All right, let's get things going. Hi, everyone. My name is Rich Law. I'm a senior biotech analyst at Goldman, and it is my pleasure to introduce Jon Congleton, CEO of Mineralys, and Adam Levy, CFO of Mineralys. Gentlemen, welcome, and great to have you guys here. So very exciting time to be at Mineralys as we approach pivotal study readout in Q4 this year.
Mm-hmm.
We have a lot to discuss this afternoon regarding the design changes that the company announced yesterday.
Mm-hmm.
Before we dive into the Q&A, why don't we just turn the stage to you guys with some opening remarks, and please remind everyone here what are the upcoming catalysts that investors should be excited about?
Yeah, happy to do that. Rich, appreciate the opportunity to share the Mineralys story. You know, we're deeply focused on how do you address cardiorenal metabolic disorders, with the beachhead indication being hypertension, particularly when you have dysregulated aldosterone or elevated aldosterone. You know, we think hypertension is certainly a beachhead that's, at this point, been validated, is getting a really robust response with lorundrostat, but we think aldosterone plays a role in CKD, heart failure, and other indications. Mineralys was formed, as you know, in the summer of 2020 after we licensed lorundrostat from Mitsubishi Tanabe, who discovered and developed the compound. We took it over then, went through proof of concept study while building the company, raising capital. But really with the express purpose of how do you frankly create more healthy days for patients?
You know, hypertension still fundamentally matters. We still have not solved for it, and it contributes to about 7.5 million global deaths annually. You know, this presumption that if you just pick the right drugs, you do the right dose, and patients are compliant, everybody's fine with what we have, I think is a bit of a misnomer. And as we'll talk about, one of our studies will actually get to that point. We'll identify how big is that subset that cannot get to goal.
But for us, at this stage, you know, given the preclinical work that's been done, the phase I, now the proof of concept, I think we can comfortably say, that lorundrostat is a highly selective, highly effective, safe, and well-tolerated aldosterone synthase inhibitor that we can now begin to really direct towards, our pivotal program in hypertension, which is comprised of two studies, ADVANCE-HTN, probably the most rigorous, study done to date, and LAUNCH-HTN, a larger real-world study, that together will make up the pivotal package, for the hypertension NDA. We also have a concurrent hypertension CKD proof of concept study underway, and then we have an open label study that basically is omnibus for all subjects to go into that allows us to build out our, our long-term safety data set. But fundamentally, the company is excited about what we're doing.
We think there's a significant opportunity to make an impact on millions of patients' lives, to have significant uptake for shareholders as well from the valuation standpoint. And we're certainly excited about, you know, the data readouts that we have with the ADVANCE-HTN study in Q4 of this year, the CKD proof of concept study late this year or early next, and then the second pivotal study in the second half of 2025.
Fantastic. Yeah, we're looking forward to seeing those as well. So why don't we kick off with a couple general questions before we dive into the study design, the hypertension study design-
Sure
... and some of the changes that you guys announced. So hypertension is obviously a very large and prevalent condition.
Mm-hmm.
The market potential for lorundrostat, we think, is very large and, you know, but many of these approved drugs in this setting are generic.
Mm-hmm.
The stock has been trading below the IPO price for some time now. What do you think investors are missing or not appreciating, and what are some of the, I would say, the biggest pushbacks that you've been hearing so far?
Yeah, I think the... You know, clearly the market is huge and growing. You know, in the United States alone, there's about 118-120 million people with hypertension. I think what's maybe underappreciated is that all the drugs that we have available now that are generics or extremely accessible, extremely cheap, were developed in the 1970s and the 1980s, when, frankly, hypertension was a bit different than it is today, and that's predominantly driven by obesity, and that's predominantly driven by the concurrent rise in aldosterone-dependent hypertension. What that means is that the therapies that were developed in the 1970s and 1980s, when aldosterone-dependent hypertension was maybe 5%-10% of the population, as opposed to 25%, those therapies aren't expressly built to address dysregulated or elevated aldosterone.
And so what we need are more therapies that target aldosterone specifically. That's why I get excited about, like, ADVANCE-HTN, where we put subjects, prior to randomization, on, frankly, a maximized AHA-directed treatment guideline with the currently available treatments. And if patients get to goal, great, we don't randomize them. But we know from, you know, the conduct of the study so far, there are significant numbers that are not getting to goal with that regimen, which to us, further supports the fact that aldosterone, which is the main pathway that that standardized treatment's not addressing, needs to be addressed, and we think lorundrostat can do it. And so I think the size of this market, but also very specifically how we're trying to target in on just those that need lorundrostat.
We're not doing this development like it was done in the '70s and '80s, kind of an all-comer approach. We're really trying to identify within our cohort of studied subjects, those that respond very exquisitely to lorundrostat, and by definition, probably have that aldosterone-dependent form of hypertension. We know from our proof of concept that obesity cohort was predictive of enhanced response. We'll continue to dig in on that. And that's what we're continuing to try to convey to not only investors but physicians, when we do research with payers, is really the fact that the underlying biology of hypertension has shifted, and by definition, it requires innovation like we're doing with lorundrostat.
Right. And what have been the biggest pushbacks from from investors? And also maybe extend that a little bit to pushbacks from KOLs or clinicians?
I think with the KOLs, it's, it's not as, there's not really a resistance. I think there's a, an appreciation that there is a cohort of subjects, even if they are compliant on the right drugs, cannot get to goal. So I, I think there's a desire for innovation, that we're seeing from the industry right now, right? You, you have several ASIs in development, and then the endothelin receptor agonist, antagonist got approved in the last quarter or so. You have the, angiotensinogen-directed therapy. So you're seeing more innovation coming. You're seeing physicians that are welcoming that. I think the if there's a, lack of appreciation, is just for how big the unmet need is. You know, that there's this a little bit of a perception that if patients just took their drugs, they'd be fine.
And again, that's why I like the rigor of the study that we chose to do with ADVANCE, because it's not only going to show the value of lorundrostat, but it's going to kind of answer that question, right? When we really pick high dose of AHA-directed therapies, there is still a sizable cohort that cannot get to goal.
Mm-hmm.
And so I think that study not only shows the value of lorundrostat, but I think it answers some of the questions investors have about, "Well, can't people just get to goal with what we have?" And the answer is going to be no.
Fantastic. Okay, sounds good. Why don't we jump into the, the study design?
Sure.
Can you remind us of the pivotal study designs for ADVANCE and also for LAUNCH-HTN?
Yeah.
What changes did you make to the primary endpoint on these two studies?
Yeah. Let me talk about the construct and the intent of both, because they're a little bit different. So ADVANCE-HTN, again, is probably going to be noted as the most rigorous study ever done. Again, we're taking subjects who have at screening, a systolic BP over 140 millimeters of mercury. If they meet that, plus some other inclusion criteria, we put them into a screening period, where we basically take them off of their prescribed treatment, and we put them onto a standardized regimen, that's one of two combinations. The first is, if they were on two meds at screening, we put them on olmesartan , an ARB at high dose and a diuretic at high dose.
If their pre-existing background meds were 3, 4 or 5 medications, we put them on the ARB, the diuretic, and then the high-dose calcium channel blocker. We then follow them for 3 weeks, ensuring daily compliance via smartphone technology with a firm called AiCure that's done this for about 300 studies. And then, at the end of the 3 weeks, which we think is sufficient time to get them to peak plasma and peak response, we put a 24-hour ambulatory monitor on them, which is the gold standard for measuring BP. So we've effectively put them on the right drug at the right dose, ensured compliance, and used the gold standard to measure. If they're at goal, we don't randomize. If they are at goal, we then randomize. Now... So that's ADVANCE-HTN. That's for a 12-week measure.
We're doing ambulatory as the primary endpoint. We're doing in-office measure as secondary, as well as home blood pressure monitoring, all three. LAUNCH-HTN is more real-world. So we keep them on their existing med. We do the two-week placebo run-in. We use the in-office blood pressure monitoring, which is really akin to what we did in TARGET-HTN, just at 1,000 subjects. So it's more of a confirmatory study, but it's real-world. Again, if they don't get to goal on their existing meds after 2 weeks, we randomize and then follow them for 12 weeks. The announcement we made last night was basically nothing about the design of the study. No, it was more about the statistical analysis plan. So as is kind of standard, we went into the FDA to finalize the SAP, in this case, with the LAUNCH-HTN study.
Got to talking about the primary endpoint is 12 weeks, and the confounding aspect of that is, within both studies, one of the arms at 50 milligrams, at a certain time point, we evaluate their blood pressure and safety metrics, and we have the option to titrate up. That can somewhat confound the data at the 12-week point. So in discussion with the FDA, we basically said, "Let's change the endpoint to week 6, so that we could pool both of the active arms and then compare it to placebo." So in the case of LAUNCH, we have 1,000 subjects with a randomization rule of 1 to 2 to 1, so 1 to placebo, 2 to 50 milligrams, and 1 to 50, with the titration to 100.
So we effectively, at week 6, will have 750 patients on 50 milligrams, all consistent, exposure, compared to 250 subjects in placebo. So that doesn't really change the design, but what it does do is it basically gives us greater power to detect the difference between the 50 milligram pooled cohort relative to placebo. We also know from TARGET-HTN that the effect is of lorundrostat, is basically evident, frankly, at week 1 and maximally achieved at about week 4. So we're not concerned about losing any efficacy moving from 12 weeks to 6 weeks. And so in discussions with the FDA, as a standard course of getting the finalization of the SAP, we made that decision in concert with them, and we're going to go ahead and implement a similar design change to ADVANCE-HTN.
In that case, it's going to be at 4 weeks, which is the titration point.... So at week 4, we'll be able to pool all the 50 milligram subjects in both arms, pre-titration, and then compare them to the placebo. Again, that'll impact in a positive way, the power of the study. It doesn't mean we're not collecting 12-week data. We'll collect for both Launch and Advance the 12-week data. Those will be key secondary endpoints. From a label standpoint, it doesn't change the indication. The indication was always gonna be for the treatment of hypertension, not linked to any kind of time point. And the clinical data section will have both the 4 and the 12-week data within it. So from our standpoint, there's really no operational changes, no design changes. It's more about the statistical analysis and just improving the power to detect an effect.
I see. Got it. I mean, the studies themselves were well-powered, were sufficiently powered. I think that's what you guys mentioned to us before. So was this something that the FDA required you to do? Like, take us back to the moment that you decided that this is something that you want. What-- was that proposed by the FDA, or was it proposed by you guys?
No, it's really a collaborative discussion. The nice thing about our dialogues from the very beginning, even pre-IND with the FDA, has been they've been very positive, very supportive of what we're trying to do as far as bringing innovation in the hypertension space. I think, you know, HHS, the NIH, the FDA, are very mindful of the focus on hypertension. I think it's a top ten initiative from a government health standpoint. And so the FDA and the head of the Cardiorenal division, Norman Stockbridge and Aliza Thompson , have been very supportive of what we're trying to do, very collaborative in nature as far as dialogue.
And I think as we were talking about the SAP, I think collectively, we said that's probably the best time point to move the primary endpoint from week 12 to week 6, just because of the fact that we don't have the confounding factor of the titration arm.
Mm-hmm.
Eliminating some of the 50 milligram patients and eliminating some of the multiplicity that would have to be done from a statistical analysis standpoint.
I see. Okay. So if you didn't have the uptitration, you would still use the 12-week time frame?
I think if we didn't have the uptitration, then we'd probably just have two arms, right?
Yeah.
Placebo and 50. But the titration was important. You know, we knew from our analysis in TARGET-HTN that the majority of subjects probably would suffice from an efficacy and safety standpoint at 50 milligrams daily. But from an analysis of individual exposure response, we know there are some subjects that probably have a lower exposure or underdosed largely, that 50 milligrams was probably not enough dose. That it probably would move their BP, but that they would probably get to goal, maybe better with 100 milligrams. And, you know, having been in the hypertension space, dating back to the beginning of my career in the eighties, titration is a pretty standard approach within hypertension. And we wanted to make sure that the 100 milligrams was available for those subjects that may need it.
I see. Okay. So I know you don't think that there's gonna be an impact to the efficacy by moving up. But when we look at this, some of the data, I think we do see some risk. Maybe not a lot of risk, but some risk that by measuring efficacy too early before lorundrostat can maximize its performance. In TARGET-HTN, I think we saw that efficacy improved slightly further in the 50 mg QD dose when you move from 4 weeks to 8 weeks. And then when you look at spironolactone PATHWAY-2, we also saw a numerical improvement in SBP, although you could argue that's not significant.
I mean, the data seems like there's further improvement in efficacy and so just wanna hear your thoughts about that and the risk of showing something that may not reflect the maximal performance of the drug.
Yeah, I think the TARGET-HTN, you know, the trick with that is smaller cohort. We saw the JAMA supplement you're talking about, the error bars are fairly big.
Mm-hmm.
From the 4-week to 8-week, there may be some modest change, but how much of that's within the error bars? That was with the in-office measurement, which, you know, we had fairly good control of with the technique we used, but it has more variability-
Right
... than the 24-hour ambulatory measurement does, that we'll be using in advance. In launch, we go out to 6 weeks, which I think accounts for a little bit of the heterogeneity of the background medication and the AOBP use. So, from our standpoint, you know, when we set the titration, which was really the first thing we set, the titration time into 4 and 6 weeks, we really felt that was the time point that you're gonna really see the maximal response, short of somebody not, you know, being on the low exposure side with the drug. So we remain confident that given the conduct of the trial, the way they're constructed and the timing for it, that, we're not gonna miss a lot from a magnitude of effect.
And at the end of the day, we are capturing the 12-week, so that if there is some residual benefit that's seen, we're gonna have that data. It'll be part of the dataset for lorundrostat-
Mm-hmm.
and I think we're comfortable with the whole conduct of that analysis-
Right
... that we're gonna see the whole picture for the drug. And that's why the studies were designed originally out to 12 weeks, because I think it's important, for clinicians, for payers, to see the whole temporal profile, and that's why we're gonna continue to collect efficacy data in the open label section as well.
So when you say you'll collect data up to 12 weeks, at 12 weeks, maybe a little bit about how do you... What are the time points that you do collect data in your study protocol? Is it every 2 weeks, from 4 to all the way to 12?
No, I apologize in advance. We collected at baseline, week 4, and week 12. And we collect home blood pressure monitoring, I think it's every 2 weeks. And in-office measurement, I think it's every 4 weeks. And then in the LAUNCH-HTN, we just have the AOBP, the in-clinic visit, and I think that is temporally at baseline 4-week, 8-week, 12-week.
I see.
So we'll have the temporal time points. Not to the point that we had in TARGET-HTN, which was more our proof of concept-
Yeah.
- dose range finding, which we had weekly visits, smaller study. But the bigger size study, we don't have quite as frequent, visits.
I see. Okay. So your competitor, baxdrostat, is still using the 12-week time point. And interestingly enough, aprocitentan or Tryvio, was approved based on a 4-week time point.
Mm-hmm.
Is there any advantages or disadvantages from a competitive perspective? Perhaps shorter time point could imply a faster onset of action.
No, I think... You know, as we talk to physicians, the thing that motivates them and gets them excited about the data that we've shown them from TARGET-HTN, and as we put a target product profile forward, what really motivates them is our targeted approach in what we've seen as far as initially with the impact on obesity. In fact, we just completed some qualitative research, and that continues to resonate. Being able to have an agent that can have that kind of a profound effect or an enhanced effect. You know, we saw an 8-10 mmHg change for the ITT-
Mm-hmm.
But we saw an even more robust effect in the obese population. Giving them that kind of capability, as opposed to, hey, lower blood pressure within 2 days, 7 days, 4 weeks, it's more, "Help me get those patients that are difficult for them to manage, that they know are at greater risk of comorbidities, show an advantage there." And so I think that's what's been resonating with the physicians that we've talked to within the research that we've done, and just anecdotally in conversations.
I see. Got it. So based on this change, what does it mean for the 100 mg dose? So I know you said that you moved the time point for the 50 mg. In regards to showing efficacy for the 100 mg dose, getting that 100 mg dose approved, what are the implications?
Really none. You know, the 100 milligram will still be a part of the dataset, will be part of the label. We'll have clear titration data. You know, once we complete the study and then blind everything, we'll have a clearer sense of what proportion of subjects could, you know, benefit from the 100 milligrams as far as getting a bigger response. But as far as inclusion in the label, availability to the marketplace, it doesn't change any of that.
I see. And is the approval based on comparison to the 50 mg dose, or how, how does that work?
It's predominantly with, within subjects, so where were they at baseline? Where were they at the titration point-
Right
... of the 4, 6 weeks, and then with the addition of the 100 milligrams. So it's kind of a within-subject comparator. But then I think there's also some statistical work that we can do looking relative to placebo as well.
I see. Interesting. So would you say by this change, that it somehow favors the 100 mg a little bit more? Because now you would run the patient, say, on 50 mg for either 4 weeks or 6 weeks.
Mm-hmm.
Then the rest of the 12 weeks, or the remaining from the 12-week study, you would run them on the 100 mg arm, so they would get more a longer duration at a 100 mg.
No, I don't think it either favors or disfavors. I mean, at the end of the day, the intent and in the dialogues with the agency, it was all about: how do we simplify the stats for the 50 milligrams? And then bear in mind that in that third arm of both ADVANCE-HTN and LAUNCH-HTN, where there's the titration option, not all subjects will get titrated.
Right.
Right? So there, again, it's our presumption that probably the majority of patients with 50 milligrams are gonna get the right combination of efficacy and safety. So it's only a portion of those that will get titrated, and that's why we want to look within subject and see, for those that needed to be titrated, was the additional exposure to lorundrostat that delivered the intended outcome? And the intended outcome is, if someone didn't get the goal at 50, does the 100 help them get the goal, and does it do so safely?
I see. Okay, so now let's talk about the ADVANCE-HTN. So you take the patients off their current therapies.
Mm-hmm
... to a standardized, I think you mentioned 2-3 background therapies. So one of the risks that we see, for these patients who are on 4-5 therapies is that they're taken off their 4-5 therapies, they're put on 3 therapies.
Mm-hmm.
So they come down a little bit in terms of the number of background therapies. And then you add lorundrostat to it. Do you see any risk that these patients are more difficult to treat, compared to, like, those on two or three background therapies, and they may not perform as well on lorundrostat?
I think broadly, we're not overly concerned about that. I'll tell you why. We know that, you know, monotherapy. So the first antihypertensive, which tends to be an ACE inhibitor or ARB, you see a pretty profound reduction, 10, maybe even 15 millimeters of mercury. But if it doesn't get them to goal, as you add a second, as you add a third, based on meta-analysis, you see about a 5-6 millimeter incremental improvement. So it's not like you get another 10, another 10, another 10. It's this kind of law of diminishing returns, and I think that's. While I haven't seen the meta-analysis on 4 or 5 lines, I think that kind of plays out to be true. You mentioned Pathway. I think Pathway is indicative of that, because if you looked at that study, there were subjects on standardized background of ACE, ARB, diuretic-
Mm-hmm.
Calcium channel blocker, and they looked at alpha, beta, and MRA blockers. The alpha and the beta just had incremental improvement. It was the MRA that saw the benefit. And so for me, as I think about it, you know, going from 3, 4, 5 background meds, where you're likely throwing a medication that's not hitting what's driving their hypertension, which we know today is more and more prevalent, aldosterone, that bringing an ASI into the story there, I think, is actually going to address their underlying cause. So I don't really have concerns that we're stacking the deck, quote, unquote, "against," lorundrostat. In fact, I think by really taking them off of what is a real mixed bag of background treatments-
Mm-hmm.
We've done some macro analysis with IQVIA on the data, and it is a real mixed bag out there.
Mm-hmm.
Taking them off that, standardizing them to what the AHA guidelines are, which is an ARB or an ACE, then a diuretic, then a calcium channel blocker. At that point, if they're still not a goal, I think we are, in fact, enriching for an aldosterone-
Yeah
Independent subset, that... Not saying it's stacking the deck for, but it's creating an opportunity for us to really show the value of lorundrostat.
Mm-hmm. So one thing that I find unique about ADVANCE-HTN is that you guys allowed patients who were previously treated on MRAs or spironolactone to the study, but you did not allow that for the phase II TARGET-HTN or the phase III LAUNCH-HTN. Do you think that these patients could potentially not perform as well because they could have been resistant on spironolactone, which is MRA? And there's a lot of overlap between that mechanism and aldosterone and your mechanism. And I mean, why wouldn't they be resistant to lorundrostat?
Yeah, I think it's, it's a fair question. While there's overlap, there's clearly some distinctions. We know with all MRAs, not just spironolactone. Spironolactone has it, probably worst of any, MRA. But when you treat with something like spironolactone, you see aldosterone increase 2- to 3-fold. So if you've got a patient that has aldosterone-dependent hypertension, where they already are in an elevated state, you're just exacerbating that. And we know that creates some competition with the MR, with spironolactone in and of itself, but we also know there are other pathways that aldosterone affects that can drive things like oxidative stress, inflammation, fibrosis, that can further counteract the benefit you're hoping to get by blocking the MR, from a volume standpoint.
So, you know, there's some confounding factors with spiro that could lead to, you know, a negative outcome with spironolactone that I don't think would read through to lorundrostat. I think of equal importance is, you know, what was the reason that they broke through or didn't have control with spironolactone? Was it related to tolerability, adverse events? Was it a compliance issue? And fundamentally, we know that all of those off-target effects that you see with spironolactone are not evident with lorundrostat, just... And the ASI class writ large. You just don't see the gynecomastia, the fertility issues, the issue with glucocorticoid buildup.
I don't lose a lot of sleep over the fact that in the patient's history, they had maybe tried and failed, spironolactone, because I think that failure can be related to a lot of things that are frankly not evident with an ASI like lorundrostat.
Right. Got it. So, ADVANCE-HTN is reading out in Q4 this year?
Correct.
I think you mentioned 8-10 millimeter reduction as expectation. What have you been hearing from investors' expectation, and how does that differ from your expectation?
Yeah, it's something that we have, at this point, I think, done two or three physician surveys, qual and quant, as well as payer surveys. And what the physicians are telling us is, if we can replicate what we saw in Target in Advance, particularly in this population, that is, you know, completely maxed on currently available AHA-directed guidelines, and get that kind of reduction on top of that, that's transformative data. We shared that, not just our view with investors, but we share the voice of the customer with the investors.
I think that resonates with investors, that if we can see that replication from Target into Advance, and do the conduct of the study like we did in Target and not, frankly, run into what CinCor ran into, which was a lot of variability that led to one positive, one negative-
Mm-hmm
... study, I think that's validating to investors. So, you know, not only the data, but to make sure we continue the kind of operational excellence-
Right
... that we've done from a study conduct standpoint. That's what matters, and I think that's what people are excited to see at the end of this year.
and now, looking back at PATHWAY-2, I think they were able to show something similar, I think 8 or 9 millimeter reduction. Why not set the bar a little higher and say, "We're gonna be a little bit better than that?
Well, trust me, I'll be happy if it delivers on that. But I think fundamentally, the market is saying, to a degree, if we can deliver spironolactone-type efficacy without all of the baggage of spironolactone... then that's clearly a win. You know, we look at the 8-10 target, but we know that one of the distinctions between target and advance is, and then so to me, that's 8 to 10 and may hold promise for beyond that. But again, PATHWAY-2 is really instructive. Clearly, the spironolactone was better than the beta blocker, better than the alpha blocker at fourth line. You look at the macro numbers of prescribing in the U.S., and the drug's not used in hypertension. It's 2.5% market share.
It should be higher based on PATHWAY-2 data, but there are so many, so much baggage with spironolactone. It's been around since 1959, so you have so many physicians that have one or two bad experiences that just jades them to it. We need more than just Spiro to address Aldo when it's driving hypertension, and we think lorundrostat is gonna be that alternative.
I think got it. So now looking at LAUNCH-HTN, it's a larger study, more real-world based study. And you're not gonna see as many obesity patients there. You don't proactively interfere with the poor adherence, and you don't standardize the background therapies. So how do you expect the to ADVANCE-HTN?
Yeah, I don't know if they'll differ. They're definitely different constructs of populations, but, you know, of the two studies, Launch is probably most akin to Target, right? It's background existing background regimen. It's the in-office blood pressure measurement as a primary endpoint. The main distinction is Launch. They have to have a diuretic as part of their pre-existing background, and again, we know that there's an interplay within all of that. And so if we think about Target and the similarity with Launch, I think, again, replicating that 8-10, where Advance is clearly different with the standardized background, but they are much more difficult to control by virtue of the fact that we've hit them heavy with an AHA-directed treatment regimen and high dose. So that 8-10 kinda makes sense within that cohort.
It's a bit of a different construct, but Launch, to me, is, is very similar to what we saw in TARGET, just a bigger scale study. And to your point about obesity, you know, this is our first global study. We are bringing Europe, Australia, Canada into the mix. Fortunately for them, they don't quite have the obesity epidemic we have, but there's still a pretty tight correlation to uncontrolled resistant hypertension and obesity, so it's not like we're suddenly skewing with a, a much thinner population. The U.S., I think, will still be a sizable portion of LAUNCH-HTN from a recruitment in the 33 range. So I don't know that we really give up a lot, as far as the cohort population. That's why we think there's a high likelihood we'll see a similar response given the similar construct to TARGET-HTN .
Got it. So we have a couple more minutes left. If the audience have any questions, please raise your hand, and we'll get to you. So why don't we talk about CKD?
Yeah.
So you have an ongoing phase two study. What is the roadmap for CKD from here?
Yeah, I think the reason that Explore-CKD is an important... proteinuria always rates out as a key attribute just in the treatment of hypertension, setting CKD aside. When we talk to physicians about what are key attributes, lowering blood pressure, always number one. Doing it safely, number two, but always within the top three or four is have an effect on proteinuria. We're gonna be looking at that in ADVANCE and in LAUNCH, but Explore-CKD very specifically, that's a key exploratory endpoint, and we're going lower eGFR. In the pivotal studies, we go down to 45, and Explore-CKD, we're going down to 30. So from our standpoint, it's gonna be very informative for the label and hypertension as far as giving us guidance on the eGFR range that lorundrostat could be used.
It'll give us a sense for BP within this population, 'cause that is the primary endpoint within Explore-CKD , but it's also gonna give us some really important information as it relates to effect on proteinuria in a hypertensive subject. From there, we'll look at the data, and we'll make a determination. Do we think there's an opportunity to move forward in the CKD? We know BI presented some really compelling data last fall that I think de-risks this program. But how we move forward is something we'll still evaluate. Do we do it as a monotherapy? Do we do it as a fixed-dose combination? Do we do it as part of a cardiorenal metabolic disorder? It's. We just need to see.
Fantastic. Final question from me. So commercial preparation usually starts around the pivotal study data readout.
Mm-hmm.
Have you—like, how is that going? Have you guys started that preparation, or are you guys thinking about finding a commercial partner to commercialize lorundrostat, or are you looking at do commercializing the drug yourself in the U.S.? Maybe walk us through your mindset.
Yeah, I think our goal commercially aligns with how we thought about this clinically, and clinically, it's been very much we think we have best-in-class molecule. We think we have a path to potentially first the market. We've moved cautiously to create a real sense of safety around this molecule, and then most importantly is the toolkit, the targeting. How do we really, as we develop the drug, identify those predictors of enhanced response?... We're not looking to develop lorundrostat for the whole 120 million subjects out there with hypertension, but really those subjects that maybe a quarter of them that have a prevalent elevated aldosterone level.
That toolkit then becomes part of the key commercial strategy as far as really being able to bring payers for their treatment algorithms and physicians a means to identify, because aldosterone is not a good marker by itself, a means to identify somebody that would be an enhanced responder to the product. So we continue to do a lot of market assessment, doing market research, testing that thesis. It continues to resonate. Like I said, obesity, which is the leading indicator of that predictive model, resonates with prescribers, it resonates with payers. As we continue to do the clinical development to support that strategy, you know, we're continuing to evolve what is the best commercial path forward to maximize the value of lorundrostat. You know, we know that big pharma is coming back into cardiorenal metabolic.
We know that chronic conditions are really of import to bigger pharma. So I think from a partnering standpoint, given the value of this asset, the near-term nature of its revenue-generating potential, I think we'll be able to find some opportunities to really maximize the value of the asset through partnering through big pharma.
Have you started building out that commercial team or capabilities at all?
I think we're really waiting for the data to mature a bit further and continue to evolve our thinking as far as what's the best way to bring the product forward commercially.
I see. Got it. Right, I think we're out of time. Well, gentlemen, thank you so much. Pleasure to be hosting you. That was a lot of fun for me. Any final words?
No, just I appreciate the time. Always appreciate the dialogue and discussion with you, Rich. We're obviously thrilled about the opportunity in front of us, and fundamentally, we stand to make an impact on millions of patients' lives if we can deliver the kind of value that I think we can. And it's needed because we haven't solved hypertension yet, nor all the downstream effects of hypertension. So we have reading out in the future.
Fantastic. Thanks, everyone.
Great. Thank you.