Mineralys Therapeutics, Inc. (MLYS) September 2026 Conference Transcript

Hi, everyone. Thanks for joining us at the Wells Fargo Healthcare Conference. My name is Sadia Rahman. I'm one of the biotech analysts here at Wells, filling in for this session for Mohit. And it's my pleasure to introduce Mineralis Therapeutics. For Mineralis, we have John Congleton, CEO, Adam Levy, CFO, and Eric Warren, Chief Commercial Officer. So thanks for being here. I'll hand it over to you for any opening remarks, and then we can get into Q&A.

Yeah, we're appreciative of the opportunity to join the Wells Fargo Conference. It's always a productive time for us. Look, we're very excited about the opportunity that's in front of us. Larendra's dad 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've generated went into the NDA that we filed late last year. I would say those dialogues continue to be productive with the agency targeting the PDUFA data of December 22nd of this year. I'm sure we'll 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. So we're excited about the opportunity in front of us. We're excited about the opportunity of really making a meaningful difference in the lives of patients that are dealing with uncontrolled and resistant hypertension with equal understat stands to be a really transformative treatment for those patients.

Great. Yeah, so as you transform into a commercial stage company now, You know, I'm sure there are a lot of changes as an organization. Maybe can you just give an overview of the changes, you know, where you are now in that transition, any remaining work that's 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 will understand. at. So 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. And 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 Pidoof and eventual launch in June. And so making payers aware that there are gonna be two ASIs, the value proposition of Lorondrastat. 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 can build in 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. And then as we've guided, our intent is to have our sales force in place ahead of the Padufa date that would enable us on presumed successful approval, rapidly moving and into launching it in Lerunderstat 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 Lerunderstat? We're not done with the clinical work. We're continuing to evaluate where do we wanna go next with this transformative agent, but always with a mind to be lean, being efficient, and really focused on value that we can generate with each person that we bring into the organization.

And in the launch, like, what metrics do you plan to provide investors to help gauge, you know, 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 access, accessible choice, if you will. Eric can talk more about that, but creating an 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 to 50 percent 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 omni-channel tapping into the efficiencies of digital and so all of that we'll 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 or understand, but probably guiding to that later this year, maybe early next.

Are you saying anything about those 50,000 prescribers, how you're planning, like your strategy for covering that prescriber base, you know, 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 kind of a layered approach with that. I think those, you know, 50,000 or so physicians, we would have intent to address the vast majority with Salesforce and then overlay that with omni-channel. That digital strategy enables us to go beyond the 50 but do it in a very efficient, high ROI way. And that's part of what we would be looking to provide guidance on once we get to the appropriate stage to provide that.

Great. So 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? And, you know, 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 mineralysis formation. So it informed how we did our proof of concept program and 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. So that third line or later is where our data really resides. And we don't see a difference in response, whether it started third line or fourth line. So 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 go on countless drugs so 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 we want to be able to move earlier within that and I think that's that thesis is validated from what we're seeing in the early days of the Baxter stat launch I think the 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. And I think more importantly, if you dig kind of deeper beyond just line of therapy, if you look at the data that we've generated, we have diversity within those populations. So 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. So we have data sets that speak very specifically to females with uncontrolled and resistant hypertension and certainly with black African-Americans. We had 28 percent of our 1,082 subject study were black or African-American and ADVANCE-HTN to confirm uncontrolled and resistant hypertension was 53 percent. So we're not only going to be able to just speak to fourth line but to very specific sub segments 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? And when are we expecting the guidelines to be updated, and how could ASIs be reflected?

Yeah, so gaining experience in fourth line is a natural kind of 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 27 which will time well with our launch.

And what are you hearing from KOLs I think you indicated right now they'll start with fourth line use but just about how they might evolve use might evolve to to include third line patients like how quickly could that happen fairly rapidly the comorbid conditions create a bridge so there's more likelihood of those third-line patients that have CKD, for example.

But there's a real need to address this culprit, if you will, aldosterone, which is contributing to uncontrolled and resistant hypertension. So fourth-line early opportunity, third-line comorbid bridge, which then translates into broader third-line use.

Got it. Let's just talk about pricing. So how are you thinking about pricing and rebate strategy to support broad access while also competing effectively with AstraZeneca?

Yeah, and 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. So I don't want to create a kind of a downward spiral. role. 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 kind of 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.

I think, and just to add to that, I, you know, we've, we've got a price out there now with Baxter stat at $900 per month. I think it's 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 agencies ASI is staying to be.

And how are pairs valuing this class versus older alternatives like spironolactone? And are you seeing a lot of step edits required today, especially with MRI?

Yeah, I think the research that we've 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, I mean, the payers understand how these patients are cycling through countless meds, still not getting the goal. The payers understand the implications, particularly in resistant hypertension, to outcomes and their overall cost. So I think that the economic clinical value is clearly appreciated. And I think what we're seeing play out in the early days of the Baxter stat launch is an exhibit of that. So rather than just being research, we're actually seeing a case study in front of us right now. And, you know, 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 gotten asked about more times than I care to comment. And it just, the market research didn't support that. In reality, we're not seeing a PA through that. We're seeing a step at it, you know, failing, you know, 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 at a process right there. So 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-adets or utilization management related to failing to get to goal on pre-existing meds.

And 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. So 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.

And 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, you know, 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, you know, so from 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 gonna get drawn into comparisons, the low-undercept Baxter stat. 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 goals. So beta blockers, alpha blockers, calcium channel blockers, There's all of these older drugs that just provide incremental clinical benefit and not the kind of meaningful benefit that we see right now. So the goal is parity, ensuring access to both, and then really allowing physicians and patients to make the choice.

Got it. So not a rebating strategy for preferred positioning, but parity access to Baxterstat.

I think it's an accessible choice.

And just talk about Medicare formulary access. You know, how much could lack of Medicare coverage in 2027 impact the uptake curve?

So we'll point back to BaxterStat launch. And BaxterStat is gaining Medicare utilization. So Medicare, to kind of cover that period where there is not preferred coverage, creates a medical exception opportunity that is typically to label and we're seeing those patients now flow into Baxter stat via that medical exception so anticipate something would be very similar for lower under set got it and now that Baxter has launched and we're seeing some of the early numbers what are you learning about prescription trends maybe patient makes prescriber mix and physician willingness to use ASIs in various settings?

Have there been any surprises relative to what you expected?

I mean, 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 and in patients we've also seen the type of practitioner validated so primary care cardiology nephrology are ultimately prescribing and those are those high volume uncontrolled resistant primary care providers and we're also seeing the spectrum of coverage so we're seeing commercial Medicare some Medicaid come into play as well and then as John mentioned earlier we're seeing fourth line represents about 80 percent of their patients but 20 percent of their patients have been in that third line

position at it I'm just wanted to talk about that Lauren just adds clinical profile you know what we've seen from the trials and how could that be reflected in the label so advanced HTN do you expect that to be represented separately in section 14 of the label and you know which physician segments could find that most valuable and how could it help drive uptake.

Yeah I mean all of this is gonna be pending negotiations with the the FDA on the label that'll happen a little bit later this year. You know through the course of the dialogues we've had with the agency they've always been very productive supportive you know uncontrolled resistant hypertension is a target for HHS and that reads through the FDA as far as being a good partner giving us guidance. I think one of the things that resonated with me and some of those dialogues was they view the label as a way to inform the prescribing audience on how to use a drug and so from our standpoint when we submitted the NDA we put three studies into the NDA and had them represented in some in distinct ways within the label. And as it comes to Section 14, it was launched HTN, again, the largest hypertension trial done with an ASI. The data there we feel is very compelling, absolute reduction of 19 millimeters of mercury, placebo-adjusted 11.7 with really low incidence of hyperkalemia above 5.5. That data we fully expect to be represented in Section 14. I mean, ADVANCE-H10 is one of the most distinct hypertension studies done, and certainly within ASI, it's 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 lorunderstat can be used with really high-dose ARB, high-dose diuretic, and in some of the patients, high-dose calcium channel blocker. And that's really a study that's gonna inform from your specialist, your cardiologist. And then explore CKD, the blood pressure data that was generated out of that study, again, we're gonna argue should be part of the label because as Eric pointed out, hypertension does not exist alone. There are comorbidities, so being able to speak to what Larendrostat can do in a lower kidney function population from a blood pressure standpoint is important. Plus, we'll also be on section 14, look at other parts of the label where we can differentiate. And Explore CKD basically speaks to experience in subjects with an EGFR as low as 30. Baxter's stats label speaks about experience above 45. And so, you know, again, these are all partner negotiations we'll 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 LORunderstat and what to expect when they do.

Apart from Explore CKD, you also presented recently a post-hoc analysis of LaunchHTN and people with CKD. What does that analysis tell us about the benefit-risk profile of lorandrostat, specifically hyperkalemia risk in those patients?

Yeah, we were really excited to share that data at the European Society of Hypertension meeting in June. And what we did is we took LaunchHTN, 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 a higher rates of albionuria and wanted to look at not only their blood pressure change as a subset but also what happened to their UACR and over the 12-week period we saw about a 52% reduction in improtinuria which is a real marker for renal progression so it allows physicians to have a sense for if they're using lorunderstatin in a patient who has uncontrolled or resistant hypertension and comorbid either CKD or protein or albinary that they're gonna be able to see a benefit on that 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 and so we think that was a really important data set that affirms what we saw in explore CKD but over a longer term period.

As far as the doses that could be reflected in the label, you've looked at 25, 50, 100 megs in your trials. Can you discuss how much support there is for the 25 meg and if you could see that reflected as a down titration option in the label?

Yeah, we included both 25 and 50 in our package submitted to the FDA. We believe there's utility for both. I think the 50 milligrams will be the recommended starting dose, but the 25 milligram is there for those patients that may be more compromised from a renal standpoint. The 25 milligram is what we said in an Explore CKD study, knowing that these patients are gonna be more sensitive to electrolyte changes just because the impaired renal function, but 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. But our goal is to get both doses approved. And again, the 50 milligram being the predominant starting dose for most patients, but knowing that they can use 25 in distinct populations and not give up on the efficacy side.

And we've seen the hyperkalemia rates reflected in the Baxter stat label when they're summarized in the label for lorandrostat, like what potassium threshold and methodology do you expect the FDA to 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, factitious 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 and what was confirmed. I would anticipate though it'll be the confirmed data that will 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 Would that be different from what's reflected in Baxter's stats label? 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, I think it's around 12%, and what we've seen within the LAUNCH-HTN study was about 6.5%. So I would say we'll probably end up landing somewhere in that regard as it relates to the label.

And then the frequency of potassium and sodium monitoring is left to clinicians in Baxter Stats 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. And I think the ACE inhibitors and ARBs condition physicians for a pretty standard treatment paradigm that the ASIs are going to fit in very nicely. And 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. and then bring subjects back in about two to 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. And so the profile of lorandrostat fits very easily into the existing workflow that physicians have and how they're managing their hypertension patients in both measuring efficacy and also looking at safety markers.

Maybe if they have experience with spironolactone, like they're familiar with how to monitor for hyperdome.

The experience actually comes out of the ACEs and ARBs. We see the same thing. 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 thing you see with the ASI. So 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, Spiron-Lacton.

Okay, so as you get, just wanted to ask a few questions on partnership. You know, 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?

So 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 their understat that could look like a partner that helps commercialize more broadly around the world, potentially help develop their understat. We haven't given specifics on conversations or sort of updates on how that's going.

Mm-hmm. 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 laurandristat in-house, or are you seeing interest from companies more broadly?

It could be, but it doesn't have to be. I think that the really, if there is a desire to work in this space, I think Lerunderstat could be sort of 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?

So 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.

And in your discussions, partnership discussions, are potential partners focused on the broader opportunity, broader cardiorenal opportunity, you know, with development and additional indications, or are there some that are solely focused on hypertension?

It's certainly of interest to us. As John mentioned, aldosterone is a node that's important in a variety of diseases. And our first sort of step has been to go into hypertension and then deepen in hypertension. But there's other disease areas that could be of interest. 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?

So 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 Pharmacon. 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 Pharmacon facility, we believe we're fully funded for their understat commercialization.

How are you thinking about expanding the pipeline, maybe starting other trials and additional adjacent indications?

So 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 our understat, as well as potentially looking at other indications.

If Baxterstat, I think they have trials going on in primary aldosteronism, CKD, heart failure, if if they expand into those additional indications could you see any impact to lorandrostat you know could they have like competitive advantage with those doctors that are prescribing in those indications no i mean there's there's a over the last five years having gone and i was just at the european society of cardiology i mean and i've seen the interest and the focus on aldosterone just progressively grow and it's just continues to build we're seeing obviously BaxterStat, LerunderStat, I think being the first transformation from an innovative standpoint in hypertension in 2025 years. You see AZ doing additional programs like you identified, most of those with fixed dose combination with that, but glyphosone as part of the life cycle management. BI 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 lorunderstat. I don't know if we're in a place where I would guide that we're going to do a large outcomes trial, but we're certainly going to continue to add to the clinical data that supports what we think is the best-in-class ASI, and so I think there's both competitive attention 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 is you see things like the CKM guidelines come out from AHA and say you need to be thoughtful about everything from metabolic to vasculature with hypertension and everything in between. And I think Laura understands to be a key player within that over the next several years, decade.

And AstraZeneca has framed a $5 billion opportunity across those indications that they're going after? I know you're not going to give guidance on how big you think the opportunity is, but just how do you think about the opportunity and hypertension alone?

Yeah, you know, to your point, I'm not going to give guidance on a peak sale revenue like that, but I think it comes down to fundamentally these 20 million patients that continue to cycle through and 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. So I think that number that they've staked out there represents the opportunity for clinically meaningful innovation like the ASIs and specifically that LaRunderstat provides. So that's where our focus is, that's why we're, you know, Eric and his team are working the way they are to ensure a successful launch of Lerunderstat to address that significant market opportunity. And as he said, this is not about a battle Baxter-Stattler-Lerunderstat. This is about getting a new treatment armament area like ASIs into the space and really providing better alternatives than what there currently is in third and fourth line.

Perfect. Well, we're out of time, so we'll end there. But thank you so much for being here. Appreciate it.

Thank you again. Appreciate it.