Greetings. Welcome to Mineralys Therapeutics' 2024 Financial Results Conference Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. If anyone should require operator assistance, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce Dan Ferry of LifeSci Advisors. Please begin. Thank you, Operator. Good afternoon, everyone, and welcome to our third quarter 2024 conference call. After the close of market trading today, we issued a press release providing our third quarter 2024 financial results and business updates. A replay of today's call will be available on the investor section of our website approximately one hour after its completion. After our prepared remarks, we will open the call for Q&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 in today's press release and our SEC filings, including our annual report on Form 10-K and subsequent filings. Please note that these forward-looking statements reflect our opinions only as of today, November 11th. 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. John? Thank you, Dan. Good afternoon, everyone, and welcome to our third quarter 2024 financial results and corporate update conference call. I'm joined today by Adam Levy, our Chief Financial Officer, and Dr. David Rodman, our Chief Medical Officer. I'll begin with an overview of the business, our clinical programs, and recent milestones. Then Adam will review our third quarter financial results before we open up the call for your questions. I want to kick things off with a recap of the progress the Mineralys team has made these past several months advancing our pivotal clinical development of lorundrostat in hypertension and then discuss the upcoming milestones we anticipate throughout the first half of 2025. We recently completed enrollment in our pivotal Advance-HTN trial, which is evaluating the efficacy and safety of lorundrostat 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. Subjects were randomized across three arms, including placebo, lorundrostat 50 mg once daily, or lorundrostat 50 mg once daily with the possibility to titrate up to 100 mg once daily. We announced the key characteristics of subjects enrolled in the trial include more than 66% of the subjects have a BMI equal to or greater than 30, more than 40% of the subjects are women, and more than 50% of the subjects are Black or African American race. Notably, in terms of demographics, we took extra steps to broaden the diversity of the subjects in this trial to provide a better representation across different populations with the goal of showing equivalency across race and sex. As a reminder, this trial was designed in collaboration with the Cleveland Clinic based on the most rigorous standards. The trial will be utilizing 24-hour ambulatory blood pressure monitoring, or 24-hour ABPM, which is the gold standard for blood pressure measurement and historically has shown lower rates of white coat hypertension and has better managed placebo responses compared to other measurement approaches. Additionally, 24-hour ABPM has the ability to assess nighttime blood pressure and nighttime blood pressure dipping status, which have been shown to play a role in adverse cardiovascular risk and outcomes. Advance-HTN is utilizing smartphone-based technology to track and manage participant compliance to lorundrostat with a partner called AiCure, which helps ensure the participants take all medication as prescribed under the trial protocol. The primary endpoint for this trial is change in 24-hour ambulatory systolic blood pressure at week 12 from baseline for active cohorts versus placebo. The planned analysis includes several important subset analyses in an effort to identify predictors of enhanced response to lorundrostat, such as obesity that was demonstrated in the phase II Target-HTN trial. Subjects with uncontrolled or resistant hypertension were stratified, providing balanced distribution across each of the three arms of the trial to allow us to perform a formal test in each population. We believe demonstrating robust efficacy in confirmed resistant hypertension, the area of highest unmet medical need, will be important in positioning lorundrostat for rapid access and uptake by payers and physicians. Positioning lorundrostat for obese uncontrolled hypertension patients who are at increased cardiovascular risk will provide an expanded market opportunity. In addition, as we accrue more experience and data with lorundrostat, we plan to continue to explore other positive and negative predictive factors, including using artificial intelligence to expand the precision toolkit for targeting lorundrostat to individuals with uncontrolled or resistant hypertension who are likely to derive long-term clinical benefit. We look forward to announcing the top line data, which we anticipate sharing in March of 2025. Moving to Launch-HTN, our second pivotal trial, which is designed to be a confirmatory trial with the objective of evaluating lorundrostat in a real-world setting when added to a subject's previously prescribed antihypertensive regimen. We were excited to announce just a few weeks ago that we completed enrollment in this trial. With enrollment of Launch-HTN completed ahead of schedule, we updated our guidance for top line data, pulling these results forward to mid-first half 2025. Launch-HTN is a phase III trial of lorundrostat for the treatment of subjects with uncontrolled or resistant hypertension as add-on therapy who failed to achieve blood pressure control on their existing prescribed background treatment of two to five antihypertensive medications. Subjects enrolled in the trial who failed to achieve blood pressure control on their existing prescribed treatment were randomized one to two to one to either placebo, once daily 50 mg of lorundrostat, or once daily 50 mg of lorundrostat with the option to titrate to 100 mg once daily as needed at week six. The primary endpoint for this trial will be the change in systolic blood pressure as measured by automated office blood pressure at week six for the pooled 50 mg subjects compared to placebo. This trial is well-powered at six weeks for the primary endpoint, as well as subset analysis such as BMI status to inform the clinical label of lorundrostat. We believe this trial is reflective of clinical practice utilizing the real-world in-office measurement and when lorundrostat is added to an existing treatment regimen that will be relevant to primary care providers. In addition to our pivotal program in hypertension, we are conducting the Explore-CKD phase II clinical trial for lorundrostat when added to background treatment with SGLT2 inhibitor in patients with uncontrolled or resistant hypertension in stage two to three B chronic kidney disease. Enrollment is ongoing, and we anticipate announcing top line data in the second quarter of 2025. Explore-CKD is a within-subject comparison trial designed to demonstrate the benefit of lorundrostat in reducing blood pressure and provide supportive evidence for potential benefit for subjects with chronic kidney disease on the background of stable SGLT2 inhibitor treatment. This proof of concept trial will enroll approximately 60 subjects with hypertension in stage 2 to 3 B CKD. Before I turn the call over to Adam, I just want to remind everyone that a replay of the KOL event we hosted October 30th is still available on the investor section of the Mineralys website. We are very fortunate to have three leaders in the hypertension field join us on the call, including Dr. Luke Laffin of the Cleveland Clinic, Dr. James Luther of Vanderbilt University Medical Center, and Professor Rhian Touyz of McGill University Health Centre. They each offered valuable insights on the unmet medical need in uncontrolled and resistant hypertension, as well as the potential for lorundrostat to change the current treatment paradigm. We also included a detailed review of the ongoing Advance-HTN and Launch-HTN pivotal trials and their designs. I'll now turn the call over to Adam to review our financial results for the quarter. Thank you, John. Good afternoon, everyone. Today, I will discuss select portions of our third quarter 2024 financial results. Additional details can be found in our Form 10-Q, which will be filed with the SEC tomorrow, November 12th. We entered the quarter with cash, cash equivalents, and investments of $263.6 million as of September 30th, 2024, compared to $239 million as of December 31st, 2023. The company believes that its current cash, cash equivalents, and investments will be sufficient to fund its planned clinical trials as well as support corporate operations into 2026. R&D expenses for the quarter ended September 30th, 2024, were $54 million compared to $22.5 million for the same quarter of 2023. The increase in R&D expenses was primarily due to increases of $26.1 million in preclinical and clinical costs driven by the initiation of the lorundrostat pivotal program in the second quarter of 2023, $3.4 million in clinical supply, manufacturing, and regulatory costs, $1.7 million in higher compensation expense as resulting from additions to headcount, increases in salaries and accrued bonuses, and increased stock-based compensation of $0.3 million in other research and development expenses. G&A expenses were $6.1 million for the quarter ended September 30th, 2024, compared to $3.8 million for the same quarter of the prior year. The increase in G&A expenses was primarily due to $1.7 million in higher compensation expense resulting from additions to headcount, increases in salaries and accrued bonuses, and increased stock-based compensation, and $0.8 million in higher professional fees, partially offset by a decrease of $0.2 million in other administrative expenses. Total other income was $3.8 million for the quarter ended September 30th, 2024, compared to $3.5 million for the same quarter of 2023. The increase was primarily attributable to increased interest earned on the company's investments in money market funds and U.S. Treasuries. Net loss was $56.3 million for the quarter ended September 30th, 2024, compared to $22.8 million for the same quarter of 2023. The increase was primarily attributable to the factors I described earlier. With that, I'll ask the operator to open the call for questions. Operator? Thank you. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. And for participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment while we pull for questions. Our first question is from Michael DiFiore with Evercore ISI. Please proceed. Hey, guys. Thanks so much for taking my question and congrats on all the progress. Three for me. First one is just in reviewing the Target-HTN data set, looking at the nighttime blood pressure results and in the sensitivity analysis, even after the white coat hypertension patients were eliminated, we noticed that there wasn't any nocturnal dipping at eight weeks in the 50 mg QD group. Any color explaining that would be great. And then I have two follow-ups. Yeah. So this is Dave Rodman. Why don't I take that question? So first of all, you're absolutely right that the big value driver in 24-hour ambulatory measurements is, first of all, you get a lot of measurements, so you get much quieter data, a lot less noise. But you also get to segment it into nighttime and daytime. And as you mentioned, nighttime is particularly important because untreated nocturnal hypertension is a big risk factor for adverse cardiovascular outcomes and MACE. So if I can point you first to the 100 mg cohort where we had very little white coat hypertension, there the nighttime response to lorundrostat was comparable to what was seen in wakefulness, even though the dose was taken in the morning and those measurements were in the evening. And so that's what you would expect. The 50 mg is a little more problematic to interpret because there was a very high proportion of patients who on the ABPM appeared to have kind of a lower blood pressure than they had with AOBP or so-called white coat hypertension. So we had to subtract all those people out to do the sensitivity analysis. And when we did that, it was about a 50% reduction compared to daytime. I think it's unlikely that that's true because the numbers got too small. I do think the 100 mg is probably a better guidepost. But in any event, we'll be looking and controlling for that in the trial so we'll have the accurate answer for that. Got it, Dave. Thank you. Very helpful. My two follow-ups are, we're just reviewing the early safety database of the first-in-human study data set. I noticed that in the phase I MAD trial, there was one case of sinus tachycardia at 360 mg. My question is, how big of a safety margin relative to the NOAEL is 360 mg? Separately, in the same data set, there was also one case of dysgeusia at 40 mg. Just asking because that could potentially be a functional unblinding type of thing. Any explanation of those two AEs would be great. Thank you. The first one, I'll take the first one first. That's a pretty big dose, 360 mg. How does this drug work? Well, acutely, it causes volume loss. So you urinate out sodium and water. The response to that is sinus tachycardia. So when you get dehydrated or volume depleted, that's what happened. So it's not really a safety finding. It's a pharmacodynamic effect of a healthy volunteer having too much volume depletion. And so that we don't expect to read through at the lower doses, especially in these hypertensive patients. Now, your second question, dysgeusia, I got no idea on that one. I just don't know. We haven't seen it again. Whether it's unblinding or not, it just hasn't been a functional problem in our trials. Okay. Now. Appreciate it. Very helpful. Anything else, Mike? No, that's it. Thank you. Appreciate it. Okay. You bet. Thank you. Our next question is from Richard Law with Goldman Sachs. Please proceed. Hey, guys. A couple of questions from me. The first one is for Advance-HTN. You guys are tracking and proactively enforcing adherence. Can you discuss what is the adherence rate for Target-HTN and how much do you think that adherence can improve in Advance-HTN? So the question was, what's the adherence rate in the Target-HTN trial versus Advance-HTN, or? No, you're looking for what is the goal. Rich, can you restate your question again? Sorry. Yeah. So for Advance-HTN, you guys are tracking and proactively enforcing adherence, but you guys didn't do that for Target-HTN. So just curious to see what was the adherence rate for Target-HTN and how much do you think that could improve as you move into Advance-HTN by that proactively tracking and enforcing? Okay. Gotcha. Good question. So the only thing we did really was to do pill counts when people came in to see if they had taken their drug or not. We piloted some technologies, but we didn't really use the data. That's how we ultimately ended up choosing the AiCure method that we're using now. So I can't give you any accurate information because pill counts are notoriously ineffective because people know you're doing it, and so they might just dump them in the sink or whatever, but in the Launch trial, we are also doing adherence, but we're not actively supporting that in terms of reaching out or telling them much, and so other than the normal reminders, and there we're going to do a subset analysis that looks at your question, which is how much is non-adherence a problem in terms of responses. We'll do a sensitivity analysis on people who took more than 75% or not. I can't really comment too much on the target, but we will have an answer to your question. I see. Got it. And then another question. You guys mentioned a lower absolute SBP value with the ABPM measurement. How do you think about a placebo-adjusted ABPM, and how would that change compared to placebo-adjusted AOBP, for example, in Advance-HTN? Is it safe to assume that both are very similar if the study is well controlled? I'll give a quick heads-up on that, Rich. We typically see with 24-hour ambulatory, it's plus or minus 1, maybe 2 mmHg with a placebo with that 24-hour AOBP, you see a little bit more variability with that because it's in-office. It's a single time point from a measurement standpoint. From Target-HTN, because of the technique we use in doing five measurements in a quiet room unattended and averaging the last two, we saw about a 4-mmHg change. We know prior studies that have used different methodologies around that, such as the SPRINT trials, actually saw higher figures than that. So from our standpoint, following the recommendations from the AHA, we're continuing to repeat our technique for in-office measurement and have not only 24-hour ambulatories as the primary and Advance-HTN along with in-office. We also have in-home. So we have three different measures within Advance-HTN and then the in-office practice that we use for Launch-HTN. And so we feel confident that we've controlled for the variables within the different techniques. And that's based on the work that we've done with Target-HTN. Hey, Rich, one other comment here is that the measurements with ABPM, because they average in nighttime, which tends to be lower in people that don't have, say, sleep apnea, tend to be about 5 mmHg lower. And response to hypertension drugs is proportionate to the level of the baseline blood pressure. So if you have a lower baseline blood pressure, you can go down less, so you have a little bit smaller response. So most people say you have one or two millimeters smaller placebo-adjusted treatment effect when you do ABPM versus AOBP. And then, as John mentioned, those numbers are just shifted up with the ABPM, but there's more variability in the placebo effect there. So they're just a little bit noisier. Maybe that was more than you wanted to know, but just thought I'd pass it on. No, I think that helps a lot. So you're saying about five or so on an absolute basis, but once you adjust for placebo, that should be about one to two. Not sure of that. So the difference is that with ABPM, because of all the multiple measurements, your placebo effect is going to be pretty small. I would say one to four is what I've seen in the literature. In a big enough study, it'll be one or two. And that's what we were with our target study. ABPM, up to seven. AOBP. I mean, AOBP, sorry, up to 7 mmHg. Or even if you look at baxdrostat, they had nine, I think, in their first trial. Up to seven is acceptable. In general, it's in the range. We had four. And we put a lot of work into making sure we get the best data we can. Obviously, when you get to bigger trials and more sites, you tend to have slightly more variability. I'm not sure I understood your question per se, but I hope that gives you the answer you needed. Okay. Got it. Thanks. And then just one final question. You guys mentioned greater than 66% patients with BMI greater than 30. What is the power assumption for that greater than 30 and less than 30 BMI group from that 66% number? I think you guys mentioned a 90% powering assumption for the overall group. So I just want to see what that powering assumption looks like once you go down to these pre-specified subgroups. And thank you. Yeah, Rich, thanks for the questions. Advance-HTN overall is 90% power for a 7-mmHg change relative to placebo. Launch-HTN greater than 95% power for the same reduction, and we haven't disclosed at this point in time any of the subset analysis power calculations. Okay. Thanks, guys. Thank you. Our next question is from Annabel Samimy with Stifel. Please proceed. Hi. Thanks for taking my question. Just wanted to clarify a couple of things. For Advance-HTN, the primary endpoint is at 12 weeks with titration at four weeks, and then Launch has up titration at six weeks with the primary endpoint there, but runs to 12 weeks, if I'm reading your presentation correctly. So is the six weeks sufficient for that separation given the possible additional noise that might be introduced with real-world background meds? I guess, how are you managing the placebo response in that scenario? Are there going to be more confounding results possibly? And is six weeks sufficient? I guess, why not run it to 12 weeks with that kind of background variability? Yeah. Annabel, appreciate the question. I think it's important to think of Launch-HTN very much as a confirmatory study to Target-HTN. There are a lot of similarities as far as the construct. As you know, in Target-HTN as in Launch-HTN, we allow subjects to stay on their background medication of two to five antihypertensive treatments. We have that two-week run-in period on placebo where we get them compliant to their existing background meds. We're using AOBP in Launch-HTN, same technique, same technology that we used in Target-HTN. What we saw in Target-HTN was about 70% plus or minus of the effect at week two. And by week four, the vast majority of the effects. We're comfortable that that six-week data readout, we're not going to be missing really any significant reduction in blood pressure within that time course, just based on what we saw within Target-HTN at week four, and I'll just highlight that maybe one of the biggest distinctions between the two studies is we definitely saw a potential synergy with the diuretic in Target-HTN where about half the subjects were on a diuretic, and by design, both in Advance-HTN and in Launch-HTN, all subjects were on a diuretic, so I think we've factored in the profile of lorundrostat within this confirmatory design of Launch-HTN that we don't feel we're going to be missing anything. Plus, as part of the secondaries, we will be looking at that 12-week time point for both the 50-mg arm and the 50-mg up-titrated to 100-mg arm. Okay. Got it. And just to go back to the last question, for I mean, I know you haven't disclosed the powering for obese versus non-obese, but is there a possibility to see statistical significance separation between the two? I think we'll be looking at, as we did in Target-HTN, these pre-specified subsets in both Advance-HTN and in Launch-HTN. The primary benefit of moving the primary endpoint of Launch-HTN from week 12 to week 6 was not power for the primary, but was power for those subset analysis. We feel very confident that we're going to be able to, if the trend reconfirms as we saw in Target-HTN, be able to have the statistical power to evidence that. Again, we've got to get to the data, but that's going to be part of the pre-specified analysis as we did in Target-HTN. Okay. Got it. And then just to also clarify, should we expect any dose response between the 50 mg and the 100 mg arms, or is this more about getting patients to the right exposure so they can actually have a response as opposed to, in other words, should we be looking for a dose response, or should we just be looking for blood pressure control, period? Yeah. What a good question. So two ways to look at that. At 12 weeks, say, let's just talk about Advance. At 12 weeks in Advance, there'll be three arms, right? And the same thing's true in Launch. There'll be a placebo group. There'll be a group that stayed on 50 mg, and then there'll be a group that got escalated if they hadn't reached goal to 100 mg. And so if people didn't have a high enough exposure at 50 mg because they didn't absorb it well or whatever, 100 mg might fix that. If people just have a lot of aldosterone production and they aren't completely suppressed at 50 mg, then 100 mg would fix that. So we won't know for sure if it's exposure to drug or individual biology until we start looking at maybe downstream mechanistic biomarkers, which won't come for a while. So I hope that answered your question. You're absolutely right. Yeah. Okay. Thank you. That's helpful. Thanks. Thanks, Annabelle. Our next question is from Mohit Bansal with Wells Fargo. Please proceed. Hi. This is Sadia Rahman on for Mohit. Thanks for taking our questions. So you've outlined patient demographics for the Advance-HTN trial. I'm wondering if in Launch-HTN you're targeting similar demographics in terms of the percentage of obese patients and the percentage of African Americans. Will they be similar, or should we expect differences in any of these? And can you remind us how these rates in Advance-HTN compare to the population that was enrolled in Target-HTN? Yeah. We haven't updated on the demographics of Launch-HTN. We may do that in the future. Target-HTN, I believe we had about the BMI average was 31 or mean. In Target-HTN was 31, what is it, kilograms per meter squared. The Black or African American population, I believe it was around 39%. So not terribly dissimilar from what we saw in Advance-HTN. I think it's fair to point out that both Advance-HTN and Target-HTN are probably beyond what you typically see as far as representation for Black or African American. We think that's important to really show equivalency between Caucasian and Black or African American hypertension patients because that's not always the case with all antihypertensives. Sometimes you can see disparity in response. We wanted to be able to evaluate that as a part of our precision toolkit. As far as Launch-HTN, it is a global study. We've gotten questions, is that going to dilute the BMI effect? I think the counterpoint to that is the obesity correlation with hypertension holds pretty strong globally, and so we don't have a concern that the makeup of Launch-HTN is going to look too terribly dissimilar from what we saw in Target-HTN, even though it is a global study versus U.S. alone for Target. John, if I could just add one thing, and that was a very nice discussion. There's a difference between African Americans and Black Africans as well as the European population, which tends to be doesn't have the same admixture of the white of the Caucasian genes. So African Americans are, on the whole, super sensitive to aldosterone. Lower levels of aldo produce more hypertension. That's not true in Europe, and so since we have European sites, we are going to have to distinguish between those two, and we will. Got it. That's helpful. Thank you. And then with respect to the number of sites and geographies that are being enrolled in Launch versus the other trials, how are you thinking about the placebo response in Launch? Do you think there could be a higher placebo response, and was that part of your powering assumption for Launch? Thanks. So Launch is pretty much super- powered because it's such a big study and looking at similar effect size. So if your question is, well, if there's an upward shift from the placebo effect, which presumably would affect both arms, is that going to introduce more variability and therefore decrease the power? And the answer is it won't be a significant problem in a trial of that size with the powering it has. Got it. Thank you. Thank you. Our next question is from Rami Katkhuda with LifeSci Capital. Please proceed. Hey, guys. Thanks for taking my questions as well. Just a couple of quick ones from me. I guess, based on the inclusion criteria, Advance and Launch are recruiting patients with lower eGFR than those in Target. Does that have the potential to affect hyperkalemia rates at all in the pivotal studies? You're right, Rami. We looked at 60 eGFR and above for Target-HTN. Based on that, we were comfortable going down to the 45 for both Launch-HTN and Advance-HTN. I think it's too early to tell at this point. We'll have to see what the data indicates. But we know from the 50-mg arm and Target-HTN, we really saw a modest change in potassium, similar to what you would expect with an ACE or an ARB. The Explore-CKD study where we're going down to an eGFR of 30 is allowable. We've actually reduced the dose to 25 mg QD. I think it's within that population that we want to move cautiously as we investigate lorundrostat and both the benefits as well as the safety profile specifically related to this pharmacological effect on sodium and potassium. Got it. Makes a lot of sense. And then in Launch-HTN, obviously, compliance is not being enforced as it is in Advance-HTN. Do you plan to do kind of an analysis of those patients who were compliant throughout the trial versus those who are not? Yeah. The technology of AiCure is really it's been validated, but it's really just a next-level advancement in how do we really ensure patients take the drug. For those that may not be aware, subjects have to take a picture of not only their background meds, but also either the placebo or the active ones. They're randomized. They also have to film themselves consuming it. That technique and that technology is being used both in Advance and in Launch. In Advance, we're proactively reaching out to subjects if they're not being compliant and reminding them of the importance of that. As you note, in Launch, we are not, but we are going to pre-specify an analysis looking at compliance. I believe it's for those above 75% compliant and those below 75%. So we'll have that as a pre-specified analysis so that we can look at that impact. And I think just to build on Dave's point, we saw really nice compliance in Target-HTN, but it was with less advanced technologies that are not completely foolproof. In other words, pill counts are kind of a standard way to do it, but we know patients can manipulate that. We're progressively trying to use technology to help patients help us with one of the most important things they can do, and that is being compliant to the pill. So I think we've currently using state-of-the-art but validated technology to really help ensure that we've addressed one of the bigger questions in these kinds of studies that we know has been an issue with other hypertension studies contemporaneously. Got it. Thanks so much. Thanks, Rami. Our next question is from Matthew Caulfield with H.C. Wainwright. Please proceed. Hey, good afternoon, guys. So you kind of touched on this with the powering, but for Advance-HTN, during the KOL event, it was mentioned that 6 mm to 8 mm of ambulatory BP benefit could be clinically meaningful. Does that range translate the same to potential target ranges or better for Launch-HTN and Explore-CKD to be considered successful? Thanks a lot. Matt, appreciate the call. Yeah. I think the KOL call was really instructive because I think they started by highlighting the fact that one or 2-mmHg change, particularly in a truly resistant or even uncontrolled hypertension patient, is meaningful as far as reducing cardiovascular risk. So it's always important to put that into context. I think the 6-mmHg to 8- mmHg that Luke Laffin alluded to in a broad population is absolutely on point. There's a clear correlation to reduced risk from an outcome standpoint. Based on the market research we've done with payers and with physicians, that's certainly within the realm of what's important and transformative for them. We've always guided that that 8-mmHg to 10-mmHg change that we saw in Target-HTN, if replicated in Advance-HTN and Launch-HTN, would be truly meaningful to the market. That's based on meta-analysis that show with currently available generic treatments, when you add a third or fourth line agent, you typically get a 5 mm Hg further reduction in systolic. New advances like renal denervation or aprocitentan have found 4 mmHg-6 mmHg reduction. That replication of 8 mmHg-10 mmHg is truly meaningful. If we find subsets such as an obese population that have a more pronounced effect, that becomes even more transformative. Ultimately, the goal is getting patients below their prescribed BP goal. That's something we'll be looking at within both of these studies as well. It's not only the absolute and placebo-adjusted reduction, but what is the percentage of subjects actually getting to goal and having a foundational shift in their cardiovascular risk profiles. Very helpful. And you would say that applies to Explore-CKD as well? Yeah. I think it does. It certainly does. And Explore is not only that benefit from a BP standpoint, but really investigating what we think is now a de-risk benefit of an ASI in combination with an SGLT2 on renal function as well. Very helpful. I appreciate that. You bet. Thanks, Matt. With no further questions in the queue, I would like to turn the conference 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've made thus far in 2024 in advancing our clinical programs, and we remain enthusiastic about the upcoming data milestones planned for the first half of 2025. We look forward to updating you as our pivotal program for lorundrostat continues to advance. With that, we will close the call. Thank you. This does conclude today's conference. You may disconnect at this time, and thank you for your participation.