From Mineralys, I have here with me today Jon Congleton. Jon, thanks for joining us. Just gonna hand it over to Jon for some opening remarks before we dive into some Q&A.
Thanks, Tina. Appreciate it. Appreciate the opportunity to participate in the Bank of America conference. It was a positive conference for us. Jon Congleton, CEO of Mineralys. We had a very productive year and a half, I would say, like last year with a lot of data readouts culminating in the submission. We had our earnings call last week, announced that, you know, in Q1 we had the acceptance of the NDA, significant milestone for Mineralys. It puts us one step closer to getting lorundrostat to patients that fundamentally need this drug. That NDA, I'm very proud of what the team put together. I think it's a very distinct and differentiated data set that is going in front of the FDA for review.
Effectively five clinical trials showing very consistent, robust benefit that lorundrostat has on lowering blood pressure, doing so safely with predictable profile that I think fits easily into the current use case that physicians have for those uncontrolled and resistant hyper. We talked past. Is that better? Obviously only you in the room got the opening preamble. That data set, to me is very important because it speaks to the 20 million patients in the United States. that are on two or more meds and cannot get to goal. For those of you that have met me in the past, you know I started my career as a sales rep in the hypertension space, and so I saw the great innovation and how transformative that was in the '80s and '90s. We've lacked innovation, fundamental innovation for 20, 25 years.
Aldosterone is the uncovered target that's gonna help a significant portion of those 20 million patients get to goal. We think the data set that we have generated to date shows that benefit. The market research that we do, whether it's with patients or physicians or payers, the demand, the intent to prescribe, the interest, the enablement of access is all there. I think really focusing in on, and we started guiding to this at our earnings call, the resistant hypertension patient population is probably the beachhead. That's the low-hanging fruit. That's where there's just continuous churn within this marketplace that notes the dissatisfaction with currently available treatments, that notes there's still energy and interest in trying to get to goal or get closer to goal, and that's where I think lorundrostat can certainly provide benefits.
This year with the NDA acceptance, we're continuing to prepare for a successful launch for this molecule. What that means is we've stood up a national account team in Q1. We're having those PIE or those pre-approval information exchange dialogues with the payers as we speak. We've got MSLs out in the field going deeper into the advocacy space. We know baxdrostat has potential FDA action coming up, but I think it's important to realize that while they may have six months ahead of us, we're not silent in that marketplace. We're having the dialogues with the key constituents, both payers and KOLs. They're gonna be important to really ensure we have a successful uptake of this drug, presuming positive FDA action later this year.
Great. You can dive a little bit more into some of the commercial things you outlined, you know, looking ahead to lorundrostat's approval and potential launch. With lorundrostat being about six months behind baxdrostat's launch, what are you kind of looking to learn from AstraZeneca's launch? Is year one more about establishing product differentiation or just building out market and awareness for this, you know, new approach in the HTN space?
Yeah. I think it'll be interesting to see the label. It'll give us some insight into the FDA, how they viewed that package. That'll be informative for us as we head into our negotiations with the FDA later this year. What studies were included, the indication, how Section 14, which has all the clinical data, then beyond just the approval, their launch, how they think about pricing, access, go to market, all of that'll be very informative for us. I think that creates a bit of an advantage being six months behind is to see all of those moves, and then we can kind of have our countermoves that we have in mind relative to that. The first year I think is gonna be a little bit of both.
I think it is going to be about building the awareness, building the awareness around the importance of targeting aldosterone, the use of an ASI relative to that, but also the differentiation between these two molecules, between these two data sets. Again, I think that that data package that we have is gonna speak very distinctly to the constituent prescribers within this resistant hypertension space. We know it's partially made up of cardiologists. It's why we did Advance-HTN. Probably the most challenging study done as far as any confirmed resistant and uncontrolled hypertension population. Launch-HTN, the largest ASI hypertension study done to date, will speak to the primary care prescribers. Things like Explore-CKD will also speak to the nephrologists who are dealing with patients with a lower eGFR with uncontrolled and resistant hypertension.
That is the number one target these nephrologists look for to help control CKD, and that is get their blood pressure below or down to goal where it needs to be.
You put some numbers around kind of physicians that, you know, are responsible for certain percentage of third line, you know, prescribing. About 60,000 physicians are responsible for about 50% of that third line HTN prescribing. What is that split between primary care versus specialist, and what role do you see dedicated sales force versus DTC playing?
You know, when we think hypertension, we tend to anchor to the 120 million patients that have hypertension in the U.S. alone. That immediately gives you this view, "Man, it must be a ton of prescribers." There are. When you begin to get further into the lines of treatment, that population narrows. It's a typical pyramid of prescribing. To your point, we've noted about 60,000 doctors control about half of the prescribing third-line and later. What's interesting about that is they also influence the other half because these are the, you know, kind of the top pyramid. They're usually in hypertension centers. Whether they're cardiologist or primary care, they're the ones that are driving the volume, and they're influencing the other part of the volume. The split is about 60/40 primary care to cardiologist.
It doesn't mean that there won't be nephrologist or even endocrinologist within that mix, but largely it's 60/40 primary care and cardiology. I think, you know, DTC is but a tool to use along this continuum. I think where I get excited about where we're at in 2027, which could be a potential launch year, is there are technologies, digital, that enable a company like Mineralys to actually act and be bigger than we are by foot. Certainly we'll have the appropriate sized sales force to affect the behavior of those 60,000 physicians, but we can also use digital non-personal power technology to extend the reach, augment those sales reps, get to white spaces where we may choose not to have sales reps, just as far as discrete use of the capital.
DTC, DTP, all of that may play a bit of a mix within that. Part of the goal, again, back to, I think your question, it's a combination of raising awareness of the role of aldosterone, the need to target aldosterone, and the differential story of lorundrostat.
You've kind of mentioned that fourth line setting, is where you at least initially see uptake for lorundrostat. Can you just speak to when we could see or when you expect expansion earlier to third line and what the drivers behind that could be?
I think the way we view it and what we hear in the market research we do, is at launch there could be interest, and there even could be access. As we talk to payers, it's not just fourth line and only fourth line. There are some payers that see the absolute need of helping their patients get to goal. You know, having their constituent, they being the payers, the PBMs, having their constituent population to goal is part of their quality score. Whether it's Stars or HEDIS, we're seeing hypertension and getting those patients to goal is becoming more and more important to payers. Fourth line is kind of the ideal target. Third line, where it really gets more compelling for payers, for prescribers, is when there are comorbid conditions.
If you have hypertension and CKD, which is why we did the Explore-OSA study because there's such an overlap of OSA with hypertension. Having those more complex patients, having a data set that speaks to that complex patient population is what I think begins to open third line. I think also just in due time, that fourth line utilization, having access created, having physicians prescribing, is then going to engender utilization earlier in the treatment paradigm. Fundamentally, that dysregulated aldosterone doesn't just suddenly appear in a fourth line resistant hypertension patient population. Frankly, they probably had it throughout their journey of treatment and are finally getting to a point where they need a very exquisitely targeted aldosterone therapy. Getting earlier in the lines of treatment is part of the story that lorundrostat will have over its life.
You know, this is a space where kind of the hypertension guidelines, you know, pretty clear and drive a lot of the prescribing patterns. You know, at what point do you kind of see the hypertension guidelines begin to incorporate the data from the Launch and Advance trials? You know, could it happen before Launch? You know, what are your expectations kind of on timing for that?
Yeah. We've been meeting with various constituent bodies, meeting with KOLs, who are part of those committees, making sure they're aware of lorundrostat, our data set. The guidelines used to be fairly rigid. The guideline committees used to be fairly rigid as far as how frequently they would update the guidelines. I think they're acknowledging now that we're in a bit of a renaissance with new technology, new therapeutics coming in, have become less rigid. When there's innovations, they want to make sure that they're guiding their constituents on how to think about utilizing those. I don't know the specific timing of it. I do know that that's been something top of mind for us going back five years when we began meeting with Steven Nissen and Luke Laffin at the Cleveland Clinic. That was why we did the Advance-HTN study.
Fundamentally, we wanted to go to the guideline committees with the absolute best form of evidence for inclusion. Advance-HTN, frankly, is probably going to be a bit of a lift for baxdrostat as a class because we anticipate the class will be treated fairly similarly by those guidelines. We definitely have the data set that will be most informative for those guideline committees on how to think about utilizing lorundrostat and ASIs in third and fourth line.
Mindfully can't comment necessarily on label. You touched upon this a little bit before, what are your expectations, or sorry, what are the most important, like, label variables in your view? You know, how are you thinking about? You know, you mentioned comorbidities, the data you have being an important value proposition. How do you think the Explore-CKD data could be reflected in the label? Maybe your thoughts on doses, like how those would be. You know, is the 25 mg dose gonna be included in the label?
Yeah, I think, you know, it's back to one of your earlier questions. I think seeing the presuming the positive action with baxdrostat's data, seeing their label is gonna give us a little bit of insight into how the agency's looking. I think our working assumption is right now both of these drugs will have near identical indication. Treatment from uncontrolled blood pressure, inadequately controlled blood pressure on top of background meds. It won't prescribe the number of meds, it won't prescribe resistant hypertension only. It'll just be a fairly broad. That's consistent with what the FDA has talked to us about for five years. I think the indications will be quite similar. I think the Section 14 is where you'll potentially see some distinction. You know, BaxHTN is certainly gonna be part of that approval.
What role does Bax24 have? Other data they have, how does that get incorporated? From our standpoint, again, it's why we did a very distinct clinical development program for lorundrostat. I would anticipate both Launch and Advance being included in Section 14. Explore-CKD, the blood pressure reduction, which is again, a very important thing to be able to convey to nephrologists. In a lower eGFR population, you can safely use this drug and see blood pressure reduction. We did include both 25 and 50 mg in the NDA submission. Again, it'll be part of label negotiations with the FDA, but we would anticipate both those as being available.
We think that's important because when you get to patients that have more complicated, uncontrolled and resistant hypertension, such as those with lower eGFR, you gotta be mindful of the safety profile, specifically for the on-target adverse events like hyperkalemia, hyponatremia, change in eGFR. Having a lower dose we think was important. It's why we tested that. I think fundamentally, the distinctions that are seen with the clinical development programs have the potential to be seen and revealed within the distinct labels between these two. Again, time will tell, and that'll be part of the negotiations that we'll have with the agency later this year.
You mentioned hyperkalemia. Do you think there's gonna be a need for physician monitoring of potassium levels? If so, how frequently?
Yeah. I think the beauty of the ASIs is they fit within an existing treatment paradigm that physicians already have, and that's driven by ACE inhibitors and ARBs. They have a very similar profile. These are RAS inhibitors. At the end of the day, ASIs are part of that RAS system. You see a very similar construct of response that fits the current use case. What does that mean? That means currently, when a physician prescribes an ACE or an ARB, they get a blood panel, they do blood pressure draw, they start them on an ACE or an ARB, and bring that patient back in two to four weeks. Again, they get a blood draw, they look at potassium, they look at sodium, they look at change in eGFR, and then they get a blood pressure measurement.
The ACE inhibitors and ARBs tend to have that profile shift within about two to four weeks, and then it stabilizes. What we've seen with lorundrostat is a very similar construct. Within two to four weeks, you see 70% or so of the blood pressure reduction. You see any increase in potassium, decrease in sodium, and change in eGFR occur within that two to four-week period, then tends to stabilize. That fits very nicely into the existing treatment paradigm that physicians have, and I think we're gonna see that reflected in the label as well. The labels for the ACEs and ARBs follow that construct. Get a blood panel, measure blood pressure, bring them back in two to four weeks, do the same, and then monitor periodically.
I would anticipate that's what the label will guide, and I would anticipate that's likely to be a class effect. I don't think there'll be a distinction between the two.
Maybe turning to, the OUS opportunity. How are you thinking about the relative importance of the OUS market versus the U.S. market? OUS, what in your view, are the key geographies?
Yeah. You know, our goal ultimately, purpose we talk about at Mineralys a lot is more better days. Three simple words that are fundamentally linked to what better control of blood pressure means for patients. We know it's frankly why we'll get an outcomes claim if we get approved, because there's such strong linkage between lowering BP and better long-term outcomes. Our goal within that is to get this drug to as many appropriate patients as we can, and that's not just in the United States, that includes outside of the United States. I've been clear in the past that Mineralys will not be the one that'll introduce lorundrostat outside of the United States, that we'll do that through partners.
We haven't guided to specific targets, you know, by region or by country, but it is important that we create access for patients, create partnerships that may be global in nature. That's where our main focus has been as opposed to regional, but to ensure that we get this drug to as many appropriate patients as we can.
Can you just give us the latest on your thoughts on the OUS regulatory submission? You know, is it gated by partnership discussions? What's kind of the timeline there? Just kinda, you know, your latest update there?
I don't know that it's gated by partnering. I think we have the appropriate data set in hand. Certainly for Europe, Japan, we may need to build some additional in-population data, but even that I think is becoming more streamlined. We haven't given specific guidance on the regulatory. Our main focus right now has been on the U.S., on working with the FDA to get lorundrostat approved in the United States and preparing from a commercial launch standpoint within the U.S.
On that commercial launch, maybe on thinking about the size of the field force gearing up to invest in that, when do you kind of plan to update the street on, you know, sales and marketing costs to support your U.S. launch? What are some of the pushes and pulls relative to comp launches that historically might have involved a very large, you know, 700 person sales force team?
Yeah, we haven't guided on the size of the team yet, or specifics around our go-to-market model. Part of that is just frankly a little bit of competitive protection, so that we don't reveal our strategy too soon. We may do that in future guidance. To date, we haven't done that. If we feel it's appropriate, I think we've always tried to be as transparent as we can with investors, but we also need to be mindful of the competitive nature of the market we're going into.
Okay. Me turning to pipeline and label expansion opportunities here. For OSA, you shared some data earlier this year. Just maybe curious your kind of, your thoughts on that data. Did the phase II study design, you know, kind of limit the lorundrostat's ability to show benefit? Curious your thoughts there, and where does OSA kind of go from here? What's the path forward?
I think it's important, you know, why'd we do that study? We did that study because when you get to a resistant hypertension patient population, you have a convergence of a lot of factors. It's not that patients just in isolation have resistant hypertension. I think about 85% of OSA patients have resistant hypertension. There's massive overlap with obesity within this population, and we saw that within the baseline characteristics of this study. I think the BMI average was somewhere 37, 38. A significant portion were morbidly obese with a BMI over 40. The AHI, which is the index of how severe your OSA is 48. Severe OSA begins at 30. That means they had 48 apnea hypopnea events per hour, and they were resistant hypertension.
This study was intended to be a quick four-week crossover design study. I think it was very informative for us. Again, we saw a very consistent reduction in blood pressure that we've seen, you know, had seen in five studies or four studies preceding that. While we didn't see a signal in OSA, I don't know that it means the pursuit of that is done because frankly, future studies we're gonna do, we're gonna see that overlap, and we'll be able to continue to dig into that, see if with longer time, maybe in a less affected population, that that translates not only into a benefit on BP reduction, but potentially on the symptoms of OSA. Fundamentally, and make no mistake, lowering the blood pressure is what's improving the cardiovascular risk for this population.
There have been countless studies, whether it's with CPAP, other agents that lower AHI but have not impacted blood pressure. That does not change their cardiovascular risk profile. It's having that control of BP that fundamentally translates into that reduction in CV risk. That's why I think there's a lot of positive data that comes out of the study. It was not part of the NDA submission, but by virtue of if we get approved for the reduction of blood pressure, we're gonna be able to use that study as part of our communication, whether it's promotion or MedCom, because it's all about lowering BP in these more complicated patients.
You spoke a little bit about this, but do these data impact your view on probability of success for other profiling studies or other adjacencies? Yeah, you know, heart failure, CKD, kind of those other opportunities for lorundrostat.
No, I don't think it does. I mean, certainly CKD, Explore-CKD de-risked that. In fact, it gave us a dataset that would enable us to go in and speak to physicians who are treating patients with uncontrolled or resistant hypertension and CKD, lower eGFR. That's why in that study we had a key exploratory was reduction in UACR, and just in four weeks we saw a 30% reduction in UACR. Clearly we know there's a benefit with lorundrostat on BP, on kidney function. If you look at where the medical community is going as far as how they think about kidney disease and heart disease and heart failure, they're not in these silos or isolated syndromes, which is I think where medical community was 15, 20 years ago.
They're now realizing, and they're even doing the CKM initiative, that these are all interrelated. You go to a heart meeting, you're gonna hear about the kidney. You go to a kidney meeting, you're gonna hear about the heart. Aldosterone sits at the nexus, and I think we progressively de-risked, obviously lorundrostat for blood pressure benefit, but even beyond that, what it can do for kidney, for heart, likely for stroke as well. I think hypertension is the beginning of the story, not the end. I think where we've taken this molecule to date, de-risked the profile of it, opens up a lot of opportunities for further clinical development.
On that further clinical development, should we kind of be thinking about, you know, these studies or how you're gonna pursue, you know, these indications in the future? Is it about indication expansion versus label boosting?
I think it may be a little bit of both. It's part of the partnering dialogue as well. Partnering is not just about the commercial, it's not just about promotion, either U.S. or ex-U.S., but it's also about how we continue to expand the value of lorundrostat in these other indications. If I look back at what we've done to date, and again, it's why we did very distinct studies, they really bolstered the hypertension profile itself. Because again, hypertension is not in isolation. It's driving these other conditions. Showing a benefit on BP in these other conditions builds that value prop, but it also is about indication, expansion, and just growing that value.
How important are, you know I know you guys haven't put out kind of a peak sales opportunity or anything there, but how important do you view these comorbidities to, you know, its lorundrostat's multi-billion peak sales opportunity?
I think it's one, bolstering the use case for hypertension itself. Again, as we go out and speak to physicians and ask what attributes matter to you, we see reflected back that complexity that they're dealing with. Having data that speaks to not only blood pressure, not only safety, but what's happening with the kidney? Can I use this with a comorbid OSA patient? All of that takes us deeper into that resistant and eventually uncontrolled resistant hypertension population. The penetration of lorundrostat into the use for that uncontrolled and resistant hypertension. I think it also builds into, you know, other categories, kind of the end of the journey. CKD, heart failure, heart disease.
Could you discuss where the company's at from financial standpoint, kind of cash runway, and maybe the importance of a partnership to extend cash runway and where that kind of fits in to, yeah, your expectations of kind of gearing up to support a launch?
Yeah. Our Q1 earnings call, we noted we have about $646 million in cash equivalents and investments. That takes us into 2028. That includes ongoing clinical development, corporate needs. That obviously includes the presumed commercial launch on successful FDA action. None of that is dependent upon any kind of partnering capital inflow. It's an alternative that we continue to evaluate, but we're very comfortable with our cash situation right now, and how it covers us into 2020.
Great. Thank you so much, Jon. Appreciate you being with us here today