Mineralys Therapeutics Aktie

Welcome to the Mineralys Therapeutics Second Quarter 2026 Conference Call. [Operator Instructions] As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Dan Ferry of LifeSci Advisors. Please go ahead, sir.

Thank you. I would like to welcome everyone joining us today for our second quarter 2026 conference call. This afternoon, after the close of market trading, we issued a press release providing our second quarter 2026 financial results and business updates. A replay of today's call will be available on the Investors 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 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 11, 2026. 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. Welcome to our second quarter 2026 financial results and corporate update conference call. I'm joined today by Adam Levy, our Chief Financial Officer; and Eric Warren, our Chief Commercial Officer.

I'll begin with an overview of the business and recent milestones. Eric will then provide a commercial update, and Adam will review our second quarter financial results before we open the call for your questions.

Before I get started with the business update, I would like to take a moment to welcome Dr. Terry Ferguson to the team. Terry joins us as Chief Medical Officer, succeeding Dr. David Rodman, who will continue to play an important role as a full-time strategic adviser to the company. Terry brings more than 35 years of experience in cardiovascular medicine, clinical development and executive leadership. He served as Cardiovascular Therapeutic Area Head at Amgen and held senior cardiovascular leadership roles at AstraZeneca and The Medicines Company. He also spent more than 20 years on the faculty of the Texas Heart Institute and in cardiovascular medicine, a proven track record of -- Terry's deep expertise in cardiovascular medicine and a proven track record of advancing innovative therapies positions him well to lead our medical and late-stage clinical activities as we continue preparing for the potential commercialization of lorundrostat.

I want to thank David for his dedication and hard work over the past several years. During his time as Chief Medical Officer, he guided the development of lorundrostat from proof of concept through the pivotal program and our recent new drug application filing with the FDA.

In the second quarter, our focus was on commercial launch readiness, the evaluation of partnering opportunities and the next steps in the clinical development of lorundrostat. In the third quarter, we continue to build our commercial infrastructure as we approach our December 22 PDUFA date.

Turning to our clinical progress. Our Transform-HTN open-label extension trial continues to generate valuable long-term safety and efficacy data that further supports lorundrostat's potential best-in-class profile. In May, we presented a post hoc analysis from our pivotal Launch-HTN trial at the European Society of Hypertension's Annual Meeting. The analysis focused on participants with chronic kidney disease, a high-risk and difficult-to-treat patient population. Despite entering the trial with more severe hypertension and greater use of background antihypertensive therapies, these participants experienced statistically and clinically meaningful blood pressure reductions comparable to those observed in the broader trial population.

In addition, participants with baseline albuminuria achieved a 52% placebo-adjusted reduction in urine albumin to creatinine ratio, an important marker of kidney injury and disease progression. Just a few weeks later, at the Endocrine Society's Annual Meeting, ENDO 2026, we presented late-breaking proteomic data from our Launch-HTN and Advance-HTN trials, demonstrating that lorundrostat was associated with significant reductions in multiple biomarkers of heart failure risk.

While exploratory in nature, these coordinated biomarker changes provide additional biological evidence that lorundrostat use may favorably modulate disease pathways implicated in heart failure. We believe these findings further strengthen our understanding of the broader biological implications of aldosterone and the potential for lorundrostat to provide benefits in hypertension and related comorbidities. We continue to evaluate further clinical development for lorundrostat, and we'll keep you informed on our progress as appropriate.

We also completed several corporate initiatives that enabled our long-term value creation objectives. During the quarter, we announced an agreement to repurchase the potential future royalty payments due to Tanabe Pharma Corporation related to lorundrostat. Under the terms of the agreement, Mineralys agreed to pay Tanabe $200 million upfront and up to $100 million once certain commercial milestones are met. Our aggregate potential future milestone payments to Tanabe are now up to $265 million. We believe this represented a unique strategic opportunity to enhance the long-term value of lorundrostat as we approach commercialization.

Concurrently, we completed a $150 million equity offering and entered into a $500 million committed senior secured term loan facility with funds managed by Pharmakon Advisors. Beyond funding the royalty repurchase, this facility provides Mineralys with access to additional capital and financial flexibility while positioning Mineralys to capture the long-term value of lorundrostat.

As we look ahead to the remainder of the year, we believe lorundrostat is entering an exciting new phase in its evolution. We have continued to build the clinical evidence supporting lorundrostat, enhanced the long-term value of the asset, expanded our access to capital and continue to make meaningful progress preparing for a potential commercial launch. In parallel, we continue to evaluate partnering opportunities and engage in strategic discussions to enhance value and enable us to reach more patients who could benefit from lorundrostat.

With that, I'll turn the call over to Eric to provide a commercial update.

Great. Thank you, Jon. Approximately 20 million adults in the United States have uncontrolled or resistant hypertension. And despite the availability of numerous anti-hypertensive therapies, these patients remain unable to achieve their blood pressure goal. These patients face significant increased cardiovascular and cardiorenal risk, highlighting the need for new treatment options that address an underlying driver of disease.

Our extensive market research continues to reinforce the value proposition lorundrostat could offer if approved. Physicians consistently tell us they are seeking new therapies that deliver meaningful and durable blood pressure reductions, demonstrate a favorable tolerability profile and fit naturally within existing treatment algorithms. We believe lorundrostat's clinical profile aligns well with these expectations and differentiates the compound from both currently available and emerging therapies.

Now over the past several quarters, we have systematically executed against the key elements of our commercial launch planned. As a result, many of the foundational components of our commercial infrastructure are now in place, and our efforts are increasingly focused on final launch readiness and execution.

First, we've established strong relationships with leading hypertension specialists and key opinion leaders who we believe will play an important role in shaping clinical practice following a potential approval. Second, we've made significant progress in our initial payer engagement activities. The payers we have engaged with to date collectively account for the vast majority of covered lives in the United States. Our discussions have centered on clinical and economic burden associated with uncontrolled hypertension and the value proposition supported by lorundrostat's clinical data package. These conversations continue to reinforce our belief that payers recognize the unmet need in this patient population.

Third, we're well underway in the development of a differentiated launch campaign that's designed to educate both health care providers and patients. We've done extensive research to understand the optimal messaging, resources and communication platforms that will drive rapid adoption. Lastly, we're in the final stages of building the field organization that will support our launch. Our experienced sales leadership team is now in place, bringing a track record of successfully launching and commercializing cardiovascular therapies.

We've also completed detailed geographic mapping to identify the regions with the highest concentrations of physicians treating patients with uncontrolled or resistant hypertension, allowing us to optimize field deployment. And perhaps most importantly, we expect our sales organization to be staffed in advance of our December PDUFA target date, positioning us to execute swiftly and decisively following a potential approval.

We've built our commercial organization around clear objectives, which are to ensure physicians have the education, resources and support needed to identify appropriate patients and if approved, make lorundrostat available to those patients as efficiently as possible. We continue to be encouraged by the feedback we are receiving from physicians payers and thought leaders and believe Mineralys is well positioned to execute a successful commercial launch.

I'll now turn it over to Adam to review our second quarter financial results.

Thank you, Eric. Good afternoon, everyone. Today, I will discuss select portions of our second quarter 2026 financial results. Additional details can be found in our Form 10-Q, which will be filed with the SEC today. We ended the quarter with cash, cash equivalents and investments of $661.4 million as of June 30, 2026, compared to $656.6 million as of December 31, 2025. We believe that our current cash, cash equivalents and investments will be sufficient to fund our planned operations, including the commercial launch of lorundrostat into 2028.

R&D expenses for the quarter ended June 30, 2026, were $221.4 million compared to $38.3 million for the quarter ended June 30, 2025. The increase in R&D expenses was primarily due to the $200 million upfront payment to Tanabe in June 2026 in connection with the license agreement amendment. The increase was also due to $0.6 million of increased personnel-related expenses resulting from headcount growth and increased compensation and $0.2 million of increased clinical supply, manufacturing, regulatory and other costs. These increases were partially offset by $17.8 million of lower preclinical and clinical costs, primarily due to the conclusion of the lorundrostat pivotal program in the second quarter of 2025.

G&A expenses were $24.7 million for the quarter ended June 30, 2026, compared to $8.5 million for the quarter ended June 30, 2025. The increase in G&A expenses was primarily due to $8 million in higher professional fees, $8 million in increased personnel-related expenses resulting from headcount growth and increased compensation and $0.2 million of increased other administrative expenses.

Total other income net was $5 million for the quarter ended June 30, 2026, compared to $3.5 million for the quarter ended June 30, 2025. The increase was primarily due to $2.3 million of increased interest earned on investments as a result of higher average cash balances, partially offset by $0.8 million of interest and amortization expenses related to the senior secured term loan entered into in June 2026.

Net loss was $241.1 million for the quarter ended June 30, 2026, compared to $43.3 million for the quarter ended June 30, 2025. The increase was primarily due to the factors impacting our expenses that I just described. With that, I will ask the operator to open the call for questions. Operator?

[Operator Instructions] The first question is from Richard Law from Goldman Sachs.

Congrats on all the progress as we approach PDUFA. And I also want to extend our welcome to Terry and look forward to working with him. So a couple of questions for me. I see that you guys have a lot of postings on the territorial manager positions. How are you finding the quality of candidates after Baxfendy's launch, which I assume will be competing for talent out there as well? And also, are there any key attributes that you guys are looking for regarding like hypertension experience -- or on certain drugs? And also, when are you guys going to start hiring for the rest of the sales reps given the launch is nearing in four months?

Rich, this is Jon. Thanks for the question. I have to admit it was a little bit garbled. So I'm going to paraphrase your question back and tell me if I got it on point. I think your question is about the field sales force, the phenotype we're looking for and our likelihood of having those in position ahead of the PDUFA. Is that the paraphrase of your question?

Yes, exactly. So basically, the -- how are you guys finding the quality of candidates given that Baxfendy's launch already been happening? So I assume there's competition for talent there. So what you guys, are looking for in terms of experience? And also, like when are you guys going to hire the rest of the sales force given that the launch is four months away?

Yes. I think as Eric alluded to, our goal is to have the team in position ahead of the PDUFA date. I'll tell you, I'm really excited about the quality of not only the sales representatives, territory managers that we're seeing, but also of the first-line sales managers. I think Mineralys represents the kind of exciting opportunity that attracts high-level talent that are energized by the kind of innovation that lorundrostat represents and the impact that it could have on millions of patients. So I think that in and of itself becomes a very exciting offering that attracts high-level talent.

I will tell you, there's not a one phenotype that we're looking for. There's certainly a lot of cardiovascular experienced reps that are out there, but we're also looking for those kind of individuals that we believe align to our values, the purpose that we have and are energized by the opportunity. So I'm very comfortable with the quality of candidate and our ability to hit that target of having the full team in position ahead of the PDUFA.

Fantastic. And then just to follow up on that. And how are you seeing the payers in terms of -- are they waiting for lorundrostat's approval before deciding on how to manage both ASI products? Is there anything that you guys are seeing that Baxfendy is doing well or not doing well with payers or other commercial aspects that you can do differently or better?

I'll give you a quick thought, and then I'll turn it over to Eric. I think the feedback we're getting from our national account team that was in place in Q1 of this year continues to be very bullish on access for this kind of innovation, particularly in the third and fourth line position. But Eric can give you maybe some more specifics behind that.

Yes. Thanks, Jon. Rich, so from a payer perspective, payers, it's still early for baxdrostat, obviously. But I think it's encouraging to see that there's recognition of the innovation that the ASI class brings. We haven't seen a lot of payer decisions yet, but we're firmly in a position to believe that both of these agents will be in an equivalent position that will give HCPs the ability to choose, and that's where our differentiated profile comes into play.

The next question is from Michael DiFiore from Evercore ISI.

Two for me. You said in the past that the label and post-marketing conversations typically start a couple of months out prior to PDUFA. Has that process begun? And has anything in the -- at least your initial conversations changed in terms of what you expect to negotiate in the label? And then second question is on pricing. When do you actually plan to lock in that decision? And would you communicate that ahead of the launch or at the launch?

Yes. Thanks, Mike. The label and post-approval commitments that typically occurs a couple of months ahead of the PDUFA. So I would expect sometime in the October, November time frame. I would say -- I would characterize the current dialogues with the agency, no surprises from us. I think the data package that we put together was robust from the pivotal studies, Launch-HTN, Advance-HTN, including Explore-CKD and the open-label extension. So we feel very confident with the package that we have, and I think the dialogues to date have been regular course.

From a pricing standpoint, obviously, we've seen the price of baxdrostat. We're continuing to do our analysis. We weren't overly surprised by the price point they came out with. It's in that non-specialty tier pricing area. But I would not anticipate us sharing the price until approval and subsequently probably around launch.

The next question is from Jason Gerberry from Bank of America.

A couple from me. Just in terms of the early AZ launch, any learnings as you interrogate the data so far in terms of perhaps good, bad or just too early to formulate any conclusions? And then as a follow-up to the point you raised about confidence around parity payer access. I'm not sure you can say much, but directionally, I'm just curious like your -- I guess, sort of the gross to net deductions in order to achieve parity access is that coming in perhaps in line, better, worse than maybe you would have expected, say, 6 to 12 months ago?

Yes, Jason, I'll take the first part and have Eric address your question about payer access. I think your point you made, it's still early days to gauge from the numbers that you see the same things we do publicly on the baxdrostat launch.

I will tell you anecdotally, I think there's enthusiasm and excitement for this new class of therapy. It's been over 20 years since there's been a meaningful introduction of an antihypertensive therapy. We know there's significant patients, 20 million on two or more meds that cannot get to goal right now. We know the implications of that.

And so I think the enthusiasm that we're seeing anecdotally in the marketplace for this class of drugs speaks for the opportunity that, and I know we're excited about with lorundrostat. But as to the payer dialogues, I'll let Eric comment.

So payer dialogues have been very, very positive. I would say the level of rebate that we're hearing that's coming from baxdrostat is very consistent with what we expected, and that's obviously on the commercial side. From the Medicare side, so far, it looks like access is this medical exception, which then allows us to go to label. So --so far, again, without giving any kind of precise indicators of what we're doing, generally as we would expect, Jason.

The next question is from Seamus Fernandez from Guggenheim Securities.

This is Evan Wang on for Seamus Fernandez. Just two for me. Just I guess, first off, as you're speaking with KOLs and doing your outreach, what's really resonating with KOLs about the profile here? And then second, congrats to Terry for joining. I'm just curious, I know it's extremely early, but curious what the priority list will be as he gets settled?

Yes. The question -- and again, I apologize, the audio is not the best. I think your question was the profile they get most excited about with lorundrostat. And I think it's pretty clear. It's aligned to the attributes that matter to physicians when treating their patients. And that is the blood pressure reduction, which we know is extremely meaningful and we think best-in-class with lorundrostat, combined with safety and tolerability.

So in other words, the patients need to be able to not only get the blood pressure reduction, but get it in a way that is safe and can be adhered to over a long period of time. So we continue to believe that, that profile that we've seen from our clinical program reinforces a profile that meets the needs of physicians as they're treating these patients third line and later.

As to Terry, yes, we're very excited. I mean I'm actually thrilled to be able to expand the expertise that we're able to apply to Mineralys and lorundrostat by retaining Dave in his strategic advisory full-time role to really help continue to investigate translational opportunities for lorundrostat. We know aldosterone plays a significant role beyond just hypertension, but across cardiorenal metabolic disorders.

But having Terry come in with his expertise in latter stage development and very specifically medical affairs, I think does nothing but just augment and build on the success we've had to date. We've got our medical affairs team in place right now, adding Terry's expertise over 35 years of either clinical work or industry work, I just think really amplifies the message, the resonance, the relationships he has with KOLs. I think it's going to be a significant build for us as we continue to prepare lorundrostat for a successful commercial launch.

And Jon, I just want to add one thing. So in addition to the efficacy and the safety, the advanced data are really resonating well with the KOL audience. So having a unique data set really does differentiate us in their minds.

Great. And maybe one follow-up. I'm just curious in terms of anything you can provide in terms of the number of reps you guys are targeting out of the gate, especially as you're kind of thinking about your efforts here?

Yes. We -- our focus is really on those prescribers that are going to control a significant volume of third line or later prescribing. We've talked about in the past, that's plus or minus 50,000 physicians. So we'll ensure that we have a very strong share of voice within those predominant prescribers of the later lines of treatment. We haven't guided to a specific number. We may in due course. But at this point in time, we just want to hold some of those cards a little bit closer to our vest.

The next question is from Annabel Samimy from Stifel.

This is Kyle speaking for Annabel. Maybe two questions on the label. Exactly what are you guys looking for in terms of a differentiated label for -- in comparison against Baxfendy? And then based on -- I know you mentioned discussions early, but based on your current interactions, what do you think is required to warrant a language, specifically calling out resistant hypertension or CKD? And then do you think having a dedicated randomized controlled trial like Advance or Explore-CKD could be the new mover?

Yes, Kyle, thanks for the question. From a label standpoint, I think there'll be a few similarities. I think the indication will look fairly similar. That's for inadequately controlled blood pressure on top of background meds. I think we'll get the similar treatment as far as the outcomes claim related to that blood pressure reduction that's become standard based on FDA guidance.

I think where there's going to be an opportunity for differentiation and all of this, obviously, is dependent upon dialogues with the agency, but it's the representation not just of Launch-HTN, which is the largest hypertension trial conducted with an ASI, but also Advance-HTN, which, as Eric said, is very unique and distinct from, frankly, a lot of studies done in hypertension given the nature of that trial where we were confirming uncontrolled and resistant hypertension based on moving subjects to an AHA approved background treatment and only randomizing after they cannot get control even on an optimized treatment.

So I think Advance-HTN certainly will be a part of our discussions with the agency as an important data set to include in the label on top of Launch-HTN. And then I believe data from Explore-CKD is also informative to physicians who are prescribing an ASI in a subject who have -- may have lower kidney function based on eGFR. We know the label for baxdrostat speaks to eGFR I believe, down to 45 and Explore-CKD went down to 30. And so we'll be making a point to the agency that it's important that physicians have guidance from the label that would reflect that.

We know collectively, if you look at the efficacy data, even just from Launch-HTN, there are clear differentiators based on the absolute and placebo-adjusted reductions in systolic BP as well as milder cases of electrolyte change, specifically hyperkalemia. So we believe that the data set that we've generated to date creates good evidence for differential points within the label, but obviously, those will all be part of discussions with the FDA.

The next question is from Mohit Bansal from Wells Fargo.

Before I start, so thank you very much, David, for all your help over the years. And congrats, Terry, for the new role. Looking forward to work with you.

So I have a couple of questions here. So number one, assuming that you get similar label to bax, is there anything in the clinical data or the trials like -- Advance-HTN was a differentiated trial that you could use to appeal to certain specialties? Or it would probably be seen more similar than different from that aspect? And the second one is AZ is running this primary aldosterone trial. And that could read out for bax next year. So how do you see that trial in case it is positive, impacting the class or specific molecule? Like how do you see the result of that trial impacting the positioning there?

Yes, Mohit, thanks for the questions. To your first question, I do think there are some distinct points within the label that can create differentiation. I think overall, the aldosterone synthase inhibitors are going to be a transformative new introduction to the treatment of hypertension. We're seeing really pronounced and clinically meaningful reductions in similar patient types, those on two or more background meds that are failing to get to goal.

But within those similarities and then really the two key areas that are fundamental to a prescriber, blood pressure reduction and safety signals, specifically hyperkalemia, I think they each have favorable views relative to lorundrostat. And we've -- you've seen the market research we've done where we put up the results of BAX-HTN relative to Launch-HTN. And there's about a 2:1 preference for the profile that emerged with lorundrostat relative to Baxdrostat based on those two fairly similar trials.

And so again, presuming that data from Launch-HTN is in the label, which we anticipate, I think that gives us from a promotional standpoint and an educational standpoint, an opportunity to really show the benefit of using the most selective ASI with what we think is an ideal half-life of 10 to 12 hours. So I believe that's how it's going to translate.

From a primary aldosterone perspective with the PA study, I think there's a lot of interesting movement as far as how PA was originally characterized to being a secondary form of hypertension to where dysregulated aldosterone is really more of a spectrum. And so I think the data we generated to date is going to resonate with physicians that are looking to address dysregulated aldosterone, whether it's classified as typical PA or dysregulated or elevated aldosterone.

So it will be interesting to see that data. But I know that physicians that are treating patients who have aldosterone as a driver of their uncontrolled or resistant hypertension are certainly excited about the lorundrostat profile.

The next question is from Rami Katkhuda from LifeSci Capital.

I guess, given the December PDUFA, how should we be thinking about the cadence of payer coverage through '27? And is there a risk that missing the initial Medicare Part D formulary cycle could make next year more of an access building year? And then secondly, when do you expect the next major hypertension guideline updates to be? And how important could a formal inclusion of ASIs be for the class?

Yes. I'll take your -- the second question, Rami, on the guidelines and Eric can comment on the first one as far as the cadence of coverage. We've been identifying and working with the committee members, making sure that they have the information that is required as they contemplate guideline inclusion. I think probably five years ago, there was a more rigorous cadence of every four or five years, an update to the guidelines. What we've heard from those committee members is they're going to try to be more reactive to new information like the ASIs. And so I would anticipate sometime in 2027, an update of those guidelines that would reflect where the ASI should fit within that.

I think that's where we made some really discrete and important choices from the clinical development of lorundrostat, not only Launch-HTN providing real-world kind of case studies, but also Advance-HTN for those specialists that are optimally treating patients and yet still failing to help them get to goal. Advance-HTN that we did with the Cleveland Clinic was specifically designed and executed with the guidelines in mind. So I think we've got a very strong case for lorundrostat. That may be a benefit that extends to the class. But I think fundamentally, the ASIs, given the clinically meaningful reduction that we're seeing will have a really clear place within the guidelines for patients, certainly at latter line of treatment. But Eric can talk about cadence of coverage...

Yes. And you've characterized it well. So a progressive increase in coverage over the course of 2027 with commercial outpacing Medicare. But it's important to note, as I said before, that Medicare relies upon medical exception, which has a very favorable approval rate. It's important to note, and I didn't say this before, but we'll also stand up a field reimbursement manager team to support prior authorizations and we're making a good emphasis and focus on prior -- and patient support to ensure that the patient gets on therapy quickly, and there's tools to help navigate the process. So progressive increase is the core message, commercial first, Medicare coming along, but Medicare exceptions are pretty straightforward.

The next question is from Tara Bancroft from TD Cowen.

So I want to follow up on one of the first questions that was asked. So I'm curious in what ways you think you could improve access and adoption as a second to market relative to Bax, especially as it comes to pricing. So is it possible maybe to price at a discount and take more share that way? I know you've previously communicated the SGLT2 class as good pricing comps for the Street to anchor to, but maybe should we anchor more so to AZ now?

Yes. Let me give some high-level thoughts and Eric can follow up. I think the -- I've been asked before, does baxdrostat pricing create an anchor. And I don't know if it's an anchor. I think it's informative. I think the key element was in the rationale that we, looking from the outside in, saw with baxdrostat price was not specialty tier, which we think was critical to ensure access to patients. And so we'll continue to evaluate that. We're going to continue to do our analysis of it. And maybe Eric can speak to some of that work we're going to continue to do.

Yes. I mean -- and again, I'll just reinforce the baxdrostat price is very consistent with the research that we conducted with payers as well as ad boards that we convened. From a pricing perspective, we've got a pretty good sense of where we'll price, but we're still in the final stages of finalizing that. Again, a core tenant is to maximize ultimate value and not create a kind of a downward pricing spiral.

So I won't get into too much more than that, but I just want to reinforce that, again, pricing of baxdrostat is very consistent with our expectations, and we're finalizing our strategy, but we definitely need to make sure that we're preserving value.

The next question is from Matthew Caufield from H.C. Wainwright.

One question that we haven't really covered is looking back to Explore-CKD. What could be the next important catalysts or possible time frames for further lorundrostat evaluation in CKD patients? Is that something on the radar at this stage kind of above and beyond the PDUFA and launch focus?

Yes, Matthew, thank you for the call. This is why I'm excited to have both Terry and Dave here. Dave obviously has 5.5 years' experience with lorundrostat, and we're going to be able to augment that with Terry's cardiovascular experience and medical affairs experience as well as clinical development.

We know that at this stage, lorundrostat has a really robust and meaningful reduction in systolic BP and blood pressure. But we also think -- and we've talked about this in the past, there's multiple mechanisms that aldosterone can drive, specifically things like inflammation, fibrosis and oxidative stress that I think we've already seen what that translates to. I referred to it in my prepared remarks that in Launch-HTN, we saw a 52% reduction in placebo-adjusted UACR, which is a clear marker of kidney protection. We've seen further within the ENDO presentation, benefits from a proteomic standpoint on markers of heart failure.

So not only do we have the opportunity to address really the genesis of all of these cardiorenal metabolic syndromes, and that's blood pressure, but I think there's an opportunity to really show value beyond just the blood pressure reduction, and that is around elements like heart failure, chronic kidney disease and related conditions. So that's part of what we're continuing to analyze at this point. That's where Dave and some of his translational science team are really digging into what makes sense for the next clinical development of lorundrostat.

I think we've validated the best-in-class profile as it relates to blood pressure reduction. We know where AstraZeneca and Boehringer Ingelheim are going with their ASI-SGLT2 combos. I think there are other interesting opportunities that we could pursue in other indications that we're contemplating. And once we've aligned on those final plans, as appropriate, we'll communicate that to the market.

The next question is from Dennis Ding from Jefferies.

I have one and then one follow-up. So Jon, you've always alluded to and emphasized that you guys are looking for a global partner. So can you go through exactly what you're looking for in a partner, at least on the U.S. side? And how important is it for a partner to have a presence in nephrology specifically?

And the reason I bring that up is -- and this is my follow-up is because you've talked about leveraging your CKD data to get earlier line use in the third line. And I feel like that could be an area where you can get us more over AstraZeneca. So I'm wondering how much overlap with CKD is there in the cardio setting where you can perhaps go after that population with the cardio sales force? Or maybe it's a priority for you to go into nephrology in a dedicated way, either on your own or through partners?

Yes. Thanks, Dennis. We've stated before, and I think you kind of alluded to it, our goal from a partnering standpoint has tended to be more of a global nature. We've stated pretty clearly that the commercialization of lorundrostat outside of the United States would be through a partner. But ideally, we find a global partner that not only has the commercial interest, but also the development interest.

As I alluded to in my response to Matthew, I think aldosterone is kind of becoming one of those foundational nodes that are going to be really critical to address cardiorenal metabolic disorders. The CKD data that we have is very compelling, very interesting. I do think it does create an opportunity to move earlier in lines of treatment because we know there is just huge overlap of these conditions. And it's not just hypertension and CKD, but it's hypertension, CKD, it's cardiovascular risk, be it in the form of heart failure, just overall cardiovascular risk.

So I don't know that there's a specific type or therapeutic area of focus for a partner. I think it's more an understanding of the opportunity that we have near term with lorundrostat to address uncontrolled and resistant hypertension, but then more broadly, the role that aldosterone plays in cardiorenal metabolic as, frankly, a critical node that needs to be addressed and looking at development opportunities to tap into its full potential.

This concludes the question-and-answer session. I would like to turn the conference back over to Jon Congleton for closing remarks.

Thank you, operator. We believe Mineralys is entering an exciting and important period. With our NDA under FDA review, we remain focused on execution as we work towards that December PDUFA target date. I want to thank everybody for joining us today. We look forward to keeping you updated on our progress, and we wish everyone a great evening. Thank you.

This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.

All right. Let's kick off our next session. It is my pleasure to be -- to host Mineralys Therapeutics. Here with me, Jon Congleton and Adam Levy, CEO and CFO of the company. Gentlemen, welcome. Always a pleasure to be hosting you guys for these events. I appreciate the -- looking good this year.

With...

We looking good this year compared to the first time we hope that we're -- that there was a [indiscernible]

we were talking about that earlier.

So before we -- I have a lot of questions to ask, but before we go to that, I'll turn it to you for opening remarks.

Yes. No. We're very excited about 2026 and the opportunity in front of us. As we noted, the NDA for Lorundrostat was submitted late last year. The PDUFA date was declared in March of this year that PDUFA is interactions with the FDA standard course, we continue to feel very positive about the opportunity, the approval we're using this year to continue to prepare for a successful launch of Lorundrostat, have built out our market access team, our medical affairs team, we've optimized and obviously, look forward to bringing Lorundrostat to, frankly, the 20 million patients in the United States that could benefit from it significantly in lowering their BP and their cardiovascular risk.

Fantastic. So recently, you guys announced a deal with Tanabe, where you guys ended up buying the IP rights to Lorundrostat and also all the royalty obligations. It would be great if you can go over the terms and the commercial milestone implications related to this deal.

Absolutely. So we had the opportunity to buy back the royalties from Tanabe for $200 million upfront and $100 million in future potential commercial milestones. The future milestones are based on certain thresholds, and we believe that they will be totally paid for by the savings in the royalty.

I see. Okay. And then you guys mentioned that this transaction is accretive to investors. But then I think a lot of investors took it the other way and given how the stock reacted when it came out. Like maybe just walk us through like how this transaction came about? And why do you believe it's accretive to investors?

The feedback we've gotten from investors has been very positive on the transaction. So -- the -- it was really opportunistic. It came up as Bain Capital had acquired Tanabe, and they were looking to monetize assets that they viewed as noncore. They saw this potential future stream of cash flows as noncore to them, and they look to sell it, and we were in the right place at the right time and had the opportunity to buy it at a value that was attractive to us. When we look at the return on investment, we believe that it's quite attractive. And with the cash flows that would come in versus the $200 million upfront, it looked like a great investment for us.

Right. I see. Okay. And what was your assumption given the deal size of that $300 million that went into the modeling of how you guys came up with that price?

So we looked at our base case model, high case, low case, did some analysis and looked at not only what the returns were, but also what we thought would be reasonable for us given that we're cash flow negative. And we also have other investments that we want to make in R&D. And it was really driven more by the market opportunity than us modeling it. We offered something that we thought was attractive and it worked for them. So we made a deal.

I see. Okay. Got it. So some investors saw what you guys did with this deal and then you guys end up raising $150 million to equity and another $500 million debt facility, which is the first time that you took on such large debt. So they saw that you guys are giving up on BD. Is that a fair statement?

So it's really unrelated to business development. We have been thinking about how we capitalize the company for quite some time. We've thought about the range of options to fund, whether we would do additional equity, debt, maybe convertible notes, sell a royalty. And this really matched how we look at our cash flows going forward. So even though it's $500 million committed, we only brought in $100 million upfront. We have additional tranches. The next tranche is available at FDA approval and then beyond that will be $150 million additional. And then there's another $250 million available to us at certain commercial thresholds that's really at our discretion. We can pull it if we want, but we're not required. So this was a good way to put us in a position where we're funded but reduce the cost of capital versus equity.

I see.

And I think -- I mean, if I can add, if you're a fundamental believer in the value of Lorundrostat, which we are, getting uncapped royalties back at what we thought was a fair deal makes a ton of sense for us, and it is not incongruent with the BD strategy because it's fundamentally the value of Lorundrostat. And so to me, there was a congruence to it that fit the strategy that we proclaimed forever with Lorundrostat. -- building value on our own and enabling them being open to partnering.

Right. What was this royalty buyback inspired by some of the partnership discussions that you guys have? I mean, is this to help -- I can expedite that those efforts?

So the royalty buyback was opportunistic. It was something that Bain and Tanabe put up for sale, and we had the opportunity to acquire. That said, whether we're alone or with a partner or if someday a company wanted to acquire us, it builds value in any case by consolidating those cash flows and increasing the profitability of the business.

Right. Yes. No, that makes a lot of sense. So now the -- we're waiting for the PDUFA date. When do you expect to hear from the FDA regarding that the proposed label? And when does that negotiating process typically start?

Notably towards the back half of the year, probably in Q4, typically a couple of months before the PDUFA date is when we'll begin negotiating the label and we'll begin to talk about any kind of post-marketing commitments. I think looking at the baxdrostat data label, we feel very confident in some of the common things will be there, but also some of the differentiating points. But all of that will be part of Q4 activities.

Q4. Okay. Got it. And then you guys recently presented data from Launch-HTN at the ESH conference and where you compare patients with CKD and those without CKD among a pool 800 patients treated with that 50 mg dose. What are some of the key highlights in that study? And why is it important from a commercial perspective or from a future development perspective?

Yes. The -- this was data presented by Liffert Vogt, who is one of our PIs in Launch-HTN, it's post-hoc analysis, so in fairness to that. But he wanted to look at the difference in response within Launch-HTN for subjects that had CKD and those that did not. And so using, I think it's KDIGO-related criteria, specifically around albuminuria, which was not part of the inclusion criteria, but we had over 1,000 subjects. So we -- I think we had between 80 and 90 subjects that met that definition of CKD. And so looking at response to Lorundrostat on blood pressure reduction, there was no change whether the patients had CKD or not. So a nice effective reduction in BP, looked at safety. There was no incidence of hyperkalemia in the non-CKD population. I think just 2% in those that were defined as CKD by albuminuria. And then obviously, the ones that had albuminuria at baseline over the 12-week period saw a 55% reduction in albuminuria. Now UACR is a really nice surrogate for a drug that may provide renal protection. So if you see a reduction in UACR, that's conferring a level of protection in the kidney. That's very congruent to the Explore CKD data that we released last June. In that study, we showed over just a 4-week period of time, safe reduction in BP and about a 31% absolute reduction in UACR, so very congruent to that. Why that's important is as we go out and talk to physicians that are treating uncontrolled and resistant hypertension and ask the question, what attributes matter to you? Lowering blood pressure is always #1, doing so safely is always #2. But having a benefit on proteinuria is always a top 5 attribute that if they can make their ideal antihypertensive, it would have an effect on proteinuria. So we've now seen in two separate data sets that you can safely reduce blood pressure and provide a benefit on the kidney. That becomes relevant because if you think about third and fourth-line patients, these are patients that are not just uncontrolled or resistant hypertension patients in isolation. They have other comorbidities. -- that are related to that decade, decades of uncontrolled BP. And so being able to confer that benefit beyond just blood pressure reduction of the patient and the offering that Lorundrostat can provide for that.

Yes, you're right. I think the UACR, you guys saw a 55% reduction at the 12 weeks. I mean what's the implication of this? Like how do you use to leverage this from a commercial setting to help drive uptake? And what does it mean for you to think about CKD as a future indication or future development opportunity?

I think to the latter part, it derisks a CKD program if we were to choose to go there. But I think it's also fair to say that coming at the CKD market from the avenue of hypertension, we're going to be able to provide value to patients at launch with a hypertension label. We're not -- even though this is really nice data, it doesn't mean we're going to have an indication for the treatment of CKD per se. But again, there's such overlap. I think 2/3 to 3/4 of all CKD patients have uncontrolled or resistant hypertension and 1/4 of hypertension patients have CKD. So these are not independent disease states. These are overlapping. If you talk to any nephrologist who's treating the CKD patient who has uncontrolled resistant hypertension, they will say the #1 goal is to get blood pressure under control because that will confer a benefit and provide kidney protection. And so this data with the label for hypertension, I think, will enable us to go and speak to those physicians who are dealing with uncontrolled and resistant hypertension in a population with CKD, use Lorundrostat for the control of blood pressure, but be able to do so with confidence that they can do it safely and that they are likely to see a benefit on proteinuria. So it actually enables an opportunity to have physicians use Lorundrostat in that setting and do so on the background of an SGLT2. And we know that there are programs under development with ASI and SGLT2 in CKD. We're certainly going to be able to compete within that space for those that are uncontrolled and resistant hypertension.

I see. Okay. Got it. So let's go into the hypertension market [Audio Gap] ask you guys, how do you think payers will manage lower line setting -- so -- and I think maybe in the past when I asked you this question that you felt like the third line is pretty fair game and then you could have access to it. But in the last call, you guys mentioned that the fourth line is the optimal entry point. And then that's where you would go and build, I guess, benefit and establish benefit there before you would move into the third-line setting at some point. So when people hear that, it sounded like there may not be an opportunity to third line because who knows how long that takes for you to establish the benefit. Is there a path to that third line? And what does that look like?

Yes. So as we do market research with physicians, there's high demand in third and fourth line. And as we do research with payers, the access entry point is probably a little bit quicker for fourth line. It doesn't mean that third line is not something that's available. It's a little bit dependent upon plan and upon payer. I think the point I was trying to make is the fourth line, if I combine access and demand, that's the easy entry point. It doesn't mean that third line won't be used. It doesn't mean that physicians won't be prescribing it. It just means the access aperture is going to be a bit broader for the fourth line.

But again, the demand is clearly there. We anticipate third line use. But the fourth line, just based on our current research with both payers and physicians, I think, is where it's really going to take off. And then with that success, build into the third line very quickly, that demand will progressively open up the aperture from an access standpoint.

I see. And what does that time line look like? I mean, is it years? Is it...

No, I think it begins at launch. And again, I hate to use this aperture, but it progressively opens up with that demand. And some of it is based on book of business, commercial, is at Medicare. Some of that is plan specific. But I think both markets that uncontrolled and resistant are going to be in play immediately. I just think that fourth line, there's a bit of a broader open lens.

I see. Okay. Okay. Got it. So basically, optimal from a point that it's easier to access those patients immediately and then -- but it doesn't mean that there's not going to be a third line.

I think you're going to see the drug used in both lines of therapy. I just think the access barrier is going to be a lot lower.

I see. Okay. Okay. Got it. So in that fourth line optimal entry point, what would the step edits look like? Will that include like an MRA or such as that as part of the process. What do the patients have to do to get on [indiscernible]?

Yes. I think there is a growing appreciation. It's already there in the medical community. I think it's growing within the formulary and those are manned by physicians and PharmDs that aldosterone is the emerging target that's not addressed properly right now. That Spironolactone is the only one that's there. And so for the 5 years that I've been involved in Mineralys, the natural question that you just asked is what about MRA, what about Spironolactone step-through? And progressively, the feedback has been, we're not going to make a step through an MRA. A, the use in hypertension is exceptionally low; b, these formulary decision-makers understand the difficulty that patients have in staying on that drug, having a successful outcome with that.

And the titration, do...

Well, I think it's titration -- I think it's not just off-target effects like [indiscernible], but it's also to push dose to get more efficacy, you push the rates of hyperkalemia. And so it's just -- for a lot of reasons, it's just not used. I think what has progressed as our pivotal data read out and as we now have market access team members out in front of the field is that it will be -- for that fourth-line setting, it will be a step through 3 drugs. It will be a look back in their EMR, step through 3 drugs, but kind of indiscriminate what those drugs are. There will just need to be evidence that a patient has a history in the last 6 to 9 to 12 months of being on 3 drugs or more, failing to get to goal, and that is, in essence, the check the box for the step edit.

There's likely to also be a PA to label for I think the vast majority of that will be an electronic PA. So that's -- I think both of those are going to be fairly low hurdles because if we think about the volume of patients, roughly 10 million patients that are going to have within their existing EMR that experience base. It's a quick look back, check, step edit and access to lorundrostat. And I think -- I don't know if this is on your mind, but I think where we've seen baxdrostat price, based on the research we've done, I think that's a reasonable price point that they've identified that fits within that utilization management based on the research that we've done.

Yes. Yes. No, I have some questions on that, too. So how long would that process when you go do a step edit before they can get on lorundrostat?

No, I think it's going to be variable by plan. Yes. I don't know if I'd want to hazard a guess it may be a 30-, 60-day period, but it's going to be variable by the plan.

Yes. I see. Okay. Another key point that I think we discussed before was that the ongoing PBM reforms where the rebates are now being completely passed through to the plan. So it used to be that the PBMs have some financial incentives to use branded medications like lorundrostat or ASI, maybe even ahead of some of these generics or parity to generics because they can have some of the rebates, they can keep some of the rebates. But now that's been passed through and kind of shift some of the incentives away from that. How do you think -- just given that dynamic, how does it affect when you think about getting it on the formulary, thinking about competing with these generics with these payers?

Yes. I think the old model, there were 2 incentives for PBMs. And one was the retention, their portion of the rebate that they retain. But there was -- in fairness to PBMs, there was another incentive, and that was trying to identify good clinical value to their customers ultimately. And so creating access to novel innovations that could help their constituent customers, populations address whatever medical need, in this case, getting their blood pressure under control. So that's always an element of the PBMs within this context. So it's not just give us the rebates, but it is providing good service and good value from a clinical standpoint to their constituents.

I think if we look at the model now, that clinical value piece still sits there as a supposition that if there is true innovation and given the fact that half the patients in the United States cannot get to goal that are treated, that becomes part of that clinical value prop. Now what has shifted is the rebate transparency has pushed that through, but what has emerged for that are the service-based fees as a percentage. So whether it's an admin fee, a data fee, there are new fees that have emerged that are a bit more transparent, but it's kind of from one hand into another hand. So there are several elements from a PBM standpoint that they'll drive value from having a branded asset introduced into a market that's purely generic right now.

I see. And then when we look at PBMs, they often use these preferred and exclusive contracting tactics especially when multiple players come into the market with similar drugs. It just happened, we saw that with the PCSK9, obesity now and also many others. Are you expecting this to be the case for ASIs as you launch lorundrostat with baxdrodstat already out there? And then how are you preparing for this scenario?

Yes. I think we put our market access team in place in Q1 of this year. So we're doing what's called PIE pre-approval information exchange so that these payers are aware of our timing, our clinical value proposition, the unmet need and how we're thinking about positioning lorundrostat, which is in that third line or later setting. To your point, I think payers like to have, from their standpoint, multisource of new innovations like this. So having 2 is kind of an ideal setting for them. I don't know that they necessarily drive and force for a preferred. I think it's more of from a sponsor standpoint, do we want to move to a preferred setting if we want to do that, then there's going to be a cost related to that.

Our going-in position is really going to be more about how do we ensure fair access, parity access, we'd be fine with. We're somewhat interpreting as we make some assumptions about our launch plan that AstraZeneca may come in with a parity kind of position as well as opposed to anybody who wants to move to a one of one, then you're going to have to buy into that preferred state and offer more rebate. So I think it's -- from our standpoint, it's more about let's create profitable access, let's look for parity and then let's create opportunity for physicians and patients to choose.

But going back to my previous question about the PBM reform, do you see because of that instead of shifting away from these PBMs, do you also see that there's a shift in terms of how they're managing it and maybe less use of these preferred exclusive type of contract?

No, I think there's still the opportunity through other rebate structures to create preference if one chose to do that. But again, that becomes -- there's a potential slippery slope with that as far as risking your margin in doing that. And I think our goal, again, is how do we create equitable fair access for when physicians and patients choose lorundrostat and keep it in the parity position. So it is a choice of the physician as opposed to a forced choice from the payer.

I see. Okay. And you guys -- so you mentioned, I think, last time that the sales force usually, you would hire them typically around 90 days before launch. And obviously, you can't just post the position at 90 days before launch because you have to -- there's a whole process of hiring them, making the offer, negotiate background checks, notice periods and stuff like that. How many sales do you foresee needing for that initial launch? And then how soon do you have to really like get the ball rolling on that?

Yes. The actual number, we haven't disclosed yet. And that's predominantly just for a level of competitive insulation. We're just not willing to signal yet to AstraZeneca, who's in the market right now, how we plan on doing our go-to-market model and our sales force size. As I noted, we put our market access team in place in Q1. We've optimized our size of our MSL medical science liaison team in Q2 of this year. We're beginning to put our sales leadership team structure in place right now. And as you know, there's head of sales, the next level and next level of management in sales territories.

We're confident in the timing that we have, the positions that we put in place right now, the physicians we're recruiting for that all of that enables 90 days prior to that PDUFA that we could have the vast majority of our targeted sales force in place in that time frame. And then that gives us time for those reps to get acclimated to their geography, meet their customers, do all the proper training, begin to do some of the disease awareness communication that's allowed pre-approval up to and including compliant communication with the goal ultimately being upon PDUFA that we can quickly pivot to full commercial launch.

Right. Okay. And then Baxfendy recently approved on May 18 for the list price of $900 per month. So this was higher than what we were expecting. I think some of the market were expecting. What is your impression for that price given sort of like the sensitivity around drug pricing at this point? And then how do you -- like have you tested that price range? And how do payers would react to that price?

Yes. I think that, that price fits within the research we've done, the one-on-one dialogues our team is having right now, it's not a specialty tier, which was one of the key points that if the net price for an ASI would have fallen in the specialty tier, then that would have greatly restricted access. This is a non-specialty tier price point just at WACC, let alone what the net would be. And so I think with the positioning of the drug later in treatment, not first line, not even second line, but third line or later with the step edits that I identified earlier, I think that price point, coupled with what will eventually be the rebate percentages fits well within the research that we've seen.

Now, will that be the exact price that we land on? That's part of what we'll continue to analyze through the course of the next 6, 7 months. But I think it was a reasonable price. And I don't think it narrows that 20 million third and fourth-line patients that we've talked about in the past. I think that fits within that population based on the research we've done.

And how have you been hearing how payers are looking at Baxfendy at this point?

It's early days.

Like in your PIE discussion, does it get brought up?

It's very, very early days. Obviously, the price point just got communicated in the last couple of weeks. But I don't know that there's been any surprises. I don't know that there's been any shock around the price point. I don't know that we have seen a great deal to date on the contracting strategy that will be something that will unfold over the next couple of months.

Right. Okay. Got it. So basically still aligns to your -- what you said earlier about the fourth line being the optimal entry for them also at that price point?

I think the payers view this transformative class, and I think that's a fair statement to say. I think they've been impressed with the clinical value proposition. And I think they're viewing both lorundrostat and baxdrostat similarly as it relates to access to fourth line and in some cases, with some payers third line as well.

Okay. Got it. So I want to shift gears to some of the partnership questions and then later on the Baxfendy label. So from a partnership perspective, you guys have been talking about exploring potential partnerships for some time now. Now with the December PDUFA date fast approaching, and there are some key uncertainties and risk. I mean, are there any key uncertainties and risks that are sort of holding things back? I mean I was just kind of looking at the macro environment and how -- potentially how payers are managing this class, maybe you want to see clarity on that. Like from that partnership point for your ongoing discussion with partnerships, are there things that are holding back, do you think?

No. We've shared that we're always open to having dialogues about increasing the value of lorundrostat by definition, Mineralys through partnering, open to the point of acquisition if it made sense. But fundamentally, we've been driving to ensure that we have a successful launch in the United States. I think there -- what I can share within those dialogues with partners, there's an appreciation of the value proposition of lorundrostat, the appreciation for the value of the ASIs as a class and an appreciation for the market size. I don't know that any of the macro elements I would characterize as limiting. I think it boils down to the value proposition at large. And I think like I said, there's a true appreciation for that.

Right. I see. And throughout this year of discussion with strategic do you see -- like how would you characterize sort of that interest level throughout this period of time? Is there -- is it similar since you guys started? Is it becoming -- there's higher interest now or lower interest now?

I think return of large pharma to cardiorenal metabolic. I mean -- so I was the first hire when Mineralys was put together through the licensing of lorundrostat. This was late 2020, early '21. Maybe a handful of pharma were really focused on cardiorenal metabolic. I think today -- and I think part of it is due to the success that Novo and Lilly have generated with the GLP-1s in the anti-obesity space. I think today, the vast majority of pharma have returned to this space and appreciated not only the market opportunity, but the unmet need. You and I have talked in the past. I mean you go -- just go to global -- The Lancet's global burden of disease study, 3 of the top 8 drivers of loss of life or loss of quality of life are kidney disease, stroke and heart disease. And what underpins those 2 are cardiovascular like blood pressure and metabolic like diabetes or obesity underpinning that. So I think there's clearly a return of interest to this space and an appreciation for the significant value opportunity.

I see. Okay. So now with that PDUFA fast approaching and then after a certain time period, there may not be enough time for a partner to come in to kind of properly prepare for lorudrostat's launch or be able to participate in that label discussion. Is there a window that closes for a potential strategic to come in ahead of the PDUFA? Or do you see sort of these ongoing discussions would go past PDUFA?

Yes. I don't -- I appreciate the question. I don't know that I hold that there's a window. I think at any time it could be right for us, it could be right for a partner. That's why -- and I'll pick on the word that you used there properly. I think -- and it goes back to what we did with the proof of concept. I think we properly ran a proof of concept. I think we properly ran a pivotal program that put together a very robust NDA. And last year and into this year, I think we're doing all of the things -- if you were to blind Mineralys and put in any big pharma name, you would see what we're doing to prepare for a successful launch of lorundrostat looks the same, the investments in market access, the investments in medical affairs, the readiness for sales force.

And so all of that supports 2 things. One, us generating value with lorundrostat as Mineralys and they go it alone, but two, enables a partnering or potentially even acquisition at any point because any pharma could look and say, you are doing everything that we would do. And legitimately, that may sound bold for a small biotech, but the team is loaded with experienced commercial med affairs, market access, commercial manufacturing staff. So we're ready that to enable successful launch, again, whether it's in our hands or that of a partner.

Okay. Got it. So let's spend the rest of the time on Baxfendy label after we -- it came out, it looks interesting in a way that we did not see the VAX-24 data in there. or at least the efficacy portion. We saw some safety portion, but not the efficacy. What is your impression of that label? And how do you think lorundrostat can differentiate?

I think it did 2 things. It affirmed some assumptions that we had. So the indication was very straightforward and it's broad, right? So inadequately controlled blood pressure on top of background meds. The outcomes claim as anticipated by the guidance was in there, lowering BP lowers risk of stroke and MI. I think the monitoring was actually a little bit more liberal than I thought it would be. It's established a baseline and then periodically check. It did not delineate time, bring back in 2, 4 weeks. And I would presume that those will be pretty common language within an approved lorundrostat label.

To your point, the VAX-24 is part of safety, but not part of the efficacy. And the BAX-HTN data as published was represented in that label. And that's where I think there becomes the opportunity for differentiation. Specifically, if launch HTN as the base case is the only clinical data set that gets into our Section 14, then we know the absolute and placebo-adjusted change is greater than what was demonstrated with baxdrostat in that study. But advanced-HTN, we think, is a highly informative, very rigorous study that we are going to make arguments for during those negotiations should be a part of the label because it's very informative for the truly confirmed uncontrolled resistant hypertension. That could become part of a differentiation aspect as well.

And there was also a statement saying that there was no clinical benefit established for eGFR less than 45 although the label does not restrict the use of these patients. Do you believe the payers would have some statement for you guys to study these patients?

Yes. We -- so that could also be a point of differentiation. We did Exlore-CKD down to eGFR 30. We made a part of our label application, will be part of our negotiations, whether that's in Section 14 or acknowledged in special populations down to EGFR 30. That said, our market access dialogue hasn't indicated that the payers are going to be looking at an EGFR cutoff specifically.

I see. Okay. Well, fantastic. We're out of time. I've probably gone through like less than half of the questions I prepared for yet. So we got to do it again sometime. Thank you so much. It's been a pleasure hosting you guys again at the GS conference.

Always a pleasure to be here and appreciate the invitation.

Any final remarks?

No, we're -- look, it's been too long. It's been 20, 25 years since there's been true innovation in this space. I think the ASI is the right medicine at the right time. The medical community is keyed up in looking at aldosterone as an untargeted driver of cardiorenal metabolic. I think they're excited about ASIs. We're very excited about the clinical profile that we've developed over the last 5 years and the commercial opportunity to really help improve the lives of millions of patients that I think will engender significant value for shareholders and Mineralys.

Great. Thanks, guys. Thanks, everyone.

From Mineralys, I have here with me today, Jon Congleton. Jon, thanks for joining us. I'm just going to hand it over to Jon for some opening remarks before we dive into some Q&A.

Thanks, Dina. I appreciate it. Appreciate the opportunity to participate in the Bank of America conference. It was a positive conference for us. So Jon Congleton, CEO of Mineralys. We had a very productive 1.5 years, I would say, last year with a lot of data readouts culminating in the submission. We had an earnings call last week announced that in Q1, we had the acceptance of the NDA, significant milestone for Mineralys. It puts us one step closer to getting lorundrostat to patients who fundamentally need this drug. That NDA, very proud of what the team put together, it's very distinct and differentiated data set that is going in front of the FDA for review effectively five clinical trials showing very consistent robust benefit that lorundrostat has on blood pressure, safely predict profile that I think fits easily into the current use case that physicians have for those uncontrolled and resistant -- is that better?

So obviously, only you in the room got the opening preamble. So that data set, to me, is very important because it speaks to the 20 million patients in the United States that are on two or more meds and can I get to goal. For those of you that have met me in the past, you know I started my career as a sales rep in the hypertension space.

And so I saw the great innovation and how transformative that was in the '80s and '90s, but we've blacked innovation, fundamental innovation for 20, 25 years. Aldosterone is the uncovered target that's going to help a significant portion of those 20 million patients get to goal. We think the data set that we have generated to date shows that benefit.

The market research that we do, whether it's with patients or physicians or payers, the demand, the intent to prescribe, the interest, the enablement of access is all there. I think really focusing in on, and we started guiding to this at our earnings call, the resistant hypertension patient population is probably the beachhead. That's the low-hanging fruit.

That's where there's just continuous churn within this marketplace that notes the dissatisfaction with currently available treatments that notes there's still energy and interest in trying to get to goal or get closer to goal. And that's where I think lorundrostat can certainly provide benefit. So this year, with the NDA acceptance, we're continuing to prepare for a successful launch for this molecule. What that means is we've stood up a national account team in Q1.

We're having those pie or those pre-approval information exchange dialogues with the payers as we speak. We've got MSLs out in the field going deeper into the advocacy space. We know baxdrostat has potential FDA action coming up, but I think it's important to realize that while they may have been six months ahead of us, we're not silent in that marketplace. We're having the dialogues with the key constituents, both payers and KOLs are going to be important to really ensure we have a successful uptake of this drug, presuming positive FDA action later this year.

Great. We can dive a little bit more into some of the commercial things you outlined looking ahead to lorundrostat's approval and potential launch. So with lorundrostat being about six months behind baxdrostat's launch, what are you kind of looking to learn from AstraZeneca's launch? Is year one more about establishing product differentiation or just building out marketing awareness for this new approach in the HTN space?

Yes. I think it will be interesting to see the label. It will give us some insight into the FDA, how they view their package. That will be informative for us as we head into our negotiations with the FDA later this year, what studies were included, the indication, how Section 14, which has all the clinical data. And then beyond just the approval, their launch, how they think about pricing, access, go-to-market, all of that will be very informative for us.

I think that creates a bit of an advantage being six months behind us to see all of those moves and then we can kind of have our counter moves that we have in mind relative to that. The first year, I think it's going to be a little bit of both. I think it is going to be about building the awareness around the importance of targeting aldosterone, the use of an ASI relative to that, but also the differentiation between these two molecules, between these two data sets.

Again, I think that data package that we have is going to speak very distinctly to the constituent prescribers within this resistant hypertension space. We know it's partially with cardiologists. That's why we did Advance-HTN. Probably the most challenging study done as far as in a confirmed resistant and uncontrolled hypertension population.

Launch-HTN, the largest ASI hypertension study done to date, we'll speak to primary care prescribers. And things like Explore-CKD will also speak to the nephrologists who are dealing with patients with a lower eGFR with uncontrolled and resistant hypertension that is the #1 target these nephrologists look for to help control CKD, and that is get their blood pressure below or down to goal where it needs to be.

You put some numbers around kind of physicians that are responsible for a certain percentage of third-line prescribing about 60,000 physicians are responsible for about 50% of that third-line HTN prescribing. What is that split between primary care versus specialists? And what role do you see dedicated sales force versus DTC playing?

Yes. It's -- when we think hypertension, we tend to anchor to the 120 million patients that have hypertension in the U.S. alone, and that immediately gives you this view must be a ton of prescribers.

And there are. But when you begin to get further into the lines of treatment, that population narrows. It's a typical pyramid of prescribing. And to your point, we've noted about 60,000 doctors control about half of the prescribing third line and later.

What's interesting about that is they also influence the other half because these are the kind of the top pyramid, they're usually in hypertension centers, whether they're cardiologists or primary care. They're the ones that are driving the volume and they're influencing the other part of the volume.

The split is about 60-40 primary care to cardiologists. It doesn't mean that there won't be nephrologists or even endocrinologists within that mix, but largely, it's 60-40 primary care and cardiology. I think DTC is but a tool to use along this continuum.

I think where I get excited about where we're at in 2027, which could be a potential launch here, is there are technologies digital that enable a company like Mineralys to actually act and be bigger than we are by footprint.

So certainly, we'll have the appropriate sized sales force to affect the behavior of those 60,000 physicians, but we can also use digital nonpersonal powered technology to extend the reach, augment those sales reps, get to wide spaces where we may choose not to have sales reps just as far as discrete uses of capital. DTC, DTP, all of that may play a bit of a mix within that. Part of the goal, again, back to, I think, your question, it's a combination of raising awareness of the role of aldosterone, the need to target aldosterone and the differential story of lorundrostat.

You kind of mentioned that fourth-line setting is where you at least initially see uptake for lorundrostat. Can you just speak to when we could see or when you expect expansion earlier to third line and what the drivers behind that could be?

I think the way we view it and what we hear in the market research we do is at launch, there could be interest. There even could be access. As we talk to payers, it's not just fourth line and only fourth line. There are some payers that see the absolute need of helping their patients get to goal.

Having their constituent they being the payers, the PBMs, having their constituent population to goal as part of their quality scores. So whether it's STAR or HEDIS, we're seeing hypertension and getting those patients to goal is becoming more and more important to payers.

So it's fourth line is kind of the ideal target. Third line, where it really gets more compelling for payers, for prescribers is when there are comorbid conditions. So if you have hypertension, CKD -- that's why we did the Explore-OSA study because there's such an overlap of OSA with hypertension.

So having those more complex patients, having a data set that speaks to that complex patient population is what I think begins to open the third line. But I think also just in due time, that fourth line utilization, having access created, having physicians prescribing is then getting gender utilization earlier in the treatment paradigm because fundamentally, that dysregulated aldosterone doesn't just suddenly appear in a fourth-line resistant hypertension patient population.

Frankly, they probably had it throughout their journey of treatment and are finally getting to a point where they need a very exquisitely targeted aldosterone therapy. So getting earlier in the lines of treatment is part of the story that lorundrostat will have over its life.

And this is a space where kind of the hypertension guidelines pretty clear and drive a lot of the prescribing patterns. So at what point do you kind of see the hypertension guidelines begin to incorporate the data from the launch in advance trials? And could it happen before launch? What are your expectations kind of on timing for that?

Yes. We've been meeting with various constituent bodies, meeting with KOLs who are part of those committees, making sure they're aware of lorundrostat, our data set. The guidelines used to be fairly rigid. The guideline committees used to be fairly rigid as far as how frequently they would update the guidelines.

I think they're acknowledging now that were in a bit of a renaissance with new technology, new therapeutics coming and have become less rich. In other words, when there's innovations, they want to make sure that they're guiding their constituents on how to think about utilizing those. I don't know the specific timing of it.

I do know that, that's been something top of mind for us going back five years when we began meeting with Steve Nissen and Luke Laffin at the Cleveland Clinic. That was why we did the Advance-HTN study. Fundamentally, we wanted to go to the guideline committees with the absolute best form of evidence for inclusion. And Advance-HTN, frankly, is probably going to be a bit of a lift for baxdrostat as a class because we anticipate the class will be treated fairly similarly by those guidelines, but we definitely have the data set that will be most informative for those guideline committees and how to think about utilizing lorundrostat and ASIs in third and fourth.

Mindful, you can't comment necessarily on label, but -- and you touched upon this a little bit before, but what are your expectations -- or sorry, what are the most important like label variables in your view? How are you thinking about -- you mentioned comorbidities, the data you have being an important value proposition? And how do you think the Explore-CKD data could be kind of reflected in the label? And maybe your thoughts on doses, like how those would be? Is the 25-milligram dose going to be included in the label?

Yes. I think it's back to one of your earlier questions, I think seeing the -- presuming the positive action with baxdrostat, seeing their label is going to give us a little bit of insight into how the agency is looking at. I think our working assumption is right now, both of these drugs will have near identical indication.

So treatment for uncontrolled blood pressure or inadequately controlled blood pressure on top of background meds. They won't prescribe the number of meds. It won't prescribe resistant hypertension only. It will just be fairly broad. And that's consistent with what the FDA has talked to us about for five years.

So I think the indications will be quite similar. I think the Section 14 is where you'll potentially see some distinction. [ Bax-H10 ] is certainly going to be part of that approval, what role does Bax24 have, other data they have, how does that get incorporated. From our standpoint, again, it's why we did a very distinct clinical development program for lorundrostat.

I would anticipate both launch and advance being included in Section 14. Explore-CKD, the blood pressure reduction, which is, again, a very important thing to be able to convey the nephrologist in a lower eGFR population, you can safely use this drug and see blood pressure reduction. We did include both 25 and 50 milligrams in the NDA submission.

Again, it will be part of label negotiations with the FDA, that we would anticipate both doses being available. We think that's important because when you get to patients that are -- have more complicated uncontrolled and resistant hypertension, such as those with lower eGFR, you've got to be mindful of the safety profile, specifically for the on-target adverse events like hyperkalemia, hyponatremia change in eGFR.

And so having a lower dose, we think, was important. It's why we tested that. And so I think fundamentally, the distinctions that are seen with the clinical development programs have the potential to be seen and revealed within the distinct labels between these two. But again, time will tell and that will be part of the negotiations that we'll have with the agency later this year.

You mentioned hyperkalemia. What -- do you think there's going to be a need for physician monitoring of potassium levels? If so, how frequently?

Yes. I think the beauty of the ASIs is they fit within an existing treatment paradigm that physicians already have. And that's driven by ACE inhibitors and ARBs. They have a very similar profile. These are RAS inhibitors. At the end of the day, ASIs are part of that RAS system.

And you see a very similar construct of response that fits the current use case. And what does that mean? That means currently, when a physician prescribes an ACE or an ARB, they get a blood panel, they do blood pressure draw, they start them on an ACE and ARB and bring that patient back in two to four weeks.

Again, they get a blood draw, they look at potassium, they look at sodium, they look at change in eGFR and then they get a blood pressure measurement. The ACE inhibitors and ARBs tend to have that profile shift within about two to four weeks and then it stabilizes. What we've seen with lorundrostat is a very similar construct. Within two to four weeks, you see 70% or so of the blood pressure reduction.

You see any increase in potassium, decrease in sodium and change in eGFR occur within that two- to four-week period and then tends to stabilize. And so that fits very nicely into the existing treatment paradigm that physicians have. And I think we're going to see that reflected in the label as well. So the labels for the ACEs and ARBs follow that construct, get a blood panel, measure blood pressure, bring them back in two to four weeks, do the same and then monitor periodic. So I would anticipate that's what the label will guide. And I would anticipate that's likely to be a class effect. I don't think there'll be a distinction between the two.

Maybe turning to the OUS opportunity. How are you thinking about the relative importance of the OUS market versus the U.S. market? And OUS, what in your view are the key geographies?

Yes. The -- our goal ultimately, purpose we talk about in mineralys a lot is more better days. Three simple words that are fundamentally linked to what better control of blood pressure means for patients. We know it's frankly why we'll get an outcomes claim if we get approved because there's such strong linkage between lower [ NDP ] and better long-term outcomes.

Our goal within that is to get this drug to as many appropriate patients as we can. And that's not just in the United States that includes outside of the United States. I've been clear in the past that Mineralys will not be the one that will introduce lorundrostat outside of the United States, but we'll do that through partners.

We haven't guided to specific targets by region or by country. But it is important that we create access for patients, create partnerships that may be global in nature. That's where our main focus has been as opposed to regional, but to ensure that we get this drug to as many appropriate patients.

Can you just give us the latest on your thoughts on the OUS regulatory submission? Is it gated by partnership discussions? What's kind of the time line there? Just kind of latest update there?

Yes. I don't know that it's gated by partnering. I think we have the appropriate data set in hand. Certainly, for Europe, Japan, we may need to build some additional in-population data -- but even that, I think it's becoming more streamlined. We haven't given specific guidance on the regulatory. Our main focus right now has been on the U.S. on working with the FDA to get lorundrostat approved in the United States and preparing from a commercial launch standpoint.

And on that commercial launch, maybe on thinking about the size of the field force, gearing up to invest in that. When do you kind of plan to update the Street on sales and marketing costs to support your U.S. launch? What are some of the pushes and pulls relative to comp launches that historically might have involved a very large 700-person sales force team?

Yes. We haven't guided on the size of the team yet or specifics around our go-to-market model. Part of that is just, frankly, a little bit of competitive protection so that we don't reveal our strategy too soon. We may do that in future guidance. To date, we haven't done that. If we feel it's appropriate, we want to -- I think we've always tried to be as transparent as we can with investors, but we also need to be mindful of the competitive nature of the market we're going into.

Maybe turning to pipeline and label expansion opportunities here. For OSA, you shared some data earlier this year. Just maybe curious your kind of thoughts on that data. Did the Phase II study design kind of limit the lower ability to show benefit. Curious your thoughts there. And where does OSA kind of go from here? What's the path forward?

Yes. I think it's important, why do we do that study? We did that study because there's -- when you get to a resistant hypertension patient population, you have a convergence of a lot of factors. It's not the patients just in isolation have resistant hypertension.

I think about 85% of OSA patients have resistant hypertension. There's massive overlap with obesity within this population. And we saw that within the baseline characteristics of this study. I think the BMI average was somewhere 37, 38.

A significant portion were morbidly obese with a BMI over 40 the AHI, which is the index of how severe your OSA is, is 48. Severe OSA begins at 30. That means they had 48 apnea, hypopnea events per hour, and they were resistant hypertension. This study was intended to be a quick 4-week crossover design study that was very informative for us. Again, we saw a very consistent reduction in blood pressure that we've seen -- had seen in 5 studies or 4 studies preceding that. So while we didn't see a signal in OSA, I don't know that it means the pursuit of that is done because, frankly, future studies we're going to do, we're going to see that overlap.

And we'll be able to continue to dig into that, see if with longer time, maybe in a less effective population that, that translates not only into a benefit on BP reduction, but potentially on the symptoms of OSA. But fundamentally, and make no mistake, lowering the blood pressure is what's improving the cardiovascular risk for this population. There have been countless studies, whether it's with CPAP, other agents that lower AHI, but have not impacted blood pressure. And so that does not change their cardiovascular risk profile. It's having that control of BP that fundamentally translates into that reduction in CV risk.

And so that's why I think there's a lot of positive data that comes out of the study. It was not part of the NDA submission, but by virtue of if we get approved for the reduction of blood pressure, we're going to be able to use that study as part of our communication, whether it's promotion or MedCom because it's all about lowering BP in these more complicated patients.

And you spoke a little bit about this, but do these data impact your view on probably a success for other profiling studies or other adjacencies? Yes, heart failure, CKD, kind of those other opportunities for lorundrostat?

No, I don't think it does. I mean, certainly, CKD, Explore-CKD derisk that. In fact, it gave us a data set that would enable us to go in and speak to physicians who are treating patients with uncontrolled or resistant hypertension and CKD, lower eGFR. And that's why in that study, we had -- the key exploratory was reduction in uACR. And just in 4 weeks, we saw a 30% reduction in uACR.

So clearly, we know there's a benefit with lorundrostat on BP, on kidney function. And if you look at where the medical community is going as far as how they think about kidney disease and heart disease and heart failure, they're not in these silos or isolated syndromes, which is, I think, where medical community was 15, 20 years ago. They're now realizing and they're even doing the CKM initiative that these are all interrelated. You go to a heart meeting, you're going to hear about kidney.

You go to a kidney meeting, you're going to hear about the heart. So aldosterone sits at the nexus of that. And I think we've progressively derisked obviously, lorundrostat for blood pressure benefit, but even beyond that, what it can do for kidney, for heart, likely for stroke as well. So I think hypertension is the beginning of the story, not the end. And I think where we've taken this molecule to date, derisk the profile of it opens up a lot of opportunities for further clinical...

And on that further clinical development, should we kind of be thinking about these studies or how you're going to pursue these indications in the future? Is it about indication expansion versus label boosting?

I think maybe a little bit of both. It's part of the partnering dialogue as well. It's not -- partnering is not just about the commercial. It's not just about promotion on the U.S. or ex U.S., but it's also about how we continue to expand the value of lorundrostat in these other indications. If I look back at what we've done to date, and again, that's why we did very distinct studies, they really bolstered the hypertension profile itself -- because, again, it's -- hypertension is not in isolation. It's driving these other conditions, showing a benefit on BP in these other conditions builds that value prop, but it also is about indication expansion and just growing that...

And how important are -- I know you guys haven't put out kind of a peak sales opportunity or anything there, but how important do you view these comorbidities to its lorundrostat's multibillion peak sales opportunity?

I think it's one, bolstering the use case for hypertension itself. Again, as we go out and speak to physicians and ask what attributes matter to you, we see reflected back that complexity that they're dealing with.

And so having data that speaks to not only blood pressure, only safety, but what's happening with the kidney, can I use this for the comorbid OSA patient? All of that takes us deeper into that resistant and eventually uncontrolled resistant hypertension population. So the penetration of lorundrostat into the use for that uncontrolled and resistant hypertension. But then I think it also builds into other categories, kind of the end of the journey. So CKD, heart failure, heart disease.

And could you discuss where the company is at from a financial standpoint, kind of cash runway and maybe the importance of a partnership to extend cash runway and where that kind of fits into yes, your expectations of kind of gearing up to support the launch?

Our Q1 earnings call, we noted we have about $646 million in cash, cash equivalents and investments. That takes us into 2028. That includes ongoing clinical development, corporate needs that obviously includes presumed commercial launch on successful FDA action. None of that is dependent upon any kind of partnering capital inflow. So that's an alternative that we continue to evaluate, but we're very comfortable with our cash situation right now and how it covers us into 2028.

Great. Thank you so much, Jon. I appreciate you being with us here today.

Yes, happy to. Thank you.

Welcome to the Mineralys Therapeutics First Quarter 2026 Conference Call. It is now my pleasure to introduce your host, Dan Ferry of Life Science Advisors. Please go ahead, sir.

Thank you. I would like to welcome everyone joining us today for our first quarter 2026 conference call. This afternoon, after the close of market trading, we issued a press release providing our first quarter 2026 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 up 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, May 6, 2026. 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 first quarter 2026 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 first quarter financial results before we open up the call for your questions.

Our NDA acceptance in the first quarter has been the culmination of a massive effort by our team and our mission to provide more healthy days to patients with cardiovascular disease. From an operational perspective, we're focused on preparing lorundrostat for a successful launch in the United States, while we continue to evaluate partnering opportunities and consider the next steps in the clinical development of lorundrostat.

During the first quarter, the FDA accepted the NDA for lorundrostat for the treatment of adult patients with hypertension in combination with other antihypertensive drugs and assigned a PDUFA target date of December 22, 2026. This represents a significant regulatory milestone for lorundrostat that moves us meaningfully closer to our goal of delivering a potentially best-in-class therapy to patients with uncontrolled or resistant hypertension.

The NDA is supported by a comprehensive clinical data package, including positive results from the Launch-HTN and Advance-HTN pivotal trials, Transform-HTN, our open-label extension trial and the proof-of-concept trials, Target-HTN and Explore-CKD. Collectively, these 5 trials demonstrated that lorundrostat delivers clinically meaningful reductions in blood pressure, is well tolerated and maintains a durable response across diverse patient populations.

We believe this data package supports the potential for lorundrostat to be included in prescribing guidelines, the economic value of lorundrostat to the health care system and lorundrostat as a differentiated novel therapy. Uncontrolled and resistant hypertension continue to represent areas of significant unmet medical need, affecting over 20 million people in the United States and contributing significantly to cardiorenal complications. Aldosterone dysregulation often plays an important role in resistant hypertension, where patients on 3 or more antihypertensive medications fail to achieve their blood pressure goal. The launch of lorundrostat, if approved, will be initially focused on this population with the highest need.

Our ongoing market research highlights the following 3 key factors: one, prescribers prioritize magnitude and consistency of blood pressure reduction and have stated a consistent willingness to prescribe lorundrostat in the fourth line. Two, payers recognize the high-risk nature of patients whose hypertension is uncontrolled on 3 or more medications and have expressed a willingness to provide coverage for lorundrostat. Three, patients are seeking meaningful and sustained blood pressure reductions that are tolerable and simple to integrate into their daily lives. They're very receptive to novel agents like lorundrostat that may help them achieve their goal.

As we move towards our PDUFA target date, our operational focus will continue to be on preparing lorundrostat for commercial success. Our teams are working on early market access planning and payer engagement to ensure the value proposition of lorundrostat is clearly understood.

In parallel, we continue to invest in physician advocacy with our medical communications capabilities, including broader education of the unmet need in uncontrolled or resistant hypertension through peer-reviewed publications, increased participation in scientific meetings and the continued build-out of our field-based medical science liaison team. We are also expanding our sales and marketing capabilities to ready lorundrostat for success. Together, these activities are intended to support awareness of the clinical profile and position lorundrostat for a potential commercial launch.

We continue to evaluate partnering opportunities and engage in strategic discussions. The right partner could provide enhanced value and enable us to reach more patients who could benefit from lorundrostat. Our focus on preparing for a strong commercial launch is invaluable to potential business development partners.

I will now turn the call over to Adam to review our financial results for the first quarter 2026.

Thank you, Jon. Good afternoon, everyone. Today, I will discuss select portions of our first quarter 2026 financial results. Additional details can be found in our Form 10-Q, which will be filed with the SEC today.

We ended the quarter with cash, cash equivalents and investments of $646.1 million as of March 31, 2026, compared to $656.6 million as of December 31, 2025. 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 March 31, 2026, were $24.4 million compared to $37.9 million for the quarter ended March 31, 2025. The decrease in R&D expenses was primarily driven by a $15.5 million reduction in preclinical and clinical costs following the conclusion of our lorundrostat pivotal program in the second quarter of 2025. This decrease was partially offset by $1.1 million of increased clinical supply, manufacturing and regulatory costs and $0.8 million of increased personnel-related expenses resulting from headcount growth and increased compensation.

G&A expenses were $21 million for the quarter ended March 31, 2026, compared to $6.6 million for the quarter ended March 31, 2025. The increase in G&A expenses was primarily driven by $7.9 million of higher professional fees, $6.1 million of increased personnel-related expenses resulting from headcount growth and increased compensation and $0.4 million from other general and administrative expenses.

Total other income net was $6 million for the quarter ended March 31, 2026, compared to $2.2 million for the quarter ended March 31, 2025. The increase reflects higher interest earned on investments in our money market funds and U.S. treasuries due to higher average cash balances invested during the quarter.

Net loss was $39.3 million for the quarter ended March 31, 2026, compared to $42.2 million for the quarter ended March 31, 2025. The decrease was primarily attributable to the factors impacting our expenses that I just described.

With that, I will ask the operator to open the call for questions. Operator?

[Operator Instructions] Our first question comes from Michael DiFiore with Evercore.

Two for me. Number one, in a scenario where Mineralys launches lorundrostat itself without a partner, will you conduct any more significant R&D activity or business development? Or will you preserve funds just to support the launch and focus on the launch? And separately, as you near the day 120 safety update, it may have already passed, I'm not sure, can you comment on whether safety remains consistent with the past and whether there's updated plans to publish data from the OLE?

Yes, Mike, thanks for the questions. To the first one, in the event that we launch, we, from the beginning, have been focused on how do we build value with lorundrostat, how do we do that by extension for Mineralys. We have built this organization from the beginning. I think about our clinical development program with an eye towards how do we generate the greatest value from a commercial standpoint launching, whether it's on our own with a partner or through someone else.

And so I think it's fair to say we're going to continue to look at ways that we increase value for lorundrostat and Mineralys. If you think about the development program to date, we've done that. Launch-HTN, obviously, spoke to the real-world population. Advance-HTN stands out on its own because it's a very distinct complicated population that no one else has studied with an ASI. Explore-CKD provides information for prescribers looking at the complexity of resistant hypertension in nephropathy or CKD.

So we've always had an eye towards meeting the physicians where they are, what they need with lorundrostat and building the appropriate data around that. So we'll continue to look at opportunities to build value from a clinical development perspective. And we'll continue to look at opportunities to expand the value of lorundrostat through business development.

To your second question around the 120-day safety mark, we continue to be very confident in the safety profile of lorundrostat. The Transform-HTN trial or open-label extension continues to collect that data. We think lorundrostat is well characterized from a durable effect and safety and tolerability profile perspective. And as we've noted in the past, we'll be looking to get that long-term data published in due course.

Our next question comes from Richard Law with Goldman Sachs.

A couple of questions from me. Do you get a sense that you need to compete with AZ on preferred or exclusive access with payers based on some of the discussions that you're having? And also, what is your confidence level on getting access to that 3L setting compared to fourth and the fifth L setting? Is your 3L strategy based on a broader use? Or is it more on the smaller niche population? And then I have a follow-up question.

Yes, Rich, thanks for the questions. As we've talked about in the past, our clinical development program looked at that third line or later opportunity, both Advance and Launch looked at that population failing to get to go on 2 or more because I think that's where significant need exists. I think that's where an ASI can add significant value. From a market standpoint, in at launch, we think the focus will be fourth line. I'll have Eric opine on some of the feedback we've gotten from payers to date. But clearly, the -- it's our feeling that, that fourth-line setting resistant hypertension, payers appreciate the risk that these patients are under and the lack of satisfactory alternatives that are currently available relative to what lorundrostat has shown in our clinical program.

But Eric, do you want to add some? Yes, Richard. So it's all about sequencing, Richard, so that fourth line as the entry point. But obviously, there is a need for those comorbid patients that are third-line patients. So the opportunity will be to gain that experience, gain that confidence and then make that transition to the third line using that comorbid condition as a bridge. And this has been well vetted with payers in research and advisory boards and as our team is now out there engaging payers with our account executives.

You also asked about whether we're going to try to position ourselves in a different way than baxdrostat. Obviously, there's an opportunity for both ASIs and having parity access is something that's a focus for us.

I see. Got it. And then a follow-up. So we heard that AZ been saying that bax can potentially achieve like $10 billion peak if we can succeed in other indications beyond hypertension and CKD that they're developing. And I also remember, Jon, I think you mentioned that when you think of a partner, an ideal partner would be the one who would recognize lorundrostat's potential. So when I hear that, I think you meant that the potential beyond hypertension.

So in your discussion with potential partners, how many of them like recognize the value of lorundrostat outside hypertension? And what are these like indications that you believe that partners are bullish on and or the ones that they're not bullish on and based on the unmet need of the drug mechanism?

Yes. Thanks, Rich. As we noted before and made in the comments, our prepared remarks, there are 20 million patients that are struggling to get to goal on 2 or more meds right now. We know the clear linkage of uncontrolled or resistant hypertension to poor outcomes, whether they're cardiovascular or renal. I think at this stage that we can clearly say that what lorundrostat has demonstrated in reducing blood pressure that, that blood pressure reduction is a clear surrogate for what we could expect as far as a reduction in cardiovascular risk.

So I'm not surprised by AstraZeneca's bullish position on baxdrostat. I would say we've shared that given the fact that just in the United States alone, there are 20 million patients at risk. We talked in the past about having a partner that is more global in nature and has a holistic view of this asset. I don't think that view has changed. I can't really opine on how some of those discussions have looked at different indications. But clearly, we know that aldosterone is going to be a key target for the next several years into the 2030s as it relates to not only hypertension but the related comorbidities.

Our next question comes from Seamus Fernandez with Guggenheim Partners.

So I guess I'll address the -- I'm going to ask you to address the elephant in the room, which is you guys have been talking about potential partnering for quite some time. You've had the data and now you've had the NDA sort of firmly established in terms of the PDUFA date for some time. What is it that you're looking for at this point in a potential partner that perhaps you're seeking but hasn't quite matched up? Or should we anticipate that you are in active discussions along those lines? I think we're all just trying to kind of metric what is the timing for either selection of a partner or that go-it-alone -- a potential go-it-alone strategy in the U.S.

Yes, Seamus, I appreciate the question. And as we've said in the past, we're interested in finding the right partner. In response to Rich's question, I talked about the global nature of that. We're routinely evaluating those partnering opportunities. As you can imagine, and I think appreciate we're not in a position to really provide color or specifics around the level of dialogue, the timing, the structure, but it's something that we're mindful of.

We have, as noted, continue to focus on how do we build value going forward. And that's why operationally, we're focused on commercial readiness for this asset. I think it's an important part of those partnering dialogues. But clearly, looking for a partner to build on that value continues to be something we're focused on.

Great. And maybe if I can just ask one follow-up question. As you kind of look at the sort of opportunities to partner your asset with other mechanisms specifically, what would you say are kind of the core mechanisms that you're particularly excited? We've got a whole host of new cardiovascular mechanisms that are advancing and potentially looking to emerge outside of hypertension. So just -- which would you say would be particularly exciting from your perspective to partner with lorundrostat?

Yes, Seamus, it's a great question. I think what's key as an opportunity for Mineralys is we have the core foundational molecule, and that's being lorundrostat as an ASI, given the nature of aldosterone to be a driver of not only hypertension, which is the beginning point of all of these other cardiorenal metabolic disorders, but also just the role that aldosterone plays in CKD and heart failure and other disorders. So I think it begins with the fact that we've got really the core foundational molecule there. There are other mechanisms.

Certainly, the SGLT2s are what our competitors are looking at. I think the fact that dapagliflozin is going generic or is generic at this point, given the data that we've generated to date within our pivotal studies, but specifically Explore-CKD, I think gives us an entree to put lorundrostat forward in a hypertensive nephropathy or CKD population. But there are other mechanisms that we're looking at from a cardiorenal standpoint. We're not in a position right now to opine on those. But I would come back to the fact that we've got the core product that really addresses the key driver of pathology, and that's lorundrostat.

Our next question comes from Jason Gerberry with Bank of America.

As you guys are doing a lot of your prelaunch activities, how are you thinking about like the physician segments that you think are going to be the most likely to drive early adoption, especially in that fourth-line setting, where it sounds like maybe you won't be focusing on doctors that maybe focus on comorbidities like CKD, but maybe more cardiology-driven hypertension? So just wondering if you can kind of discuss maybe some of the learnings from the prelaunch activities and how you're thinking about sort of the early adopter.

Yes, Jason, thanks for the call. I would say that we've been thinking about this going back 3, 4 years when we framed the pivotal program for lorundrostat. Clearly, there's a primary care portion of the audience that is key prescribers in fourth line. They would be part of a launch target, but cardiologists as well, and that's why Advance-HTN is such a critical differentiating piece of our data story.

Now these are the patients that a cardiologist is truly seeing. They're maximized with treatment. They've tried various alternatives and still cannot get to goal. That was the test that Advance-HTN put lorundrostat through and lorundrostat came through with flying colors. And that is a key and distinct data set that AstraZeneca, frankly, does not have. And so the cardiologist will certainly be a part of that target-based nephrology as well. We know that nephrologists deal with uncontrolled and resistant hypertension with comorbid CKD.

And as we speak to those nephrologists, the #1 goal for them to try to arrest the progression of their kidney disease is to get their blood pressure to goal. And so I think we've been thinking about the target population, thinking about the prescribers and the use cases they have -- and I think that's why we've built out a very distinct and diverse data set that's going to provide information about how to use lorundrostat, where to use lorundrostat and the expected benefits they can see in the blood pressure control and beyond such as proteinuria.

And as a follow-up, is there any 1 or 2 things you'll be looking at in the first 3 to 6 months of your competitors' launch that may alter your go-to-market strategy?

I don't know if I would say it will alter it. Certainly, it will be informative, but we've got a view of the data package we have. Eric and his team have done a really nice job of identifying where the unmet need is, who the key prescribers are, where that beachhead indication is for fourth line and what's important to them in prescribing. And so we'll obviously be looking at AstraZeneca's launch, and we anticipate it's going to be a successful launch given the significant unmet need here and the lack of innovation in the last 20-plus years.

But given the data that we've generated and specifically speaking to the different prescribers that you -- the first part of your question alluded to, I think we're very confident in our ability to tap into that, assuming approval and launch very quickly after that.

Our next question comes from Annabel Samimy with Stifel.

So I'd love for you to just talk about who you might think might be driving a process of guideline changes that would position the new ASI class as the next drug to try after third-line agents have failed. You have just a tremendous amount of data across the spectrum of uncontrolled and resistant patients as well as safety in CKD and OSA. Like how important is it to have that wealth of data to drive those conversations? Or do you think that it's the first to market that drives the conversations? Just want to understand the mechanics behind that.

Yes, Annabel, thanks for the question. I think it's safe to say that we've been interacting with those physicians that are part of the guideline committees, appropriately sharing the information that we have. To your point, and again, it's -- it's something we contemplated 3 years ago, and that's why we work with the Cleveland Clinic and Steve Nissen and Luke Laffin with Advance-HTN because we knew there had been a lack of innovation in this space. This is a heavily genericized space and the guidelines would be a critical component.

Advance-HTN becomes that study that addresses all of the questions the guideline committees are going to have about, is it apparent or is it truly confirmed hypertension. That data set, I think it's going to be an instrumental component of our argumentation for inclusion in the guidelines. Launch-HTN is an important part as well. I don't want to dismiss Launch-HTN because it speaks to the primary care physicians. Explore-CKD, Explore-OSA, as you alluded to, each of those provides additional data that's informative that speaks to the unique complexities, particularly of the resistant hypertension population. So from that standpoint, we're in front of the right physicians who are part of those guideline committees, and we have the right data and data set with lorundrostat to make a compelling argument.

And if I could just follow on, on the physician segmentation that you're thinking about. Given the launch trial and the fact that primary care is a big prescriber of hypertensive agents, do you expect the focus to be cardiologists, nephrologists and hope for trickle down into primary care? Or do you expect to, I guess, include high prescribing primary care physicians within that first set of physician targeting?

Yes. I'll have Eric add some additional color here. I don't know that our view has changed. We're continuing to narrow in on those prescribers that control approximately 50% of that third and fourth line, predominantly fourth line. And within that, there are primary care as well as specialists. But Eric, you can add some more to that.

Yes. No. Well said, Jon. So cardiologists, nephrologists, but there are primary care physicians that function very well within this fourth-line state. So they're actively prescribing. We've looked at the segmentation. We looked at the [ deciling ], and there will be primary care that's included in that initial go-to-market strategy.

Our next question comes from Mohit Bansal with Wells Fargo.

So one question I have is regarding differentiation. So do you expect to see any kind of differentiation when it comes to labeling between lorundrostat and the competitor here based on market -- your market research, like what feedback are you getting from physicians that they see any differentiation between these molecules?

Yes. Mohit, thanks for the question. To the first part on the label, I think there'll be a level of uniformity, certainly within the indication. But I'll step back to a point that I've been making here. There's a distinct difference between the data sets that we generated with lorundrostat and baxdrostat. Certainly, Launch-HTN is speaking to the real-world audience. But again, Advance-HTN, I don't want to be redundant here, but it's a very distinct and differentiated data set that really provides information to cardiologists specifically who are dealing with these very difficult confirmed hypertension case patients.

And then Explore-CKD. We know that proteinuria and having a benefit on proteinuria is a key attribute in physicians' minds when they think about an antihypertensive and how they view its utilization. Certainly, for nephrologists, having a benefit on proteinuria, it's a key signal or surrogate, if you will, for slowing renal progression.

Launch HTN, Advance-HTN and Explore-CKD as well as our long-term open-label extension Transform-HTN were all part of our submission in the NDA. Now what language, what portions of those studies get into the actual label, that will be part of negotiations with the FDA. But certainly, having that data, whether within label for promotion or through medical information, I think it's going to be very instructive and informative for those distinct physician population prescribers.

Got it. And the physician feedback I mean the second part?

The physician feedback has been very robust. Eric, do you want to.

Yes. So the 2 things I'll highlight, Mohit, is, number one, the absolute systolic blood pressure reduction. That is really what shines from a physician perspective, that 19-millimeter that we demonstrated in launch, but also the diversity and the well representation of our trial populations, and I'll call out the black African-American populations between 28% and over 50% of our patients depending upon the trial. Physicians really appreciate the inclusivity of our populations.

Our next question comes from Matthew Caufield with H.C. Wainwright.

So we covered a couple of my questions. But I think overall, the sense is that baxdrostat's possible approval midyear helps the overall ASI receptivity and awareness just at a high level. Do you anticipate there being any headwinds with that approval? Or do you see it only as a positive as we get closer to the December PDUFA?

I think there's certainly a significant opportunity within this space. As I noted previously, Matt, the lack of innovation, I think, speaks to the high interest from physicians to have a novel agent or a novel class of agents. So I do think there is an opportunity to see this market opportunity grow as AstraZeneca launches 6 to 7 months in advance of a potential approval for lorundrostat.

I think it's important to highlight that we will have voice in the market during that 6- to 7-month period. We've had national account executives in front of payers going back to quarter 1. We have our MSL team in place going out building advocacy within those top tier and regional tier KOLs. And so I think it's really both companies out there progressively talking about the role of aldosterone and the importance of addressing it within ASI that grows this market opportunity.

And I think it's important to realize this is -- whether you look at it from a revenue projection that AZ guided to, whether you look at it from the 20 million patients that we target, this is a massive market opportunity that is sitting on significant interest in the novelty of this class of drugs. And so I think it's a net positive.

Our next question comes from Rami Katkhuda with LifeSci Capital.

I guess given that ASTRO will likely set the initial pricing benchmark for the ASI class with baxdrostat, I guess, are there any other market access levers that you can pull to differentiate lorundrostat? And then maybe secondly, I know there's not many recent cardiovascular launches, but what do you view as the most relevant commercial analog for lorundrostat at this point?

Yes, Rami, thanks for the questions. Relative to AZ, certainly, presuming approval, they'll be setting the initial price point. I've been asked, is that an anchor point. I think it's a guiding point. I have no idea where they're going to price it at this stage. Clearly, they're bullish on the revenue opportunity, but it will be informative for us. I think going back to the differentiation and the payer discussions, we're seeing that right now as we have dialogues with payers, the distinction of the data set, whether it's Advance-HTN, which I've commented on previously in a very distinct population that AstraZeneca can't speak to, whether it's the Black African-American population that Eric just alluded to, we know that's a critical high-risk population.

We believe we have the data set that's going to be very informative for those payers from an access standpoint. And I think the feedback that we've gotten from payers to date is they're open and willing to create access in this fourth-line setting and potentially in due course, third line. And they're also interested in having 2 assets to evaluate. So it's not as if from our perspective, baxdrostat is going to launch and secure all access from a payer standpoint. Rami, can you comment -- the second question was commercial analogs. Is that right?

Exactly, yes.

Yes. I think it's a fair question. It's hard to answer because there just hasn't been a lot of innovation within the cardiovascular space for quite some time. I think an interesting analog for me, it's a gen med category. It's not cardiovascular, probably migraine with the gepants, the orals. And so I think when you come out with something that's truly novel from a clinical profile standpoint, match that to a market with significant unmet need, you can see significant commercial opportunity. And so I think that's an informative analog that we think about as we prepare the commercialization of lorundrostat.

Our next question is from Tara Bancroft with TD Cowen.

So I just have a follow-up from Mohit's question before that was helpful to hear about label differentiation. But maybe can you tell us more about how you'll react to WACC pricing, especially when it comes to your pricing strategy? And I know how important access is to physicians, as you've been saying, but we're curious about the strategy that you're thinking there? Like could you launch with a lower WACC price? Or should we assume rebates will be the primary mechanism to drive access or something else? Just more thoughts there would be really helpful.

Yes. Tara, I appreciate the question. And I hope you appreciate that it's really early to opine too much on that. We'll see where AstraZeneca comes in with pricing. We've guided in the past that thinking about Farxiga, Jardiance WACC or list price is probably a good barometer to work from. We'll see where they go from a pricing standpoint. We'll evaluate what makes sense for lorundrostat. The key for us at the end of the day is to ensure that patients that physicians believe could benefit from lorundrostat get access to that. And there are a lot of different levers we could pull from contracting to what we do with our patient assistance program. But I would say it's too early to give you maybe the level of color that your question would require.

Okay. Great. That makes sense. I guess maybe then I can ask a different question. So as we are looking at this launch as a proxy to lorundrostat, can you maybe talk about how you would think about cadence of that launch? It's hard without recent hypertension proxies to look at, but do you expect that there would be initial bolus of patients within the hypertension population or anything like that, that could help us understand what a good first couple of quarters could potentially look like?

Yes. I appreciate the question again. I think the best proxy, and we have this in our non-con deck that's on our website. The best proxy is if you look at the turnover within this space right now. So what we have in our slide deck is 2024 IQVIA data that shows third line or later, there are about 8.8 million patients that are turning over trying new medications. And that's in the absence of any innovation, right? That's with existing treatments that have been available for 20-plus years.

And so as an old marketer to me, what that tells me is that there's a market that has a great deal of dissatisfaction. Physicians that haven't given up, they continue to trial their existing medications, helping patients get to goal. So there's, I think, significant pent-up demand. There's significant focus and appreciation of the risk these patients are under if they don't get to goal. And so fundamentally, that to me is a bit of a proxy.

Now how that translates to baxdrostat's launch quarter-over-quarter, I don't know that I can opine on that. I just know looking at fairly recent data from 2024, there's a lot of movement within this marketplace, and I think that creates opportunities for novel agents like lorundrostat.

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

Thank you, Rob. In closing, we remain encouraged by the FDA acceptance of our NDA based on a strong clinical data package that I've just spoken about through the question and answers. From an operational perspective, we're focused on executing on our pre-commercial readiness strategy, while in parallel evaluating partnering opportunities and considering the next steps in the clinical development of lorundrostat. We believe Mineralys is entering an important next phase in its evolution. This reflects the dedication of our entire team, the physicians and researchers who have supported the lorundrostat program and, most critically, the patients whose needs continue to guide our daily work.

Thank you to everyone for joining us today. We appreciate the continued interest and support, and we look forward to providing further updates in the quarters ahead. With that, we will close the call. Have a nice day, everyone.

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

Greetings, and welcome to the Mineralys Therapeutics Fourth Quarter and Full Year 2025 Conference Call. At this time, all participants are in a listen-only mode. [Operator Instructions] Please note, this conference is being recorded.

I will now turn the conference over to your host, Dan Ferry of LifeSci Advisors. Please go ahead.

Thank you, operator. I would like to welcome everyone joining us today for our fourth quarter and full year 2025 conference call. This afternoon, after the close of market trading we issued a press release providing our fourth quarter and full year 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 differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties earnings 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, March 12, 2026, and 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 fourth quarter and full year 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 fourth quarter financial results before we open up the call for your questions.

We're pleased to have this opportunity to provide a corporate update as this call comes on the heels of our announcing the FDA's acceptance of the NDA for lorundrostat for the treatment of adult patients with hypertension in combination with other antihypertensive drugs. In connection with the acceptance, the FDA has signed a PDUFA target action date of December 22, 2026. This NDA submission followed a successful clinical program which culminated in the completion of 5 positive clinical trials that consistently demonstrated clinically meaningful blood pressure reduction, 24-hour control and a favorable safety profile.

This comprehensive data set has generated broad interest across the medical community, underscoring the significant clinical need in uncontrolled and resistant hypertension and the desire for innovative solutions that help patients meet their blood pressure goals. The NDA includes the positive data from the launch of HTN in advanced HTN pivotal trials, as well as the roof of concept trial Explore CKD and our open-label extension trial transform HTN. Each of these trials demonstrate that lorundrostat maintains a durable and clinically meaningful response across diverse patient populations, a key consideration for its potential as a new treatment for patients with hypertension.

Uncontrolled and resistant hypertension remain major unmet needs, affecting over 20 million people in the United States and attributed to nearly 700,000 deaths per year. As we have noted previously, roughly 30% of all hypertension patients have disregulated aldosterone -- we are progressively seeing research and updated guidelines that highlight the need to identify and address aldosterone dysregulation in these patients. Our clinical data highlights the differentiated value of targeting aldosterone with an aldosterone synthase inhibitor like lorenderostat, especially when compared to current third- and fourth-line treatment options.

To catalyze the successful launch of lorundrostat we have begun market access planning and payer engagement to ensure the value proposition of lorundrostat is understood and appreciated. We have also expanded our medical communications efforts, which will include increased peer-reviewed publications, a larger presence at scientific meetings and an expanded team of field-based medical science liaisons which will support broader data dissemination for this potentially transformative therapy. These activities are intended to drive a rapid uptake of under stat and feed into potential partnering opportunities.

I would now like to briefly touch on the other development activities we're pursuing to enhance and extend the lorundersat profile into hypertension with comorbid conditions which are largely driven by inadequately controlled blood pressure in this regulated aldosterone. Earlier this week, we issued a press release announcing the top line results of our exploratory trial, Explore-OSA. This 4-week trial, which enrolled 48 participants evaluated the safety and efficacy of lorundrostat in participants with moderate to severe obstructive sleep ana and hypertension.

This trial enrolled a high-risk population with an average body mass index of 38, an average apnea hypopnea index or AHI of 48 and and baseline systolic blood pressure of 142 millimeters of mercury. While lorundrostat did not demonstrate a clinically meaningful difference relative to placebo on the primary endpoint, AHI, -- the trial did show clinically meaningful reductions in blood pressure and a favorable safety profile in this population with difficult to control hypertension. In the preplanned parallel arm analysis of the first period -- the trial demonstrated an 11.1 millimeter of mercury blood pressure reduction with laronderstat and 1.0-millimeter mercury reduction with placebo at 4 weeks.

There was a 6.2 millimeter mercury placebo-adjusted reduction in blood pressure in the crossover analysis. Lorundrostat demonstrated a favorable safety profile and was well tolerated with no serum potassium excursions above 5.5 millimoles per liter. Our analysis is ongoing for other endpoints in the trial and will be reported in future publications or medical meetings. Our clinical development strategy has been and will continue to be focused on generating a comprehensive data set that reflects the complexities that physicians face when treating their hypertension patients.

We remain focused on fulfilling our mission to develop lorundrostat as a potential best-in-class therapy for patients with uncontrolled or resistant hypertension. We believe the strength of the lorundrostat data generated to date and the significant clinical needs for uncontrolled and resistant hypertension offer substantial opportunity as we prepare for the upcoming milestones. We are continuing to evaluate further clinical development for lorunderstat in comorbidities and other potential indications. We will keep you informed on our progress as appropriate. I will now turn the call over to Adam to review our financial results for the fourth quarter and full year 2025. .

Thank you, Jon. Good afternoon, everyone. Today, I will discuss select portions of our fourth quarter and full year 2025 financial results. Additional details can be found in our Form 10-K, which will be filed with the SEC today, March 12. We ended the year with cash cash equivalents and investments of $656.6 million as of December 31, 2025, compared to $198.2 million as of December 31, 2024. We believe that our 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 year ended December 31, 2025, were $132 million compared to $168.6 million for the year ended December 31, 2024. R&D expenses for the quarter ended December 31, 2025, were $24.4 million compared to $44.6 million for the quarter ended December 31, 2024. The annual decrease in R&D expenses was primarily driven by $49.3 million reduction in preclinical and clinical costs largely attributable to the conclusion of lorunderstat pivotal program in the second quarter of 2025.

The annual decrease was partially offset by increases of $9.9 million in compensation expenses resulting from headcount growth, higher salaries and accrued bonuses and increased stock-based compensation as well as $3 million in clinical supply manufacturing and regulatory costs. G&A expenses were $38.6 million for the year ended December 31, 2025, compared to $23.8 million for the year ended December 31, 2024. G&A expenses were $13.9 million for the quarter ended December 31, 2025, compared to $7.2 million for the quarter ended December 31, 2024. The annual increase in G&A expenses was primarily attributable to $8.9 million in higher compensation expense driven by headcount growth, higher salaries and accrued bonuses and increased stock-based compensation.

The annual increase was further attributable to $5.3 million in higher professional fees and $0.6 million in other general and administrative expenses. Total other income net was $16 million for the year ended December 31, 2025, compared to $14.6 million for the year ended December 31, 2024. Total other income net was $6 million for the quarter ended December 31, 2025, compared to $2.8 million for the quarter ended December 31, 2024. The annual increase was primarily attributable to higher interest earned on investments in money market funds in U.S. treasuries, resulting from higher average cash balances invested during the year ended December 31, 2025.

Net loss was $154.7 million for the year ended December 31, 2025, compared to $177.8 million for the year ended December 31, 2024. The Net loss was $32.2 million for the quarter ended December 31, 2025, compared to $48.9 million for the quarter ended December 31, 2024. The annual decrease was primarily attributable to factors impacting our expenses described earlier.

With that, I will ask the operator to open the call for questions. Operator? .

[Operator Instructions] And our first question will come from Michael DiFiore with Evercore ISI.

Congrats on all the continued progress. Two commercial question for me. Now that the potential launch of lorundrostat is roughly 6 months behind, your direct competitor. What are you hoping to learn from this competitive launch that would optimize the success of lorundrostat's launch? And second, could you offer any additional color on the prelaunch payer interactions you've been having like -- have there been any unexpected changes in anticipated coverage, et cetera?

Yes, Mike, thanks for the questions. We're obviously excited about the time line we're on now. The day 74 letter giving us the PDUFA date we clearly see a significant market opportunity here with -- as we've stated before, about 20 million patients in the United States alone dealing with uncontrolled and resistant hypertension. We're obviously aware that AstraZeneca potentially is going to be launching in the second quarter. I think there'll be some interesting things to identify as far as how they think about pricing, their footprint in the space. But fundamentally, we think this is a large market opportunity.

There's certainly room for to novel therapeutics and what I think may be a transformative class overall. We clearly are very bullish on the profile that we've seen with lorundrostat with its best-in-class profile. As it relates to some of the dialogues that we've had with payers, we continue to feel bolus as it relates to access, particularly where we've targeted orders that use. And that's that third line or later, we think resistant hypertension is the natural opening space and with experience both from a physician standpoint and demand growing into the third line usage.

I think it's also important to point out and I talked about it in my opening remarks, the comprehensive nature of the data set that we've built. When we think about resistant hypertension patients -- it's rare that they're isolated to only be dealing with elevated blood pressure. There are so many comorbidities. These patients are dealing with. Certainly, that's why we did the Explore-CKD study. That's why we did the Explore SA study. even though we did not achieve a benefit on AI, we know there is significant overlap, over 50% overlap with resistant hypertension and OSA.

And so being able to show the kind of robust safe benefit we have on blood pressure in this population. We think we'll have a significant translation into reduced cardiovascular risk for these patients. .

Our next question comes from Rich Law with Goldman Sachs.

Congrats on the PDUFA day and [indiscernible] NDA acceptance. A couple of questions from me. So when you look at the results from the Phase III OSA study, do you think the limited lorundrostat has potential to show benefit in the HI primary end point I mean, the study was much shorter than the historical MRA studies with only 4 weeks and you allow CPAP and APUs. And then the study population was also different from MRA trials.

So it's not clear to meet the study duration and define really asset lorundrostat one way or the other. How confident are you on the finding? And where do you go from here in regards to OSA? And then I have a follow-up. .

Yes, Rich, let me give you some opening thoughts, and I'll turn it to Dave. As I noted, the reason we did this study was because we think it's important for the prescribers, they're going to be utilizing lorundrostat to have a clear sense of both efficacy and safety within these complex patients. And so being able to show a really robust reduction in BP and doing so safely in these patients that clearly are high risk, particularly the ones that we studied in Explore-OSA with the BMI over 38 with AHI over 48 when severe OSA ticked off above 30 million -- these are patients that have a pretty high cardiovascular risk when you compound that with elevated blood pressure. So for us, it was an important study to complete. Again, we believe that we're going to be able to operate with our existing label within this population, just given the fact that they have uncontrolled hypertension and elevated cardiovascular risk. But I'll have Dave talk about some of the design features and his thoughts.

Thanks for the question, Rich. Good thoughts. I have a couple of things I want to say. But first of all, directly, was it long enough it's it's unclear. It could have taken longer than the 4 weeks. But I think there's probably a major interaction between that and the actual study population demographics. In other words, we saw these people were extremely obese. They had extremely high AHI close to 50, and their BMIs were 28 with many of them as high as 40.

38 on average.

I'm sorry, their AHI.

AHI was 48, BMI 38, but please.

Okay, sorry, 38%. You're right. And so -- so we think the mechanism here, which is -- the mechanism is your fluid overloaded when you lay down the fluid goes up into the veins of the neck, and that further obstructs the airway. In this population, there's so much extra adipose tissue that it may be that, that compartment is already obstructing the airway enough just from that structural the piece that you wouldn't see any more with decreasing volume. So I think the thing to look at it going forward, should we want to answer the question, is take a more representative population similar to the ones that were used in studies like a period and spinolactone intestine.

But I want to make a different point, if you could just give me a minute, which is this -- we did this because we wanted to know about AHI mainly because that's the easier way to register and drug if you want to claim for treatment of OSA. But that's not necessarily our objective. Our objective is to know whether we're going to have a benefit on long-term outcomes in patients with OSA. And the interesting point is if you make AHI less than 5 with CPAP, -- it doesn't reduce your blood pressure, and there's no compelling evidence that it makes your long-term cardiovascular outcomes any better.

So it's really simply a way to look at the regulatory effect. On the other hand, the reduction in blood pressure we saw is comparable to -- predict rather, and the agency gives you sort of the claim for improved outcomes. And at the 10 millimeters of mercury that we saw in the point estimate analysis, that's been shown to have about a 17% in terms of reduced coronary heart disease, 27% of stroke and 28% of heart failure. So what we learned here was that we have the potential to be disease-modifying in sleep apnea.

And as Jon mentioned, we can get to that point with the label we have, we're going to have already for treatment of uncontrolled resistant hypertension. It's been reported that 80% of these patients have uncontrolled or resistant hypertension. So that's the long and the short of it. We don't need to prove it works in AI because our objective isn't to make a therapy for upper airway obstruction. It's to make a therapy that makes these people live longer, better lives.

Okay. Got it. And then just to kind of -- for my second question, I know you guys are exploring the partnership, but with the PDUFA date now set in December, which is about 9 months from now, -- can you discuss like what kind of commercial capability have you been building? And how large is the commercial team now? And what commercial hires are you still holding back while you're continuing to explore the partnership? And then is there any urgency to build a full commercial capability now in case a partnership may not occur until after the PDUFA date? .

Yes. Thanks, Rich. I'll take you back 5 years ago, we've always made discrete investment choices that support this molecule and put it in its best position to deliver value for the most appropriate patients possible. And so early days that was CMC, that was Clint Farm. Where we're at now is we're making those right investment choices. And we began this late last year, as you're aware, we're continuing that now to ensure that we're preparing the market, and so that's why Eric and his team are beginning to have dialogues with payers. It's why we're expanding our medical affairs capabilities from continued data dissemination. I mean we have just a wealth of clinical data that we've accumulated last year and even as recently as they Explore-OSA that we're going to continue to put in the public forum via medical meetings and publications.

We're expanding our MSL team. I don't want to give numbers, Rich, other than to say we're continuing to do everything we can to ensure a rapid uptake on the potential approval of lorundrostat for uncontrolled and resistant hypertension. And I think fundamentally, that's the right thing for us to do because it also -- it becomes very informative and potentially catalyze those partnering dialogues. And we've heard that from potential partners, and we need to make sure that we're continuing to invest in this asset. So upon approval, it does have a rapid uptake and a rapid launch.

We'll go next to Seamus Fernandez with Guggenheim Partners.

So just a follow-up on the commercial side of things. Can you just help us understand what you believe the number of reps would be to launch the lorundrostat effectively versus AstraZeneca. And do you envision having a sort of differentiated approach to market than Astra, if there is a differentiated approach, what would that be? .

Yes. I don't know that I'll give you a specific number, Seamus, and we're continuing to evaluate that. But as you've heard us say before, when we look at where we've developed this molecule third line or later -- and in the United States, who prescribes there, it's about 60,000 physicians that are responsible for half of the script, third line or later. So that's kind of a broad way to look at the market. I don't want to give too much on our intended commercial strategy. But I will say that if you look at the comprehensive data set that we have advanced HTN confirmed hypertension. That was a study we did with the Cleveland Clinic. Explore-CKD that looks at hypertension and comorbid chronic kidney disease. And then if you look at the OSA population, the data that just came out of the Explore-OSA that's going to begin to inform how we think about subsegments of physicians that are treating specific types of hypertension with related comorbidities.

And so we'll begin to look at the broad IMS data, but then also in the context of these subsegments that we think can give us rapid uptake within the resistant hypertension population. And then with experience move rapidly in the third line as well.

Great. And then maybe just as a follow-up. Is there kind of a timing-related dynamic, how much of a derisking event, not just for minerals, but perhaps for strategics, would you say the availability, the assignment of a PDUFA date actually is broadly speaking.

Yes. I think each step along this journey, there's a level of derisking and level of increasing value. That began last year with the readout of Advance and launch -- it continued with the submission of the NDA last year. I think the day 74, both acceptance of and PDUFA date for lorendrstat further derisks the molecule and brings value nearer-term -- maybe related to that, when is an ideal time to identify a partnership. I think that these partnerships they have a life of their own, a time line of their own. Our goal is to really identify a means to generate the greatest value with lorundrostat, which means getting the molecule in front of the most appropriate patients in the United States and in due course, outside of the United States.

So those are all of the things that go into the calculus as we think about maximizing the value of the render staff through partnering.

Moving next to Jason Gerberry with Bank of America. .

Just wanted to quickly follow-up on the payer access discussions. I think the comment was maybe favorable access with a certain segment of payers. So I was wondering if you can expand upon that a little bit and just get a sense of your confidence in breadth of quality coverage, 3L+ as, I guess, you've articulated in the past? And then one CFO question here. Just -- from an R&D perspective, thinking about 2026 R&D relative to 2025, should we be thinking about, I don't know, cash burn mitigation effort? Or is 2025 a good run rate for the company -- and then last one for me is just on the OUS regulatory submissions, apologies if I missed this in the past commentary from you guys, but is that in any way gated at all by the partnership discussions as you can give us a sense of when you anticipate the OUS submissions. Thanks.

Let me maybe give some quick thought on payer and then I'll have Eric add some additional color. We've done a great deal of research in this area. Obviously, it's probably one of the most critical vectors to ensure that we get lorundrostat to the appropriate patients with as few barriers as possible. I think we continue to feel very strong about the value proposition of lorundrostat, the need, specifically in the resistant hypertension population, and so we believe that both the combination of appropriate price and rebate is going to create that access.

But Eric, I don't know if you want to add some additional thoughts, I know your team continues to work aggressively on this.

Yes. And Jason, I'm just back from a large payer conference in Orlando, PCMA, where the team was engaging Medicare as well as commercial payers. I will say we're on their radar. They're very well aligned with the positioning that Jon spoke of, and we're now in the midst of scheduling these preapproval information exchange or pie discussions. So -- we've got a favorable footprint and interaction kind of cadence with payers.

And then, Jason, on to your second question, Adam, do you want to add some thoughts?

So Jason, we haven't intended to give guidance on R&D, but I can tell you that in 2025, we are running a number of trials. We had launched HTN, Advanced HTN Explore-CKD for part of that year, Explore-OSA, plus the open label extension. So it was a heavy lift on R&D for us in 2025, when you roll into 2026, we've been wrapping up the costs on the OSA trial. We still have the open-label extension running -- there may be other R&D that we decided to do this year, but I would expect that there's less R&D activity in 2026 and we had in 2025, at least occurring to our existing plans.

So does that help? And Jason, to your last question, if I recall it right, ex U.S. and how do partnerships play within that. As we've spoken about in the past, our goal is certainly to try to get a understand to as many patients in the United States as well as outside of the United States. As appropriate, we know there are some complexities right now between MFN and tariffs that we're continuing to evaluate partnering may play a role in that, and it may play a role beyond just a co-promotion. This is where codevelopment becomes an interesting opportunity I think David and his team have done such an excellent job of characterizing lorundrostat, not just in hypertension, but in so many of these related comorbidities, that, that creates an opportunity for us to assess what is the appropriate way to introduce lorundrostat outside of the United States is it as a monotherapy as a potential anticfixed-dose combination strategy.

Those are still things we're evaluating. And once we've made a solid plan relative to that, we'll certainly be communicating that. Thanks. .

Moving on to Annabel Samimy with Stifel.

Just a little bit more on the commercial side. Maybe you can help -- I know it's probably too early to talk about pricing. But is there any scenario where the competitor kind of angle for third line while you're putting yourself in fourth line first, -- are you thinking about the possibility of you saying pricing as a competitive lever? And what kind of things do you need to do to get yourself into third line? And then as a follow-up to that, just with Explore-CKD and Explore-OSA are you actually seeking to put it in the label as a differentiating feature or just how the data available for presentation and publication.

Yes. I think it's too early to give you too much specificity on pricing. I can't really speak to where AstraZeneca may go from a pricing line of treatment approach. I can tell you, as Eric kind of alluded to and I did in my prior comments, that based on the research we've done with payers right now, the value proposition of lorundrostat certainly resonates fourth line with some payers even third line. I think it's going to be as I noted, a beach had a fourth line, that's clearly where there is unmet need. That's clearly where the value proposition resonates. And with experience and demand, I think that begins to open up third line. We've talked in the past, Anabel that as a guidance or a frame for pricing, we've always directed to probably more of an SGLT2 branded price point, Entresto price point broadly to WACC, but have guided as it relates to rebates.

To your second question, as I noted in my prepared remarks, we do anticipate having Explore-CKD is part of the NDA application that will be part of a negotiation. What portion of that data may be reflected within the label -- we believe that the blood pressure reduction data from Explore-CKD is informative for prescribers and that will be part of our positioning from a negotiation standpoint. Explore-OSA was not part of the original NDA application that may be part of continued safety updates, but the actual data was not available at the time the NDA submission was made -- but we do think both of those trials will be very informative to the medical community.

We will be using medical meetings, publications, and our medical science liaison team to certainly convey the important messages contained within both of those studies.

Okay. And is there any possibility to share other comorbidities you might be interested in exploring that could be particularly impacted by by hypertension lowering agents? .

Yes. I think I'd go a little bit deeper than hypertension agents, very specifically aldosterone-driven conditions. -- when we talk about 30% of hypertension patients have dysregulated aldosterone, I think by extension that goes into other conditions like CKD, like OSA, as David has spoken about before, heart failure, we've mentioned is a place we're clearly aldosterone plays a significant role in the risk profile of those patients. There are some other indications that we continue to look at that we haven't really spoken about yet. But as I said, in a previous response to a question, we believe that there are significant opportunities. Some of those are ones that we would pursue on our own.

I think some of those others are ones that we've thought about having partnering involvement with. But yes, it's clearly, at this stage, lorundrostat extremely well characterized for what does to aldosterone how it safely addresses that, and we think it opens up a lot of other opportunities. And as we said in the remarks, as we solidify those development plans, we'll be sure to convey those tothe market.

And our next question will come from Mohit Bansal with Wells Fargo.

Congrats on all the progress. Just one question. Just try to double click on the 60,000 prescriber number, Jon, you mentioned. Wondering, is this primary care heavy or these are specialists that you would be targeting? And then what sort of role direct-to-consumer market marketing type of mechanism could play for a market like this? .

Yes. Mohit, I think it's important that there's 2 vectors that Eric and his team are looking at. And it's the broad prescriber data that everybody can look at the IQVIA data, and that's where the 60,000 as a broad target comes from it's about a 60-40 split primary care specialty, the bulk of the specialty being cardiologists. But then there's another vector that we're looking at this, and that is for those resistant hypertension patients with comorbidities who's managing those patients. So hypertension and CKD, hypertension and OSA confirmed hypertension and even the Black African-American population because we know we have done a considerable job to make sure we have proper representation within our clinical trials. And so we're taking the broad macro data from a prescribing standpoint, but also informing that with primary market research to see where are the true targets that can really ensure that we're getting renders that is rapidly to as many appropriate patients as possible.

And I'm sorry, I think you had a second part of your question, Mohit.

Yes. So yes, thank you for this. But second part was more about the direct-to-consumer marketing sort of mechanism? Like what sort of role it could play for a company like yours?

Yes. I don't know that we're in a position quite yet to talk about the consumer strategy, but obviously, we want to be speaking to patients reiterating the importance of getting their blood pressure under control. seeking different means to do that, whether it's diet, exercise or therapeutics and the benefits specifically of lorundrostat, particularly if they have overlapping comorbidities where we have data that can speak to the the opportunity for lorundrostat to help them get to goal and subsequently have hopefully longer lives and better lives.

Will go next to Rami Katkhuda with LifeSci Capital.

I guess I know it was a small study, but did you observe any differential treatment effects in blood pressure reductions or AHI across any kind of key groups in Explore-OSA? And I guess, a particular focus in those receiving and not receiving CPAP -- and then maybe secondly, I know you touched upon potential future indications. Is the goal to be first-in-class for those indications? Or are they large enough similar type retention where it doesn't matter?

I'll let Dave answer the first part, and then I'll address your second one on other indications. Rami.

So we're in the midst of examining deeper into the data and one of the things we're doing right now is looking at your question of subsets -- you're right, it is a small trial, so it will be hypothesis generating more than proving hypotheses, but that's still really useful. And we intend to present that kind of analysis that future duplications and meeting presentations. So just stay tuned for that. In terms of the CPAP, about 1/3 of the subjects or a quarter we're on CPAP, and we didn't see any difference between those groups, but again, a pretty small number. So I don't want to hang my hat on that.

And Rami to your follow-up question as it related to go ahead when you repeat it for one more time, I want to make sure I address it specifically. .

Yes, I just wanted to check in and see if those indications, the goal is to be person class there? Or could you kind of pursue larger indications? I know you mentioned heart failure, where to large enough to encompass multiple winners here in the ASI class?

Yes. I think what our intent is to not be a follower. And what do I mean by that? We know that depacleplasone is going to be generic potentially this year. I think some of what's been done with the ASI tend to be more life cycle management combined with an SGLT2 I don't know that we're looking to frankly get into that mud bite. I think there's going to be ample opportunity and with the data that we have for physicians to use lorundrostat with the SGLT2 of choice. If patients have an overlapping comorbidity like CKD with our high retention, as I noted in the previous response, we know that this regulated aldosterone plays a significant role across the spectrum of cardiorenal metabolic disorders.

That's what's informing how we think about where is the white space, where is the opportunity for us to take what you believe to be the best-in-class aldosterone synthase inhibitor in either alone or in some distinct combinations bringing forward solutions for those patients.

And going next to Dennis Ding with Jefferies.

This is George Bank on the line for Dennis Ding. Maybe a little bit more on the potential partnerships. And if you could talk about what an ideal partnership looks like in terms of capabilities and also creative deal structuring. Obviously, the commercial infrastructure is important, but what other nuances are important to you, maybe in terms of R&D funding or bigger indications in payer relationships. I know that you mentioned that there's opportunity in pursuing some indications on your own and others involved maybe partnering it on. Any color there would be helpful.

Thanks, George. No, it's a good question, and I'll repeat what I've said in the past. We would love to find a partner that sees the opportunity with lorundrostat the way we do. And how is that, and that is with the best-in-class aldosterone in phase inhibitor in the near term, generating significant value for patients, for physicians and for the health care community at large and helping to control uncontrolled and resistant hypertension, but then also more broadly, fully realizing the value of the asset from a development standpoint. So co-development, I'm not going to talk about what kind of deal structures that would look like, but really extending the value of lorundrostat beyond hypertension and some of its related comorbidities.

And then within that, becomes addressing the complexity that exists just right now with branded assets that you want to get into the hands of patients outside of the United States. And so it's really what's been informing the dialogues that we've had is finding a partner that thinks more holistically about the opportunity -- as we've stated before, Lorendostat has excellent IP out to 2035 patent term extension probably to 2039. There's a significant time period there to fully realize the value of this asset and bring that value to patients.

This concludes our question-and-answer session. I would like to turn the floor back over to Jon Congleton 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 those related comorbidities. This is an exciting time for our team the patients with hypertension who may benefit from treatment with lorundostat, the physicians and researchers that have worked so hard in support of bringing lorundrostat through our clinical trial program and our shareholders.

We look forward to sharing updates with you in the coming quarters. And with that, I'll say thank you, operator, and thank you to everyone for joining us today. We'll now close the call.

Ladies and gentlemen, thank you for your participation. This concludes today's teleconference. You may disconnect your lines, and have a wonderful day.

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 of 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 for women, the majority of participants were overweight or obese and over half had resistant hypertension, requiring 3 or more background on hypertensive 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, 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 disregulated 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 sphere of 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, 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 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 permit 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 our crude 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, 2020. 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 AstraZeneca has been highlighting for bags is the longer half-life. So in that '24 presentation over a weekend, I think we saw -- I mean it was interesting to see that the bags show 14-millimeter placebo-adjusted SVP reduction for both day and night. Have you guys looked at that the day and night for Advance-HTN? And was there any difference between the 2? And then I have questions later on follow-up.

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, 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?

And 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 said 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 Lincoln and 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 -- going 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 be 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 when I take the class? And the related question is, that AstraZeneca has talked about this being a multibillion-dollar opportunity. Some of it is unlocked -- some of it would be unlocked with the combination and all those trials. So to help enable those trials what kind of partnerships you as a company would be looking at? And what kind of partners would be the better partner for you to collaborate with at this point?

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 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 aldosterone-reducing agent so safely and effectively. We know that aldosterone plays a critical rolling 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.

AstraZeneca seems to have only enrolled a small number of African-American patients in bax 24 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 lorundrostat in this patient population? And then secondly, have you noted what percentage of patients get to goal with lorundrostat in Advance or Launch?

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 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 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 African-American, you're going to respond to the renders that 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 bax 24 data, where they used a [ 1 30 ], we used a more stringent [ 1 25 ]. I'll also say that it wasn't just bax 24 that didn't have a high quantity of Black or African-American patients. It was also bax HTN 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 dogs 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 call 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.

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