Let's get started. Welcome, everybody. This is the second day of our conference. With me right now is the management team of Mineralys Therapeutics, Jon Congleton, CEO, and Adam Levy, CFO. Gentlemen, welcome. Thank you so much for coming down to Miami to spend time with us. Would love to, before we get into Q&A, would love to hear your state of the union of the business and what we could look forward to, perhaps in the next six to 12 months.
Yeah, happy to do it. And on behalf of myself and Adam, thank you for the opportunity. It's always a great conference to come down to, particularly when it's freezing cold in Philadelphia. So thank you for that. Look, it's been a dynamic and really exciting year for Mineralys. We've spent 2023, 2024 really building up a very broad, deep, and comprehensive clinical development program. And we've had three data readouts this year. The two pivotal studies, Advance-HTN and Launch-HTN, that are really forming the basis of our NDA application, showed really profound reduction in blood pressure in a well-tolerated, safe profile. In June, we had additional exciting data with Explore-CKD looking at hypertension with comorbid proteinuria CKD and again showed a really profound reduction in BP, as well as a reduction in proteinuria.
A really compelling data set that I think is needed at this point. We know there are significant amounts of patients, upwards of 20 million, that we think we can target with lorundrostat that continue to struggle getting to goal. We know the implications of not getting to one's blood pressure goal as it relates to stroke, cardiovascular risk, kidney risk. We're excited about what we've been able to bring forward with lorundrostat that we believe is the best in class, aldosterone synthase inhibitor, which is frankly really critical when you think about the importance and transformative nature of this class in cardiorenal metabolic disorders. The team has done a phenomenal job executing that program. We've now turned our focus on NDA preparation. We anticipate filing our NDA by the end of this year or first quarter of next year.
The team is putting together a high-quality submission that we're very excited about that is representing the robustness of the data that we're going to be able to bring forward. So look forward to the questions and sharing any updates.
Great. Thanks, Jon. So just to drill down on the NDA filing, again, expected very soon, latest 1Q 2026. That will include the Target, Advance, Launch, the phase II CKD, and the open label extension data, correct?
Correct.
OK. Are there any gating factors at this point that remain?
No. The pivotal studies, Advance and Launch, were done in March. The Explore-CKD study was completed and communicated in June. One of the key elements of a submission for a drug like lorundrostat that potentially could be used by millions of patients is a well-characterized long-term safety profile. That's something that we've been talking to the FDA about over the last four years as we've been preparing the lorundrostat for market introduction. For us, it was critical to have an appropriate percent of that open label extension study with subjects all the way through 52 weeks available. We have the ability at a 120-day safety update to update the file, but we need to make sure that we have an appropriate portion of that open label extension for the initial parts of the review to avoid any kind of delays in the review cycle.
Got it. Maybe speaking about the commercial scale readiness, all of your batches, speed in terms of your NDA audit status, things like that, anything that's not on track?
Yeah. We have, from the beginning, I think, made really important decisions around investment and use of capital to ready and enable maximal value of this asset, and that goes back to the proof of concept study that we did and how we did our CMC work there. It's a long way to say that we've been making these investments for readiness for rapid uptake, rapid success of this drug. From a CMC standpoint, we're very comfortable with the commercial scale that we have with that, with the CMC portion of the file. We've done audits of all of our manufacturing sites and are very comfortable with that, their inspection and readiness, not only of the manufacturing, but of clinical sites as well, so we know that quality is a key component of this NDA application, and we're very comfortable and very confident in what we've put together.
Got it. How many reps do you need? How many reps do you need to launch this properly? And what type of advertising spend do you need? Because I think the conversation is quickly turning to what type of OpEx build-out will be needed. And I'm curious, Adam, from a capital situation too, how are you thinking about that?
Maybe I'll address the first part, and Adam can address the capital. We're looking at what does an optimized commercial footprint look like in the U.S. I presume you're focused on the U.S. I'll maybe step back from the number of reps needed and talk about the market dynamics. We've developed lorundrostat from the very beginning of the proof of concept study, looking at subjects, patients who are failing to get to goal on two or more meds, so third line uncontrolled, fourth line or later resistant hypertension. Within that population in the U.S., patients on two or more meds that can't get to goal, it's about 20 million patients. When you look at IQVIA, these big massive data sets, we looked at about 1.6 billion claims and said, all right, who is predominantly driving the prescriptions for third line or later prescribing?
It's about 60,000 doctors that control 50% of that market from a prescription standpoint. And frankly, they influence the other 50%, which is a larger portion of physicians. It's the tail of the prescribing, but it's that first five deciles, 60,000 docs that are predominantly primary care, about 60%, 40% cardiologists. You could effectively hit those physicians when you factor in access and all of that with maybe 400 sales reps. Now, is that the optimal number? That's part of what we're evaluating. It could be less. It could be more. But just thinking about the drivers of rapid market uptake of launch of a new therapeutic like lorundrostat, those 60,000 doctors are the ones that are going to be really driving that uptake. And you could effectively, again, hit those with about 400. You talked about other means of promotion, whether it's DTC, DTP, omnichannel.
I think we're in a time now where there are some really hyper-efficient tools that enable us to do non-personal promotion, more so than when I launched COPAXONE 30 years ago. And that's why I love having Eric Warren here, who's our CCO. He's got experience with how you augment Salesforce with non-personal power, omnichannel, to really get greater efficiency, greater uptake of lorundrostat when it's launched.
But I guess, sorry, Jon, just so I have it right, do you need a $200 million + worth of SG&A build to launch it the way you want to launch it? Or you think you can do it in a narrower set of resources?
I'll give you my perspective. What we've guided to with the cash we have on our hand, which was $594 million at the end of quarter three, gets us through the pre-commercialization work, closes out our clinical trials, the NDA submission. It gets us through launch in 2027, cash into 2028. It does not get us to profitability, but enables a very efficient launch of this product and appropriate pre-commercialization. We're going to continue to evaluate that go-to-market model and what the capital needs are relative to that.
Adam, how are you modeling this through? I mean, you're a former banker, so I'm sure you're running all types of scenarios on base case, low case, high case.
Yeah, we definitely are looking at various scenarios. And the base case that Jon laid out, this would be in the absence of a partner. Cash into 2028 would allow us to get through the launch. We have been spending a significant amount of time trying to evaluate the right opportunity to partner. And certainly, that could change the dynamics and the capital needs significantly. But with the base case scenario, as Jon mentioned, getting through the clinical development, the pre-commercial work, commercial launch into 2028 with the cash that we have on hand.
When is the filing again?
Filing is by the end of this year, Q1 next year.
OK. So is this a late 2026 launch?
It could be anywhere from late 2026 to Q1 2027.
Got it.
Yeah, assuming everything goes smoothly with the FDA, obviously. Yeah.
Got it. OK. And one last thing. As you think about the launch spend, especially into 2027 and 2028 outside of the commercial build-out, is a meaningful advertising spend also baked in? Because I got to believe AstraZeneca will be putting several hundred million, perhaps, into this launch. So there will have to be some sort of counter from Mineralys' side as well.
I think it's too early to guide on what is going to be the promotional focus, how we're going to use all the channels that we have available. It's something that we're continuing to evaluate within our go-to-market model. I think it's clear that AstraZeneca is bullish on baxdrostat equally as we are with lorundrostat. But to give you a view on what are those channels, what are those costs, I think it's too early to really opine on that.
Jon, any initial thoughts on potential discounting? Because you're competing with AstraZeneca, and I'm sure they'll bundle to gain preferential formulary status. Any initial thoughts on how you may counteract that or?
Yeah, sorry, that said something. Our perspective is the focus as we go into 2026 is not only on the NDA, but it's also on commercial readiness for this product. So that has really two early vectors in 2026. It's continued build-out of the medical communications group. So that means not only a bigger presence at congresses, more publications from all the data we've generated in 2025, but also MSLs in the field to build out the awareness and enthusiasm and excitement for what lorundrostat could bring to the treatment of hypertension. The other vector is account executives in the field, in front of the PBMs, in front of the health plans, making them aware of the clinical profile of lorundrostat, the clinical value proposition, but also making them aware, presuming that baxdrostat maybe launches in Q2 of 2026, aware that lorundrostat is shortly on the heels of that.
In my experience, payers tend to like to have two entrants within one class before they make any kind of restrictive contracting decisions. So while there is a separation of maybe six-to-nine months relative to the launch of these drugs, we don't think that's going to be a hindrance to our ability to create contracts, create access for lorundrostat.
Interesting. OK. I was going to ask your thoughts on baxdrostat's most recent trial. But in light of their press release yesterday, it seems like they're only using one trial to file and not the most recent trial. So just, I mean, it seems like, aside from the product's half-life and aldosterone synthase selectivity, you got their 374x, their 100x. Some people say these drugs seem more similar than they are different. What would you say to that?
I would say that we're very confident in the data that we've put together. We believed we had best-in-class molecule going back four or five years ago based on some of the criteria you just talked about, selectivity and what we think is an ideal half-life. And I don't think it's a shorter half-life. I think it's an ideal half-life. It's rare to see drugs, certainly in cardiovascular, have a 24- to 31-hour half-life. Ours is 10- to 12 hours, four different studies. We've shown 24-hour control. We've shown best-in-class efficacy and best-in-class safety as it relates to on-target effects. To me, that distinction is coupled with the data set we've put together. And what I mean by that is we have three really distinct data sets. We have Launch-HTN, which is our over 1,000-patient study, real-world in-office measurement, keeping patients on the drugs they're on.
It's how the drug is going to be used at launch. We also have a study that we did in partnership with the Cleveland Clinic that was very onerous. It was Advance-HTN. We took patients off their background meds. We optimized their background treatment. We confirmed that they had truly uncontrolled and resistant hypertension. We did that because that's the kind of data set that specialist cardiologists are going to want to see. That's the kind of study that's going to get rapid adoption by the hypertension guideline committees. We also did Explore-CKD, which is, again, looking at a key attribute that prescribers of antihypertensives have noted to us. That is, is there a benefit on proteinuria? We can now say yes. You're not only going to get a reduction in BP.
You're not only going to be able to use this drug safely in a lower kidney function population, but you're going to see a benefit on this key attribute of proteinuria, so we believe that these three studies form the backbone of a really not just thorough NDA application, but a very informative label to speak to a variety of patients that physicians are going to be treating, whether they're GP or specialist, and lastly, I would add, we're very proud of the diversity that we have within this, because there are some very distinct populations in the United States with uncontrolled hypertension that are at the greatest risk of the outcomes of poorly controlled hypertension, and that's Black or African-American patients, where we had 28% representation in Launch-HTN. We had 53% representation in Advance-HTN.
That is quite distinct from the data set that AstraZeneca has put forward. We're very comfortable with the breadth and depth of this program, as well as the best-in-class profile that's emerged that we had signals of early days with the selectivity and the half-life.
Fair enough. Great points. I guess the next catalyst, aside from the NDA submission, is your obstructive sleep apnea trial. Just remind us when that's going to read out, and we'll just go from there.
Yeah, the EXPLORE-OSA is going to read out top-line data sometime in Q1 of next year. Now, we've done this study because there's significant overlap. And I think this is an important point to make about how we think about hypertension. It's rare to have a patient with just hypertension in isolation. If you want to think about hypertension as a journey and the destination, if it's uncontrolled, it's either stroke, cardiovascular risk, CKD risk, other systems disorders. We're very mindful of showing the benefits of this drug beyond just lowering the BP and doing it safely. And so EXPLORE-OSA is a case in point because there's significant overlap between resistant hypertension and obstructive sleep apnea. And there's actually a biological linkage. It tends to be excess fluid.
We know that in the case of lorundrostat, part of its mechanism is a diuresis and a fairly rapid one. Within two to four weeks, we see about 70% of the 70%-80% of the blood pressure lowering effect that's due to that volume reduction. We think that volume reduction is likely going to serve as a benefit in an OSA patient as well for their symptoms of obstructive sleep apnea, which are called apnea-hypopnea events.
Got it. And I'm just looking at the entry criteria to the study. I mean, patients on CPAP can be allowed in the study. But yet, the criteria specifies that you're enrolling moderate to severe OSA. So how many patients on CPAP would actually qualify?
Yeah, I think it's a good question. You know, if we step back, we know that OSA is greatly underdiagnosed. We know that patients can get benefit out of CPAP, but it is not used. It's not complied with very frequently because it's cumbersome. It's aesthetically not enjoyable. It can't control that. The problem partially with CPAP is this lack of compliance of full eight hours to get the benefit from that. We make sure that patients are compliant to their CPAP at least four hours a night. And the issue is that that does not always resolve their symptoms of OSA. So even if they're compliant with CPAP at least four hours a night, they still have to have the moderate to severe symptoms to enroll in this study.
And so a portion of the subjects in EXPLORE-OSA are on CPAP, but are failing to get full resolution of the symptoms.
I see. And when we think about the typical diurnal pattern of aldosterone, where there's a surge in the early morning, right? It peaks in the afternoon. Why dose lorundrostat at night in this trial?
Yeah, the simplest response to that is these patients who have moderate to severe OSA have a completely disrupted aldosterone cycle. The best way to think about OSA is it's a stress response almost akin to waterboarding. These patients have so much excess fluid that when they lay down, you have this caudal-rostral redistribution of that fluid, and those apnea-hypopnea events are stress responders. They drive heart rate. They drive blood pressure. They drive aldosterone, and so the reason we're dosing lorundrostat in the evening is because that's when the trigger for this patient population of their aldosterone production occurs, and we know with our half-life of 10-12 hours, we get 24-hour control. But in that period of sleep, we're going to get almost 100% suppression of aldosterone, which is going to help those patients potentially manage their symptoms of OSA.
But also, more critically, in what's causing them increased CV risk is not only reduce BP, but reduce the variability of that BP response related to the apnea-hypopnea events.
Last question on this trial. The trial only has a four-week treatment period. Are you confident that that's enough to adequately reduce the AHI index?
That's the exploratory nature of this study. We're confident that within two to four weeks, we see that fluid shift that has led to the really profound BP reductions that we've demonstrated in all four trials we've done in hypertension. Part of the exploratory nature of this study is to say, all right, does that same fluid shift benefit these OSA subjects by measurement of their AHI events?
Got it. In the final minute we have left, guys, what's the latest update on your search for a commercialization and/or development partner? Based on comments in the past, these may not be one and the same, correct? It may be two different entities.
Yeah, I think I'd tie it back to Umer's question. We're very much focused right now, as we have been for the last five years, on successful readiness of this molecule through its various stages, from proof of concept to clinical development to now pre-commercialization. So what are the appropriate things we need to do to ensure success of this molecule? Because for us, that A makes sense for us if we choose to be the natural owner of this molecule, but it's also an important part of the partnering. And so our partnering dialogues continue to progress. It's something from my standpoint, we know that we've got a valuable asset. Does a partner augment that value? Yes or no? And to your point, it is not just about feet on the street, but it's also about potentially expanding the indication profile of this drug.
Got it.
Jon, can I ask a semi-controversial question, if I may, because everyone's been obsessed on this? There's been investor assumptions around the recent share sale you did and trying to draw implications from that over to, oh, if there were any conversations ongoing with partners, lawyers wouldn't necessarily allow that. Maybe if you and Adam could expand on how that practically works in terms of if something was very late stage, only then would lawyers necessarily prevent any share sales, et cetera? But ongoing conversations could continue in routine course, and they may not be necessarily affected. I mean, just having a little more perspective on how it works at an operational level might be helpful.
Sure. So when you do an SEC filing, like a registration statement, a 10-Q, a 10-K, you do full disclosure. And those share sales were done right after that. So that's kind of a very natural time within the disclosure. And if you talk to legal counsel, is that OK to sell stock around? Then that's when they would advise you is the sort of optimal time after full disclosure is done. Obviously, if the company was in a blackout date, then you couldn't sell shares. So as far as how close to partnering or some material announcement, I think they know it when they see it.
So Adam, is it fair to say the way you're describing it is folks shouldn't necessarily make any direct read across from that to partnership conversations that are presumably ongoing and routine?
That's right. It was all personal decisions by the people that sold within the company. One of our board members is involved with an investment fund that, through its normal course, sold some shares as well. And that was kind of their choice. Either distribute to the shareholders, and then there can be an overhang, or sell it. They were able to sell it in a block trade, and it was very clean. So there's no read-through on prospects of the company, the feelings of management or board members on the prospects of the company, or any business development activities.
And does your counsel define what's imminent in terms of figuring out whether a share sale can happen or not based on a certain timeline that if something is imminent? Or is that there's not a hard timeline, like if something's imminent as weeks or months?
I think that as the compliance officer, I will make a judgment call and then run it by counsel if there's any kind of questions on what needs to be done. So it's very much case by case. You sort of know it when you see it. I think that enough time has passed since the share sales have happened that you can see in hindsight there wasn't some corporate announcement right after.
Got it. Well, I just want to say thank you guys for being so forthcoming with this question just because it's been something on investors' minds. So I appreciate you guys addressing it.
Sure.
Thank you so much.
Thank you.
Thanks.