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© 2025 Mineralys Therapeutics, Inc. © 2025 Mineralys Therapeutics, Inc. All Rights Reserved. November 2025 Targeting Aldosterone in the Treatment of Cardiorenal Diseases
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© 2025 Mineralys Therapeutics, Inc. Forward-Looking Statements and Market Data Mineralys Therapeutics cautions you that statements contained in this presentation regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to, statements regarding: future results of operations and financial position, business strategy, research and development plans; the potential therapeutic benefits of and market opportunity for lorundrostat; the Company’s expectation that aldosterone synthase inhibitors with an SGLT2 inhibitor may provide additive clinical benefits to patients; the Company’s expectation that Advance-HTN and Launch-HTN may serve as pivotal trials in any submission of a new drug application (NDA) to the United States Food and Drug Administration (FDA); the anticipated timing of NDA submission and the FDA's review of the same; the Company’s ability to evaluate lorundrostat as a potential treatment for chronic kidney disease, uncontrolled hypertension, resistant hypertension or obstructive sleep apnea; the planned future clinical development of lorundrostat and the timing thereof; and the expected timing of commencement and enrollment of patients in clinical trials and topline results from clinical trials. Actual results may differ from those set forth in this presentation due to the risks and uncertainties inherent in our business, including, without limitation: topline results that we report are based on a preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data related to the clinical trial and such topline data may not accurately reflect the complete results of a clinical trial; our future performance is dependent entirely 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 the feedback from the completed end of Phase 2 meeting, including whether the proposed pivotal program will support registration of lorundrostat which is a review issue with the FDA upon submission of an NDA; any delays in the FDA's review of our planned NDA submission, including as a result of a government shutdown or reductions in agency funding or personnel; the results of our clinical trials, including the Advance- HTN and Launch-HTN trials, may not be deemed sufficient by the FDA to serve as the basis for an NDA submission or regulatory approval of lorundrostat; our 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; unfavorable results from clinical trials and nonclinical studies; 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; our ability to maintain undisrupted business operations due to any pandemic or future public health concerns; regulatory developments in the United States and foreign countries; our reliance on our exclusive license with Mitsubishi Tanabe Pharma to provide us with intellectual property rights to develop and commercialize lorundrostat; and other risks described in our filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our annual report on Form 10-K, and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. These and other factors could cause results to differ materially from those expressed in the estimates made by the independent parties and by us. 2© 2025 Mineralys Therapeutics, Inc. 2
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© 2025 Mineralys Therapeutics, Inc. 3© 2025 Mineralys Therapeutics, Inc. Targeting Aldosterone in the Treatment of Hypertension and Cardiorenal Diseases Lorundrostat is a selective aldosterone synthase inhibitor (ASI) targeting aldosterone • Dysregulated aldosterone is the driver in 30% of uncontrolled and resistant hypertension (u/rHTN) • Lorundrostat potential best-in-class Aldosterone Synthase Inhibitor (ASI) • Meaningful 24-hour BP reduction and safety of once- daily dosing of lorundrostat in u/rHTN • HTN+CKD trial demonstrated benefit in HTN and related CKD + albuminuria • OSA proof-of-concept trial designed to demonstrate benefit in HTN and OSA symptoms • 20M u/rHTN patients in the United States • Increased market opportunity in comorbid CKD or OSA • NDA filing late 2025 / Q1 2026 3
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© 2025 Mineralys Therapeutics, Inc. © 2025 Mineralys Therapeutics, Inc. All Rights Reserved. Dysregulated Aldosterone In Hypertension and Related Comorbidities
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© 2025 Mineralys Therapeutics, Inc. Aldosterone Non-Genomic Effects (GPR30 RECEPTOR) Drives endothelial and renal tubular oxidative stress, microvascular fibrosis, inflammation and HF Abnormally Elevated Aldosterone Impacts Multiple Biological Pathways and is a Key Driver in Cardiorenal Diseases 1. Sim JJ, Bhandari SK, Shi J, et al. Am J Hypertens. 2012;25(3):379-388. 2. Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Hypertension. 2018;72(3):658-666. 3. Monticone S, D'Ascenzo F, Moretti C, et al. Lancet Diabetes Endocrinol. 2018;6(1):41-50. 4. Ferreira N, Tostes RC, Paradis P, Shiffrin E. Am J Hypertens. 2021, 34(1):15-27. Aldosterone-driven Cardiorenal Disorders Genomic Effects (MINERALOCORTICOID RECEPTOR) Na+ and water retention drives blood volume and blood pressure UNCONTROLLED AND RESISTANT HYPERTENSION (uHTN; rHTN)1 CHRONIC KIDNEY DISEASE2 HEART FAILURE HFpEF & HFrEF3 VASCULAR AND SYSTEMIC INFLAMMATION4 5
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© 2025 Mineralys Therapeutics, Inc. Lorundrostat Potential Benefit Across Spectrum of CRMS1-5 Targeting dysregulated aldosterone in overlapping CRMS conditions with high CV risk and large unmet need BP, blood pressure; CRMS, cardio-renal-metabolic syndrome; CKD, chronic kidney disease; CV, cardiovascular; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HTN, hypertension. 1. Ndumele CE, et al. Circulation. 2023;148:1606-1635. 2. Buglioni A, et al. J Am Heart Assoc. 2015;4:e002505. 3. Ebinger JE, et al. Eur J Prev Cardiol. 2023;30(10):960-968. 4. Marassi M & Fadini GP. Cardiovasc Diabetol. 2023;22:195. 5. Alterki A, et al. Int J Mol Sci. 2023;24:6807. CKD in the U.S. >25% increase in CV risk vs controlled HTN Kidney injury link to u/rHTN & hyperperfusion of kidney ~23M HTN + CKD patients TREATMENT- RESISTANT HYPERTENSION HFpEF & HFrEF CHRONIC KIDNEY DISEASE VASCULAR & SYSTEMIC INFLAMMATION OBESE UNCONTROLLED HYPERTENSION OBSTRUCTIVE SLEEP APNEA Aldosterone HTN in the U.S. 30% prevalence of dysregulated aldo in u/rHTN Visceral adiposity link to dysregulated aldo ~20M u/rHTN patients OSA in the U.S. Nighttime BP link to CV risk 70-80% prevalence of rHTN in OSA ~22M Moderate-to- Severe OSA 6
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© 2025 Mineralys Therapeutics, Inc. 0 4,000,000 8,000,000 12,000,000 High systolic BP Dietary risks High LDL cholesterol Ambient particulate matter pollution Smoking High fasting plasma glucose High BMI Kidney dysfunction Number of Global CV Deaths in 2021 Uncontrolled and Resistant Hypertension Is the Leading Global Modifiable Risk Factor for Cardiovascular Death BMI, body mass index; BP, blood pressure; CRMS, cardio-renal-metabolic syndrome; CV, cardiovascular; LDL, low density lipoprotein. 1. Vaduganathan M, et al. J Am Coll Cardiol. 2022;80(25):2361-2371. 2. Ettehad D, et al. Lancet. 2016;387(10022):957-967. 10.8 million G L O B A L C V D E A T H S D U E T O H I G H S Y S T O L I C B P I N 2 0 2 1 Top 8 Global Modifiable Risk Factors for CV Deaths in 20211 CRMS-Related Risk Factors -13% -17% -20% -27% -28%-30% -25% -20% -15% -10% -5% 0% All Cause Mortality CHD Major CV Events Stroke HF Risk Reduction Risk Reduction per 10mmHg Reduction in Systolic BP 2 7
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© 2025 Mineralys Therapeutics, Inc. The Unmet Need in u/rHTN is Largely Driven by Dysregulated Aldosterone 20-40% of hypertension patients are uncontrolled or resistant HTN • Half of the treated HTN patients in the U.S. fail to achieve goal1 • Prevalence of apparent rHTN demonstrated to be ~20%2 • In optimized background treatment trials, 30-40% of participants fail to achieve goal3 • Kaiser optimized regimen trial – 20% of patients fail to achieve goal4 Aldosterone the primary culprit in u/rHTN • Approximately 30% of all HTN patients have dysregulated aldosterone5 • Aldosterone breakthrough demonstrated in 30-40% of ACEi or ARB treated patients • Obesity epidemic (visceral adiposity) linked to dysregulated or elevated aldosterone 1. millionhearts.hhs.gov 2, Prevalence of Apparent Treatment-Resistant Hypertension in the United States, Hypertension. 2019;73:424-431. DOI: 10.1161/ HYPERTENSIONAHA.118.12191.3. Identifying and treating resistant hypertension in PRECISION: A randomized long-term clinical trial with aprocitentan, DOI: 10.1111/jch.14517 4. Improved Blood Pressure Control Associated With a Large-Scale Hypertension Program, JAMA. 2013 August 21; 310(7): 699–705. doi:10.1001/jama.2013.108769. 5. Primary Aldosteronism and the Pathogenesis of Hypertension, Physiol Rev. 2018;98(1):103-137 8
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© 2025 Mineralys Therapeutics, Inc. © 2025 Mineralys Therapeutics, Inc. All Rights Reserved. Lorundrostat Clinical Efficacy and Safety
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© 2025 Mineralys Therapeutics, Inc. 25-31 10-12 4.5-5.5 Highest Selectivity Lorundrostat - Potential Best-in-Class Once-Daily Aldosterone Synthase Inhibitor LORUNDROSTAT BAXDROSTAT2 VICADROSTAT3 LORUNDROSTAT ADVANTAGE SELECTIVITY 374X 100X 250X Allows aldosterone inhibition, without cortisol impact PAC REDUCTION 40 – 70% 60-65% 66% ~50% reduction achieves robust clinical benefit ADRENAL INSUFFICIENCY OR CORTISOL DECREASE No No Yes No risk of cortisol inhibition © 2025 Mineralys Therapeutics, Inc. Information provided in the table above is for illustrative purposes only and no head-to-head clinical trials have been conducted evaluating these product candidates. Differences exist between study or trial designs and participant characteristics, and caution should be exercised when compar ing data across studies. ▪ Lorundrostat 10-12 hour PK half-life profile is optimal – Long enough to provide 1x daily dosing / 24 hour coverage – Short enough to provide sufficient “off time” for kidneys to clear potassium / sodium – Appropriate for fixed dose combinations ASI Half-life Profiles Number of hours Baxdrostat1 Lorundrostat Vicadrostat4 1, 2 3, 4 1. Bogman K, Schwab D, Delporte ML, et al. Hypertension. 2017;69(1):189-196. 2. AZ ESC2025 Management Presentation 3. BI presentation at ASN 2023 4. Schulze, Schaible, et al Naunyn-Schmeideberg’s Archives of Pharmacology 10
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© 2025 Mineralys Therapeutics, Inc. -7.9 -7.3 -16.9 -19.0 -20.0 -16.0 -12.0 -8.0 -4.0 0.0 Change in AOBP SBP (mmHg) u/r/HTN participants on prescribed regimen of 2-5 AHTs (n=1,083 randomized) Primary registration trial with N=1083 (¾ in active arms) and p<0.0001 Reductions in BP of this magnitude have been linked to significant reduction in overall cardiovascular risk 44.1% percent of lorundrostat 50mg QD patients achieved BP goal at week 6 versus 24.1% on placebo, odds ratio 3.4 (p=0.0033) Clinically Meaningful Reduction of 16.9mmHg at Week 6, Increasing to 19mmHg at Week 12 WEEK 6 PRIMARY ENDPOINT WEEK 12 PREDEFINED ENDPOINT PLACEBO- ADJUSTED -9.1 p<0.0001 PLACEBO ABSOLUTE VALUE PLACEBO ABSOLUTE VALUE PLACEBO- ADJUSTED -11.6 p<0.0001 Whelton PK, Carey RM, AronowWS, et al. 2017 Hypertension. 2018;71(6):1269-1324. 11
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© 2025 Mineralys Therapeutics, Inc. Lorundrostat in a “Specialty” Setting for Patients with Confirmed u/rHTN – on Two or Three Medications High risk population who fail to achieve goal despite AHA guidelines, maximum dose treatment with confirmed daily compliance via smart phone technology. Change in 24hr ABPM in mmHg (n=285 randomized) -6.2 -7.4 -11.5 -15.4 -16.0 -12.0 -8.0 -4.0 0.0 ABPM SBP Change in mmHg WEEK 4 SECONDARY ENDPOINT WEEK 12 PRIMARY ENDPOINT PLACEBO- ADJUSTED -5.3 P < 0.001 PLACEBO 50 mg ABSOLUTE VALUE PLACEBO 50 mg ABSOLUTE VALUE PLACEBO- ADJUSTED -7.9 P = 0.001 • 41% percent of lorundrostat 50mg QD patients achieved BP goal by week 4 versus 18% on placebo, odds ratio 3.3 (p<0.001) 12
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© 2025 Mineralys Therapeutics, Inc. Lorundrostat 25mg QD Demonstrated Benefit in SBP and UACR Reduction Add-on to SGLT2i trial provided comparative results to AZ and BI go/no-go trials of FDC (ASI+SGLT2i) PLACEBO 50 mg ABSOLUTE VALUE • Baseline eGFR of 55 ml/min/1.73m2 • Percent change in eGFR (Cystatin-C) of -6.8% with lorundrostat 25mg QD versus - 2.2% on placebo -1.8 -9.3 -10 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 LORUNDROSTAT 25mgPLACEBO Change in AOBP at Wk 4 (mmHg) (n=60 randomized) -6.6% -30.5% -35 -30 -25 -20 -15 -10 -5 0 LORUNDROSTAT 25mgPLACEBO % Change in UACR at Wk 4 (n=60 randomized) Systolic BP (AOBP, mmHg) Percent change in UACR PLACEBO- ADJUSTED -25.6% P = 0.0015 PLACEBO- ADJUSTED -7.5 P = 0.0024 13
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© 2025 Mineralys Therapeutics, Inc. 0.4% 0.6% Favorable Safety and Tolerability Profile across Patient and Prescriber Types SAEs (%) Potassium > 6.0mmol/L* 3.2% 6.4% Very low rates of serious adverse events and treatment discontinuations N=6 N=3 (“Real World”) Lorundrostat: N=538 Placebo: N=270 (“Specialist”) Lorundrostat: N=94 Placebo: N=95 (“Compromised Kidney Function”) Lorundrostat: N=58 Placebo: N=57 3.3% 2.4%N=13 N=9 0.0% 3.4%N=2 0.0% 2.1% 0.0% 5.2% N=3 N=2 N=3 Lorundrostat 50mg QD Placebo * Confirmed potassium readings N=1 14
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© 2025 Mineralys Therapeutics, Inc. Lorundrostat Potassium Profile Similar to ACE Inhibitor and ARBs – Predictable and Modest • Lorundrostat potassium levels are very mild and consistent with observed levels of ACE inhibitors and ARBs today* • Potassium levels were mild even in Advance- HTN trial with high-dose ARB background • Shorter Lorundrostat half-life vs. Baxdrostat allows kidneys to clear Potassium more quickly • Change in Potassium is an on-mechanism response for any RAAS inhibitor Hyperkalemia (K+ > 6.0) at Study Visit and Repeat Test (%) 0.6 0.8 2.1 2.8 ACE Inhibitor ARBs Mild Potassium Profile, Increase Typically Resolves Within Two Weeks * Sadjadi, et al Pathology and Laboratory Medicine International 9 July 2009 ** Confirmed potassium readings ** ** 15
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© 2025 Mineralys Therapeutics, Inc. 4 WEEKS4 WEEKS Background treatment may include CPAP therapy Recent GLP-1 agonist usage and/or significant weight change excluded 2 WEEKSUP TO 3-WEEK RUN-IN LORUNDROSTAT 50 mg QPM PLACEBO QPM LORUNDROSTAT 50 mg QPM PLACEBO QPM WASHOUT WASHOUT End of Study Follow UpScreening OSA Airway Obstruction & Nocturnal Hypertension Proof-of-Concept Trial INCLUSION CRITERIA • BMI ≥27 kg/m2 • Moderate-to-severe OSA • Morning SBP (AOBP) ≥130 and ≤180 mmHg PRIMARY ENDPOINT Placebo-adjusted change in Apnea/ HypoxiaIndex (AHI) at week 4 SECONDARY ENDPOINTS Placebo-adjusted change in nighttime average SBP (noninvasive, continuous BP measurement) at treatment week 4 All analyses using within-participant change from baseline at end of active treatment v. placebo treatment period 2 WEEKS 16
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© 2025 Mineralys Therapeutics, Inc. Lorundrostat Development Program with Positive Pivotal Data and Market Expansion Proof-of-Concept Trials Trial Safety Proof of Concept Pivotal Status Hypertension Completed Completed On-going Hypertension + CKD Completed Hypertension + OSA Topline Q1 2026 u/rHTN Optimized background AHT HTN + CKD Open-Label Extension u/rHTN Existing background AHT HTN + OSA 17
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© 2025 Mineralys Therapeutics, Inc. © 2025 Mineralys Therapeutics, Inc. All Rights Reserved. Significant Commercial Opportunity in CRMS
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© 2025 Mineralys Therapeutics, Inc. Large Total Addressable Market: 20M People in U.S. with Uncontrolled or Resistant Hypertension and Related Comorbidities UNTREATED 60M TREATED 60M PATIENT POPULATION BREAKDOWN IN THE U.S HTN under control ~30M ~10M uHTN (1 AHT) ~10M uHTN (2+ AHT) ~10M rHTN uHTN 3rd LINE rHTN 4th LINE ~120M HTN PATIENTS IN THE U.S. Millionhearts.hhs.gov IQVIA data project May 2024 Addressable Market 20M u/rHTN • 3M have HTN + CKD • 6.5M have HTN + OSA 19
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© 2025 Mineralys Therapeutics, Inc. 8.8 Million u/rHTN Patients per Year Try New Treatments - Dissatisfaction with Current Treatments is an Opportunity for Lorundrostat 74% 26% 0% 20% 40% 60% 80% 100% % of Patients 2024 New to Line Existing 65M Treated HTN patients 26% New to Line patients 8.8M 3L & 4L+ New to Line patients with HTN Eligible New Patient Pool per year 22% 27% 22% 15% 15% New to Line Patients -- 2024 1st 2nd 3rd 4th 5th+ New to Line Patient Line of Therapy Distribution 52% 3rd Line+ New to Line vs Existing Patient Distribution 30% in 4L+ (5.1M pts) 22% in 3L (3.7M pts) More than half of new-to-line patients each year would be eligible for lorundrostat 3L+ treatment 20
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© 2025 Mineralys Therapeutics, Inc. SERMO Survey (completed March 2025): Tested data Launch-HTN & Advance-HTN including efficacy & safety/tolerability 21 Majority of PCPs, Cardiologists and Nephrologists Are Likely to Prescribe Lorundrostat Based on Efficacy and Safety Profile of PCPs are likely to prescribe lorundrostat for uncontrolled or resistant hypertension (n=212)95% of Cardiologists are likely to prescribe lorundrostat for uncontrolled or resistant hypertension (n=101)95% • The 7.5mmHg placebo adjusted reduction in SBP and 25.6% placebo adjusted reduction in UACR @ 4 weeks clinically meaningful and likely to influence prescribing decisions • Hyperkalemia observed in 5% of patients appears largely manageable First Word Pharma Survey (completed June 2025): Tested data from Explore-CKD including efficacy & safety/tolerability in HTN patients with CKD 75% of HCPs are likely to prescribe lorundrostat for u/rHTN with CKD (n=133) 21
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© 2025 Mineralys Therapeutics, Inc. Lorundrostat Commercial Positioning and Growth Strategy in rHTN , uHTN and HTN Related CKD & OSA • Successful launch in rHTN (4th line) based on Advance-HTN and Launch-HTN efficacy & safety in apparent and confirmed rHTN, inclusion in guidelines and demand • Expansion opportunity into HTN comorbidities overlap of HTN with CKD and OSA creates growth opportunities and reduces risk for next stage of development • Growth into uHTN (3rd line) ~physician experience in 4th line, may drive earlier interest and use, expanding the opportunity rHTN 10M in the U.S. OSA CKD Lorundrostat reduces BP & modifies comorbid conditions uHTN ~10M in the U.S. 3M in the U.S. 6.5M in the U.S. 22
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© 2025 Mineralys Therapeutics, Inc. Financial Summary Balance sheet supports activities to execute on upcoming milestones 23© 2025 Mineralys Therapeutics, Inc. Nasdaq MLYS Q3 2025 Cash Balance* $594M Shares of common stock outstanding† 79,689,711 *Includes cash, cash equivalents, and investments. †As of November 3 2025 and includes 549,755 shares underlying pre-funded warrants. 23 Research Analyst Coverage BofA Securites Tim Anderson /Jason Gerberry Evercore ISI Umer Raffat/Mike DiFiore Goldman Sachs Richard Law Stifel Annabel Samimy Guggenheim Securities Seamus Fernandez Wells Fargo Securities Mohit Bansal Jefferies Dennis Ding LifeSci Capital Rami Katkhuda HC Wainwright Matthew Caufield
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© 2025 Mineralys Therapeutics, Inc. Mineralys Leadership Team Jon Congleton Chief Executive Officer 30+ years of experience: Marion, HMR, Aventis, Teva, Nivalis, Impel Pharma David Rodman, MD Chief Medical Officer 15+ years of academic experience and 15+ years of industry experience: Novartis, Vertex, ProQR Adam Levy Chief Financial Officer 15+ years of banking experience: Merrill Lynch, Jefferies, BAML; and 9+ years of industry experience: Miragen, Brickell, Sanifit Eric Warren Chief Commercial Officer 30+ years of experience: Merck, Genzyme, Pfizer, Sanofi, Nabriva, Esperion Agile and experienced in developing novel, leading therapies Jessica Ibbitson EVP Operations 20+ years of experience: ProQR, Vertex, TransTech, Nova Scotia Health Authority 24
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© 2025 Mineralys Therapeutics, Inc. © 2025 Mineralys Therapeutics, Inc. All Rights Reserved.