Hi, everyone. Thanks for joining us at the Wells Fargo Healthcare Conference. My name is Sadia Rahman. I am one of the biotech analysts here at Wells, filling in for this session for Mohit, and it is my pleasure to introduce Mineralys Therapeutics. From Mineralys, we have Jon Congleton, CEO, Adam Levy, CFO, and Eric Warren, Chief Commercial Officer. Thanks for being here. I will hand it over to you for any opening remarks, and then we can get into Q&A.
Yeah, we are appreciative of the opportunity to join the Wells Fargo conference. Always a productive time for us. We are very excited about the opportunity that is in front of us. Lorundrostat has proven over the last five years to really be a meaningful introduction in the treatment of hypertension as well as some of the related comorbidities. Targeting aldosterone, which we think is a key node and will be for the, frankly, next decade or so in trying to address and alleviate the concerns around cardiorenal metabolic disorders. The data that we have generated went into the NDA that we filed late last year. I would say those dialogues continue to be productive with the agency targeting a PDUFA date of December 22 of this year.
I am sure we will get a chance to talk about it, but Eric and his team have done a really outstanding job ensuring we have a successful launch, building out the key vectors of market access, med affairs, marketing, and building out to a sales team. We are excited about the opportunity in front of us. We are excited about the opportunity of really making a meaningful difference in the lives of patients that are dealing with uncontrolled and resistant hypertension. We think lorundrostat stands to be a really transformative treatment for those patients.
Great. As you transform into a commercial stage company now, I am sure there are a lot of changes as an organization. Maybe can you just give an overview of the changes, where you are now in that transition, any remaining work that is needed ahead of the launch?
Yeah. We've progressively, over the last two years, been, I think, appropriately building the functions that are necessary to ensure a successful launch of lorundrostat. Eric joined us in April of 2025, put his leadership in place for market access, marketing. We had had a medical affairs presence going back to 2024, really highlighting the importance of aldosterone, the role that plays in cardiorenal metabolic disorders, building advocacy. As we entered this year, we continued to add to the various key levers that are going to be important to ensure that successful launch. So in Q1, we put in place a national accounts team, getting in front of the payers, the PBMs, the insurers. We knew that AstraZeneca would be there as well with their anticipated PDUFA and eventual launch in June.
Making payers aware that there are going to be two ASIs, the value proposition of lorundrostat. In Q2, we augmented and expanded our medical science liaisons as a field-based medical staff to really continue to go deeper into the advocacy network and build an energy, enthusiasm, and appreciation for aldosterone as a target, ASIs as a treatment approach. The marketing team has been progressively preparing messaging the creative, the branding that goes behind that. As we've guided our intent is to have our sales force in place ahead of the PDUFA date, that would enable us on presumed successful approval, rapidly moving into launching it and lorundrostat in the hands of the patients. Behind that, we've continued to really focus on how do we prepare this organization for that transition. How do we continue to look at the development of lorundrostat?
We're not done with the clinical work. We're continuing to evaluate where do we want to go next with this transformative agent. But always with a mind to being lean, being efficient, and really focused on value that we can generate with each person that we bring into the organization.
In the launch, what metrics do you plan to provide investors to help gauge how many patients are on drug, payer access, prescriber depth and breadth?
Yeah, I think it's a bit early to provide the specific metrics we're going to look at. We may do that down the road. I think the way we think about this market opportunity can be informative, and we're really looking to create accessible choice, if you will. Eric can talk more about that. But creating accessible choice is a key strategic vector for us. We've always talked about there's a really targeted population that are treating probably 40%-50% of all of these third line or later uncontrolled or resistant hypertension patients. About 50,000 doctors, plus or minus, can be a very efficient sales footprint. Eric's got great experiences, does his team, with then overlaying that with an omnichannel, tapping into the efficiencies of digital.
All of that will speak to the strategy that we're doing, and from that, we'll determine what is going to be ideal to help inform investors on the launch of lorundrostat, but probably guiding to that later this year, maybe early next.
Are you saying anything about those 50,000 prescribers, your strategy for covering that prescriber base starting in the launch? How many could you cover at the outset? How many would take more time?
I think we're going to be able to have a layered approach with that. I think those 50,000 or so physicians we would have intent to address the vast majority with sales force, and then overlay that with omnichannel. That digital strategy enables us to go beyond the 50, but do it in a very efficient, high ROI way. That's part of what we would be looking to provide guidance on once we get to the appropriate stage to provide that.
Great. You've talked a little bit about the market dynamics. You've talked about a sizable population of 10 million patients in each of uncontrolled and resistant hypertension. How do you think about the relative segmentation in 3L versus fourth-line? How much of that market is addressable early on in the launch versus something that would take more time to develop?
Yeah. It's something that we've been thinking about really almost at the outset of Mineralys's formation. It informed how we did our proof of concept program. It informed how we did our pivotal program, and it was really looking at the dynamics from an access standpoint, a payer standpoint, and the biology of uncontrolled and resistant hypertension. That third-line or later is where our data really resides. We don't see a difference in response whether it started third-line or fourth-line. There's going to be utility from a treatment standpoint for both those 10 million patient populations. I think our view going into the marketplace is we'll make physicians aware of that utility, but I think the payer landscape will probably be more open at the fourth-line initially.
It's based on the research that we had done over the last several years that fourth-line is, for lack of a better term, the low-hanging fruit, where you've got physicians that, by their electronic medical record, have a history of trial and failing to get to goal on countless drugs. They are, in essence, pre-approved. Third-line we know will have some utility at launch, but I think with success of prescribing in fourth-line, physicians will want to be able to move earlier within that. I think that thesis is validated from what we're seeing in the early days of the baxdrostat launch. I think the vast majority of those prescriptions seem to be at fourth-line. There is some third-line utilization, and where there's access for that, I think there will be commensurate demand, and we've got the data to support that.
I think more importantly, if you dig deeper beyond just line of therapy, if you look at the data that we've generated, we have diversity within those populations. A case in point, I think we had a higher percentage of females within LAUNCH-HTN and ADVANCE-HTN than you typically see within trials. We have data sets that speak very specifically to females with uncontrolled and resistant hypertension, and certainly with Black African Americans. We had 28% of our 1,082-subject study were Black or African American, and Advance-HTN that confirmed uncontrolled and resistant hypertension was 53%. We're not only going to be able to just speak to fourth-line, but to very specific subsegments within that, with very compelling data, with very rich data, and very representative of the populations these physicians are seeing on a daily basis.
Is there anything specific you would point to that needs to happen for broader uptake in the third-line setting, like incorporation of ASIs into guidelines? When are we expecting the guidelines to be updated, and how could ASIs be reflected?
Yeah. Gaining experience in fourth-line is a natural predictor of increased third-line utilization. Guidelines very well could play a role in that as well. We anticipate guidelines sometime in the early part of 2027, which will time well with our launch.
Mm-hmm. What are you hearing from KOLs? I think you indicated right now they'll start with fourth-line use, but just about how use might evolve to include third-line patients, how quickly could that happen?
Fairly rapidly. The comorbid conditions create a bridge. There's more likelihood of those third-line patients that have CKD, for example. There's a real need to address this culprit, if you will, aldosterone, which is contributing to uncontrolled and resistant hypertension. Fourth-line, early opportunity. Third-line, comorbid bridge, which then translates into broader third-line use.
Got it. Let's just talk about pricing. How are you thinking about pricing and rebate strategy to support broad access while also competing effectively with AstraZeneca?
Yeah, not the right time to disclose the pricing strategy. As we get to launch, we will. But I've stated before, parity access is a focus for us. I don't want to create a downward spiral. I want to make this the choice of the physician to be able to determine what is the right ASI for them. I also want to shift the focus from ASI versus ASI and make sure that we're focused on the broader opportunity, which are those 20 million patients that are in need.
Just to add to that, we've got a price out there now with baxdrostat at $900 per month. I think fairly reasonable based on the market research we had done ourselves. I think it's an informative point. I don't know that it's an anchor point, but it's certainly informative. As Eric noted, we'll, at the appropriate time, provide clarity on the price that we're looking at. But I think it fits within this parity access strategy that we have and is a reasoned value for the kind of transformative ASIs stand to be.
How are payers valuing this class versus older alternatives like spironolactone? Are you seeing a lot of step edits required today, especially with MRA step?
Yeah, I think the research that we'd done over the last several years, there was a clear appreciation of the value proposition, and certainly once we had our pivotal data out for fourth line, and even third line within some payers, but certainly in fourth line. The payers understand how these patients are cycling through countless meds, still not getting to goal. The payers understand the implications, particularly in resistant hypertension to outcomes and their overall cost. I think the economic clinical value is clearly appreciated. I think what we're seeing play out in the early days of the baxdrostat launch is an exhibit of that. Rather than just being research, we're actually seeing a case study in front of us right now. The utilization management that we're seeing and that we're getting feedback from our national accounts team is what was anticipated. It's step edits.
It's not prior authorization through spironolactone, which I've got asked about more times than I care to comment. The market research didn't support that, and in reality, we're not seeing a PA through that. We're seeing a step edit, failing either two or three meds. Again, if you think about the fact that there are 10 million patients with resistant hypertension who, in their electronic medical record, have a history of being on three or more meds and not at goal, that is, in essence, a pre-approved step edit process right there. It's not like they've got to suddenly go through three drugs. They're sitting there with that experience right now and in a position to quickly address any kind of step edits or utilization management related to failing to get to goal on pre-existing meds.
What's nice about our strategy is we're not trying to displace an effective generic that's getting a patient to goal. We're trying to complement or supplement a series of generic products that aren't getting the patient to where they need to be. Payers really appreciate the fact that we're not trying to take something that's cheap and effective away, but we're helping them manage those difficult patients.
Mm-hmm. On net price, how should we think about any benchmarks for gross to net, and just factors early in the launch that could influence net price, such as free drug mix, that could shape the early curve, and then where could it eventually stabilize? How should we think about that?
Yeah, I think like the pricing strategy, the rebate strategy, I think we'll keep close to the vest for right now. I'll come back to the ultimate goal here is accessible choice. From our standpoint, parity, ensuring they have access to one or the other. Eric made the point, and I don't think it can be missed, and that is, yes, we're going to get drawn into comparisons, lorundrostat, baxdrostat. That's not the really interesting value-driving discussion. I think it's more about ASI relative to what has been typically used in fourth line, third line, that is failing to get patients to goal. Beta blockers, alpha blockers, calcium channel blockers, all of these older drugs that just provide incremental clinical benefit and not the kind of meaningful benefit that we see right now.
The goal is parity, ensuring access to both, and then really allowing physicians and patients to make the choice.
Got it. Not a rebating strategy for preferred positioning, but parity access to baxdrostat.
I think it's accessible choice. Yeah.
Mm-hmm. Just talk about Medicare formulary access. How much could lack of Medicare coverage in 2027 impact the uptake curve?
We'll point back to baxdrostat launch, and baxdrostat is gaining Medicare utilization. Medicare, to cover that period where there is not preferred coverage, creates a medical exception opportunity that is typically to label. We're seeing those patients now flow into baxdrostat via that medical exception. I anticipate something would be very similar for lorundrostat.
Mm-hmm. Got it. Now that baxdrostat has launched and we're seeing some of the early numbers, what are you learning about prescription trends, maybe patient mix, prescriber mix, and physician willingness to use ASIs in various settings? Have there been any surprises relative to what you expected?
I'll say validating is the word that comes to mind. It's validating the unmet need, the innovation that ASIs present. We've seen progressive week-over-week increases in their number of scripts in patients. We've also seen the type of practitioner validated. Primary care, cardiology, nephrology are ultimately prescribing, and those are those high volume, uncontrolled, resistant primary care providers. We're also seeing the spectrum of coverage. We're seeing commercial Medicare, some Medicaid come into play as well. As Jon mentioned earlier, we're seeing fourth line represents about 80% of their patients, but 20% of their patients have been in that third-line position.
Mm-hmm. Got it. Just wanted to talk about lorundrostat's clinical profile, what we've seen from the trials, and how could that be reflected in the label. ADVANCE-HTN, do you expect that to be represented separately in Section 14 (Clinical Studies) of the label? Which physician segments could find that most valuable? How could it help drive uptake?
Yeah, all of this is going to be pending negotiations with the FDA on the label that will happen a little bit later this year. Through the course of the dialogues that we have had with the agency, they have always been very productive, supportive. Uncontrolled resistant hypertension is a target for HHS, and that reads through to the FDA as far as being a good partner giving us guidance. I think one of the things that resonated with me in some of those dialogues was they view the label as a way to inform the prescribing audience on how to use a drug. From our standpoint, when we submitted the NDA, we put three studies into the NDA and had them represented in some distinct ways within the label. As it comes to Section 14 (Clinical Studies), it was LAUNCH-HTN, again, the largest hypertension trial done with an ASI.
The data there we feel is very compelling. Absolute reduction of 90 mmHg, placebo-adjusted 11.7 mmHg, with a really low incidence of hyperkalemia above 5.5 mmHg. That data we fully expect to be represented in Section 14. ADVANCE-HTN is one of the most distinct hypertension studies done, and certainly with an ASI. It is in a confirmed population, as you know. We took patients off their background med, put them on an optimized treatment to confirm were they uncontrolled or resistant, and then randomized. That study becomes very important because it shows that lorundrostat can be used with really high-dose ARB, high-dose diuretic, and in some of the patients, high-dose calcium channel blocker. That is really a study that is going to inform your specialist, your cardiologist.
EXPLORE-CKD, the blood pressure data that was generated out of that study, again, we are going to argue should be part of the label because, as Eric pointed out, hypertension does not exist alone. There are comorbidities. Being able to speak to what lorundrostat can do in a lower kidney function population from a blood pressure standpoint is important. Plus, we will also, beyond Section 14, look at other parts of the label where we can differentiate. EXPLORE-CKD basically speaks to experience in subjects with an eGFR as low as 30. Baxdrostat's label speaks about experience above 45. Again, these are all part of the negotiations we will have with the agency, why we think each are important for the constituents that are distinct and different in treating hypertension and informing them about how to use lorundrostat and what to expect when they do.
Apart from EXPLORE-CKD, you also presented recently a post-hoc analysis of LAUNCH-HTN in people with CKD. What does that analysis tell us about the benefit risk profile of lorundrostat, specifically hyperkalemia risk in those patients?
Yeah. We were really excited to share that data at the European Society of Hypertension meeting in June. What we did is we took LAUNCH-HTN, those 1,082 subjects, and parsed them out. It was not part of the inclusion criteria, but we parsed them out by those that had higher rates of albuminuria and wanted to look at not only their blood pressure change as a subset, but also what happened to their UACR. Over the 12-week period, we saw about a 52% reduction in proteinuria, which is a real marker for renal progression.
It allows physicians to have a sense for if they're using lorundrostat in a patient who has uncontrolled or resistant hypertension and comorbid, either CKD or proteinuria, albuminuria, that they're going to be able to see a benefit on that would be related to not only the blood pressure reduction, but the mechanism of the drug itself. From a safety standpoint, again, we saw a really mild hyperkalemia profile. We think that was a really important data set that affirms what we saw in EXPLORE-CKD, but over a longer term period.
Mm-hmm. As far as the doses that could be reflected in the label, you've looked at 25 mg, 50 mg, 100 mg in your trials. Can you discuss how much support there is for the 25 mg, and if you could see that reflected as a down titration option in the label?
Yeah. We included both 25 mg and 50 mg in our package submitted to the FDA. We believe there's utility for both. I think the 50 mg will be the recommended starting dose, but the 25 mg is there for those patients that may be more compromised from a renal standpoint. 25 mg is what we studied in the EXPLORE-CKD study, knowing that these patients are going to be more sensitive to electrolyte changes just because of the impaired renal function. Also to give utility for physicians if they've got a patient that they feel they want to start at a lower dose and then titrate up. They've got the flexibility for that.
Our goal is to get both doses approved, and again, the 50 mg being the predominant starting dose for most patients, but knowing that they can use 25 mg in distinct populations and not give up on the efficacy side.
We've seen the hyperkalemia rates reflected in the baxdrostat label. When they're summarized in the label for lorundrostat, what potassium threshold and methodology do you expect the FDA to rely on?
Yeah. There's two ways to look at potassium. It's any reading, and then there's the confirmed reading because there's a lot of issues in how you collect blood samples, how you measure potassium. You get a lot of false readings, fictitious readings. Our view is the confirmed is what should be used because that's the true representation of what you see. Part of that will be, again, the FDA doing their own adjudication of what was initial report, what was confirmed. I would anticipate, though, it'll be the confirmed data that'll show up there. Either way, we see, again, a really mild profile as it relates to electrolytes, and certainly within the context of the kind of clinical benefit that we see as far as reducing blood pressure.
Mm-hmm. Would that be different from what's reflected in baxdrostat's label? They have, I think-
I don't know that they speak specifically to were those numbers confirmed or initial reported. But I do know the data that they put in there related to potassium above 5.5 mg, I think it's around 12%. What we've seen within the LAUNCH-HTN study was about 6.5%. I would say we'll probably end up landing somewhere in that regard as it relates to the label.
The frequency of potassium and sodium monitoring is left to clinicians in baxdrostat's label. What are you seeing clinicians do in the real world? How are they handling that?
Yeah. I think we can actually look at what they've been doing, frankly, for decades. I think the ACE inhibitors and ARBs condition physicians for pretty standard treatment paradigm that the ASIs are going to fit in very nicely. That is upon initiation, you get not only a baseline, obviously, blood pressure level, but you also get a blood panel and a urine sample that gives you a baseline on the electrolytes. Then bring subjects back in about two, four weeks, check the blood pressure to see if they're getting the kind of response they want, and replicate either the blood or the urinalysis to look at the electrolyte profile. We see this shift in electrolytes with ASIs occurs at about two weeks and then stabilizes.
The profile of lorundrostat fits very easily into the existing workflow that physicians have in how they're managing their hypertension patients, in both measuring efficacy and also looking at safety markers.
Maybe if they have experience with spironolactone, they're familiar with how to monitor for hyper-
The experience actually comes out of the ACEs and ARBs. We see the same thing.
Okay.
You typically see the ACEs and ARBs have a shift in the electrolyte profile-
in the same kind of temporal cadence two to four weeks in. You see eGFR with ACEs and ARBs goes down slightly when that blood pressure comes down and then stabilizes the same that you see with the ASIs. I think the use case, and I think it's ideal for adoption, it doesn't ask the physicians to really do anything differently than they've done with ACE inhibitors and ARBs, and in your case, spironolactone.
Okay. Just wanted to ask a few questions on partnership. As you get closer to a potential launch, has there been any shift in the type of interest you're getting from strategic partners, as far as the breadth or quality of the parties that are interested? Do you get a sense that some potential partners are maybe waiting for approval and label clarity now before they engage in further discussions?
We've been interested in partnering, and we've publicly discussed our desires to partner if there's the right opportunity to maximize the value for lorundrostat. That could look like a partner that helps commercialize more broadly around the world, potentially help develop lorundrostat. We haven't given specifics on conversations or updates on how that's going.
Do you think the strongest fit could be with companies that already have a cardiorenal infrastructure or potential combination agents that could be combined with lorundrostat in-house, or are you seeing interest from companies more broadly?
It could be, but it doesn't have to be. I think that really, if there's a desire to work in this space, I think lorundrostat could be an anchor asset for a company that wanted to work with us to build a cardiovascular franchise or a group that already has experience in the space.
Is there a point where you might engage with partners that are interested in carving out ex-U.S. geographies?
We have gone down the path of commercially launching in the U.S. We don't have intentions of launching outside the U.S., so a partner that would be interested in those geographies could be of interest to us, but it has to make sense, and it has to put us in a position where global pricing makes sense.
In your partnership discussions, are potential partners focused on the broader cardiorenal opportunity with development in additional indications, or are there some that are solely focused on hypertension?
It's certainly of interest to us. As Jon mentioned, aldosterone is a node that's important in a variety of diseases, and our first step has been to go into hypertension and then deepen in hypertension. There's other disease areas that could be of interest.
So you've been making investments in the commercial build-out this year. How should we think about the cadence of commercial spend from here?
In the end of June, we had $661 million in cash on the balance sheet. We have said that that will bring us into 2028. We also entered into a credit facility with Pharmakon. We drew down $100 million of a $500 million commitment at the close. We have $150 million available on FDA approval, and then another $250 million available upon certain commercial milestones. So together with the cash on the balance sheet and the cash available from the Pharmakon facility, we believe we're fully funded for lorundrostat commercialization.
How are you thinking about expanding the pipeline, maybe starting other trials and additional adjacent indications?
We do have the intention of doing additional R&D. We haven't publicly talked about where the next step is, but when the time is right, we will disclose, and we think there's an opportunity for broadening the potential penetration into hypertension with lorundrostat, as well as potentially looking at other indications.
If baxdrostat, I think they have trials going on in primary aldosteronism, CKD heart failure. If they expand into those additional indications, could you see any impact to lorundrostat? Could they have competitive advantage with those doctors that are prescribing in those indications?
No, over the last five years, having gone, and I was just at the European Society of Cardiology, and I've seen the interest and the focus on aldosterone just progressively grow. It just continues to build. We're seeing, obviously, baxdrostat, lorundrostat, I think being the first transformation from an innovative standpoint in hypertension in 20, 25 years. You see AstraZeneca doing additional programs like you identified, most of those with fixed-dose combinations with dapagliflozin as part of the life cycle management. Boehringer Ingelheim is doing the same. I think there's going to be a class benefit to a degree. As Adam said, we're not done by a long stretch with the development of lorundrostat.
I do not know if we are in a place where I would guide that we are going to do a large outcomes trial, but we are certainly going to continue to add to the clinical data that supports what we think is the best-in-class ASI. I think there is both competitive tension and competitive opportunity as more and more data comes out and shows the value of targeting aldosterone in these cardiorenal metabolic conditions that are frankly, slowly kind of merging into one treatment approach as you see things like the CKM guidelines come out from the AHA. You need to be thoughtful about everything from metabolic to vasculature with hypertension and everything in between. We think lorundrostat stands to be a key player within that over the next several years, decade.
AstraZeneca has framed a $5 billion opportunity across those indications that they are going after. I know you are not going to give guidance on how big you think the opportunity is, but just how do you think about the opportunity in hypertension alone?
Yeah. To your point, I am not going to give guidance on a peak sale revenue like that. I think it comes down to fundamentally these 20 million patients that continue to cycle through in trial and fail to get to goal, the impact and import of getting to goal relative to improved outcomes across the spectrum, kidney, heart, brain. We just see such a benefit if patients can get to goal. I think that number that they have staked out there represents the opportunity for clinically meaningful innovation like the ASIs, and specifically that lorundrostat provides. That is where our focus is. That is why Eric and his team are working the way they are to ensure a successful launch of lorundrostat to address that significant market opportunity. As he said, this is not about a battle, baxdrostat, lorundrostat.
This is about getting a new treatment armament material like ASIs into the space and really providing better alternatives than what there currently is in third and fourth line.
Perfect. We are out of time, so we will end there. Thank you so much for being here.
Appreciate it.
Thank you.
Appreciate it.