MLYS - NASDAQ

Greetings, and welcome to Mineralys Third Quarter 2025 Earnings Conference Call. [Operator Instructions] As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Dan Ferry. Thank you. You may begin.

Thank you, operator. I would like to welcome everyone joining us today for our third quarter 2025 conference call. Earlier this afternoon, we issued a press release providing our third quarter 2025 financial results and business updates. A replay of today's call will be available on the Investors section of our website approximately 1 hour after its completion. After our prepared remarks, we will open the call for Q&A. Before we begin, I would like to remind everyone that this conference call and webcast will contain forward-looking statements about the company. Actual results could materially -- could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified by the cautionary statements contained in today's press release and our SEC filings, including our annual report on Form 10-K and subsequent filings. Please note that these forward-looking statements reflect our opinions only as of today, November 10, 2025. Except as required by law, we specifically disclaim any obligation to update or revise these forward-looking statements in light of new information or future events. I would now like to turn the call over to Jon Congleton, Chief Executive Officer of Mineralys Therapeutics.

Thank you, Dan. Good afternoon, everyone, and welcome to our third quarter 2025 financial results and corporate update conference call. I'm joined today by Adam Levy, our Chief Financial Officer; Dr. David Rodman, our Chief Medical Officer; and Eric Warren, our Chief Commercial Officer. I'll begin with an overview of the business, our clinical programs and recent milestones, followed by Adam to review our third quarter financial results before we open up the call for your questions. We're excited to have this opportunity today to provide an update on the progress our team has made over the past couple of months. Last month, we received pre-NDA feedback from the FDA. There were no surprises in this feedback and we're moving ahead with our NDA filing, which we expect to submit either late this quarter or in the first quarter of 2026. In preparation for the submission, we developed a robust data package featuring results from multiple clinical trials across the spectrum of distinct and diverse participants with lorundrostat, which we believe support its potential as a best-in-class treatment for high-risk patients with uncontrolled or resistant hypertension and beyond. Earlier this year, we announced data from the Launch-HTN and Advance-HTN pivotal trials. The results from both trials demonstrate that lorundrostat offers a clinically meaningful and sustained reduction in systolic blood pressure. These data have generated broad interest across the medical community, underscoring the unmet need, the desire for innovation and the management of hypertension and the commercial potential of lorundrostat. These findings form the foundation of our NDA submission, which includes data demonstrating that lorundrostat maintains a durable and clinically meaningful response across diverse patient populations, a key consideration for its potential use in treating uncontrolled and resistant hypertension. This includes subgroup analysis from the Phase III Launch-HTN trial and data from confirmed hypertension patients in the Advance-HTN trial. The Launch-HTN trial enrolled a diverse group of participants. Nearly 1/3 were black or African-Americans, half the participants were women, the majority of participants were overweight or obese and over half had resistant hypertension, requiring 3 or more background antihypertensive medications. Across all subgroups, lorundrostat 50 milligrams once daily demonstrated consistent, statistically significant and clinically meaningful reductions in blood pressure. All systolic BP reductions generated in Launch-HTN were measured at 24 hours after a dose, proving the sustained effect and true once-daily profile. The Advance-HTN trial designed and executed in conjunction with the Cleveland Clinic, enrolled a diverse group of hard-to-treat participants with confirmed uncontrolled and resistant hypertension by design with over half of the subjects being black or African-Americans. Now let me pause for just a second to describe what I mean by confirmed. In any trial that allows participants to remain on their existing background medications such as Launch-HTN, patients may have apparent hypertension, meaning if they optimize their treatment with the existing medications, they may get to goal. In Advance-HTN, participants' existing background medications were removed, and they were started on an optimized background treatment, aligned with the AHA guidelines, confirmed daily compliance with smartphone technology and randomized only if they remained hypertensive after a 3-week run-in, utilizing the measurement of 24-hour ABPM. In these most difficult-to-treat participants, lorundrostat again demonstrated a significant and clinically meaningful reduction in systolic blood pressure and was well tolerated. I would now like to briefly touch on the other development activities we're pursuing to enhance and extend the lorundrostat profile in hypertension with comorbid conditions, which are largely driven by inadequately controlled blood pressure and dysregulated aldosterone, starting with our proof-of-concept Explore-CKD trial, which evaluated the safety and efficacy of lorundrostat in subjects with hypertension and comorbid chronic kidney disease on a background of SGLT2 inhibitor. Last week, we were excited to have data from this trial presented during a late-breaking session at ASN's Kidney Week 2025. Lorundrostat demonstrated a clinically meaningful reduction on systolic BP in 4 weeks and was well tolerated. The key secondary outcome measure of reduction of urinary albumin creatinine ratio, or uACR, an accepted surrogate for renal protection was clinically meaningful and highly statistically significant. Immediately after the release of these data, First Word Pharma surveyed 133 health care professionals, with 77% indicating they would consider prescribing lorundrostat to CKD patients with uncontrolled hypertension on either an ACE inhibitor or an ARB. Turning to the ongoing Phase II Explore-OSA trial. In the third quarter, we completed enrollment in this trial, which is evaluating the safety and efficacy of lorundrostat in participants with moderate-to-severe obstructive sleep apnea and hypertension. We anticipate reporting top line results from the trial in the first quarter of 2026. If the trial is successful, these data would complement the previously announced Explore-CKD results and further our strategy to extend lorundrostat's profile in treating patients with hypertension and comorbid conditions. Our rationale for targeting OSA is clear. A significant portion of patients with obesity and resistant hypertension also have OSA, which is often undiagnosed and untreated. These conditions are biologically linked, as blood pressure and the hypoxia rise during sleep due to upper airway obstruction. Both are drivers of major adverse cardiovascular events, including death. Prior small studies of MRAs or adrenalectomy have demonstrated reduction in AHI, which is the primary endpoint of the Explore-OSA trial. The trial will also test the effect of lorundrostat on nighttime blood pressure using 24-hour ABPM as well as the novel measurement of continuous blood pressure through the evening. While we have already clearly demonstrated lorundrostat's efficacy as a once-daily morning antihypertensive, this trial will explore nighttime dosing since the triggers for aldosterone production in OSA or reduction in oxygen delivery leading to increased sympathetic activation of aldosterone production that occurs in the night during sleep. Uncontrolled and resistant hypertension remain major unmet needs, affecting over 20 million people in the U.S. and contributing significantly to cardiorenal complications. Our clinical data highlight the differentiated value of targeting aldosterone with an aldosterone synthase inhibitor like lorundrostat, especially compared to current third and fourth-line therapies. As we advance toward commercialization, we are prioritizing market access planning and payer engagement to ensure the value of lorundrostat is well understood. We have also expanded our medical communications capabilities to support data dissemination through peer-reviewed publications, scientific meetings and our field-based medical science liaisons. These efforts are central to ensuring commercial readiness for this potentially transformative treatment and the successful launch of lorundrostat. As we near the end of 2025, we've seen significant advances in the ASI space, including multiple trial readouts. As we reflect on these data and their clinical relevance, we are more confident than ever in lorundrostat's best-in-class profile based on the meaningful blood pressure reduction that demonstrated 24-hour control, its benefit across the spectrum of difficult-to-treat patients and its safety and tolerability. As we move forward with our NDA submission, we do so with confidence in the strength of our data, our team and our mission to develop lorundrostat as a potential best-in-class therapy for the high-risk often difficult to treat patients living with uncontrolled or resistant hypertension. I will now turn the call over to Adam to review our financial results for the third quarter of 2025. Adam?

Thank you, Jon. Good afternoon, everyone. Today, I will discuss select portions of our third quarter 2025 financial results. Additional details can be found in our Form 10-Q which will be filed with the SEC later today, November 10. We ended the quarter with cash, cash equivalents and investments of $593.6 million as of September 30, 2025, compared to $198.2 million as of December 31, 2024. We believe that our current cash, cash equivalents and investments will be sufficient to fund our planned clinical trials and regulatory activities as well as support corporate operations into 2028. R&D expenses for the quarter ended September 30, 2025, were $31.5 million compared to $54 million for the quarter ended September 30, 2024. The decrease in R&D expenses was primarily due to a decrease of $26.8 million in preclinical and clinical costs, primarily impacted by the conclusion of the lorundrostat pivotal program in the second quarter of 2025, partially offset by increases of $3.2 million in higher compensation expense resulting from additions to headcount, increases in salaries and accrued bonuses and increased stock-based compensation and $1.1 million in higher clinical supply manufacturing, regulatory and other costs. G&A expenses were $9.7 million for the quarter ended September 30, 2025, compared to $6.1 million for the quarter ended September 30, 2024. The increase in G&A expenses was primarily due to $2.2 million in higher compensation expense resulting from additions to headcount, increases in salaries and accrued bonuses and increased stock-based compensation, $1.3 million in higher professional fees and $0.1 million in other administrative expenses. Total other income net was $4.2 million for the quarter ended September 30, 2025, compared to $3.8 million for the quarter ended September 30, 2024. The increase was primarily attributable to increased interest earned on investments in money market funds and U.S. treasuries as a result of higher average cash balances invested during the quarter ended September 30, 2025. Net loss was $36.9 million for the quarter ended September 30, 2025, compared to $56.3 million for the quarter ended September 30, 2024. The decrease was primarily attributable to the factors impacting our expenses that I described earlier. With that, I will ask the operator to open up the call for questions. Operator?

[Operator Instructions] Our first question comes from Umer Raffat with 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?

Umer, thanks for the question. Maybe Dave can opine on this. But the -- we haven't done that analysis. It wasn't part of the plan. And from our standpoint, you have to account for all subjects enrolled that account for the execution within the study, discontinuations and patient outcomes as well. But Dave, do you want to give some comment to that?

Yes. So you're right, Jon. We did exactly what we negotiated with the FDA should be done in the situation of missing data. As you probably know, numbers above 15% and certainly 20% are extremely problematic. And sometimes those trials can't be evaluated by the agency. So we wanted to make sure. So we really didn't do that. And I will caution you that it's complicated to do any kind of estimates on imputation because you need the raw data. You can't take, say, the [ lead square ] means and try to figure out what it would be. But it can be a reasonably substantial reduction. So you're right, it would -- it can go up or down 3 to 5 millimeters of mercury depending on what sort of imputation you do, et cetera.

Our next question comes from Rich Law with Goldman Sachs.

Congrats on the progress. So one advantage that Astra

Rich, the 24-hour control, long-term acceptable tolerability profile, these are all things that physicians are looking for as they're treating the chronic condition like hypertension. With 4 studies completed, we're very confident in the 50-milligram and the 25-milligram once daily, providing that 24-hour control. And with the profile that's going to really aid long-term adherence compliance. I noted it in our prepared remarks, I think it's worth repeating. We have always measured blood pressure in the morning before that day's dose. So we're measuring it at trough. Lorundrostat in Mineralys is the sponsor. We're the first to look at 24-hour ambulatory metrics with an ASI with our Target-HTN study. We're very comfortable with daytime and nighttime blood pressure reduction. Advance-HTN, the most rigorous study down in the truly confirmed population, which is distinct from any other steady population of at least temporal current ASI studies, again, validated the 24-hour control. We've yet to publish or disclose the nighttime, but we're comfortable with what we're seeing from Target-HTN, Advance and really for the entire program and providing 24-hour control for patients.

I see. Got it. And then -- so then, I want to follow up to your previous discussion on the data, the missing data and how to handle that. Based on your understanding of FDA's requirement, are you -- can you exclude any missing data or invalid baseline measurements in the primary analysis? Do you have to consider the entire population, the ITT population and then perform imputation to it? So just curious to see how your -- what your thoughts are in terms of what the FDA require in these scenarios?

As Dave noted, and I'll have him add some color to this. In the case of Advance-HTN, this was pre-discussed with the FDA and set in the SAP. But Dave, do you want to maybe add some color to Rich's question?

Yes. Thanks for the question, Rich. So one thing I'll mention is you can't go back and do it. You have -- it needs to be in the statistical analysis plan and spelled out. And depending on what the circumstances are you will probably have to do a number of different ones. And one is called jump to reference. That means you have to assume every single person randomized to active actually behave like placebo, that's obviously the most conservative, but it's also the one that they're going to want to look at. There are other ones that are more complex. And -- but you have to negotiate all that in advance. And generally speaking, you would do that by looking ahead and seeing what you're missing these numbers are and then decide whether a conversation like that is needed. We did that when we had a risk of missing data and we're able to handle the problem. So it's complicated. But if you haven't already done it before database lock, you can't just do it later and try to make up for it.

Our next question comes from Tim Anderson with Bank of America.

This is Alice on for Tim. So you mentioned there were no surprises in the pre-NDA feedback. But are you able to provide any more color on this feedback? And could you update us on any final steps before filing? And then I have a follow-up as well.

Yes, Alice. We're -- we haven't really disclosed that, but we're comfortable with the feedback. As I noted, there were no surprises. We're very confident in the data set we've put together across Advance-HTN, Launch-HTN and Explore-CKD. As I noted in the past, in public statements, the other critical part is the on-label extension, having sufficient long-term safety data, including the randomized treatment withdrawal, all of that is progressing well. So we're comfortable with the guidance that we've given, and that is mentioned by the end of this year or into Q1 of next year.

And then just following the -- now that you're on track for submission, can you provide any updates on any partnering discussions you may be having?

Thanks, Alice. No, we continue, as we've said in the past, believing that partnering is going to be a key component of the Mineralys story. That is for ex U.S. commercialization opportunity, maximization of value, but also in the United States. We feel very confident in the best-in-class profile that exist with lorundrostat right now. We want to make sure that we give it the appropriate commercial lift in the United States as well as rest of world as well as looking at co-development partnerships. And so I think we have a well-characterized molecule at this point on the cusp of an NDA submission. And I think that continues to support the partnering dialogues that we're having. We're at the end of the day, we're focused on how do we maximize the value of lorundrostat for patients, for physicians and certainly for investors.

Our next question is from Annabel Samimy with Stifel.

This is Jayed, I'm on for Annabel. Just 2 questions. The first one is around the open-label extension trial. What are your expectations there? And when can we expect an update on the data?

Yes. We continue to progress well with the open-label extension. There's been no surprises as we continue -- it's open label, obviously, so we can see data within that, the DSMB continues to review it. We continue to be confident with the safety profile that we're seeing. We will certainly look to publish the results of the open label as well as the randomized treatment withdrawal when the last subject has completed that aspect.

Got it. And then one more on the ongoing Explore-OSA trial. How do you expect to leverage the data that comes out of that trial?

Yes. Our goal with Explore-CKD and Explore-OSA is really an acknowledgment that lorundrostat has a benefit that extends beyond just the reduction of blood pressure. And we know there are comorbid conditions that hypertension patients are dealing with chronically, whether it's proteinuria, whether it's CKD, whether it's OSA in the basically related cardiovascular risk that each carry. And so from our standpoint, adding further data beyond blood pressure reduction to the profile of lorundrostat is going to help its image and view within the prescribing population. It's going to help inform how they think about providing benefits to their patients that don't just deal with blood pressure but are dealing with the related comorbidities. And so I think it really fully round out the profile of lodrundrostat and shows the promise of this molecule for addressing hypertension, but again, for those related comorbidities.

Our next question comes from Mohit Bansal with Wells Fargo.

Congrats on all the progress. So I have 2 questions. So I wonder -- overall, Jon, based on the data we have seen so far with lorundrostat and Bax so far, do you see any major differences between the 2 at this point? Or do you think it kind of validates -- like all those data validate the class? And the related question is, that Astra

Yes. Thank you, Mohit. I would say -- and going back to my remarks, we've seen a lot of data in 2025 from us with lorundrostat as well as competing ASIs in the space. We feel very comfortable with our best-in-class profile at this point. Clearly, the ASIs are going to be a differential class and addressing the significant unmet need, a population of 20 million just in the United States alone that could benefit from a drug that's targeting the dysregulated aldosterone that we believe is probably accounting for a significant portion of those patients not being able to get to their ideal goal and basically risking poor cardiovascular outcomes if they do not. At this stage, where we have a complete data set from Advance-HTN, where we are truly looking at the most difficult to manage because they are confirmed hypertension to the really broad study Launch-HTN as well as Explore-CKD. We feel very confident in the consistent effect that we're seeing. The magnitude of reduction of systolic blood pressure that builds over time. We see a nice response within 2 weeks that continues to grow out to the 12-week period of these studies. The safety profile, clearly, the on-target safety signals with electrolytes. We believe we've got best-in-class molecule as far as the really modest increase in potassium that's transient upon reducing or discontinuing the drug, and the tolerability of the profile. So again, I think this is an exciting time for us. I think it's going to be informative for our partnering dialogue. It's very easy at this point to say this molecule is being derisked as an aldosterone-reducing agent and doing so safely and effectively. We know that aldosterone plays a critical role in conditions beyond hypertension, such as CKD, such as OSA, conditions like heart failure. We believe that it's that breadth of opportunity that will continue to inform those partnering dialogues, and that's why it's critical for us. We've said it early on. We've not -- we've not had a "for sale sign" in front of this company. We've been developing this molecule to make sure that we maximize the value for that. I think at this stage, we've done so. We think there's continued value that we can unlock on our own, but certainly a partner both in the commercial and the developmental perspective would help inform that and drive that even further.

Our next question comes from Rami Katkhuda with LifeSci Capital.

Astra

Yes. Rami, thanks for the question. It was with intent that we really wanted to ensure that we had a good diverse representation of patients within our clinical program. We know that black or African-American patients tend to be underrepresented in studies. We also know they carry some of the largest cardiovascular risk for uncontrolled hypertension. So I was really proud of what the team did across the program. In Advance-HTN, over 50% of those studies were black or African-American descent. In the larger global study, Launch-HTN, we're nearly at 30%. And so we have a really clear understanding of the benefit that lorundrostat can provide these patients. In the case of both trials, when we look at forest plots, we see that race is not a determinant of response. In other words, whether you're white or black or African-American, you're going to respond to lorundrostat and have a significant opportunity to get to your respective goal. And so it was important for us to have that population within our clinical program to be able to speak to the effect of lorundrostat to that at-risk population that typically is underrepresented. As to the percent to get to goal, what we have shown in the past was, I believe, 44% in Launch got to goal at week 6, and I believe it was 42% got to goal at week 4 with Advance. I want to make sure I got that right, 44% with Launch, 42% with Advance. And I believe for the placebo groups, they were about half. I do know the odds ratio of getting to goal was over 3 in each study within those time frames that I described. And I hope that answered your question, Rami.

Definitely, yes.

I'll just add -- Rami, it's Eric. I'll just add that the definition of goal was different when you're looking at that Bax24 data, where they used a [ 1 30 ], we used a more stringent [ 1 25 ]. I'll also say that it wasn't just Bax24 that didn't have a high quantity of black or African-American patients. It was also BaxHTN where they were about 8%.

And this is Dave. As long as we're all jumping on this question because it's such an important question. As a developer, my perspective is this. There's a reason why we had a high percentage of people in the Advance-HTN trial of confirmed uncontrolled and resistant hypertension. 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. I think that's important distinction because as we've said many times, doing that trial and getting established confirmed hypertension is what the experts ask us to do, and it's what the real gold standard is to know what this drug can do beyond generics. And in African-Americans, it's obviously an extremely effective drug there.

We have reached the end of the question-and-answer session. I'd like to turn the floor back over to Jon for closing comments.

Thank you, operator. We believe the strength of the clinical results for lorundrostat show the potential benefit for uncontrolled and resistant hypertension and related comorbidities such as CKD. We look forward to our upcoming NDA submission and results from Explore-OSA. This is an exciting time for our team. The uncontrolled and resistant hypertension patients who may benefit from treatment with lorundrostat, the physicians and researchers that have worked so hard and supported bringing lorundrostat through our clinical trial program and our shareholders. We're excited for upcoming key milestones and look forward to sharing updates with you in the upcoming quarters. With that said, I'll thank everyone. Thank you for joining us today, and we'll close the call now. Thank you.