Greetings, and welcome to the Mineralys Second Quarter 2025 Earnings Call. It is now my pleasure to introduce your host, Dan Ferry of LifeSci Advisors. Thank you. You may begin.

Thank you, operator. I would like to welcome everyone joining us today for our second quarter 2025 financial results and business updates. Earlier this afternoon, we issued a press release providing our second quarter 2025 financial results 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 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, August 12, 2025. Except as required by law, we specifically disclaim any obligation to update or revise these forward-looking statements. 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 second 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 will begin with an overview of the business, our clinical programs and recent milestones, followed by Adam to review our second quarter financial results before we open the call for your questions. We're proud to be leading the way in the development of aldosterone synthase inhibitors or ASIs for the treatment of hypertension and comorbid cardiorenal conditions such as chronic kidney disease and obstructive sleep apnea. Earlier this year, we became the first company to announce pivotal data for an ASI with the readouts from Launch-HTN and Advance-HTN. These results have since been presented at leading scientific conferences and published in the New England Journal of Medicine and the Journal of the American Medical Association. The clinically meaningful and sustained reductions in systolic blood pressure demonstrated underscore the unmet need, the desire for innovation in the management of hypertension and the commercial potential of lorundrostat. To better understand how our data could translate into clinical use, we surveyed approximately 300 cardiologists and primary care physicians. The key takeaway from that survey was that 95% of these practicing clinicians indicated that based on the data from Launch-HTN and Advance-HTN trials, if lorundrostat is approved, they would likely prescribe it broadly for patients with uncontrolled or resistant hypertension, specifically third line or later. This intent to prescribe was based on the differentiated efficacy and safety profile, which truly set lorundrostat apart from agents typically used in the third line or later treatment position. We've also completed a project with IQVIA that showed nearly 9 million patients in 2024 started new treatments in the third line or later position. These data are reflective of the dissatisfaction in the market and the challenges physicians face in addressing uncontrolled hypertension. Both of these data sets speak to the strong need and demand for innovative solutions that physicians want in their treatment armamentarium to address uncontrolled and resistant hypertension. Uncontrolled and resistant hypertension are significant unmet medical needs, impacting more than 20 million patients in the United States and directly contributing to adverse cardiorenal risk. Our clinical results reinforce the differentiated clinical impact of targeting aldosterone with an ASI like lorundrostat as compared to the current standard of care used in third and fourth-line treatment physicians. We are continuing to focus our pre-commercial efforts on market access and payer value assessment for this novel treatment. We have expanded our medical communications team to disseminate the data we're developing on lorundrostat via publications, medical conferences and field-based medical science liaisons prelaunch readiness to generate awareness, interest, and enthusiasm for lorundrostat. 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. Our focus on and rationale behind making reduction in blood pressure the primary outcome measure in the Explore-CKD trial was the central role of uncontrolled blood pressure in chronic kidney disease progression. Lorundrostat demonstrated a clinically meaningful reduction on systolic blood pressure in this trial. The key secondary outcome measure of reduction of UACR, an accepted surrogate for renal protection was also highly significant and comparable in magnitude to that observed in trials of lorundrostat and finerenone when combined with an SGLT2 inhibitor. It should be noted that all participants in Explore-CKD were treated with lorundrostat while on a stable therapeutic dose of SGLT2 inhibitor, most commonly dapagliflozin. Immediately after the release of these data, First World Pharma surveyed 133 health care professionals and confirmed that these data were clinically meaningful, with 77% of the surveyed health care professionals indicating they would consider prescribing lorundrostat to CKD patients uncontrolled on either ACE inhibitor or ARB with an SGLT2 inhibitor. The rationale for our EXPLORE-OSA trial relates to the substantial portion of patients with obesity and resistant hypertension who also have OSA, which is often undiagnosed and untreated. A majority of OSA patients have uncontrolled or resistant hypertension as well as elevated nighttime blood pressure and hypoxia, which are drivers of major adverse cardiovascular events, including death. Prior small studies of mineral corticoid receptor antagonist or adrenalectomy patients demonstrated an approximate 50% reduction in AHI, which is the primary registration endpoint. EXPLORE-OSA is powered for the AHI both 24-hour ABPM as well as a novel measurement of continuous blood pressure. We have clearly demonstrated that lorundrostat dosed once daily in the morning is a highly effective antihypertensive. Given the contribution of nighttime aldosterone production in OSA patients, the EXPLORE-OSA trial will be evaluating lorundrostat dosing at night, the effects on nighttime blood pressure and 24-hour blood pressure control. Based on the rate of enrollment in EXPLORE-OSA, we anticipate having top-line data in the first half of 2026. The next step in providing lorundrostat to the millions of patients who could benefit from its clinical profile is its regulatory approval. We have a pre-NDA meeting with the FDA scheduled to take place in the fourth quarter of 2025. In summary, we have now demonstrated the clinically meaningful benefit-risk profile of lorundrostat in individuals with uncontrolled or resistant hypertension in four clinical trials. We continue to evaluate lorundrostat's use in prevalent comorbidities of hypertension such as OSA and CKD, for which normalizing aldosterone production may result in meaningful clinical benefit. I will now turn the call over to Adam to review our financial results for the second quarter of 2025.

Thank you, Jon. Good afternoon, everyone. Today, I will discuss select portions of our second quarter 2025 financial results. Additional details can be found in our Form 10-Q, which will be filed with the SEC later today, August 12. We ended the quarter with cash, cash equivalents, and investments of $324.9 million as of June 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 2027. R&D expenses for the quarter ended June 30, 2025, were $38.3 million compared to $39.3 million for the quarter ended June 30, 2024. The decrease in R&D expenses was primarily due to a decrease of $4.5 million in preclinical and clinical costs driven by the conclusion of the lorundrostat pivotal program in the second quarter of 2025, partially offset by increases of $2.7 million in higher compensation expense resulting from additions to headcount, increases in salaries and accrued bonuses and increased stock-based compensation, and $0.8 million in higher clinical supply and manufacturing, regulatory and other costs. G&A expenses were $8.5 million for the quarter ended June 30, 2025, compared to $5.9 million for the quarter ended June 30, 2024. The increase in G&A expenses was primarily due to $1.9 million in higher compensation expense resulting from additions to headcount, increases in salaries and accrued bonuses and increased stock-based compensation, $0.6 million in higher professional fees, and $0.1 million in other administrative expenses. Total other income net was $3.5 million for the quarter ended June 30, 2025, compared to $4.2 million for the quarter ended June 30, 2024. The decrease was primarily attributable to decreased interest earned on investments in money market funds and U.S. treasuries as a result of lower average cash balance invested during the 3 months ended June 30, 2025. Net loss was $43.3 million for the quarter ended June 30, 2025, compared to $41 million for the quarter ended June 30, 2024. The increase was primarily attributable to the factors impacting the company's expenses described earlier. With that, I'll ask the operator to open the call for questions.

And our first question comes from Michael DiFiore with Evercore.

On the progress, I have a couple of questions. One question we receive often is about AstraZeneca's full Phase III BAX-HTM data that will be released soon at ESC. I'm curious about how different the rates of Grade 1 and Grade 2 hyperkalemia would need to be for physicians to view lorundrostat as more or less safe. I also have a separate follow-up question regarding any updates on partnership discussions and initiatives.

Yes, Mike, thank you for the call. I appreciate it. In response to your first question, it's challenging for me to comment on what AstraZeneca's data may reveal regarding potassium levels and differentiation. We are very confident in the package we've developed over the past 4.5 years, particularly in the last six months with the readout of Launch-HTN, Advance-HTN, and Explore-CKD. We believe we have well established the efficacy and safety of this drug across a range of patients, which was intentional. Launch-HTN is an ideal trial to examine how this drug will be used in most patients alongside existing treatments that, while not optimized, reflect real-world physician practices. We observed an 11.6 millimeter mercury placebo-adjusted change and a 19-millimeter absolute change, with hyperkalemia rates above 6 millimoles per liter in only 0.6% of patients. This demonstrates a well-characterized, robust clinical benefit paired with a favorable safety profile. As referenced in the prepared remarks, 95% of physicians are likely or very likely to prescribe it if granted access after approval. Regarding partnership discussions, as mentioned previously, we are eager to partner, particularly outside the U.S. where we do not plan to commercialize lorundrostat alone, but also within the United States. Our goal in the U.S. is to reach as many physicians as possible to impact as many patients as we can, ultimately maximizing the value of lorundrostat, which we believe will be significant in managing uncontrolled and resistant hypertension.

Our next question comes from the line of Rich Law with Goldman Sachs.

The first is that when you think about lorundrostat outside hypertension, do you see any opportunity for lorundrostat to combine with other drugs besides SGLT2 inhibitors in CKD? And then I have a follow-up.

No, just anything outside hypertension and maybe outside like SGLT2.

Is there any other disease areas or indications that you see potential combination strategy with lorundrostat?

Yes. What we've observed so far with four successful trials is that aldosterone is a significant factor not only in hypertension but also in related comorbidities. Hypertension contributes to chronic kidney disease (CKD), heart failure, and obstructive sleep apnea (OSA). In the four studies we've conducted, we are seeing strong responses. When considering hypertension in comparison to other treatments like alpha blockers, beta blockers, renal denervation, and endothelin receptor antagonists, lorundrostat shows compelling clinical benefits, highlighting both the effectiveness of the molecule and the unmet need in cases of dysregulated aldosterone. This extends to related comorbidities, such as hypertension with CKD and hypertension with OSA. Given that lorundrostat is a small molecule, we have contemplated some interesting fixed-dose combinations; however, I can't provide details on that at this moment. Acceptance of fixed-dose combinations varies by region. In Europe, there is a tendency to use these combinations more frequently than in the United States, where there is a preference for keeping medications separate to allow for dose management. This is particularly interesting concerning CKD, especially with the dynamics expected in the SGLT2 market due to potential generics. As SGLT2s quickly become the standard care for CKD and with the anticipated launch timing of lorundrostat for hypertension, along with our data collected to date for both hypertension and CKD, there might not be a necessity for fixed-dose combinations since lorundrostat could effectively address the aldosterone aspect of the condition. We have already seen swift adoption of SGLT2s as a standard of care in that patient population.

Okay. Got it. So going back to your previous discussion on the BAX data at ESC, in what scenarios do you think that readout could negatively impact your discussions with potential partners or the outlook for lorundrostat? Additionally, do you believe that most partners you've been speaking with consider both of these drugs similar because they share the same mechanism of action, or are they looking for a best-in-class drug over the other?

Yes. Again, it's hard to opine on what may be seen with the baxdrostat data. I'll go to what we do know. And we know at this point, four successful trials are very well characterized and beneficial clinical profile with lorundrostat that based on the unmet need in the marketplace, I think stands to generate significant value for patients and commercial value for shareholders. And so that's what we're focused on. As to the placement of or the availability of two ASIs. I think we've always said there's certainly room for two within this marketplace. We have a distinct offering as it relates to its selectivity and its half-life and the spectrum of data we've generated within the clinical development program. But with 20 million patients failing to get to go on two or more meds, we think there is significant opportunity for more than just one player in this space.

Our next question comes from the line of Seamus Fernandez with Guggenheim Partners.

So a couple of quick ones here. Just in terms of drug-drug interactions and anything that could impact an outside assessment of lorundrostat, would you guys maybe just help us understand the cited PPI drug-drug interaction that you called out in your 2023 10-K. I think this is a very minor issue, but just wanted to confirm some of the details that you have around the PPI utilization in your trials as well as just kind of what your market research shows in terms of the frequency of use there, if there are any limitations at all? And then the second question really comes down to the sort of 24-hour profile. One of the things that AstraZeneca does cite is the prospect of potentially being differentiated in terms of the half-life. Just interested to know how you guys think about the profile of lorundrostat from a 24-hour perspective and what you might be hoping to see in your OSA study as well as those data emerge later this year.

Great. Thanks, Seamus. The first part of the question, the PPI, from the research that we've done, PPI use is in about 10% of adults, maybe about 15% in older adults. For both our launch and Advance-HTN study, we allowed PPI use three times per week. We recommended if people were using an H2 antagonist dosed in the evening, whereas lorundrostat was dosed in the morning. The reason for that is lorundrostat is the basic salt requires a level of acidity for full bioavailability. So, the question is not one, Seamus, of safety. It's about exposure and ensuring coverage of that patient's blood pressure. Now as you're aware, the 50 milligram is the intended target starting dose. We have shown in Explore-CKD the 25 milligrams is active. From the Explore-CKD, we saw about a 7.5-millimeter mercury placebo-adjusted change at 4 weeks. And so, we believe the 25-milligram is clearly an active dose. And so, if somebody is on 50, they have to be on a chronic PPI, we would just suggest that the physician monitor their blood pressure. But again, within the two pivotal studies, we allowed periodic use of that and clearly saw robust clinical benefit. To your second question about 24-hour profile, I've heard that before. I would say after 4 clinical studies where we measure the in-office blood pressure the same way, and that is in the morning at trough before that day's dose, we're very confident in the 24-hour blood pressure control that we provide for patients. So, looking at Launch-HTN with 11.6 millimeter mercury placebo-adjusted change, 19 absolute to Advance that had almost 8-millimeter mercury placebo adjusted and 15.5 millimeter mercury absolute. Those were all done in the morning. The advance was the 24 hour. So, we clearly see that. And the numbers that I explained for Explore-CKD, the same thing, morning measurement at trough. So, we're very confident in the 24-hour control.

And just a question on OSA, timing for OSA and what you might be hoping to see in that data set?

Yes, sorry for missing that. As mentioned in the prepared remarks, there are interesting but small studies indicating that with a mineral corticoid receptor antagonist or a unilateral adrenalectomy, there is an improvement in AHI, notably with a 50% reduction in event range. Current treatments like GLP-1s and CPAP are effective as needed for patients. That's why we're conducting the study now with AHI as the primary endpoint, which is also the registrational endpoint to guide further clinical development for the program. Regarding the blood pressure reduction, it's difficult to estimate. The nighttime dosing is designed to target the aldosterone surge we believe is linked to OSA symptoms during the evening. We're aiming to align lorundrostat with the timing of increased aldosterone production.

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

This is Alice speaking on behalf of Tim. My first question is about the percentage of payers you expect will implement a step edit, meaning requiring patients to first use spironolactone. The second question is whether there has been any hesitation from potential partners in collaborating with you, and if so, what specific areas do they need more clarity on? What is the main point of contention?

Yes, Alice, thank you for your questions. Let me take the second one, and I'll turn it over to Eric for your first one. As to any dialogues with prospective partners, we really haven't gotten into specifics on that. Again, I'll just pivot to the unmet need within this space, which we think is significant, coupled with the clinical profile that we've developed with the four studies to date that we think can be significant as far as addressing that unmet need. As regards to the payers, I'll let Eric provide.

Sure, Alice, thank you for your question. We do not expect to require a step through spironolactone. We specifically inquired with payers during our market research about this. The reason they won't require us to go through spironolactone is due to its approximately 2% share in the hypertensive market that payers acknowledge. Instead, we are likely to go through two generic classes, which will create an electronic step edit that is easily navigable through the cloud. Our ultimate goal is to ensure that the utilization management criteria are relatively modest, prescriber-friendly, and that we optimize the net price.

Our next question comes from the line of Jayed Momin with Stifel.

This is Jayed on for Annabel. We have a couple of questions. The first one is about your shift towards a commercial strategy. Who will be your initial target audience, and how do you plan to stage the launch given the size of the company and your potential reach?

Yes. I'll go ahead and take that question. I think it's too early to get into the commercial strategy, staging, targeting. As I noted in the prepared remarks, I think the big focus right now is really on two vectors. One is just the payer strategy, and the value proposition based on the clinical data that we've generated to date. And then the second is really using medical affairs to ensure that we're disseminating the data that we've generated to date through conferences.

And I've got one more here. How are you preparing for the pre-NDA meeting with the FDA? You've been pretty collaborative with the Cleveland Clinic and you also had a lot of comprehensive data in your clinical trials. What expectations do you have coming to the meeting? What kind of questions do you expect the FDA might have?

No, we're confident it goes back to the end of Phase II meeting where we intended clinical development program, the purpose behind that as well as, as you're well aware, all the other elements from CMC to nonclinical. So, we're confident in the package that we put together and the comprehensive nature of it. I think the intent for the FDA when they review any new drug, is it well characterized across distinct populations. And we believe with Launch-HTN being existing background, Advance-HTN being truly optimized and Explore-CKD looking at subjects with hypertension, lower eGFR that we have a fairly comprehensive package going into those discussions with the FDA.

Great. I'm sorry, I have one more quick question. Regarding baxdrostat, I know their data hasn't been published, but they did reach their goal. Can you discuss any counter-detailing messaging that may be starting?

No. I think we'll wait to see what their study reveals and how the data compares from both groups. There are still targets that haven't been addressed in treating not only hypertension but also its related comorbidities. We expect to see positive data, as they have indicated, but it's too early to even start developing our messaging until we can analyze their data in relation to ours, which always presents challenges across trials.

Our next question comes from the line of Rami Katkhuda with LifeSci Capital.

Two quick ones for me. First, has AstraZeneca noted whether they're taking the average of 3 blood pressure readings similar to the SynCor Phase II studies? Or are they taking a similar approach to what you guys did in Launch and Advance? And I guess, how could that influence placebo response rates at the end of the day?

Yes. Rami, I only know about their measurements in relation to what they are doing with those automated devices. From a design perspective, that approach has been effective in helping us manage the noise from the placebo effect. I am uncertain about the strategies or operational plans that AstraZeneca has implemented to address the placebo noise, which was somewhat problematic in the earlier baxdrostat trials, particularly HALO.

Got it. And then I know it's a bit of a race to become the first ASI in hypertension with lorundrostat before you can ultimately file an NDA?

No, they don't give specific guidance to that, Rami. It's in consultation with the consultants, helping us with this. It's just making sure that we have what we feel to be an appropriate amount of the safety data for the FDA to begin their review and then not overload that submission with a 120-day safety update.

Our next question comes from the line of Mohit Bansal with Wells Fargo.

This is Sadia Rahman on for Mohit. For ahead of the baxdrostat data, any trial design differences that you'd highlight for launch compared with Bax-HTN that could contribute to differences in either the efficacy or on the safety side? And would you expect differences on hyperkalemia rates to be driven more by trial design aspects or by pharmacokinetics of these drugs?

Yes. I think as the Bax-HTN data becomes available, I think if you think about the breadth of our program, the most comparable study is probably Launch-HTN. The commonalities are both studies are looking at subjects failing to reach goal on two or more meds. It's using in-office blood pressure measurement. But beyond that, it's hard to opine on what else they may be doing within that study. And to your secondary question, how that may or may not impact from a design standpoint, rates of hyperkalemia, again, it depends upon how they characterize it, how they capture it, so it's just difficult from a design standpoint for me to give a view on that. The pharmacokinetics, specifically the selectivity in the half-life, we know is distinct from lorundrostat.

Got it. Regarding the open-label extension trial, do you plan to release any data from that trial later this year? Can you also discuss the potassium rates of hyperkalemia that we might observe?

Yes. To broadly answer your question, we're excited about the data we're capturing within the open-label extension. That study will provide not only a longer-term view of efficacy and safety, but we also have our randomized treatment withdrawal study, which is part of the NDA submission as well. We plan to continue publishing data from both the open-label extension and the randomized treatment withdrawal study, and we intend to share that data publicly in due course.

Our next question comes from the line of Matthew Caulfield with H.C. Wainwright.

Great to see the success. So, I think KOL takeaways for lorundrostat safety have been that the serum potassium is to be expected, it can be managed, and it's not expected to add to accruing levels over time. Could you foresee any reason the agency could be more scrutinizing of the serum potassium safety assessment as we head into the pre-NDA meeting in the fourth quarter?

No, Matt, thanks for the call. Again, I think it's why it was important that we built the program the way we did, the way that Dave designed it was to really give us a sense for lorundrostat's profile across the spectrum of patients. And so, I think that's something the FDA actually will value and appreciate that we've characterized not only the clinical benefit, but also the safety profile in an existing kind of real-world population and an optimized treated population in a population with CKD and proteinuria. And so, we're very confident with the package that we have right now to go to the FDA to characterize lorundrostat's profile in some of these distinct populations.

Our next question comes from the line of Dennis Ding with Jefferies.

There seems to be a general consensus regarding the technical difficulties between both ASIs. I'm curious about whether it's related to the size of the sales force, the length of relationships with doctors, or the extent of rebating. What specific factors will you focus on? Additionally, concerning R&D synergy for an ASI, CKD and heart failure are clear, but what other indications do you believe an ASI could enhance further beyond standard care?

Yes. Dennis, thanks for the question. So, the first one, I think what we're looking broadly at within a partner is how we can maximize reach to both prescribers and patients. If we look at how we've developed this molecule to date, it's been with a pretty keen eye towards the commercial marketplace, realizing that it's highly genericized, knowing that going first line would probably have significant barriers. But as you heard Eric opine later or earlier on, in that third-line position with proper pricing and rebate strategy, we believe that access is very manageable. And the reason for that is the significant unmet need there. Now that prescribing is driven to a fairly large degree, and we note this in our corporate deck by about 47,000 to 50,000 doctors in those top five deciles of third line or later prescribing. And that's a mix of cardiologists and primary care. So as we think about partnering, we factor that into that consideration. Relationships, those are all informative to how we think about a partner. To your second question as far as the increment of an ASI and other categories, I don't know that I could share with you all of the different areas that we thought about. You highlighted certainly CKD and heart failure.

Got it. And I had a quick follow-up. I think many people feel that lorundrostat could be used, and where your better selectivity could eventually come out positive. So, are you considering going after that indication? And why or why not?

Yes. Thanks, Dennis. I think I would put primary aldosteronism into some of the other categories. It's certainly something we're contemplating. Clearly, that's probably the extreme edge of hypertension with aldosterone as a driver for that. As we look at all the different options that are out there.

And we have reached the end of the question-and-answer session. I would like to turn the floor back over to CEO, Jon Congleton, for closing remarks.

Thank you, operator. I appreciate everybody's attention today. We believe the strength of the clinical results for lorundrostat showed the potential benefit for uncontrolled and resistant hypertension and those related comorbidities such as CKD and OSA we discussed today. We do look forward to our upcoming pre-NDA meeting with the FDA later this year. This is an exciting time for our team. Thank you to all the physicians and researchers that have worked so hard in support of bringing lorundrostat through our pivotal program. We're excited for key upcoming milestones and look forward to sharing updates with you in the upcoming quarters. With that said, I'll say thank you, operator, and thank you to everyone for joining us today. With that, we'll close the call.

Thank you. And ladies and gentlemen.