Hey. Good morning, everyone, and welcome to the Mineralys Therapeutics session. Happy to have Jon Congleton, CEO of Mineralys, with us this morning. As you know, Mineralys is developing a new class, or has developed a new class of drugs, aldosterone synthase inhibitors, for uncontrolled and resistant hypertension. Jon, why don't you give a quick overview and the lay of the land, and we'll just launch into questions.
Yeah, happy to do it, and good to see you, Annabel, and thank you again to the Stifel team. Always enjoy the conference and the opportunity to talk about Mineralys. As you said, we're thrilled to be a part of a new class, aldosterone synthase inhibitors. As Annabel knows, I started my career as a sales rep in this space, and I've seen how transformative new treatments can be.
Given the fact that about half of the treated patients in the U.S. cannot get to goal with currently available treatments, I think having innovations like aldosterone synthase inhibitors and lorundrostat are really critical. We've spent the last 5+ years, I think, building a very robust, diverse data set that went into our NDA about a year ago.
We are progressing towards our PDUFA date, December 22nd, of this year, and have progressively built out a readiness to ensure that we have a successful launch going into 2027.
Great. Let's talk about that PDUFA date. December 22nd, is obviously approaching very quickly, and you have a, I would say, a pretty impressive large trial package. How are you seeking to leverage that wealth of data that you have to support a differentiated label? Can you potentially get a differentiated label rather than just standard uncontrolled resistant hypertension?
Yeah. The PDUFA remains on track. I think if I think about the label, there are going to be some similarities and there will be some differences relative to what baxdrostat got this summer. The similarities are going to be the indication. It is for the treatment of inadequately controlled hypertension on top of background medications.
There is also going to be a statement about reduced blood pressure, reduces the risk of stroke, MI, and cardiovascular disease. That is based on FDA guidance from 2012, and so that will look similar. Where the differences obviously come is in the body of the label, certainly section 14.
We really efforted to create a data set that reflects the population that physicians are treating when they are treating hypertension, and there is a lot of variety. There is variety in gender, race, age, obviously, but there is also a lot of overlapping comorbidities.
The work that we did with our Explore programs, looking at the benefit of lorundrostat in patients with comorbid CKD, the OSA study, and comorbid OSA, obesity, how much of that will be reflected in the label will be known by December 22nd, 2026. But I think fundamentally, having that wealth of data is going to be important for the medical community to know how to incorporate lorundrostat into their treatment paradigm.
We have different vectors to do that, right? We have the promotional team, sales and marketing. We have med affairs to disseminate publications and make sure that KOL interactions, they understand not only the data within the label, but just our broader data set and how to appropriately use lorundrostat.
When you think about the package that they have and the population that you have studied, where do you think physicians are going to be most comfortable using the drug first?
We have built a data set looking at patients failing two or more meds. So that is third line uncontrolled and fourth line resistant. I think the low-hanging fruit will be the fourth line, so the resistant hypertension population. It does not mean that we will not be promoting for both, but I think based on initial trial by physicians, initial access, fourth line is going to be the predominant area.
As far as patient subtypes within that, again, I think that is where the diversity of the patient populations that we have for fourth line can speak to it very broadly. Case in point, Black African Americans are probably the highest risk population as far as most difficult to get to their respective goals. We had 29% and 53% of our two pivotal studies were Black or African American. So physicians do not have to presume that the drug is going to work across race.
We can show them the data and say, "Lorundrostat works equally well." That is important because there is variable response based on ethnicity. Having data, not only the Explore CKD study, but Launch-HTN, we presented a subset analysis of those patients with CKD.
Really robust and meaningful reduction in blood pressure, reduction in UACR. It is these pockets of patients, and again, by physician type, primary care, cardiology, nephrology. I think we have really exquisite data sets to really speak to the specific patients they are seeing.
Can you just remind us what Baxfendy has as far as where they can position the drug in the marketplace?
Baxfendy, similar construct in the number of background meds. They looked at patients failing on two or more. Similar in that regard. Third line and fourth line is where they can position it. I think we have a little bit more diversity within our studies, both on gender and on race. I think just what has been published to date, a broader population, or broader background as far as comorbidities, things like OSA and obesity.
Okay, great. Maybe you can talk to us, okay, before we get into how you are going to launch this drug. Can you provide any color from any of the mid to late cycle stage meetings that you had with FDA? Like, any further requests post the 120-day safety update? What type of post-marketing requests might they make of you?
Yeah.
Have you do?
Yeah. I will reiterate, December 22nd, is where we are tracking to. I would characterize, because we have not really gotten into the details and specifics of where we are, but I would characterize it as kind of normal course.
You made the point, I think we have a very meaningful and robust data package that we were able to put into the NDA, very well characterized, and including Explore-CKD in the lower eGFR population, giving a full picture of lorundrostat across the spectrum of hypertension. So, feel very confident in that December 22nd date.
Okay. Baxdrostat is launched already, Baxfendy. I guess without head-to-head data, or cross-trial comparisons between the two, how are you preparing to speak to physicians about, and maybe even the payers, to evaluate lorundrostat relative to what is available to them right now?
Do you think that there is something that clearly distinguishes the two outside of just data? Are you expecting counter-detailing, or are you just planning to launch lorundrostat? Hopefully you get an easier name to say because it is killing me.
You want to buy an R?
Are you just launching the drug on its own merits, or are you going to start counter-detailing? How are you going to position it?
Yeah, it's a great question because as I meet with investors, I get asked, "Juxtapose lorundrostat and baxdrostat." I think that's missing the bigger boat. I think the real interesting opportunity is ASI relative to what's available right now.
Why that's important is there's a lot of meta-analysis that would say when you add a third or a fourth line agent of what's currently available of these generics, you get maybe 5-7 mm mercury reduction. I think that's why the medical community is really excited about the ASI class, is because you're seeing really meaningful reductions in these patients that cannot get to go on two or more meds.
Whether they're uncontrolled or resistant, in the case of lorundrostat from Launch-HTN, you're seeing a 19 mm mercury absolute change and about 11.7 placebo adjusted. I mean, that's not currently available to physicians right now, an aldosterone-directed treatment that patients can tolerate, that physicians want to prescribe.
I think my view, and I think there's literature that supports this, when you get a patient that's not at goal on two, certainly three, and beyond meds, it's likely aldosterone that is kind of still that final culprit that's really getting in the way of patients getting to goal. I think that's validated by the kind of data that we've seen.
For me, job one from a communication standpoint is not to go baxdrostat, lorundrostat, back and forth. It's to talk about why choose an ASI over an alpha blocker, a beta blocker, a calcium channel blocker, an MRA. Then once that's done, then yes, what are the similarities, what are the differences between lorundrostat and baxdrostat?
That's where I feel very confident that once the community sees that ASI is the way to go, then we'll make the comparison between the two. I think we've got a very good case that when a physician has chosen an ASI, that lorundrostat is the way they're going to want to go.
Do physicians know which patient, does the patient present in a certain way other than uncontrolled or resistant hypertension? Is it very easy to clinically diagnose which patient would be responsive to an ASI over something else?
It's a really fair question because right now, there are no markers. In other words, right now, if you were on three meds and went in and your blood pressure was still not controlled, there aren't markers that would guide and direct what a physician should choose.
It's a little bit of just trial and error going forward. In the case of the aldosterone synthase inhibitors, we're seeing the medical community progressively talk about getting aldosterone measurements, getting renin measurements, doing an aldosterone-renin ratio. I think fundamentally, given, like the case of lorundrostat,
You take lorundrostat, within two weeks, you're going to know if your patient's going to respond or not. That's durable, we've showed in Chicago out through 48 weeks. I don't know if, even though the medical community's thinking about markers more, I don't think it's going to be necessary.
I don't think it's a practice that is going to be incorporated immediately. It might in due course. I think where the fit is going to be is if a physician has a patient on three meds, they're still not at goal, and they see certain characteristics that they feel matches up to the data that we have.
Again, Black African American patient, maybe a female patient, if they have CKD or if they have OSA, that may be the initial trigger. Now, we know lorundrostat works Black or white, male or female, but there may be certain pockets that trigger for them and they get that experience. That's where I think there's a real opportunity to convince them that aldosterone's probably the problem.
ASI is this nice new innovation that is going to help you get a significant portion of them to goal, and lorundrostat has the most breadth and diversity of a dataset to really inform how they would prescribe it.
Okay. Where are you in terms of talking to, in terms of altering the guidelines?
Yeah. There are multiple guidelines out there, and directives, and things like that. We have identified all the different KOLs that are on the committees, had good dialogues with them. Obviously, they want to be a little bit standoffish and have independence, and I appreciate that. But we make sure that they have got the information, they have got all of our studies, they are up to date on most recent publications for the data that we have.
I think we are seeing progressively some of the guidelines come out. My expectation is the initial guidance will be fourth line and probably on par and parity to MRAs, and it is ASI/MRA as suggested option at fourth line. I think as data continues to progress, as experience progresses, we may see that move sooner within the treatment paradigm, third line.
The guidelines are helpful, they are informative, but they are not adhered to strictly by either physicians and/or payers. I think they are, as stated, they are a guideline. They help inform. But just because an ASI is viewed as fourth line does not mean physicians are going to trial it third line, and it does not ultimately, is it going to restrict us from third line from an access standpoint.
Okay. You did mention something where people have asked a lot of questions around. If the guidelines are that MRAs and ASIs are at the same sort of level, how are the payers approaching step-throughs of the MRAs? We know they're not ideal for this condition. I know that patients can't stay on it that long,
Right.
Tolerability, but how might that affect your ability to come before or at the same time as MRAs?
Yeah. I think that's one of the things that's been really validating about the baxdrostat launch.
Yeah, I was just going to ask you, what has Baxfendy been experiencing there?
Yeah. That is the great thing.
They are blazing the trail for you.
Exactly. The good news is we have had our account management team in place since Q1, so we are getting this real-time feedback from these payers as well in the dialogues about lorundrostat. We are also seeing in real time what is going on with baxdrostat. The bottom line is, it is not, in the vast majority of cases, a step-through MRA.
The utilization management is actually fairly straightforward, and by plan it varies, but it is a look back in their electronic medical record, and do they have a history of having uncontrolled blood pressure, and are they on either two or three, in most cases, three medicines, and it is a basket approach. It does not matter what those three are. It can be an MRA, it can not be an MRA.
As long as they have been on three or more meds and are failing to get to goal over a certain look-back period, then that becomes the step edit. That is validating because that is what the research has told us over the last five years as we have gone out and talked to payers. They understand, particularly when you get into resistant hypertension, these are the more obviously at-risk patients.
They have had uncontrolled hypertension for a longer period of time. They are the ones that are at the risk of stroke, heart attack, progressive kidney disease, so they become more relevant from an economic health standpoint for these payers. They also, certainly the pharmacy directors, understand the issues and challenges with spironolactone and know it is not a de facto choice to force patients to go through if they want to go to an ASI.
We're seeing that play out in real time right now.
Okay. I guess to that point, ICER had come out with an October 29th panel and found that ASIs have similar blood pressure effects as spironolactone or eplerenone or maybe even amlodipine.
Are there any Again, you've mentioned that probably not, payers understand that, but ICER is not putting out Is a potential recommendation by ICER saying that they're not seeing any greater benefit from ASI is going to affect anything that happens from a reimbursement perspective for any of the ASIs?
Yeah, from my vantage point, no. I appreciate ICER's remit. We have some fundamental disagreements in populations they looked at, methodology that was used. Comparing to agents that just aren't used doesn't make sense to me. I'm sorry. Because they looked at spironolactone, eplerenone, and amiloride, so a sodium channel inhibitor. They're just so rarely used. They're saved for later in line.
They should, frankly, any aldosterone-directed treatment should be used much earlier because we know the prevalence of dysregulated or elevated aldosterone. So, while I appreciate their remit, I think fundamentally we view the methodology behind that differently. I think we're seeing that with the payers as well. They appreciate the innovation of an aldosterone-directed treatment that physicians want to use and patients want to stay on.
It's a part of the ecosystem, but I don't see it as a hindrance relative to the value of the data we have and the need that's in the marketplace.
I guess payers do not feel compelled to use the ICER data at all. I mean, ICER puts out a recommendation, but no one really needs to use them?
I don't want to say nobody uses it. It probably becomes part of the calculus, but in our discussions, it's not a barrier.
Okay. One more, I guess, bit about the data that you have. How do you think that you can leverage the Launch-HTN and the Explore-OSA, or I'm sorry, Explore-CKD? I can't remember the name of the trials.
Lots of studies.
You know, OSA, Explore, all of those. CKD, OSA. How might that resonate with physicians? How do you plan on leveraging that data?
Yeah. Some of the Explore studies and the data from that were part of the submission. Explore-CKD was. Explore-OSA was not because that study read out subsequent to the NDA. Some of it is within the published medicine realm.
We've got a really strong medical affairs team, both in the field interacting with national and regional KOLs, but it's also, frankly, part of our publication plan, which is becoming progressively more important as you think about things like OpenEvidence, Doximity, all of these AI aggregators of information.
They're pulling from posters, abstracts, presentations, and manuscripts. Getting this information out that again speaks to where the field's going. There was a presentation, I missed it unfortunately, Monday in Chicago at the AHA, but it's talking about the treatment of CKM. It's this progressive shift.
It's been interesting over the six years I've been involved with Mineralys that it's not just hypertension, it's not just diabetes, it's not just CKD, but these things are all interrelated.
What does the CKM stand for?
So, cardiac, kidney, metabolic.
Okay.
It is everything. I am surprised that it has taken this long to get this energy behind it. Maybe it is some of the innovations that are coming now between the SGLT2 several years ago, the GLP-1s or anti-obesity treatments, ASIs. I think you are progressively seeing physicians trying to think a bit more holistically about those CKM conditions. We kind of saw that writing on the wall and wanted to progressively build out a robust dataset.
In the case of Explore-CKD, that we may see in the label, there were two places that that was really informative. One was special populations. So experience with lorundrostat down to eGFR of 30. We know baxdrostat's label says it is experienced down to eGFR of 45. Our two pivotal studies looked at eGFR 45, but Explore went down to 30.
Being able to go to a nephrologist and say, "If you have got an uncontrolled resistant hypertension patient with CKD down to eGFR 30, here is data that shows you what you can expect with lorundrostat." Not only on kidney function, on blood pressure, but also safety and electrolytes, because that is an important consideration. Explore-OSA is not in the label per se, but again,
That was a severely affected OSA population, AHI score of 48, very obese, BMI of 37, and just in a four-week period of time, saw an 11 mm mercury drop in systolic blood pressure. We did not see an effect on OSA, unfortunately, with AHI, but we clearly saw an effect on blood pressure. Again, it is kind of meeting the doctors where they are because these doctors are dealing with hypertension patients that are complex.
Okay. Maybe we can get into the launch expectations. How should investors think about, let us just say 2027 launch costs first, because I am sure the trajectory is not something you can speak to at this point.
Right.
Who you are targeting first. I imagine it would be cardiologists, but maybe you can segment the cardiologists for us a little bit.
Yeah. Maybe let me take a step back. We brought in our chief commercial officer in April of 2025. He built out his leadership team in the summer of 2025. So we have been progressively building towards launch readiness.
In Q1, as I noted, we put our account team in place, so calling on PBMs and insurers, making them aware of our data package and our plans coming forward. In Q2, we upsized our medical field team so that we could get deeper into the KOL aspects. Then, as we noted in our earnings call last Wednesday, our sales team is fully in place.
At this point, they are getting trained, they are getting out into their geographies, acclimating, meeting their customers, ensuring or confirming the targets that we have identified. So those targets are really a mix of predominantly three specialists: primary care, high-volume primary care, cardiologists, and nephrologists.
We have, from the last several years, really been focused on the 45,000- 50,000 doctors that control about 40%-50% of third-line or later prescribing. I know people think about hypertension,
They think about you need tons of reps for all of these doctors, but when you get into the latter lines of treatment, it really begins to narrow nicely. And those 45,000- 50,000 doctors only control a high percent of the prescribing, but they influence the other part of that.
This build-out that we have done from account management to ensure access to our MSLs, to our sales team, is really predicated on, let us target those high-volume prescribers out of the gate. And it has been interesting to see the baxdrostat launch and the data they have, as far as source of scripts, because it is a little over half primary care.
It is probably about 20%, 25% cards, and 20% nephrologists. And the nephrologists were a little bit of a surprise. We did not see that prior to the baxdrostat launch in the kind of nationwide data for third-line or greater prescribers. The nephs did not show up as much, but they are obviously embracing the ASI class, which I think is a positive for us, given the kind of data that we have.
Right, and it's probably also because of AstraZeneca's presence in the nephrology area.
Possibly, but I mean, I. Yeah.
Yeah. I guess, I know a few investors kind of looked at the baxdrostat launch and saw their result from this quarter or this past quarter and got a little bit nervous. What do you think is happening? What dynamics are you hearing? Is it fair to even look at their sales at this point and draw any conclusions? Shouldn't they just be looking at the scripts?
To me, right now, it's about scripts. The scripts that, looking at the same data that you're looking at, to me, is validating. I think it's promising. It's showing that there's market access there. It's showing that there's demand there. We also don't have visibility to everything, right?
There may be patients in the hub, there may be free goods patients that aren't showing up. Just the RXs themselves, I think, are very promising. That's kind of where my focus is, to look at revenues in early quarters. There's just so many vagaries in there and how they account for free goods and bridge and coupons. It's just hard to tell.
What kind of specialty pharmacies or hubs are you creating for patients to facilitate adoption?
Yeah, that's a really critical part. As we do market research with physicians, I mean, they absolutely respond very favorably to the efficacy, the safety of this molecule. Their big question is, all right, access. Is it going to be easy to access? This won't be through specialty. It's small molecule through retail. But we have hired just a top-notch team to basically help build out our PSP hub system.
We've got great partners that we've identified throughout this value chain that makes it very easy for a physician, once they've decided to prescribe lorundrostat, and a patient, they've decided they want to take it, to get access to it. That's really a double-pronged strategy of, how do we make it easy for the office? So, take that burden off of them.
How do we make it seamless and transparent for the patient and build that out? That's another component of the launch readiness that we've got in place.
Are you creating your own hubs or possibly leveraging other pharmacy fulfillment centers or prescription fulfillment centers?
Yeah, we've got our internal team leading that, but it is leveraging existing infrastructures. There's a lot of partners within that. I feel good is just how we'll make that seamlessly all fit together.
Okay, great. I guess as we're coming to the tail end of this, maybe you can talk about the cash that you have right now. You said, I think on the call, that it was sufficient to fund you through 2028, which is part of, I guess, the beginning of the launch. You also have, I believe, a $500 million,
Secured loan. What are the conditions where you'd be drawing on that loan rather than potentially going back to the markets for additional cash?
Yeah. As you noted, we stated in our Q3 call, $625 million in capital right now. We did the facility this summer, $500 million, pulled 100 at the close. Upon approval, we'll pull another $150 million. That leaves another $250 million that really kind of gives us flexibility. It's at our discretion.
Should we need it, should we feel that we want it, to give us some flexibility from a capital standpoint. We feel fairly comfortable, obviously, getting into 2028, but that we've got the cash and access to capital on hand to get us through the launch of lorundrostat. That is inclusive of what we did this summer. I think it was really important what we did with buying back the royalties.
I was just going to ask you about the royalties.
Yeah.
What the rationale was behind that.
Yeah. It was opportunistic. We found out that because Bain had bought Tanabe, that Bain was looking to monetize the royalties. It was happening imminently, so it was either going to be us or somebody else. We said, "We cannot let these go by if we think we can get them for quite the deal." I think fundamentally, we did.
No matter whatever scenario we play out, if it's us launching on our own, if it's with a partner, if it's an M&A, that investment made a ton of sense. As we go into the commercialization of lorundrostat, I'm thrilled. I mean, the royalties weren't onerous, but they were meaningful, 6%-10%. That now flows to the bottom line for us. That gives us strategic flexibility, as we think about access, as we think about price points.
Between making that move, I think that clearly drove value for us. The cash that we have on hand, the capital we have access to, I feel very comfortable going into the launch year of 2027 that we're going to be not only ready for launch, but have a very meaningful launch and have significant share of voice relative to AstraZeneca.
Okay. That is all the time we have, so thank you.
Yeah. Thank you.
Okay.
Appreciate the opportunity.
No problem. Take care.