Mineralys Therapeutics, Inc.

Greetings and welcome to Mineralis' third quarter's 2025 earnings conference call. At this time, all participants are on a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. 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 investor section of our website, approximately one 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 webcast will contain forward-looking statements about the company. Actual results 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 John Cogleton, Chief Executive Officer of Mineralis 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 lorunderstat, 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 lorunderstat 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 in the management of hypertension, and the commercial potential of lorunderstat. These findings form the foundation of our NDA submission. which includes data demonstrating that lorundrastat 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 a third 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 three or more background and hypertensive medications. Across all subgroups, lorunder stat 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. And 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 AHA guidelines, confirmed daily compliance with smartphone technology, and randomized only if they remained hypertensive after a three-week run-in, utilizing the measurement of 24-hour ABPM. In these most difficult-to-treat participants, LaRunderstead 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 Lurunderstad 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 Lurunderstad 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. Lurander's stat demonstrated a clinically meaningful reduction on systolic BP in four 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 healthcare professionals, with 77% indicating they would consider prescribing lorunderstat 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 lorunderstat 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 Lunderstadt'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 to hypertension also have OSA, which is often undiagnosed and untreated. These conditions are biologically linked, as blood pressure and hypoxia rise during sleep due to upper airway obstructions. 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 lorunderstat 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 lorunderstat's efficacy as a once-daily morning antihypertensive, this trial will explore nighttime dosing since the triggers for aldosterone production in OSA are 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 lorundrastat, 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 Lurunderstat 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 Larunderstat. As we're 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're more confident than ever in Larunderstat's best-in-class profile based on the meaningful blood pressure reduction, the 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 Lurunderstad 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, John. 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 10th. We ended the quarter with cash, cash equivalents, and investments of $593.6 million as of September 30th, 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 30th, 2025 were $31.5 million compared to $54 million for the quarter ended September 30th, 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 La Runderstadt 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 30th, 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 30th, 2025, compared to $3.8 million for the quarter ended September 30th, 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 30th, 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? Thank you. At this time, we'll be conducting a question and answer session. If you'd like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.

One moment, please, while we poll for questions. Our first question comes from Uma Rapid with Evercore.

Please proceed with your question.

Hi, guys. Thanks for taking my question. I have a question on your resistant hypertension population. And my question specifically is, if you don't adjust for the discontinuation, 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?

Umar, thanks for the question. Maybe Dave can opine on this, but 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 and account for the execution within the study, discontinuations and patient But, Dave, do you want to give some comment to that?

Yeah. So, you're right, John. 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 least 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, you know, it can go up or down three to five millimeters of mercury depending on what sort of imputation you do, et cetera.

Got it. Thank you very much. Thanks very much.

Our next question comes from Rich Law with Goldman Sachs. Please proceed with your question.

Hey, guys. Congrats on the progress. So one advantage that AstraZeneca has been highlighting for BACs is the longer half-life. So in the BACs 24 presentation over the weekend, I think we saw I mean, it was interesting to see that the bags show 14-millimeter placebo-adjusted SBP reduction for both day and night. Have you guys looked at that, the day and night, for advanced HTN, and was there any difference between the two? And then I have questions later on. Follow-up.

Yeah, Rich. Yeah, Rich, the 24-hour control, long-term acceptable tolerability profile, these are all things that physicians are looking for as they're treating a chronic condition like hypertension. With four studies completed, we're very confident in the 50 milligram and the 25 milligram once daily providing that 24-hour control and with a 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. Lirundrastat and Mineralis 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, advanced HTN, and the most rigorous study done in the truly confirmed population, which is distinct from any other study 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 in providing 24-hour control for patients.

I see. Got it. And then, so, Den, 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, 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 what your thoughts are in terms of what the FDA requires in these scenarios.

As Dave noted, and I'll have him add some color to this, you know, in the case of advanced HTN, this was pre-discussed with the FDA and said in the SAP, but Dave, do you want to maybe add some color to Rich's question?

Yeah, thanks for the question, Rich. So, one thing I'm going to 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 behaved 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. But you have to negotiate all that in advance. And generally speaking, you would do that by looking ahead and seeing what your missingness numbers are and then decide whether a conversation like that is needed. We did that when we had a risk of missing data and were 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.

Okay, got it. Thanks, guys. Thanks, Rich.

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

Hi, this is Alice. I'm for Tim. Thank you for taking our questions. 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. Thank you.

yeah alice we're we haven't really disclosed that but we're we're comfortable with um the feedback as i noted there were no surprises uh we're very confident in the the data set we've put together across advanced hdn launch htn and explorer ckd um as i noted in the past in public statements. The other critical part is the open 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 submission by the end of this year and Q1 of next year.

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

Thanks, Alice. We continue, as we said in the past, believing that partnering is going to be a key component of the Mineralis story. That is for ex-U.S. commercialization opportunity maximization value, but also in the United States. We feel very confident in the best-in-class profile that exists with that right now. We want to make sure that we give it the appropriate commercial left in the United States as well as rest of the 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 for patients or physicians and certainly for investors.

Our next question is from Annabelle Samimi with Stifel.

Please proceed with your question.

Hi, this is Diane. I'm on for Annabelle. Just two questions. First one is around the Open Label Extension Trial. What are your expectations there, and when can we expect an update on the data?

Yeah, 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 Glowing Explorer OSA trial.

How do you expect to leverage the data that comes out of that trial? Yeah, our goal

with Explore CKD and Explore OSA is really an acknowledgement that loranderostat 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 and the basically related cardiovascular risk that each carry. And so from our standpoint, adding further data beyond blood pressure reduction to the profile of lorunderostat is going to help its image and view within the prescribing population. It's going to help inform how they think about providing benefit 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 rounds out the profile of lorunderostat and shows the promise of this molecule for addressing hypertension, but again, for those related comorbidities.

Great. Got it. Thank you so much. Thank you.

Our next question comes from Mohit Bansal with Wells Fargo. Please proceed with your question.

Great. Thank you very much for taking my question, and congrats on all the progress. So I have two questions. So one is, overall, John, based on the data we have seen so far with and so far, Do you see any major differences between the two at this point, or do you think it kind of validates, like all those data validate the class? And the related question is that, you know, AstraZeneca has talked about this being a multi-billion dollar opportunity. Some of it is unlocked, or some of it would be unlocked with the combination and all those trials. to help enable those trials, what kind of partnerships you as a company would be looking at and what kind of partner you would be the better partner for you to collaborate with at this point? Thank you.

Yeah, thank you, Mohit. I would say, in going back to my remarks, we've seen a lot of A lot of data in 2025 from us with Lurunderstat, 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 in 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 advanced HTN, where we are truly looking at the most difficult to manage because they are confirmed hypertensive 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 two 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 dialogues. It's very easy at this point to say this molecule has been de-risked as an aldosterone-reducing agent. in 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 had a for sale sign, quote, unquote, 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. Excellent.

Thanks. Thanks, Mohit. Our next question comes from Rami Kahuta with LifeSci Capital.

Please proceed with your question.

Hey, guys. Thanks for taking my questions as well. AstraZeneca seems to have only enrolled a small number of African-American patients in Bax24, at least for the primary endpoint analysis, which doesn't seem super representative of the resistant hypertensive population. Do you think this could have affected the results? And can you remind us how large of a difference in efficacy you see with lorandostat in this patient population? And then secondly, have you noted what percentage of patients gets a goal with lorandostat in advance or launch?

Yeah. 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 advanced HTN, over 50% of those studied were of 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 Lurundersat 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 lorunderstat 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 lorunderstat to that at-risk population that typically is underrepresented. As to the percent that get to goal, what we have shown in the past was, I believe, 44% in launch got to goal at week six. And I believe it was 42% got to goal at week four 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 three.

in each study uh within those time frames that i described and i hope that answered your question rami definitely thank you guys yeah i'll i'll just add rami it's eric yeah i'll just add that the uh the definition of goal uh was different uh when you're looking at that fax 24 data where they used a 130 we used a more stringent 125. i'll also say that it wasn't just Vax24 that didn't have a high quantity of black or African American patients. It was also VaxHTN, 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 advanced 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 as the Caucasian population. I think that's an 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.

Thanks, Dave.

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

Thank you, Operator. We believe the strength of the clinical results from the LORUNDER stats 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 lorundrastat, the physicians and researchers that have worked so hard and supported bringing lorundrastat 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.

This concludes today's conference. You may disconnect your lines at this time, and we thank you for your participation.