[Corporate Update](index=1&type=section&id=Corporate%20Update) Mineralys Therapeutics provided Q2 2025 financial results and a corporate update, highlighting positive clinical trial outcomes for lorundrostat and upcoming NDA submission plans [Company Overview and CEO Statement](index=1&type=section&id=Company%20Overview%20and%20CEO%20Statement) Mineralys Therapeutics, a clinical-stage biopharmaceutical company, announced Q2 2025 financial results and a corporate update, with the CEO highlighting positive results from three clinical trials for lorundrostat and a pre-NDA meeting scheduled for 4Q 2025 - Mineralys Therapeutics is a clinical-stage biopharmaceutical company focused on developing medicines to target hypertension and related comorbidities such as chronic kidney disease (CKD) and obstructive sleep apnea (OSA), driven by dysregulated aldosterone[2](index=2&type=chunk) - CEO Jon Congleton stated that positive results from three clinical trials for lorundrostat in uncontrolled or resistant hypertension support its potential as a leading new therapy to control hypertension and reduce cardiovascular risk[3](index=3&type=chunk) - A pre-NDA meeting with the FDA is scheduled for the **fourth quarter of 2025**, advancing the company's NDA strategy[1](index=1&type=chunk)[3](index=3&type=chunk) [Recent Clinical Highlights and Upcoming Milestones](index=1&type=section&id=Recent%20Clinical%20Highlights%20and%20Upcoming%20Milestones) Mineralys reported positive results from its pivotal Launch-HTN and Advance-HTN trials, published in JAMA and NEJM, respectively, with the Explore-CKD Phase 2 trial also meeting its primary endpoint, and topline results for the Explore-OSA Phase 2 trial anticipated in 1H 2026 - Pivotal Launch-HTN Phase 3 Trial met its primary endpoint for efficacy and safety in uncontrolled or resistant hypertension as add-on therapy, with results published in JAMA (June 30, 2025) and presented at the 2025 European Society of Hypertension Meeting[4](index=4&type=chunk)[7](index=7&type=chunk) - Pivotal Advance-HTN Trial met its primary endpoints for efficacy and safety in confirmed uHTN or rHTN, reinforcing lorundrostat's favorable benefit-risk profile, with results published in NEJM (April 23, 2025) and presented at ACC.25 meeting[7](index=7&type=chunk) Explore-CKD Phase 2 Trial Key Results (Lorundrostat 25 mg) | Metric | Reduction | Placebo-Adjusted Reduction | p-value | | :-------------------------------- | :---------------- | :------------------------- | :------ | | Systolic BP (AOBP) at Week 4 | 9.25 mmHg | 7.5 mmHg | 0.0024 | | Spot UACR from Baseline at Week 4 | 30.51% | 25.6% | 0.0015 | - The Explore-OSA Phase 2 trial, evaluating lorundrostat in overweight/obese participants with moderate-to-severe OSA and uHTN/rHTN, is ongoing, with topline results anticipated in **1H 2026**[7](index=7&type=chunk) [Second Quarter 2025 Financial Highlights](index=2&type=section&id=Second%20Quarter%202025%20Financial%20Highlights) Mineralys Therapeutics reported its Q2 2025 financial performance, detailing changes in cash, R&D, G&A expenses, other income, and net loss [Cash, Cash Equivalents and Investments](index=2&type=section&id=Cash%2C%20Cash%20Equivalents%20and%20Investments) Mineralys Therapeutics reported a significant increase in its cash, cash equivalents, and investments, reaching **$324.9 million** as of June 30, 2025, up from **$198.2 million** at the end of 2024, with these funds believed to be sufficient to support operations into 2027 Cash, Cash Equivalents and Investments (in millions) | Metric | As of June 30, 2025 | As of December 31, 2024 | Change | | :-------------------------------- | :------------------ | :---------------------- | :----- | | Cash, cash equivalents and investments | $324.9 million | $198.2 million | +$126.7 million | - The Company believes its current cash, cash equivalents, and investments will be sufficient to fund planned clinical trials, regulatory activities, and corporate operations into **2027**[5](index=5&type=chunk) [Research and Development (R&D) Expenses](index=2&type=section&id=Research%20and%20Development%20%28R%26D%29%20Expenses) R&D expenses for Q2 2025 decreased slightly to **$38.3 million** from **$39.3 million** in Q2 2024, primarily due to the conclusion of the lorundrostat pivotal program, partially offset by increased compensation and clinical supply costs Research and Development (R&D) Expenses (in millions) | Metric | Q2 2025 | Q2 2024 | Change (YoY) | | :-------------------- | :---------- | :---------- | :----------- | | R&D Expenses | $38.3 million | $39.3 million | -$1.0 million | - The decrease in R&D expenses was primarily due to a **$4.5 million decrease** in preclinical and clinical costs, driven by the conclusion of the lorundrostat pivotal program in Q2 2025[6](index=6&type=chunk) - This decrease was partially offset by increases of **$2.7 million** in compensation expense (due to headcount additions, salaries, accrued bonuses, and stock-based compensation) and **$0.8 million** in higher clinical supply, manufacturing, regulatory, and other costs[6](index=6&type=chunk)[8](index=8&type=chunk) [General and Administrative (G&A) Expenses](index=3&type=section&id=General%20and%20Administrative%20%28G%26A%29%20Expenses) G&A expenses increased to **$8.5 million** in Q2 2025 from **$5.9 million** in Q2 2024, mainly attributed to higher compensation expenses, increased professional fees, and other administrative costs General and Administrative (G&A) Expenses (in millions) | Metric | Q2 2025 | Q2 2024 | Change (YoY) | | :-------------------- | :---------- | :---------- | :----------- | | G&A Expenses | $8.5 million | $5.9 million | +$2.6 million | - The increase was primarily due to **$1.9 million** in higher compensation expense (headcount additions, salaries, accrued bonuses, and stock-based compensation), **$0.6 million** in higher professional fees, and **$0.1 million** in other administrative expenses[9](index=9&type=chunk) [Total Other Income, Net](index=3&type=section&id=Total%20Other%20Income%2C%20Net) Total other income, net, decreased to **$3.5 million** in Q2 2025 from **$4.2 million** in Q2 2024, primarily due to lower interest earned on investments resulting from reduced average cash balances Total Other Income, Net (in millions) | Metric | Q2 2025 | Q2 2024 | Change (YoY) | | :-------------------- | :---------- | :---------- | :----------- | | Total Other Income, Net | $3.5 million | $4.2 million | -$0.7 million | - The decrease was primarily attributable to decreased interest earned on investments in money market funds and U.S. treasuries as a result of lower average cash balances invested during the quarter ended June 30, 2025[10](index=10&type=chunk) [Net Loss](index=3&type=section&id=Net%20Loss) Mineralys reported a net loss of **$43.3 million** for Q2 2025, an increase from **$41.0 million** in Q2 2024, primarily driven by the aforementioned changes in operating expenses Net Loss (in millions) | Metric | Q2 2025 | Q2 2024 | Change (YoY) | | :---------- | :---------- | :---------- | :----------- | | Net Loss | $43.3 million | $41.0 million | +$2.3 million | - The increase in net loss was primarily attributable to the factors impacting the Company's expenses, including higher G&A expenses and partially offset R&D expenses[11](index=11&type=chunk) [Conference Call Information](index=3&type=section&id=Conference%20Call%20Information) Mineralys Therapeutics held a conference call on August 12, 2025, to discuss Q2 financial results and corporate updates, with a replay available online [Conference Call Details](index=3&type=section&id=Conference%20Call%20Details) Mineralys Therapeutics hosted a conference call on August 12, 2025, at 4:30 p.m. ET to discuss the financial results and corporate update, with a replay of the call available on the company's investor relations website - The company's management team hosted a conference call on **August 12, 2025, at 4:30 p.m. ET**[12](index=12&type=chunk) - A live webcast and replay of the call are available on the 'News & Events' page in the Investor Relations section of the Mineralys Therapeutics website[12](index=12&type=chunk) [Disease Background](index=3&type=section&id=Disease%20Background) This section provides background on hypertension, chronic kidney disease (CKD), and obstructive sleep apnea (OSA), highlighting their prevalence, economic burden, and link to dysregulated aldosterone [About Hypertension](index=3&type=section&id=About%20Hypertension) Hypertension, or sustained elevated blood pressure, significantly increases the risk of heart disease, heart attack, and stroke, contributing to over **685,000 deaths** in the US in 2022 and imposing an estimated annual economic burden of **$219 billion** - Hypertension increases the risk of heart disease, heart attack, and stroke, which are leading causes of death in the United States[13](index=13&type=chunk) - In 2022, over **685,000 deaths** in the United States included hypertension as a primary or contributing cause, with an estimated annual economic burden of about **$219 billion** in 2019[13](index=13&type=chunk) - Less than **50%** of hypertension patients achieve their BP goal with currently available medications, and dysregulated aldosterone levels are a key factor in approximately **30%** of all hypertensive patients[13](index=13&type=chunk) [About Chronic Kidney Disease (CKD)](index=3&type=section&id=About%20Chronic%20Kidney%20Disease%20%28CKD%29) Chronic kidney disease (CKD) affects over **10%** of the global population and is a leading cause of mortality, with approximately **37 million** US adults having CKD, and dysregulated aldosterone identified as a key driver - CKD, characterized by gradual loss of kidney function, is estimated to affect more than **10%** of the global population and is one of the leading causes of mortality worldwide[14](index=14&type=chunk) - Approximately **1-in-7 (37 million)** U.S. adults have CKD, and about **22 million** people in the United States are living with both hypertension and CKD[14](index=14&type=chunk) - Emerging evidence points to dysregulated aldosterone as a key driver of both diseases, promoting sodium retention, vascular inflammation, and fibrosis, contributing to uncontrolled BP and kidney injury[15](index=15&type=chunk) [About Obstructive Sleep Apnea (OSA)](index=4&type=section&id=About%20Obstructive%20Sleep%20Apnea%20%28OSA%29) Obstructive Sleep Apnea (OSA) impacts almost **one billion** people globally, with **425 million** moderate-to-severe cases, and undiagnosed OSA cost the US approximately **$149.6 billion** annually in 2015, making it a major risk factor for cardiovascular disease - OSA impacts almost **one billion** people globally, including **425 million** moderate-to-severe cases, with around **80%** of adults with OSA being undiagnosed[16](index=16&type=chunk) - As of 2015, undiagnosed OSA is estimated to cost the United States approximately **$149.6 billion** annually from comorbid disease, workplace accidents, motor vehicle accidents, and loss of workplace productivity[16](index=16&type=chunk) - Between **30-50%** of adults with hypertension have OSA, and this number increases to between **70-80%** in adults with resistant hypertension, making it a major risk factor for cardiovascular disease, type-2 diabetes mellitus, and stroke[17](index=17&type=chunk) [Product Candidate: Lorundrostat](index=4&type=section&id=Product%20Candidate%3A%20Lorundrostat) Lorundrostat is Mineralys' highly selective aldosterone synthase inhibitor, developed for uncontrolled/resistant hypertension, CKD, and OSA, with successful clinical trials supporting its efficacy and favorable safety profile [About Lorundrostat](index=4&type=section&id=About%20Lorundrostat) Lorundrostat is Mineralys' proprietary, orally administered, highly selective aldosterone synthase inhibitor, developed for uncontrolled/resistant hypertension, CKD, and OSA, demonstrating high selectivity and a **40-70% reduction** in plasma aldosterone concentration - Lorundrostat is a proprietary, orally administered, highly selective aldosterone synthase inhibitor being developed for the treatment of uncontrolled or resistant hypertension (uHTN or rHTN), as well as CKD and OSA[18](index=18&type=chunk) - It was designed to reduce aldosterone levels by inhibiting CYP11B2, demonstrating **374-fold selectivity** for aldosterone-synthase inhibition versus cortisol-synthase inhibition in vitro, an observed half-life of **10-12 hours**, and a **40-70% reduction** in plasma aldosterone concentration in hypertensive participants[18](index=18&type=chunk) - The Company has completed four successful clinical trials, including the pivotal Phase 3 Launch-HTN trial and Phase 2 Advance-HTN trial, supporting its efficacy and safety profile with robust, durable, and clinically meaningful reductions in systolic BP[19](index=19&type=chunk) [About Mineralys Therapeutics](index=4&type=section&id=About%20Mineralys%20Therapeutics) Mineralys Therapeutics is a clinical-stage biopharmaceutical company focused on developing medicines for aldosterone-driven diseases, with lorundrostat as its lead candidate [Company Profile](index=4&type=section&id=Company%20Profile) Mineralys Therapeutics is a clinical-stage biopharmaceutical company based in Radnor, Pennsylvania, founded by Catalys Pacific, focusing on developing medicines for hypertension and related comorbidities driven by dysregulated aldosterone, with lorundrostat as its initial product candidate - Mineralys Therapeutics is a clinical-stage biopharmaceutical company focused on developing medicines to target hypertension and related comorbidities such as CKD, OSA, and other diseases driven by dysregulated aldosterone[20](index=20&type=chunk) - Its initial product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor[20](index=20&type=chunk)[21](index=21&type=chunk) - Mineralys is based in Radnor, Pennsylvania, and was founded by Catalys Pacific[21](index=21&type=chunk) [Forward-Looking Statements](index=5&type=section&id=Forward-Looking%20Statements) This section outlines cautionary statements regarding forward-looking information, emphasizing potential risks and uncertainties that could cause actual results to differ [Disclaimer and Risk Factors](index=5&type=section&id=Disclaimer%20and%20Risk%20Factors) This section contains cautionary statements regarding forward-looking information, emphasizing that actual results may differ from expectations due to inherent business risks, and the company disclaims any obligation to update these statements - Statements regarding matters that are not historical facts are forward-looking statements, based on current beliefs and expectations[22](index=22&type=chunk) - Actual results may differ due to inherent business risks, including: topline results being preliminary and subject to change, dependence on lorundrostat's success, potential delays in clinical trials, regulatory uncertainties with the FDA, reliance on third parties, unexpected adverse side effects or inadequate efficacy, unfavorable results from clinical trials, macroeconomic trends, and regulatory developments[22](index=22&type=chunk) - The company undertakes no obligation to update such statements to reflect events or circumstances that occur after the date of the press release[22](index=22&type=chunk) [Financial Statements](index=7&type=section&id=Financial%20Statements) This section presents the unaudited condensed statements of operations and balance sheet data for Mineralys Therapeutics [Condensed Statements of Operations](index=7&type=section&id=Condensed%20Statements%20of%20Operations) The condensed statements of operations provide unaudited financial results for the three and six months ended June 30, 2025, and 2024, detailing operating expenses, loss from operations, other income, and net loss Condensed Statements of Operations (in thousands, except share and per share data) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------------------------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $38,278 | $39,273 | $76,157 | $70,027 | | General and administrative | $8,468 | $5,895 | $15,036 | $10,503 | | Total operating expenses | $46,746 | $45,168 | $91,193 | $80,530 | | Loss from operations | $(46,746) | $(45,168) | $(91,193) | $(80,530) | | Interest income, net | $3,474 | $4,152 | $5,713 | $8,005 | | Other income (expense) | $(2) | $2 | $(5) | $3 | | Total other income, net | $3,472 | $4,154 | $5,708 | $8,008 | | Net loss | $(43,274) | $(41,014) | $(85,485) | $(72,522) | | Net loss per share attributable to common stockholders, basic and diluted | $(0.66) | $(0.83) | $(1.44) | $(1.54) | | Weighted-average shares used to compute net loss per share attributable to common stockholders, basic and diluted | 65,451,297 | 49,356,287 | 59,341,368 | 47,178,288 | [Condensed Balance Sheet Data](index=7&type=section&id=Condensed%20Balance%20Sheet%20Data) The condensed balance sheet data provides unaudited financial positions as of June 30, 2025, and December 31, 2024, including cash, total assets, total liabilities, and total stockholders' equity Condensed Balance Sheet Data (amounts in thousands) | Metric | As of June 30, 2025 | As of December 31, 2024 | | :-------------------------------- | :------------------ | :---------------------- | | Cash, cash equivalents and investments | $324,916 | $198,187 | | Total assets | $335,724 | $205,903 | | Total liabilities | $22,173 | $14,646 | | Total stockholders' equity | $313,551 | $191,257 |

Core Insights - Mineralys Therapeutics, Inc. announced positive results from pivotal trials for lorundrostat, a treatment for hypertension and related conditions, and plans to meet with the FDA for a pre-NDA meeting in Q4 2025 [1][3][4] Clinical Developments - The Launch-HTN Phase 3 trial met its primary endpoint, demonstrating efficacy and safety for lorundrostat in uncontrolled or resistant hypertension [4] - The Advance-HTN trial also met its primary endpoints, reinforcing the favorable benefit-risk profile of lorundrostat in high-risk populations [4] - The Explore-CKD Phase 2 trial showed significant reductions in systolic blood pressure (9.25 mmHg) and urine albumin-to-creatinine ratio (30.51%) [4] - Ongoing Explore-OSA Phase 2 trial is expected to report topline results in 1H 2026 [1][4] Financial Performance - As of June 30, 2025, the company reported cash, cash equivalents, and investments of $324.9 million, up from $198.2 million at the end of 2024, sufficient to fund operations into 2027 [5][31] - R&D expenses for Q2 2025 were $38.3 million, a decrease from $39.3 million in Q2 2024, primarily due to the conclusion of the lorundrostat pivotal program [6] - General and Administrative expenses increased to $8.5 million in Q2 2025 from $5.9 million in Q2 2024, driven by higher compensation and professional fees [7] - The net loss for Q2 2025 was $43.3 million, compared to $41.0 million in Q2 2024 [9][29] Market Context - Hypertension affects a significant portion of the population, with less than 50% of patients achieving blood pressure goals with current medications [11][12] - Chronic kidney disease (CKD) affects over 10% of the global population and is closely linked to hypertension, increasing cardiovascular risks [13][15] - Obstructive sleep apnea (OSA) is prevalent among hypertensive patients, with untreated cases contributing to resistant hypertension [17][18] Product Overview - Lorundrostat is a selective aldosterone synthase inhibitor designed to treat uncontrolled and resistant hypertension, CKD, and OSA [19][21] - The drug has shown a 40-70% reduction in plasma aldosterone concentration in hypertensive participants [19][20]

Core Insights - Mineralys Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing treatments for hypertension and related comorbidities [3] - The company will report its financial results for the second quarter ended June 30, 2025, on August 12, 2025, after market close [1][2] Company Overview - Mineralys Therapeutics specializes in medicines targeting hypertension, hypertensive nephropathy, obstructive sleep apnea, and diseases driven by dysregulated aldosterone [3] - The company's lead product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor [3] - Mineralys is headquartered in Radnor, Pennsylvania, and was founded by Catalys Pacific [3]

Core Insights - Mineralys Therapeutics, Inc. has been upgraded to a Zacks Rank 2 (Buy) due to an upward trend in earnings estimates, which is a significant factor influencing stock prices [1][3] - The Zacks rating system is particularly useful for individual investors as it focuses on earnings estimate revisions rather than subjective factors that can affect Wall Street analyst ratings [2][4] Earnings Outlook - The recent upgrade reflects a positive outlook on the company's earnings, which is expected to lead to buying pressure and an increase in stock price [3][5] - The Zacks Consensus Estimate for Mineralys Therapeutics has increased by 19.6% over the past three months, indicating a favorable shift in earnings expectations [8] Zacks Rating System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with a strong historical performance, particularly for Zacks Rank 1 stocks, which have generated an average annual return of +25% since 1988 [7] - The upgrade to Zacks Rank 2 places Mineralys Therapeutics in the top 20% of Zacks-covered stocks, suggesting a strong potential for market-beating returns in the near term [10]

Core Viewpoint - Mineralys Therapeutics, Inc. (MLYS) shows significant upside potential with a mean price target of $36.25, indicating a 154.2% increase from the current price of $14.26 [1][2]. Price Targets and Analyst Estimates - The mean estimate consists of eight short-term price targets with a standard deviation of $11.25, suggesting variability in analyst predictions. The lowest estimate is $15.00 (5.2% increase), while the highest is $48.00 (236.6% increase) [2]. - A low standard deviation among price targets indicates a high degree of agreement among analysts regarding the stock's price movement direction [9]. Earnings Estimates and Analyst Sentiment - Analysts have shown increasing optimism about MLYS's earnings prospects, with a strong consensus in revising EPS estimates higher, which correlates with potential stock price increases [11]. - Over the last 30 days, the Zacks Consensus Estimate for the current year has risen by 1.6%, with one estimate moving higher and no negative revisions [12]. Zacks Rank and Investment Potential - MLYS holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimate factors, indicating strong potential for upside in the near term [13]. - While the consensus price target may not be a reliable indicator of the extent of gains, it does provide a directional guide for potential price movement [14].

Core Insights - The Launch-HTN trial is the largest trial of an aldosterone synthase inhibitor for uncontrolled or treatment-resistant hypertension [1][2] - Lorundrostat 50 mg once daily showed significant reductions in systolic blood pressure, with a 16.9 mmHg reduction at Week 6 and a 19.0 mmHg reduction at Week 12 [1][5] - The trial demonstrated a favorable safety profile, with treatment-emergent adverse events being mostly mild and transient [1][6] Company Overview - Mineralys Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing treatments for hypertension, chronic kidney disease (CKD), and obstructive sleep apnea (OSA) driven by dysregulated aldosterone [1][11] - The company’s lead product candidate, lorundrostat, is a highly selective aldosterone synthase inhibitor designed to reduce aldosterone levels [10][11] Trial Details - The Launch-HTN trial was a global, randomized, double-blinded, placebo-controlled Phase 3 trial involving 1,083 participants who were on two to five antihypertensive medications [4] - The trial utilized automated office blood pressure measurements and allowed participants to continue their existing medications, reflecting real-world clinical practice [4] Efficacy Results - Lorundrostat demonstrated statistically significant mean reductions in automated office blood pressure, with a placebo-adjusted reduction of -9.1 mmHg at Week 6 and -11.7 mmHg at Week 12 [5] - The efficacy of lorundrostat was consistent across various demographics, including age, sex, race, body mass index, and baseline medication regimen [5] Safety Profile - The safety and tolerability profile of lorundrostat was favorable, with only a small percentage of participants experiencing elevated serum potassium levels [6][7] - There was no observed suppression of cortisol production, and serious adverse events leading to discontinuation were very low [7] Industry Context - Hypertension is a leading cause of cardiovascular disease, with less than 50% of patients achieving their blood pressure goals with current medications [8][9] - Dysregulated aldosterone levels contribute to hypertension in approximately 30% of hypertensive patients, highlighting the need for effective treatments like lorundrostat [9]

Explore-CKD Trial Results - Lorundrostat 25mg demonstrated a 9.3 mmHg absolute reduction in systolic blood pressure (SBP) at week 4[8, 19] - The placebo-adjusted change in systolic blood pressure was -7.5 mmHg (90% C.I -11.6, -3.4, p=0.002)[19] - A 31% reduction in spot Urine Albumin-to-Creatinine Ratio (UACR) was observed with lorundrostat (p < 0.0001)[8, 20] Safety Profile - The mean change in serum potassium was 0.5 mmol/L in lorundrostat treatment periods[27] - One subject (1.7%) discontinued due to potassium >6.5 mmol/L and low eGFR[27] - One subject (1.7%) discontinued due to low eGFR[28] Patient Demographics - The study population was 69% male with a mean age of 65 years[11] - 76% of participants had diabetes[11] - Baseline geometric mean spot urine UACR was 516 mg/g[12] - Mean systolic AOBP was 149 mmHg[13] Overall Conclusions - The Explore-CKD trial is the fourth positive clinical trial of lorundrostat in uHTN or rHTN[7] - Lorundrostat shows potential for aldosterone synthase inhibition in cardiorenal disorders[7] - The data demonstrates a consistent, clinically meaningful profile with the potential to benefit a spectrum of hypertension patients[39]

Summary of Minerals Therapeutics Conference Call Company and Industry - **Company**: Mineralis Therapeutics - **Industry**: Pharmaceuticals, specifically focusing on treatments for hypertension and chronic kidney disease (CKD) Key Points and Arguments 1. **Positive Clinical Trial Results**: The EXPLORER CKD trial demonstrated positive top-line data for lorundrostat, a selective aldosterone synthase inhibitor, in patients with uncontrolled hypertension and CKD [5][22][31] 2. **Efficacy of Lorundrostat**: The trial showed a clinically meaningful reduction in systolic blood pressure of 7.5 mmHg (p=0.002) and a 30.1% reduction in urinary albumin to creatinine ratio (UACR) (p=0.0001), indicating renal protective properties [15][17][22] 3. **Safety Profile**: The incidence of hyperkalemia was 12.1%, with only modest changes in mean eGFR observed, suggesting a manageable safety profile for lorundrostat in CKD patients [19][20][22] 4. **Patient Population**: The study included patients with a mean age of 65, a mean eGFR of 55, and a significant percentage (76%) being diabetic, highlighting the trial's focus on a high-risk population [13][14] 5. **Comparison with Other Trials**: The results were consistent with previous trials (ADVANCE HTN and LAUNCH HTN), reinforcing the efficacy and safety of lorundrostat across different patient populations [15][31] 6. **Regulatory Plans**: The company plans to submit a New Drug Application (NDA) to the FDA, incorporating data from the EXPLORER CKD trial, with a pre-NDA meeting anticipated in Q4 2025 [32][53] 7. **Future Studies**: Ongoing trials (EXPLORER OSA and TRANSFORM HCM) aim to further explore the benefits of lorundrostat in related conditions, including obstructive sleep apnea (OSA) [9][31][66] Other Important Content 1. **Mechanism of Action**: Lorundrostat works by inhibiting aldosterone production, which may offer advantages over mineralocorticoid receptor antagonists (MRAs) that can lead to rebound increases in aldosterone levels [26][60] 2. **Monitoring and Management**: Recommendations for potassium monitoring include checking levels 2-3 weeks after starting treatment, with adjustments based on individual patient factors [82][83] 3. **Commercial Strategy**: The company is seeking partnerships for commercialization, particularly focusing on cardiovascular franchises that align with the drug's potential in treating cardio-metabolic disorders [100][101] 4. **Patient Compliance**: Emphasis on the importance of tolerability in CKD patients, as side effects can lead to noncompliance with treatment regimens [26][27] This summary encapsulates the critical insights from the conference call, highlighting the advancements in lorundrostat's clinical development and its implications for treating hypertension in CKD patients.

Core Viewpoint - The article emphasizes the long-term journey of innovation in the pharmaceutical industry, particularly in the hypertension treatment sector, highlighting the recent advancements and unmet needs in this area [3][4]. Group 1: Hypertension Overview - Hypertension affects approximately 1 billion people globally and has seen no significant breakthroughs in core treatment targets for over 40 years [4][5]. - It is a leading cause of cardiovascular diseases and overall mortality, with 10.8 million deaths attributed to high systolic blood pressure in 2019, accounting for about 20% of total deaths [6]. - The prevalence of hypertension is approximately 1.4 billion globally, with 80 million in the U.S. and 90 million in the EU, representing 31% and 24% of the adult population, respectively [6]. Group 2: Treatment Landscape - Current hypertension treatments include lifestyle changes, antihypertensive medications, and some devices [21]. - The article outlines the classification of hypertension into controlled and uncontrolled categories based on blood pressure readings and medication regimens [14]. - The recommended initial medications for hypertension treatment include ACE inhibitors, ARBs, thiazide diuretics, and calcium channel blockers [23]. Group 3: Recent Developments - The recent success of Mineralys in advancing hypertension treatment through innovative drug mechanisms has opened new possibilities in the field [4][5]. - The article discusses the concept of "aldosterone escape," where patients experience a rebound increase in aldosterone levels despite treatment, leading to resistant hypertension [36][39]. - Aldosterone synthase inhibitors (ASI) are highlighted as a promising new class of drugs that can directly inhibit aldosterone production, addressing both RAAS and non-RAAS pathways [40][42]. Group 4: Mechanisms of Hypertension - The pathophysiology of hypertension involves multiple systems, including renal, vascular, neural, and the RAAS system, with obesity also playing a significant role [26][27]. - The article explains the mechanisms by which aldosterone contributes to hypertension, including both direct and indirect pathways [29][36]. Group 5: Clinical Implications - The article emphasizes the importance of accurate blood pressure measurement techniques to avoid misdiagnosis of hypertension, such as white coat hypertension and masked hypertension [18][20]. - It also discusses the need for personalized treatment goals based on individual patient circumstances, particularly for older adults or those with multiple comorbidities [20].

Core Insights - Mineralys Therapeutics announced positive topline data from its Phase 2 Explore-CKD trial, demonstrating the efficacy and safety of lorundrostat in treating hypertension and chronic kidney disease (CKD) [1][2][3] Efficacy, Safety and Tolerability Results - The Explore-CKD trial was a randomized, double-blind, placebo-controlled crossover trial involving 59 subjects, focusing on the efficacy of 25 mg lorundrostat in reducing systolic blood pressure (BP) and urine albumin-to-creatinine ratio (UACR) [4][13] - Lorundrostat achieved a 9.3 mmHg reduction in systolic BP and a 31% reduction in UACR, both statistically significant [7][5] - The trial showed a favorable safety profile, with treatment-emergent adverse events (TEAEs) leading to discontinuation in 3% of subjects during lorundrostat treatment [8][9] Clinical Significance - The trial results support the potential of lorundrostat as a treatment option for patients with hypertension and comorbid CKD, addressing the underlying mechanisms of these conditions [10][11] - The findings contribute to a growing body of evidence validating aldosterone synthase inhibitors in managing hypertension and CKD [10][18] Future Development - Mineralys plans to submit a New Drug Application (NDA) based on the successful outcomes of the Explore-CKD trial, along with previous pivotal trials [2][18] - Ongoing studies, including the Transform-HTN extension trial and the Explore-OSA trial, aim to further evaluate the long-term efficacy and safety of lorundrostat [11][19]