Mineralys Therapeutics, Inc. Price & Performance (MLYS)

A replay of today's call will be available on the Investors section of our website approximately one hour after its completion. After our prepared remarks, we will open up the call for Q and A. Before we begin, I would like to remind everyone that this conference call and webcast will contain forward looking statements about the company. Actual results could differ materially from those stated or implied by these forward looking statements due to risks and uncertainties associated with the company's business. These forward looking statements are qualified by the cautionary statements contained today's press release and our SEC filings, including our annual report on Form 10 ks, and subsequent filings. Please note that these forward looking statements reflect our opinions only as of today February 12, 2025. Except as required by law, we specifically disclaim any obligation to update or revise these forward looking statements in light of new information, or future events. I would now like to turn the call over to John Congleton, Chief Executive Officer of Mineralys Therapeutics. Thank you, Dan. Good morning, everyone, and welcome to our fourth quarter and full year twenty twenty four financial results and corporate update conference call. I'm joined today by Adam Levy, our Chief Financial Officer and Doctor.

David Rodman, our Chief Medical Officer.

I'll begin with an overview of the business, then Dave will discuss our Then Adam will review our fourth quarter financial results before we open up the call for your questions. And looking back over the past year, it was a tremendous period for the company. I'm very proud of the work our team has done in executing and supporting our clinical [indiscernible] Of targeting dysregulated or elevated aldosterone in patients with uncontrolled and resistant hypertension. The data for ADVANCE HTN will be available this coming March and launch HTN will be available mid first half of this year. We also have our exploratory programs evaluating LORUNDERSTAD in hypertension and chronic kidney disease as well as hypertension and obstructive sleep apnea. Our purpose in Mineralys is to create more healthy days for people dealing with cardiorenal metabolic disorders. And the trial readouts we have this year will evaluate the potential of lorounderstat to deliver on that promise. The first of the two ongoing pivotal trials is the advanced HTN trial trial that is evaluating the efficacy and safety of larunderstat for the treatment of uncontrolled or resistant hypertension.

When used as an add on therapy to a standardized background treatment of two or three antihypertensive medications. The trial enrolled two eighty five subjects and the rigor of this standardized American Heart Association recommended background regimen was designed to ensure only subjects who were enrolled had confirmed uncontrolled or confirmed resistant hypertension. As noted, we anticipate announcing the top line data for this trial next The second pivotal trial is launched in HTN. With ten eighty three subjects enrolled and is designed to be confirmatory to our target HTM proof of concept trial. The objective is to evaluate the benefit risk of lorounderstat in a real world setting. When added to a subject's previously prescribed regimen of two to five antihypertensive medications. One of which must be a diuretic. As previously guided, we anticipate top line data in the mid first half of this year. Upon completion of the treatment phase in the advance HTN and launch HTN trials, participating subjects were offered the opportunity to enter the TRANSFORM HGN open label extension trial. As we await the announcement of these pivotal top line data, I invite everyone to revisit the KOL event we held last quarter. An archived webcast is available on the Investor Relations section of our website.

This discussion focused on the unmet medical need and uncontrolled and resistant retention the long term impact of uncontrolled blood pressure, and insights into the treatment of hypertension from these leaders in cardiovascular medicine. In addition, during the event that KOLs gave their perspectives, on our highly selective aldosterone SYMPACE inhibitor, lorundrostat. As a new therapy and its potential to change the current treatment paradigm. To provide more color on our clinical pipeline and recent milestones, I will now turn the call over to Dave. Dave? Thank you, John, and good morning, everyone. Picking up from where John just left off discussing the KOL event we just had last quarter, I agree that there were a lot of great topics discussed The clinicians did an excellent job of highlighting the need for innovation and there was agreement that targeting aldosterone would address an important gap in the current antihypertensive armamentarium. They also agreed that a confirmation of the favorable safety and blood pressure reduction of eight millimeters to 10 millimeters of mercury we saw in the target HTN trial would be transformative for patients. Over the next few months, we look forward to sharing the data with you for lorunjostat from both the advanced HCN trial and launch HTN trials.

We're excited about the potential of Zoruntrostat to demonstrate a meaningful benefit in patients with uncontrolled or resistant hypertension, I would like to echo John's appreciation for the work of the Mineralys team as well as the investigators and patients in both trials to advance the hypertension development plan.

We recently had some exciting news around the rest of our clinical program including the Explorer CKD and EXPLORER OSA Phase two proof of concept trials. Both of these trials are designed to provide data that augment the antihypertensive profile of the runderestat while also providing insight into the potential benefit in reducing overall cardiovascular risk. Last week, we announced that enrollment was completed in the [indiscernible] This trial is evaluating the efficacy and safety of lorounderstat for the treatment of hypertension in subjects with an 30 and albuminuria, Despite having received stable treatment with an ACE inhibitor or an ARB, as well as an SGLT2 inhibitor. Hypertension and associated hypertensive nephropathy is a leading cause of kidney damage alone and in combination with other obesity associated comorbidities. This is another area with great unmet medical need for aldosterone synthase inhibition with Lerondustat has the potential for transformative benefit to patients. We look forward to announcing top line data from the trial in the second quarter of twenty twenty five.

In January, we announced our plans for the initiation of the Xplore OSA Phase two trial to evaluate the effect of lorodrastat in the treatment of moderate to severe obstructive sleep apnea. During the night, blood pressure increases significantly during each Hypoxic episode. This leads to resistant nocturnal hypertension that is underdiagnosed and LASA specific therapy. We are using a novel approach in this trial to measure blood pressure continuously with each heartbeat In addition, we anticipate that dosing or understood at bedtime will maximize aldosterone suppression during the period that it is being driven by hypoxia while still providing daytime blood pressure control and the favorable safety profile achieved with once daily dosing of lorounderstat. It is estimated that sixty percent to eighty five percent of patients with OSA have resistant hypertension, Establishing the benefit risk of larunderscan in treating these patients could lead to the development of lorunterstadt as a unique small molecule treatment for the adverse respiratory and cardiovascular manifestations of obstructive sleep apnea. We are very excited about our programs that are designed to evaluate the value of Norundiskat and the associated milestones expected the first half of this year.

I will now turn the call over to Adam to review our financial results for the quarter and the full year. Thank you, Dave. Good morning, everyone. Today, I will discuss select portions of our fourth quarter twenty twenty four financial results.

Additional details can be found in our Form 10 ks, which will be filed with the SEC today, February 12, We ended the quarter with cash, cash equivalents and investments of $198,200,000 as of December 3120 compared to $239,000,000 as of December 31, 2023. We believe that our current cash cash equivalents and investments will be sufficient to fund our planned clinical studies as well as support corporate operation through the first quarter of twenty twenty six. R and D expenses for the year ended December 31, 2024 were $168,600,000 compared to $70,400,000 for the year ended December 31, R and D expenses for the quarter ended 12/31/2024 were $44,600,000 compared to $23,700,000 for the quarter ended December 3120 The annual increase in R and D expenses was primarily due to increases of $88,700,000 in preclinical and clinical costs driven by the initiation of the Rundestat pivotal program in the second quarter of twenty twenty three, $10,600,000 in clinical supply manufacturing and regulatory costs dollars 7,000,000 in higher compensation expense resulting from additions to headcount increases in salaries and accrued bonuses and increased stock based compensation and $900,000 in other research and development expenses.

Partially offset by a decrease of $9,000,000 in licensing fees associated with development milestone payments in 2023 that did not recur in 2020 G and A expenses were $23,800,000 for the year ended 12/31/2024, compared to $14,300,000 for the year ended December 31, 2023.

G and A expenses were $7,200,000 for the quarter ended 12/31/2024 compared to $4,000,000 for the quarter ended 12/31/2023.

The annual increase in G and A expenses was primarily due to $6,600,000 in higher compensation increases in salaries and accrued bonuses, and increased stock based compensation $2,600,000 in higher professional fees, and $300,000 in higher other administrative expenses. Total other income net was $14,600,000 for the year ended 12/31/2024 compared to $12,800,000 for the year ended 12/31/2023.

Total other income net was $2,800,000 for the quarter ended 12/31/2024, compared to $3,300,000 for the quarter ended December 3120 The annual increase was primarily attributable to increased interest earned on the company's investments in money market funds and U. S. Treasuries. Net loss was $177,800,000 for the year ended 12/31/2024 compared to $71,900,000 for the year ended 12/31/2023. GAAP loss was $48,900,000 for the quarter ended 12/31/2024 compared to $24,400,000 for the quarter ended 12/31/2020 The increase was primarily attributable to the factors I described earlier.

With that, I will ask the operator to open the call for questions. [indiscernible] Thank you, sir. First, we will hear from Michael DeFiore, at Evercore ISI. Please go ahead, Michael.

Hey, guys. Thanks so much for taking my questions and congrats on all the products, the progress. Couple from me. I guess hypertension question. In the Phase two target trial OMD, when the QC analysis was QD group, You took out two additional patients that had improbable readings. Leaving 12 evaluable patients that were truly hypertentions.

This seems like a very small N to extrapolate to the larger pivotal study. So I guess my question my first question is, what gives you confidence that the SBP reduction seen in this 12 patients and these 12 patients can be extrapolated to Phase three?

And then I have two follow Mike, thanks for the call. Appreciate it. From our standpoint, as we looked at Both in office measurement as well as the twenty four hour ambulatory and as you noted when we looked at the twenty four hour ambulatory, we had some subjects that actually had baseline blood pressure below goal. And so that confounded the findings a bit. But as we looked at the totality of the evidence for the 50 QD, the 100 QD, even the 25 BID looked at the individual exposure response, we got very comfortable that the 50 milligrams QD provided what we believe is the ideal benefit risk as far as reduction in blood pressure as well as benefit from a safety tolerability standpoint. So obviously, as we move the 50 milligram into the pivotal program and showed our confidence in that dose to provide twenty four hour blood pressure control. Got it. Very helpful. And then just two follow-up for me. One on the OSHA trial one on the CKD trial. For the OSA trial, will improvement in the apneahypopnea index after four weeks be primarily due to fluid volume reduction or would non genomic anti fibrotic effects equally contribute over that time period?

And my final question is, for the CKD trial, for the SGLT2 naive patients who start their SGLT2 for the first time in the trial, to what extent may that compound S BP and or eGFR changes? Thank you. Okay. Why don't I take that one? This is Dave Rodman. Thanks for the call. For the questions. And so I'm going to take the first of those two questions, which was an OSA question, and oh, wait a minute, did you want me to do yes. So the OSA question, And your question there was about the apnea hypopnea index and what the mechanism is. So the as you know, first of all, that when you in two small trials with both spironolactone and eplerone, the apnea hypopnea index was reduced on a pretty short term study like two to four weeks by 50%, which is pretty dramatic.

We anticipate being at least as good as that with our mechanism And it may be mediated by both the decrease in MR activation and non genomic effects. [indiscernible] when we look at the mechanism with MR, It's volume shifts. In other words, there's something called rostrocaudal redistricting [indiscernible] These patients will have edema in their legs When they lay down, that fluid will redistribute horizontally and conversely towards the head and their neck which is already obstructed with usually with fat tissue, will then become even more obstructed. So you're right, that mechanism's volume and the combination of a diuretic plus lorunterstadt should dramatically de that effect. Now you asked about non genomic effects, The answer there is not is yes, but not fibrosis, it's inflammation most likely. So if there is a contribution it will be related to the genomic effects on inflammation, but also the effects on radical production in small vessels, which is non genomic. Does that answer that question? Yes, it does. Thank you. Now SGLT2 inhibitor we know that SGLT2 inhibitors in combination with an ASI do have some theoretical and practical advantages I would say one of them those are modest antihypertensive drugs and it's possible that there will be some additivity between the two mechanisms.

In addition, there is some loss of potassium that you have with the SGLT two inhibitor The three weeks at the run-in period in this trial, is sufficiently long for most of those effects to already be manifest by the time that we start the drug. In addition, it's a crossover study where the in the first period the placebo people will have that same effect. So it's built in that we can assess exactly the effect that you are discussing, know what it is and have a sensitivity analysis to address that possibility.

Very helpful. Thank you. Thanks, Mike.

Thank you. Next question will be from Rich Law at Goldman Sachs.

Hey, guys. Good morning. Yeah, a couple of questions for me. Given your guidance for ADVANCE and launch, readout timelines overlap with each other. Is there more refined guidance now on your base case of when each of those will be presented first? Can we assume that events will go first before launch or is there a chance that both can go together? And then I'll follow-up with that.

Yes, Rich, thanks for the question. As we noted, in our opening remarks, we're continuing to guide Advanced HTN for March and launch HTN for mid first half of this year.

Okay, got it. And then for ADVANCE, I know you potentially could present that twice. One for like a top line webinar and one at ACC. Do you see something similar for launch?

Yes, we're certainly excited about the acceptance of the late breaking abstract. For Lorunterstadt in the ADVANCE HTN trial at the upcoming ACC meeting Depending upon when we get the top line results, we'll either do a corporate announcement in conjunction with that or if we have the results sooner than that, we would anticipate doing a corporate top line announcement. As to launch, I think it's too early to opine on what communications would look like with that trial.

Got it. And then one final question. So the ADVANCE trial actively tracks and enforce adherence of the treatment. But what do you expect for the compliance for patients wearing the ABPM device for that twenty four hour period? Like, have you seen any issues of patients like taking off the device for a long period of time that could affect results? And then are patients like required not to do certain activities while wearing the device like exercise or stuff like that?

Yes, Rich. Yes, thanks. I'm glad that the team made the choice with Target HTN to not only do the in office measurement, the twenty four hour ambulatory. It gave us as a team experience with the device, with the vendor, We're working with the same vendor and technology and advanced HTN. So we've got that past experiences as far as how to use that device, how to teach and train sites and subjects on proper technique with that. We do allow subjects when they either exercise or bathe to have breaks from that. There are compliance or QC requirements with the twenty four hour ambulatory where we to get a certain percentage of the I think it's roughly 70 measurements over a twenty four hour period. So we're very confident that we have sites and subjects well trained for that. And the experience that our team has in working with that device gives us high comfort in the data and the quality of the data that we're going to get from that. And that's why we chose twenty four hour ambulatory, which as you know is the gold standard [indiscernible] are optimizing treatment, optimizing dose, optimizing compliance, using the gold standard really gives us I think a high quality data set particularly relative to what's been done with new innovations in this space and what's being done with other ASIs.

Dave, Dave had one comment.

Yes. Hey, Rich, that's a great question. It's key to have as much good data from the primary as you can. You'll never have it perfect with ABPM. But we went through the QC and procedures as a root cause for losing data in the first trial and we identified several ways to improve retention of informative data from those studies. We did lots of work on statistics and we're confident that we're going to have more than adequate good quality data to have the power that we imputed when we designed the size of the trial.

Great. And then just to follow-up on that, is there any what's the plan for like any missing data if patients take off the device and then for like say a couple of hours and then what's the plan for that?

Rich, that was part of the root cause analysis We've got that built into the algorithm. We went over it with the FDA. They approved Okay. Thank you so much. Thanks, Rich. Next question will be from Charlie Yang at Bank of America. Please go ahead, Charlie.

Hi. This is Alice on for Charlie. Thank you for taking our questions. So just on the upcoming pivotal readouts, what are your latest expectations around safety and tolerability? Whether you hope to differentiate MOS versus typical MRAs? And even if efficacy were to be slightly less, than MRAs, for example, wouldn't a cleaner drug still be a commercial winner? Thank you.

Yes. Thanks for the question. I think it's important to continue to distinguish the aldosterone synthase inhibitor class from the mineral corticoid receptor antagonist The MRAs block the effect of aldosterone at one of the biologic pathways that aldosterone affects that's Mineralys corticoid receptor. Aldosterone synthase inhibitors, however, go to the root cause of the problem and actually reduce the amount of plasmaldosterone The benefit of that is not only how well DASION can be its effects mitigated at the mineral corticoid receptor, but also at other pathways such as GPR30 that affects fibrosis inflammation and oxidative stress. So as such, the adverse events that are attributable particularly for spironolactone on blockaded BMR such as the androgenic [indiscernible] infertility issues with women, are something we don't see with this class of drugs. I think it's also fairly well accepted that the mineralocorticoid receptor antagonist seem to have a compromise trade off that as you push dose to get to F efficacy, you invariably see a push in hyper [indiscernible] From our perspective, we think there's a more modest impact on potassium within Aldosterone synthase inhibitor is something that was exhibited in target HTN And so we'll continue to evaluate that in the Pivotal program, but we believe that is the key distinguishing factor relative to the MRAs.

I have Dave at the thought as well.

Yes. So obviously, everyone thinks about this a lot. I want to point out something about just the trial designs.

When you say how are we going to compare to say MRA, as far as I know, no one's ever done a trial like our advanced trial as rigorously to deliver the data we're going to have Advance. In other words, we're looking at confirmed you failed on two or three drugs at maximum doses you took the drug and then we use twenty four hour ambulatory to prove it.

So there is no benchmark. [indiscernible] is the closest thing to a benchmark And so what I encourage you to do is look at these trials as they stand alone these will be especially the advanced trial, but also launch definitive establishment of the point estimate for how good these drugs are.

Thank you. Next will be Annabel Sami at Stifel. Please go ahead.

Hi, all. Thanks for taking my questions. Just to put things in perspective, again, can you remind us what coverage payers could give you if you hit and specific ranges like seven to nine, eight to 10 over 10. As you did just in the various subpopulations So can you help us frame how [indiscernible] within the treatment paradigm. And then I have a follow-up.

Yes, Annabelle, thanks for the call. We have to date completed four separate payer research projects in The United States and feel very bullish about our ability to get access for Lorunterstadt. And particularly in our targeted approach. We have basically put forward a base case of an eight to 10 millimeter mercury in [indiscernible] that's well tolerated And typically fourth line, we think that's a space we can own. So in that resistant population, particularly as Dave highlighted with the prior answer with advanced HTN, frankly being one of the most rigorous, if not most rigorous study ever done. That kind of data set we believe based on the research gives us an opportunity to really own the resistant hypertension space then as we look at third line and this is what we put in front payers as well. When we bring forward a a patient type or an endophenotype of responder, such as those with a BMI over 30 so that more targeted approach that is viewed favorably by payers as well with that eight millimeter to 10 millimeter mercury improvement. Now all of this obviously Annabelle's going to be based on also the pricing and the rebate strategy within that but just that clinical profile has resonated with payers in that resistant population and targeted third line.

Okay. And then I guess can you remind us the proportion of the population that [indiscernible] the third, fourth line population, how does each of those I guess how does that positioning change your opportunity within the different populations that you have?

Yes. I think the resistant populations so those failing on three or more with the diuretic is a little bit more easy to quantify. It's typically seen as about ten percent to fifteen percent of the treated population, so roughly seven point five million to ten million subjects are in that resistant hypertension category. Those that would be third line, so failing on two or more is a little bit difficult to try. You'll triangulate to with the data, but ballpark, we view that population as about ten million well. So collectively, between those that are failing on two or those are failing on three or more, it's roughly $15,000,000 to $20,000,000 I would say. As an addressable market Okay, great. All right, thank you. That was great.

Helpful. Thanks, Annabel.

Next question will be from Seamus Fernandez at Guggenheim. Please go ahead. Hi, it's Colleen on for Seamus. Thanks for taking our question.

Could you just talk a little bit about where you view the threshold for hyper klelemea rates in ADVANCE and launch, and what needs to be shown there to be differentiated in the clinic? And then just how would you expect the addition of diuretics, required in every patient impact the rates versus what we saw on target?

Yes. Thanks, Colleen. We've done a, as I said, a significant amount of payer research, we've also done a significant amount of physician research over the last several years 5% or less is what we've always tested as rate of hyperkalemia, as part of a base case. And I think that's viewed as favorable by the physicians that we've done the research with. As you may recall, we saw about a three point six percent rate in Target HTN. To your point, there is a belief that the use of a diuretic can be potassium wasting so could offset the modest rise that we know we see with aldosterone synthase inhibitors. We saw saw that with lorunterostat, saw that with Baxterstat and on par with what you typically see with an ACE inhibitor or an ARF that have been used safely for decades at this point. So I think that will be an interesting addition to the pivotal program where all septics in both studies are on a diuretic and in target HTN where we saw that modest impact only half of the subjects were on a diuretic because it wasn't required per protocol. Me have Dave add a comment on top of that, Colleen.

Yes.

I'm going to give you a clinician perspective.

And we hear this all the time. This is about benefit risk. The FDA has told us that. It's not P values. It's nothing. It's really what's the benefit and what's the risk. And what that means is the bigger the blood pressure response, the more tolerance there is or changes like potassium, And what that means for us is that we are looking at both. When you asked about the they lower potassium ensuring that people are taking their thiazide to improves benefit risk both by increasing the response and decreasing the potassium. So think about it that way, it's benefit risk. For the worst patients, the ones with CKD, the clinicians uniformly say we have great potassium binders what we don't have are great antihypertensives. And so they're willing to tolerate almost any level of hyperkalemia and just treat it to get the maximum blood pressure response to lorounderstat. Is the feedback we get. Great. Thank you.

Thank you. Next question will be from Mohit Bansal at Wells Fargo. Great. Thank you very much for taking my questions. So like I have a couple of questions. So I'll start with first. Do you think we'll see meaningful differences in the placebo adjusted results in terms of ABPM versus AOBP And then like how do you think this [indiscernible] [indiscernible] Could read to launch HTN where Office reading is the primary endpoint? And I have one follow-up. Hey, Mohit, I got your first question. Can you repeat your second one though? I'm sorry, there was a little bit Sorry about that. So what I'm saying is that, so [indiscernible] from advanced HTN, whatever you see in Office blood pressure reduction, how much you could read that for or what is the read across for LAUNCH H10 because LAUNCH H10 has AOBP as the primary endpoint?

Yes. Okay. Thank you for clarifying that. What we saw in Target HTN was about a four millimeter mercury change in the in office measurement and in the twenty four hour ambulatory about a one to two millimeter mercury placebo change. So fairly tight in accordance. I think it's a tribute to the team, the work they did to align to the recommended best practices in measuring blood pressure. We applied those same techniques for in office measurement for both advance as well as launch. I'd hate to opine on are we going to see a replication of that What's the read through from advanced to launch? They're different studies, but it's the same technology, the same technique the training that we've done with the sites, So it's difficult to to project what it could be. I just think the team has made the right choices as far as technology and technique that was validated in target HTN. That's what we're applying in advance and launch.

Fair enough. That's helpful. And then the second part is that how are you thinking about the nighttime coverage with Loranda Stret? The reason I'm asking is because half life is shorter here So do you think timing of the dose could impact the ABPM measure more than the AOBP share.

Let me I'll have Dave give a comment to this. I think it's important to reiterate that we think the ten to twelve hour half life of LaRenta said is actually ideal for, as Dave articulated earlier, the benefit risk of an ASI in the treatment of hypertension. I'll reiterate that in target HTN, when we saw that millimeter mercury drop in in office measurement. That blood pressure measurement was in the morning At trough, before that day's dose. So we have have strong confidence in the twenty four hour coverage of Lorunderstat with that ten to twelve hour half life. We also think it provides the ideal mix of efficacy and safety, particularly the on target component which is potassium and sodium, Dave, do you want to add some thoughts on top of that?

Well, I can just add a little bit. As John said, we know from Novartis and I was there that a four hour half life isn't long enough We also believe that leaving a window that recapitulates normal circadian rhythm when ALDO does go up pre arousal is the best way to try to treat it, restore the normal rhythm.

We have 100% by our healthy volunteer study suppression of Aldo, with our drug We can adjust how long that 100% lasts. And so just to reiterate that last point for John, we tune that so that it's 100% for until you go to sleep essentially, and then it slowly comes up to only 30% of pretreatment baseline which is 70% suppression and then goes back down to zero again after the morning dose. We just think that's science based on what we know about circadian rhythm and it's the most appropriate way to treat this [indiscernible] Awesome. Thank you very much for this. Appreciate it.

Thanks, Mohit. Next question will be from Ramik Kharkatah at Lifesize Capital. Please go ahead.

Good morning guys. Thanks for taking my questions.

Maybe going off a previous one, do you expect the delta in treatment effects observed with lorendostat in the pivotal studies, just given the slight difference trials and the fact that patients in ADVANCE are potentially enriched with aldosterone driven hypertension Then I have a follow-up.

Yes, Rami, thanks for the question. I think it's it's hard to predict the response in advance the response in launch in a differential. There are different studies as you I think the interesting aspect of advances that we have a truly confirmed uncontrolled or resistant hypertension population On the one hand, that may be a more rigorous challenging population to treat. On the other, it may be somewhat enriched for an aldosterone dependent form of hypertension. Launch is largely confirmatory to what we saw or what we designed in target HTN. With the exception of all subjects in launch going to be on the diuretic. And we know there was a favorable synergy as far as more enhanced response there. So it's difficult to predict across these two trials, we're just excited about design of these two, I think they address key aspects of the market, advanced being as rigorous as rigorous as it is, is really built for the specialists that are dealing with the difficult to treat patients, It's also the kind of study that gets us the opportunity to be included in hypertension guidelines and the launches the real world setting of what the primary care physicians are going to be doing with L'Erunnerstat should we be able to bring it into the marketplace.

Got it. Makes sense. And then a recent paper detailed that BIs of Austrian synthesis inhibitor has a half life of four to six hours, which is lower than what we've seen with lorendostat and baxterstat. I guess does this affect how you view their CKD data at all and Lorendrestatz I guess overall positioning in that population?

Well, that's a very good question and it is reminiscent of what happened LCI-six ninety nine oselhidrostat, which pretty much the same half life and And if you read the papers that were written, it was recommended that a longer half life would be required to develop a match only applications dose. We agree with that.

We are targeting in CKD the subset of patients who mainly have not enough control with their blood pressure, which is damaging their glomeruli, scarring them every day and driving the deterioration in eGFR. If you don't treat that adequate get it down to gold, you will continue to have progression of the CKD. So at least in it with our drug, with our tunable suppression, in that disease And you'll remember we're testing twenty five milligrams in that group, although it can be escalated in the real world, we have an optimum way to do that. I don't want to comment on somebody else's drug in their program, They probably know more than I do but we like our approach We also like the fact that we can add it on to an SGLT2 of choice which we think may also be an advantage when you're mainly going after the hypertension and not using the combination for the metabolic syndrome component mainly.

Awesome. Thanks so much. Next question will be from Matthew Caufield at H. C. Wainwright. Hi, thank you. Good morning, guys. And thanks for the updates. Morning. So kind of changing gears considering obstructive sleep apnea, Can you speak a bit more to the mechanism expectations for ASI benefit?

For those patients and then any read through from the current pivotal developments Thanks again. So let me address that in two ways. So there are two potential benefits. At this stage, near term, we're focused on the fact that these patients have sixty percent to eighty five percent resistant hypertension. And on top of that, it's not being diagnosed or treated because it's at night. And so Our goal there is to look at the aldosterone dependent mechanism, which is right the sweet spot for our hypertension program What happens in these people and it's often men and only postmenopausal women, is what's driving the algo is the hypoxia.

Remember, we say 15 apneas per hour. Think about that. Every four minutes, you're unable to move oxygen from your airway down into your lungs. Your body responds to that with a stress response that drives aldosterone. And so that's the mechanism for why they have such exceptionally high incidence of dying in their sleep, arrhythmias like ventricular and atrial arrhythmias, etcetera. So that mechanism is directly targeted by our drug. It's part of the theory for dosing the drug for that indication at night even though you're trying to go after the hypertension primarily, it's a better way to do it and still get that window. In our opinion, Now OSA piece, the extra airway obstruction itself well, we know you can treat that with CPAP. It's not a a treatment people love And if you don't use it six hours a day, you get essentially almost no benefit on either blood pressure or survival. And so again, by adding our drug in and we're going to study it during a two day period off the CPAP, you will get potentially additive benefits from the fact of the mechanisms I told you referred to before, which is primarily fluid shift and secondarily probably some inflammation.

Very helpful. Thanks a lot guys. Thanks Matt.

And at this time, we have no other questions registered. I would like to turn the call back over to John for closing remarks.

Thank you, operator, and thank you to everyone for joining us today. We're very excited about the progress we made in 2024 and thus far in '25 In advancing our clinical programs and we remain enthusiastic about the upcoming data milestones planned for the first half of twenty twenty five. We look forward to keeping you updated. With that, we will close the call.

Thank you, sir.