Core Insights - Mineralys Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing treatments for hypertension and related comorbidities, including chronic kidney disease and obstructive sleep apnea [3] Group 1: Stock Option Award - On November 24, 2025, the Compensation Committee of Mineralys granted an inducement stock option award covering 146,000 shares to a new non-executive employee [1] - The stock option will vest over a four-year period, with 25% vesting on the first anniversary and the remainder vesting monthly thereafter, contingent on continued service [2] - The award is part of the 2025 Employment Inducement Incentive Award Plan, aimed at attracting new employees [2] Group 2: Company Overview - Mineralys Therapeutics is based in Radnor, Pennsylvania, and was founded by Catalys Pacific [3] - The company's initial product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor [3]

Summary of Mineralys Therapeutics Conference Call Company Overview - **Company**: Mineralys Therapeutics (NasdaqGS: MLYS) - **Focus**: Development of aldosterone synthase inhibitors (ASI) targeting cardiorenal metabolic disorders, primarily hypertension [1][2] Industry Context - **Market Opportunity**: Approximately 20 million patients in the U.S. suffer from resistant and uncontrolled hypertension, with 10 million specifically identified as resistant hypertension patients [4][5] - **Competitive Landscape**: The ASI class is emerging as a new treatment option for hypertension, with recent data from competitors like AstraZeneca's Baxdrostat [2][3] Key Clinical Data - **Clinical Trials**: Successful outcomes from pivotal studies LAUNCH HTN and ADVANCE HTN, with significant blood pressure reductions observed [1][2] - **Efficacy**: Lorundrostat demonstrated a 15-19 mmHg reduction in blood pressure compared to the typical 5 mmHg improvement seen with existing treatments [5][6] - **Patient Demographics**: Strong representation of Black or African American patients in trials, addressing a high-risk population for hypertension [9][10] Drug Profile - **Selectivity**: Lorundrostat shows a selectivity ratio of 374:1 for aldosterone over cortisol, compared to Baxdrostat's 101:1, indicating a better safety profile [11][12] - **Half-Life**: Lorundrostat has a half-life of 10-12 hours, aligning with the diurnal pattern of aldosterone secretion, which may enhance safety [12][13] - **Safety Signals**: Lower incidence of hyperkalemia compared to Baxdrostat, with 8% incidence above 5.5 mEq/L for lorundrostat versus 11% for Baxdrostat [15][16] Market Strategy - **Target Population**: Initial focus on resistant hypertension, with plans to expand into uncontrolled hypertension as prescriber comfort increases [27][30] - **Commercialization Approach**: Open to partnerships but emphasizes the importance of selecting the right partner to maximize the drug's potential [45][46] - **Market Size**: Targeting a broad market of 120 million people with hypertension, with a focus on the top 60,000 prescribers [46][47] Future Developments - **NDA Filing**: Anticipated NDA filing by the end of 2025, with ongoing collection of safety and efficacy data beyond the initial 12-week trials [37][38] - **Additional Studies**: Ongoing studies in chronic kidney disease (CKD) and obstructive sleep apnea (OSA) to explore additional benefits and potential label expansions [42][43] Conclusion - **Investment Potential**: Mineralys Therapeutics is positioned with a best-in-class molecule in a growing market, with strong clinical data supporting its efficacy and safety, making it a compelling investment opportunity in the pharmaceutical sector [19][50]

Summary of Mineralys Therapeutics FY Conference Call Company Overview - **Company**: Mineralys Therapeutics (NasdaqGS:MLYS) - **Event**: FY Conference on November 11, 2025 - **Key Speaker**: Jon Congleton, CEO Industry Context - **Industry**: Hypertension treatment and drug development - **Unmet Need**: Hypertension remains a leading modifiable risk factor globally, causing approximately 10.8 million deaths annually due to related comorbidities [4][5][6] Core Points and Arguments 1. **Hypertension Treatment Landscape**: - There has been a lack of innovation in hypertension treatments over the past 20-25 years, with existing therapies not adequately addressing patient needs, particularly regarding dysregulated aldosterone [5][36] - Current treatment goals have become more stringent, with the target blood pressure now set at 130/80 mmHg for most patients and 120 mmHg for those with comorbidities [5] 2. **Lorundrostat's Mechanism and Efficacy**: - Lorundrostat is positioned as a best-in-class aldosterone synthase inhibitor (ASI) with a selectivity ratio of 374:1 for aldosterone over cortisol, which is critical for minimizing side effects [9][42] - Clinical trials (ADVANCE HTN and LAUNCH HTN) show significant blood pressure reductions of 15-19 mmHg, which are transformative compared to typical improvements of 5-6 mmHg seen with other agents [15][31] 3. **Market Opportunity**: - The potential market for lorundrostat is estimated at 20 million patients in the U.S., with 10 million classified as resistant hypertension and another 10 million as uncontrolled hypertension [36][37] - There is a strong demand for innovative treatments, with 95% of surveyed physicians indicating intent to prescribe lorundrostat if available [38] 4. **Safety Profile**: - Lorundrostat has a favorable safety profile, with lower rates of hyperkalemia compared to competitors, which may be attributed to its selectivity and pharmacokinetics [41][42] 5. **Regulatory Timeline**: - Mineralys plans to file for regulatory approval by the end of 2025 or Q1 2026, with expectations of overlapping review cycles with competitors like AstraZeneca [43] Additional Important Insights - **Patient Demographics**: The ADVANCE HTN study included a significant proportion (53%) of Black or African American patients, who are known to have more challenging hypertension profiles [28] - **Measurement Techniques**: The study utilized multiple blood pressure measurement methods, including 24-hour ambulatory monitoring, to ensure accurate assessment of treatment efficacy [16][17] - **Physician Engagement**: The company has conducted market research indicating that physicians are primarily focused on absolute blood pressure changes rather than placebo-adjusted figures, which influences prescribing behavior [31][32] This summary encapsulates the key points discussed during the conference call, highlighting the strategic positioning of Mineralys Therapeutics in the hypertension treatment landscape and the promising potential of lorundrostat as a novel therapeutic option.

Financial Data and Key Metrics Changes - The company ended Q3 2025 with cash, cash equivalents, and investments of $593.6 million, a significant increase from $198.2 million as of December 31, 2024, indicating strong liquidity to support operations into 2028 [16] - R&D expenses for Q3 2025 were $31.5 million, down from $54 million in Q3 2024, primarily due to the conclusion of the lorandirostat pivotal program [16][17] - Net loss for Q3 2025 was $36.9 million, a decrease from $56.3 million in Q3 2024, reflecting improved expense management [18] Business Line Data and Key Metrics Changes - The company is advancing its clinical programs, particularly lorandirostat, which has shown clinically meaningful reductions in systolic blood pressure across diverse patient populations [6][10] - The EXPLORE-CKD trial demonstrated a significant reduction in systolic blood pressure and a clinically meaningful reduction in urinary albumin-creatinine ratio, indicating potential renal protection [10] Market Data and Key Metrics Changes - The company is focusing on market access planning and payer engagement to ensure the value of lorandirostat is well understood, which is crucial for its commercial readiness [13] - The ongoing phase II EXPLORE-OSA trial aims to evaluate lorandirostat's efficacy in patients with obstructive sleep apnea and hypertension, with results expected in Q1 2026 [11] Company Strategy and Development Direction - The company is preparing for an NDA submission for lorandirostat, expected by the end of 2025 or early 2026, following positive pre-NDA feedback from the FDA [5][36] - The strategy includes expanding lorandirostat's profile to address comorbid conditions associated with hypertension, such as chronic kidney disease and obstructive sleep apnea [12][41] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strength of the clinical data supporting lorandirostat as a best-in-class therapy for uncontrolled and resistant hypertension [14][64] - The company is optimistic about upcoming milestones, including the NDA submission and results from the EXPLORE-OSA trial, which could enhance the drug's profile [64] Other Important Information - The company has emphasized the importance of diverse patient representation in clinical trials, particularly for Black or African American populations, which are often underrepresented in hypertension studies [54] - The management highlighted the need for partnerships to maximize the value of lorandirostat, both in the U.S. and internationally [38][49] Q&A Session Summary Question: What would the systolic blood pressure reduction be without adjusting for discontinuations? - Management indicated that they have not performed that specific analysis, as it was not part of the study plan [20][21] Question: Have you looked at the day and night blood pressure differences in the Advanced HTN trial? - Management confirmed that they are comfortable with the 24-hour control and have measured blood pressure at trough, but have yet to publish nighttime data [26][28] Question: Can you provide more details on the pre-NDA feedback? - Management stated that there were no surprises in the feedback and expressed confidence in the data set prepared for submission [35][36] Question: What are your expectations for the open label extension trial? - Management noted that the trial is progressing well, with no surprises, and results will be published once the last subject completes the study [40] Question: How do you expect to leverage data from the EXPLORE-OSA trial? - Management aims to enhance lorandirostat's profile by demonstrating its benefits beyond blood pressure reduction, addressing related comorbidities [41] Question: What differences in efficacy do you see with lorandirostat in the African American population? - Management highlighted that over 50% of participants in the Advance HTN trial were Black or African American, showing that race does not determine response to lorandirostat [54][56]

Clinical Trials and Efficacy - The pivotal trials, Launch-HTN and Advance-HTN, demonstrated statistically significant reductions in systolic blood pressure (BP) with lorundrostat, achieving a placebo-adjusted reduction of -9.1 mmHg at week 6 and -11.6 mmHg at week 12 in the Launch-HTN trial[102][103] - In the Advance-HTN trial, lorundrostat achieved a placebo-adjusted reduction of -7.9 mmHg at week 12, with a primary endpoint p-value of 0.001[107] - The Phase 2 Explore-CKD trial showed highly statistically significant results for lorundrostat in treating hypertension in patients with chronic kidney disease (CKD)[98] - The FDA cleared the investigational new drug application for the Explore-OSA trial, evaluating lorundrostat in patients with obstructive sleep apnea (OSA) and hypertension[101] - The Explore-CKD trial showed a placebo-adjusted change in systolic BP of -7.5 mmHg (p=0.0024) and a -25.60% change in UACR (p=0.0015) with lorundrostat 25 mg[112] Patient Demographics and Safety - Key characteristics of participants in the Launch-HTN trial included approximately 63% having a BMI ≥ 30 kg/m² and 29% being Black or African American[104] - The Advance-HTN trial enrolled participants who were on a standardized regimen of antihypertensive medications, reflecting a high-risk population[106] - Clinical safety findings from the pivotal trials support a favorable benefit-risk profile for lorundrostat, including monitoring of serum potassium and estimated glomerular filtration rate (eGFR)[108] - In the Launch-HTN trial, the incidence of treatment-emergent serious adverse events (SAEs) was 2.2% in the 50 mg arm and 0.7% in the 50 to 100 mg arm, compared to 3.0% in the placebo arm[109] - In the Advance-HTN trial, the incidence of treatment-emergent SAEs was 6.4% in the lorundrostat 50 mg arm and 8.4% in the 50 to 100 mg arm, compared to 2.1% in the placebo arm[110] Financial Overview - As of September 30, 2025, the company had cash, cash equivalents, and investments totaling $593.6 million[118] - The company raised approximately $1.0 billion in gross proceeds since inception, with net proceeds of approximately $269.6 million from a stock sale in September 2025[118] - The net losses for the nine months ended September 30, 2025, and 2024 were $122.4 million and $128.9 million, respectively, with an accumulated deficit of $424.9 million as of September 30, 2025[119] - The company expects expenses and operating losses to increase substantially as it conducts ongoing clinical trials and seeks regulatory approval for lorundrostat[119] - The company has no products approved for sale and does not expect to generate revenue until lorundrostat is developed and approved[121] Ongoing Trials and Future Plans - The ongoing Transform-HTN extension trial is evaluating the long-term efficacy, safety, and tolerability of lorundrostat, with topline results from the Explore-OSA trial anticipated in Q1 2026[117] - The company is exploring the application of lorundrostat for other indications related to dysregulated aldosterone biology, including OSA[100] Expenses and Cash Flow - For the three months ended September 30, 2025, research and development expenses decreased by $22.5 million to $31.45 million compared to $53.99 million in the same period of 2024[138] - General and administrative expenses increased by $3.6 million for the three months ended September 30, 2025, totaling $9.68 million compared to $6.12 million in 2024[141] - The net loss for the three months ended September 30, 2025, was $36.93 million, a decrease of $19.41 million from a net loss of $56.34 million in the same period of 2024[138] - Research and development expenses for the nine months ended September 30, 2025, decreased by $16.4 million to $107.61 million compared to $124.01 million in 2024[143] - General and administrative expenses for the nine months ended September 30, 2025, increased by $8.1 million to $24.72 million compared to $16.62 million in 2024[145] Cash Flow Activities - Net cash used in operating activities was $104.5 million for the nine months ended September 30, 2025, compared to $99.5 million for the same period in 2024, reflecting an increase of $5.1 million[155] - Net cash used in investing activities was $286.3 million for the nine months ended September 30, 2025, compared to net cash provided of $31.4 million in 2024, driven by a $236.7 million increase in purchases of marketable securities[156] - Net cash provided by financing activities was $494.3 million for the nine months ended September 30, 2025, significantly higher than $116.1 million in 2024, with $270.2 million from a public offering in September 2025[157] Market Risks and Economic Factors - The company is exposed to market risks related to interest rate changes, but a hypothetical 10% change in interest rates would not have a material effect on operations[167] - The company is also exposed to foreign currency exchange risks due to contracts with vendors outside the U.S., but fluctuations have not been significant to date[168] - Inflation has increased costs related to labor and research and development, which may impact future financial conditions and results of operations[169] - Operating activities cash flow was affected by increased clinical trial expenses and personnel costs, with a $19.8 million change in working capital[155] - The company has not had a formal hedging program for foreign currency, and believes that exchange rate fluctuations have not significantly impacted operations[168]

Financial Performance - Cash, cash equivalents, and investments increased to $593.6 million as of September 30, 2025, up from $198.2 million as of December 31, 2024[4] - The net loss for Q3 2025 was $36.9 million, a reduction from $56.3 million in Q3 2024[8] - Total other income, net for Q3 2025 was $4.2 million, compared to $3.8 million in Q3 2024, attributed to increased interest earned on investments[7] Research and Development - Research and Development (R&D) expenses decreased to $31.5 million for Q3 2025, down from $54.0 million in Q3 2024, primarily due to the conclusion of the lorundrostat pivotal program[5] - The company has completed four successful clinical trials of lorundrostat, supporting its efficacy and safety profile[17] - The company completed enrollment in the Explore-OSA Phase 2 trial, with topline results expected in Q1 2026[3] Future Plans - The company plans to submit a New Drug Application (NDA) for lorundrostat by late 2025 or Q1 2026[1] - The company believes its current cash reserves will fund planned clinical trials and operations into 2028[4] - The company aims to evaluate lorundrostat's use in hypertension-related comorbidities, expanding its treatment opportunities[3] Administrative Expenses - General and Administrative (G&A) expenses rose to $9.7 million in Q3 2025, compared to $6.1 million in Q3 2024, driven by higher compensation and professional fees[6]

Core Insights - Mineralys Therapeutics is preparing for the submission of a New Drug Application (NDA) for lorundrostat, anticipated by late 2025 or early 2026, following positive pre-NDA feedback from the FDA [2][3] - The company has completed enrollment in the Explore-OSA trial, with topline results expected in Q1 2026, which will evaluate lorundrostat's efficacy in patients with obstructive sleep apnea and hypertension [1][2] Financial Highlights - As of September 30, 2025, the company reported cash, cash equivalents, and investments totaling $593.6 million, a significant increase from $198.2 million at the end of 2024, indicating a strengthened balance sheet [4][25] - Research and Development (R&D) expenses for Q3 2025 were $31.5 million, down from $54.0 million in Q3 2024, primarily due to the conclusion of the lorundrostat pivotal program [5] - General and Administrative (G&A) expenses rose to $9.7 million in Q3 2025 from $6.1 million in Q3 2024, driven by increased compensation and professional fees [6] - The net loss for Q3 2025 was $36.9 million, a decrease from $56.3 million in Q3 2024, reflecting improved expense management [8][23] Clinical Development - Lorundrostat is being developed as a treatment for uncontrolled and resistant hypertension, chronic kidney disease, and obstructive sleep apnea, with a focus on normalizing aldosterone production [2][17] - The company has completed four successful clinical trials for lorundrostat, demonstrating its efficacy and safety profile [18] Market Context - Hypertension affects a significant portion of the population, with less than 50% of patients achieving their blood pressure goals with current medications, highlighting the need for new treatments like lorundrostat [10][11] - Chronic Kidney Disease (CKD) affects over 10% of the global population, and its relationship with hypertension presents a substantial market opportunity for effective therapies [12][13]

Core Insights - Mineralys Therapeutics presented clinical data for lorundrostat at ASN Kidney Week 2025, highlighting its potential in treating hypertension and chronic kidney disease (CKD) [1][2] - The Explore-CKD trial demonstrated significant reductions in blood pressure and albuminuria, supporting the drug's efficacy [2][4] - The Launch-HTN trial was recognized in the "Best of JAMA and NEJM" session, showcasing lorundrostat's robust performance in managing resistant hypertension [2][4] Clinical Trial Results - The Explore-CKD trial (NCT06150924) showed a 9.3 mmHg reduction in automated office systolic blood pressure (AOSBP) and a 25.6% reduction in urinary albumin-to-creatinine ratio (UACR) after four weeks of treatment with lorundrostat [2][7] - The Launch-HTN trial reported a 16.9 mmHg absolute reduction in systolic blood pressure at week 6 and a 19 mmHg reduction at week 12, with significant placebo-adjusted results [4][10] Safety and Tolerability - Lorundrostat exhibited a favorable safety profile, with serious adverse events occurring in only 3% of participants during treatment, compared to none in the placebo group [3][5] - Discontinuations due to treatment-emergent adverse events were low, indicating good tolerability among participants [3] Broader Implications - The results from both trials suggest that lorundrostat could address the growing burden of cardio-renal-metabolic diseases, particularly in high-risk populations [2][5] - The ongoing Transform-HTN study aims to evaluate the long-term safety and efficacy of lorundrostat, further supporting its clinical potential [5][6] Company Overview - Mineralys Therapeutics is focused on developing therapies targeting hypertension and related comorbidities, with lorundrostat as its lead candidate [1][16] - The company aims to file a New Drug Application (NDA) with the FDA by late 2025 or early 2026, based on the promising results from its clinical trials [2][15]

Core Viewpoint - Mineralys Therapeutics, Inc. is set to report its third-quarter financial results on November 10, 2025, focusing on its development of medicines targeting hypertension and related comorbidities [1] Company Overview - Mineralys Therapeutics is a clinical-stage biopharmaceutical company based in Radnor, Pennsylvania, specializing in treatments for hypertension and related conditions such as chronic kidney disease (CKD) and obstructive sleep apnea (OSA) [3] - The company's lead product candidate, lorundrostat, is a proprietary, orally administered, highly selective aldosterone synthase inhibitor [3] - Mineralys was founded by Catalys Pacific and aims to address diseases driven by dysregulated aldosterone [3] Upcoming Financial Results - The financial results for the third quarter ended September 30, 2025, will be announced after market close on November 10, 2025 [1] - A conference call will be held on the same day at 4:30 p.m. ET, with details provided for both domestic and international participants [2]

Core Insights - Mineralys Therapeutics, Inc. is focused on developing treatments for hypertension and related comorbidities, with a key product candidate, lorundrostat, being evaluated in clinical trials [1][4] Group 1: Clinical Trials and Presentations - Data from the Phase 2 Explore-CKD trial of lorundrostat will be presented at the ASN Kidney Week 2025, highlighting its safety and efficacy in participants with hypertension and comorbid CKD [1][6] - The Phase 3 Launch-HTN trial data of lorundrostat will also be featured in a prominent session at ASN Kidney Week, showcasing its relevance in treating uncontrolled hypertension [2][6] Group 2: Product Information - Lorundrostat is a proprietary, orally administered aldosterone synthase inhibitor designed to treat uncontrolled hypertension, chronic kidney disease, and obstructive sleep apnea [3][4] - It exhibits a 374-fold selectivity for aldosterone-synthase inhibition compared to cortisol-synthase inhibition and has shown a 40-70% reduction in plasma aldosterone concentration in hypertensive participants [3]