates 95% of cardiologists and primary care physicians would prescribe lorundrostat in the third-line or later setting, while payer research suggests step-through requirements will be manageable (two generic classes, not spironolactone), supporting an efficient launch targeting 47,000 high-prescribing physicians.

Setting the Scene: The Aldosterone Synthase Inhibitor Opportunity

Mineralys Therapeutics, founded in May 2019 as Catalys SC1 and renamed in May 2020, is a clinical-stage biopharmaceutical company singularly focused on developing lorundrostat, a highly selective aldosterone synthase inhibitor (ASI). The company's July 2020 license agreement with Mitsubishi Tanabe granted exclusive worldwide rights to this molecule, positioning Mineralys at the forefront of a therapeutic class that targets the root cause of dysregulated aldosterone in cardiorenal diseases.

The addressable market is substantial and underserved. Approximately 120 million patients in the U.S. have sustained elevated blood pressure, with over 30 million failing to achieve guideline goals and an estimated 15-20 million requiring three or more medications. Dysregulated aldosterone drives hypertension in roughly 30% of these patients, creating a target population of 20 million in the U.S. alone. Current standard of care relies on mineralocorticoid receptor antagonists (MRAs) like spironolactone, which block aldosterone at one downstream pathway but carry significant baggage: dose-dependent hyperkalemia, androgenic side effects including gynecomastia, and limited efficacy in diverse populations.

This is where lorundrostat's mechanism matters. By inhibiting aldosterone synthesis at its source rather than blocking its receptor, the drug reduces plasma aldosterone concentration while potentially avoiding the hyperkalemia trade-off that limits MRA utility. The economic burden of uncontrolled hypertension—$219 billion annually in the U.S.—creates urgency for better options, while the biological link between aldosterone, chronic kidney disease, and obstructive sleep apnea opens adjacent markets that Mineralys is already exploring.

Technology and Strategic Differentiation: Why Selectivity and Half-Life Matter

Lorundrostat's 374-fold selectivity for aldosterone synthase versus cortisol synthase is not merely a laboratory curiosity—it translates directly into clinical safety and efficacy. This selectivity minimizes off-target effects on cortisol production, which is critical for maintaining metabolic stability. The observed 10-12 hour half-life is pharmacologically ideal, aligning with the diurnal pattern of aldosterone elevation that occurs during sleep and contributes to morning cardiovascular events.

The Phase 3 Launch-HTN trial enrolled 1,083 participants, including nearly one-third Black or African-American patients and half women, with over half having resistant hypertension requiring three or more background medications. At week 12, lorundrostat 50 mg once daily achieved a placebo-adjusted systolic BP reduction of 11.6 mmHg—an absolute reduction of 19.0 mmHg from baseline. Critically, confirmed hyperkalemia (serum potassium ≥6.0 mmol/L) occurred in just 0.6% of subjects versus 0.4% on placebo, demonstrating that the efficacy gain does not come at the cost of meaningful safety deterioration.

The Phase 2 Advance-HTN trial, conducted in hard-to-treat patients with 24-hour ambulatory BP monitoring , showed a 7.9 mmHg placebo-adjusted reduction in systolic BP at week 12. The hyperkalemia rate was 2.1% in the 50 mg arm—still favorable compared to historical MRA rates that can exceed 10% at effective doses. Management emphasized that no prior trial has rigorously evaluated resistant hypertension using 24-hour ambulatory monitoring at trough, making these results a new benchmark for the field.

Beyond blood pressure, the Explore-CKD trial in hypertensive patients with chronic kidney disease demonstrated a 7.5 mmHg placebo-adjusted BP reduction and, more importantly, a 25.6% reduction in urine albumin-to-creatinine ratio (UACR). This UACR reduction is consistent with renal protective effects and addresses a key unmet need in CKD management. The hyperkalemia rate was 5% in this population—a manageable level given that CKD specialists are often more tolerant of potassium elevation if it means achieving BP control that slows disease progression.

Financial Performance: Pre-Revenue Execution with Disciplined Burn

Mineralys has generated no revenue since inception, incurring significant operating losses that reflect its clinical-stage status. For the three months ended September 30, 2025, net loss was $36.9 million, bringing the nine-month total to $122.4 million. Research and development expenses decreased to $31.5 million in Q3 2025 from higher prior-year levels as the pivotal program concluded in Q2 2025, though this was partially offset by increased compensation expense from headcount additions and higher clinical supply, manufacturing, and regulatory costs.

General and administrative expenses rose to $9.7 million in Q3 2025, up from prior periods due to increased headcount, salaries, bonuses, and professional fees associated with building corporate infrastructure. Total other income, net, increased modestly in Q3 due to higher interest earned on larger cash balances, though nine-month other income decreased year-over-year due to lower average invested balances.

The cash flow story reveals disciplined capital deployment. Net cash used in operating activities was $104.5 million during the nine months ended September 30, 2025, reflecting continued investment in lorundrostat development, clinical trials, and personnel. Net cash used in investing activities was $286.3 million, driven by purchases of marketable securities as the company deployed its substantial cash reserves into income-generating investments.

Balance Sheet Strength and Capital Strategy

As of September 30, 2025, Mineralys held $593.6 million in cash, cash equivalents, and investments against an accumulated deficit of $424.9 million. The company has raised approximately $1 billion in aggregate gross proceeds from various equity and warrant sales since inception, including a $116.1 million private placement in February 2024, a $188.7 million public offering in March 2025, and a $269.6 million public offering in September 2025. Management believes this cash position will fund operations into 2028, providing a four-year runway that is exceptional for a clinical-stage company approaching commercialization.

This capital efficiency matters because it eliminates the near-term financing overhang that plagues many biotech companies. The company can fund its NDA submission, commercial preparation, and ongoing Phase 2 trials in CKD and OSA without diluting shareholders or accepting unfavorable partnership terms. Future operations are expected to be financed through potential strategic collaborations and licensing arrangements, particularly for ex-U.S. commercialization, which management views as a key component of its value-maximization strategy.

Outlook and Execution: The Path to Commercialization

Management guidance points to several near-term catalysts that will define the investment thesis. The company plans to submit its New Drug Application for lorundrostat in uncontrolled and resistant hypertension in late Q4 2025 or Q1 2026, following a pre-NDA meeting with FDA in Q4 2025. The pre-NDA feedback contained "no surprises," suggesting the regulatory path is well-defined. Topline results from the Explore-OSA trial are anticipated in Q1 2026, which could open a third indication if positive.

The Transform-HTN open-label extension trial will provide 52-week safety data, with management planning to publish results once the last subject completes the randomized treatment withdrawal phase. While not required for the NDA, this data will support long-term safety messaging and differentiate lorundrostat from competitors with less robust durability data.

Commercial preparation is accelerating. Eric Warren was appointed Chief Commercial Officer to lead strategy and support partnering ambitions. Market research indicates that 95% of surveyed cardiologists and primary care physicians would likely prescribe lorundrostat broadly for uncontrolled or resistant hypertension, specifically in the third line or later. An IQVIA analysis showed nearly 9 million patients started new treatments in the third-line or later position in 2024, indicating substantial dissatisfaction with current options.

Payer research suggests that step-through requirements will likely involve two generic classes rather than spironolactone, creating an easily navigable electronic step edit. This matters because spironolactone holds only about 2% market share in hypertension, making it an impractical comparator for payers. Management aims for "modest, prescriber-friendly" utilization management criteria that optimize net price while ensuring access.

Competitive Landscape: Differentiation in an Emerging Class

The competitive landscape reveals both opportunities and threats. AstraZeneca (AZN)'s baxdrostat, acquired via CinCor Pharma, is the most direct ASI competitor. However, management highlights key differences: baxdrostat has lower selectivity, a longer half-life of 25-30 hours that may not align with diurnal aldosterone rhythms, and enrolled only 8% Black/African-American patients in its trials versus 30-50% for Mineralys. Baxdrostat's NDA was accepted in December 2025 under priority review, setting up a potential near-term launch that could validate the ASI class but also create first-mover competition.

Novartis (NVS)'s dexfadrostat focuses on primary aldosteronism, a narrower subset of resistant hypertension, while Idorsia's aprocitentan targets endothelin pathways, offering a complementary rather than directly competitive mechanism. Alnylam (ALNY)'s zilebesiran uses RNAi to target angiotensinogen, requiring subcutaneous injection versus lorundrostat's oral convenience.

Mineralys's advantages extend beyond pharmacology. The company's rigorous trial designs—particularly the 24-hour ambulatory BP monitoring in Advance-HTN—establish a new efficacy benchmark that competitors have not matched. The diverse enrollment demonstrates consistent response across subgroups, addressing a critical gap in hypertension research where Black patients historically show lower response to generic medications. As Chief Medical Officer David Rodman noted, "Black, African-Americans have a higher percentage of not being able to respond to the generic drugs as well as Caucasian patients. And so we have a higher percentage there. The need is higher and yet we showed that the response once they get on our drug is just as good as the Caucasian population."

Risks and Asymmetries: What Could Break the Thesis

The most material risk is regulatory. While pre-NDA feedback was positive, FDA review could identify issues with the application or require additional data, delaying approval into 2026 or beyond. A government shutdown, such as the one that began October 1, 2025, could hinder FDA's ability to review new products, causing material adverse effects on timing.

Execution risk looms large for a company transitioning from clinical development to commercialization. Building a sales force, establishing distribution, and achieving payer coverage are complex tasks that have derailed many biotech companies with promising drugs. The targeted prescriber base of 47,000 physicians is efficient but requires precise execution to capture market share quickly before competitors establish footholds.

Competitive dynamics could shift rapidly. If AstraZeneca's baxdrostat launches first and achieves favorable payer positioning, it could create barriers to lorundrostat's adoption despite its differentiated profile. Conversely, if baxdrostat encounters safety or efficacy issues post-launch, it could tarnish perception of the entire ASI class.

The single-asset concentration risk is pronounced. Mineralys's entire value proposition rests on lorundrostat. Any unexpected safety signal in broader commercial use or in the ongoing CKD and OSA trials could fundamentally impair the company's prospects. The hyperkalemia rate of 5% in the CKD population, while manageable, could limit uptake in that indication if physicians perceive the risk as too high relative to benefits.

Valuation Context: Pricing a Pre-Revenue Pipeline

At $38.50 per share, Mineralys trades at a market capitalization of $3.05 billion and an enterprise value of $2.45 billion. As a pre-revenue company, traditional earnings multiples are meaningless. The valuation must be assessed based on pipeline potential, cash runway, and comparable transactions.

The company holds $593.6 million in cash, representing 19.5% of market cap and providing substantial downside protection. With a quarterly burn rate of approximately $35-40 million, the runway into 2028 implies 12-15 quarters of funding, sufficient to reach commercial launch and generate initial revenue before requiring additional capital.

Comparative valuation requires looking at peers in the resistant hypertension space. AstraZeneca, with its broader portfolio and baxdrostat program, trades at $279.6 billion market cap with 24.1% operating margins and 16.2% profit margins—mature metrics that reflect successful commercial execution. Alnylam, with its RNAi platform and zilebesiran program, trades at $60.5 billion market cap despite 1.4% profit margins, reflecting platform value and growth potential. Idorsia, having launched aprocitentan, trades at a smaller valuation but with revenue growth validating the resistant hypertension market.

For Mineralys, the key valuation drivers are: (1) probability of FDA approval for lorundrostat in hypertension (appears high given Phase 3 success), (2) peak sales potential in the 15-20 million patient addressable market, (3) expansion potential into CKD and OSA, and (4) partnership value for ex-U.S. rights. If lorundrostat captures even 5% of the target population at a reasonable price, peak sales could exceed $1 billion, justifying the current valuation with substantial upside for successful pipeline expansion.

Conclusion: A Well-Capitalized ASI Leader at the Inflection Point

Mineralys Therapeutics has executed a textbook clinical development program, delivering positive Phase 3 data for lorundrostat that establishes best-in-class potential among aldosterone synthase inhibitors. The combination of superior selectivity, favorable hyperkalemia profile, robust efficacy across diverse populations, and a pharmacokinetic profile aligned with physiological rhythms creates a differentiated product that addresses a clear unmet need in resistant hypertension.

The company's financial strategy has been equally impressive, amassing a cash war chest that funds operations into 2028 while avoiding the dilution that often plagues clinical-stage companies. This capital efficiency provides strategic optionality, allowing management to pursue optimal commercialization and partnership strategies rather than accepting terms dictated by near-term financing needs.

The investment thesis hinges on two critical variables: successful FDA approval and commercial execution in the U.S. hypertension market, and positive data from the Explore-OSA trial that would expand the addressable market. While competition from AstraZeneca's baxdrostat is real, lorundrostat's differentiated profile and rigorous clinical data create a compelling value proposition for physicians, payers, and patients.

For investors willing to accept the inherent risks of a single-asset, pre-revenue biotech, Mineralys offers an attractive risk-reward profile: substantial downside protection from cash on hand, multiple near-term catalysts, and a pipeline that could address multiple cardiorenal indications. The ASI revolution in resistant hypertension is beginning, and Mineralys has positioned itself to be a leader in this emerging class.