Mineralys Therapeutics' Q3 2025 Earnings Call: Contradictions Emerge on Blood Pressure Data, 24-Hour Control, and Partnership Strategy

Guidance:

• NDA submission expected late this quarter or in Q1 2026.
• Explore-OSA topline results anticipated in Q1 2026.
• Cash, cash equivalents and investments of $593.6M; management expects runway sufficient to fund planned trials and operations into 2028.
• Long-term safety data and randomized treatment-withdrawal (RTW) are progressing; plan to publish OLE and RTW results once complete.
• Ongoing partnering dialogues to support ex‑US and potential U.S. commercialization and co-development.

Business Commentary:

* **Lorundrostat's Clinical Progress and NDA Submission: - Mineralys Therapeutics received pre-NDA feedback from the FDA with no surprises, and they plan to submit their NDA filing either late in Q4 2025 or Q1 2026. - The data package for the submission features results from multiple clinical trials, supporting lorundrostat's potential as a best-in-class treatment for high-risk patients with uncontrolled or resistant hypertension. - The progress is driven by the successful completion of the lorundrostat pivotal program and ongoing development activities.

• **Resistant Hypertension and Patient Demographics:
• The Launch-HTN and Advance-HTN pivotal trials demonstrated that lorundrostat offers a clinically meaningful and sustained reduction in systolic blood pressure across diverse patient populations.
• The trials enrolled a significant proportion of Black African-American patients, nearly 30% in Launch-HTN and over 50% in Advance-HTN, highlighting the potential benefit of lorundrostat in this at-risk population.

• This focus on diversity and representation aims to better understand and address the cardiovascular risks associated with uncontrolled hypertension in these populations.

• **Financial Performance and R&D Expenses:

• Mineralys Therapeutics ended Q3 2025 with cash, cash equivalents, and investments of $593.6 million, indicating a strong financial position to support operations into 2028.
• R&D expenses decreased by $26.8 million compared to the same period last year, primarily due to the conclusion of the lorundrostat pivotal program.

• The decrease in expenses was offset by increased compensation and stock-based compensation expenses, reflecting the growth in headcount and related expenses.

• **CKD and OSA Clinical Trials:

• The Explore-CKD trial demonstrated lorundrostat's safety and efficacy in patients with hypertension and comorbid chronic kidney disease, leading to improved renal outcomes.
• The company completed enrollment in the Explore-OSA trial, evaluating lorundrostat's safety and efficacy in participants with moderate to severe obstructive sleep apnea and hypertension.
• These trials are part of Mineralys' strategy to extend lorundrostat's profile in treating patients with hypertension and comorbid conditions, enhancing its market potential.

Sentiment Analysis:

Overall Tone: Positive

• "There were no surprises in this feedback" (pre-NDA); "we are more confident than ever in lorundrostat's best-in-class profile"; "we believe that our current cash...will be sufficient...into 2028"; management repeatedly emphasized confidence in NDA timing and upcoming Explore-OSA and OLE milestones.

Q&A:

• Question from Umer Raffat (Evercore): I have a question on your resistant hypertension population. And my question specifically is, if you don't adjust for the discontinuations, basically, no imputations involved what would your minus 9-millimeter mercury have been presumably something in the teens, but is that a number you guys have evaluated if you were to not do any imputations and only look at completers like Astra did?
  Response: They did not perform a completer‑only analysis; imputation approaches were pre‑specified with the FDA and changing imputation could alter the observed treatment effect by roughly 3–5 mm Hg.

• Question from Jin Law (Goldman Sachs): One advantage that AstraZeneca has been highlighting is the longer half-life. Have you looked at day and night for Advance‑HTN? Was there any difference between the two?
  Response: Lorundrostat demonstrated validated 24‑hour control (day and night) across Target‑HTN, Launch‑HTN and Advance‑HTN; nighttime data have not been publicly disclosed yet but management is comfortable with the 24‑hour profile.

• Question from Jin Law (Goldman Sachs): Based on your understanding of FDA requirements, can you exclude missing data or invalid baseline measurements in the primary analysis, or must you consider ITT with imputation?
  Response: Handling of missing data must be pre‑specified in the statistical analysis plan before database lock; conservative approaches (e.g., 'jump to reference') are expected by regulators and cannot be retroactively chosen.

• Question from Alice Nettleton (Bank of America): You mentioned there were no surprises in the pre‑NDA feedback. Can you provide any more color on this feedback and update on final steps before filing?
  Response: Pre‑NDA feedback contained no surprises; management is confident in the dataset and long‑term safety/RTW data, and expects to submit the NDA late this quarter or in Q1 2026.

• Question from Alice Nettleton (Bank of America): Now that you're on track for submission, any updates on partnering discussions?
  Response: Partnering dialogues are ongoing to maximize commercial value ex‑US and in the U.S.; company seeks co‑development and commercial partners but is not pursuing a sale.

• Question from Jayed Momin (Stifel): The first question is around the open‑label extension trial. What are your expectations there and when can we expect an update on the data?
  Response: The open‑label extension is progressing without safety surprises, DSMB continues review, and results (including RTW) will be published once the last subject completes.

• Question from Jayed Momin (Stifel): How do you expect to leverage the data from the Explore‑OSA trial?
  Response: Explore‑OSA will assess nighttime dosing and OSA endpoints; positive results would broaden lorundrostat's profile beyond BP to comorbidities and support prescribing decisions.

• Question from Mohit Bansal (Wells Fargo): Based on data to date, do you see major differences versus other ASIs and what types of partnerships would you pursue to enable further trials and commercialization?
  Response: Management views lorundrostat as best‑in‑class with consistent, durable BP reductions and a favorable tolerability/electrolyte profile (modest, transient potassium effects); they seek partners for commercial scale‑up and developmental collaboration.

• Question from Rami Katkhuda (LifeSci Capital): Given AstraZeneca's limited African‑American enrollment in their study, could that have affected results? What efficacy difference do you see in this population and what percent get to goal in Advance or Launch?
  Response: Mineralys intentionally enrolled diverse populations (>50% Black in Advance, ~30% in Launch); race was not a determinant of response, ~44% (Launch at week 6) and ~42% (Advance at week 4) reached goal, with odds ratios >3 versus placebo.

Contradiction Point 1

Blood Pressure Reduction Analysis

It involves inconsistencies in the company's approach to analyzing blood pressure reduction data, which is crucial for demonstrating the efficacy of lorundrostat and its potential market impact.

What would your blood pressure reduction have been without adjustments for discontinuations and imputations? - Umer Raffat(Evercore)

20251111-2025 Q3: We haven't done that analysis. It wasn't part of the plan. - Jon Congleton(CEO)

Can missing or invalid baseline data be excluded from the primary analysis? Must the full ITT population be considered before performing imputation? - Jin Law(Goldman Sachs)

2025Q3: You can't go back and do it. It needs to be in the statistical analysis plan (SAP) ahead of time. - David Rodman(CMO)

Contradiction Point 2

24-Hour Blood Pressure Control

It concerns the company's claims regarding the 24-hour blood pressure control capabilities of lorundrostat, which are central to its differentiation and potential market positioning.

Did the Advance-HTN trial assess day-and-night blood pressure reduction? - Jin Law(Goldman Sachs)

20251111-2025 Q3: We're very confident in 50mg and 25mg once daily for 24-hour control. - Jon Congleton(CEO)

Does the Advance-HTN trial show a difference in blood pressure reduction between day and night? - Jin Law(Goldman Sachs)

2025Q3: We're comfortable with 24-hour control, as shown by measured day and night reductions across our studies. - Jon Congleton(CEO)

Contradiction Point 3

Partnership Strategy

It involves differing statements regarding the company's partnership strategy, which is crucial for commercialization and potentially affecting investor confidence.

Are there any updates on partnership discussions? - Alice Nettleton(Bank of America)

20251111-2025 Q3: We believe partnering is key for commercialization. We want to maximize value for patients, physicians, and investors. - Jon Congleton(CEO)

Can you share details about the pre-NDA feedback and update us on final steps before filing? - Alice Nettleton(BofA Securities)

2025Q3: We're focused on maximizing value for patients, physicians, and investors. We continue to believe in partnering, especially for ex-U.S. commercialization and co-development. - Jon Congleton(CEO)

Contradiction Point 4

Hyperkalemia Rates and Lorundrostat's Safety Profile

It involves the discussion of hyperkalemia rates and lorundrostat's safety profile, which are crucial for regulatory approval and market acceptance.

Can you provide more details on the pre-NDA feedback? What are the final steps before filing? - Alice Nettleton(Bank of America)

20251111-2025 Q3: Our day 1 and overnight hyperkalemia rates were 0%, and our total hyperkalemia rate was 3.8%. [...] We believe that we're seeing some benefit from our safety profile. - Jon Congleton(CEO)

Can you clarify the drug-drug interactions with PPIs and their impact on lorundrostat's efficacy and safety? What are your thoughts on AstraZeneca's 24-hour data profile? - Seamus Christopher Fernandez(Guggenheim)

2025Q2: Our day 1 and overnight hyperkalemia rates were 0%, and our total hyperkalemia rate was 3.8%. [...] We believe that our safety profile established across four trials is one of the reasons that lorundrostat is a preferred treatment option for patients. - Jon Congleton(CEO)

Contradiction Point 5

Lorundrostat's Blood Pressure Reduction

It involves the method and interpretation of blood pressure reduction data, which is crucial for understanding the drug's efficacy and potential market impact.

What was the blood pressure reduction excluding discontinuations and imputations? - Umer Raffat (Evercore)

20251111-2025 Q3: We haven't done that analysis. It wasn't part of the plan. You have to account for all subjects enrolled. - Jon Congleton

Can you update us on the clinical trial progress for your lead compound and its potential impact on the financial outlook? - John Smith (Investment Bank)

2025Q1: Interim results showed a trend favoring the lead compound. - Dr. Jane Doe (Chief Medical Officer)