Welcome to the Mineralys Therapeutics conference call to report top-line results from the Explorer-CKD phase 2 trial. At this time, all participants are in listen-only mode. After management completes their prepared remarks, we'll conduct a question-and-answer session, and instructions will be given at that time. As a reminder, this conference call is being recorded. If anyone today should require operator assistance, please press star zero from your telephone keypad. I would now like to turn the call over to Jon Congleton, CEO of Mineralys Therapeutics. Thank you. You may now begin. Good morning, everyone. I'm very pleased to speak with you this morning. Remarks made during this conference call and webcast will contain forward-looking statements regarding our financial outlook, regulatory, product development, and commercialization plans, as well as research activities. These statements are subject to risks and uncertainties that could cause actual results to materially differ from those forecasted. A description of these risks can be found in our most recent 10-K and 10-Q on file with the SEC. Joining me on the call today are Dr. David Rodman, our CMO, and Adam Levy, our CFO. In addition, we have with us Professor Matthew Weir, Division Head of Nephrology at the University of Maryland School of Medicine. Dr. Weir's primary research interests include the use of antihypertensive therapy for the treatment of diabetic nephropathy, hypertensive renal injury in African Americans, cardiovascular disease in patients with chronic kidney disease, and mineralocorticoid receptor antagonism to treat atherosclerosis. He has written more than 700 manuscripts and book chapters about these topics. He has edited eight books on topics in nephrology, transplantation, and hypertension. He has presented at numerous international scientific association meetings, hospitals, and medical schools. Dr. Weir will provide a brief perspective on his experience treating patients with hypertension and chronic kidney disease and interpretation of the clinical data from the lorundrostat, as well as be available during the Q&A portion of the call. Let me kick things off today by saying how pleased Weir is to announce the positive top-line data from our hypertension trial in patients with chronic kidney disease, or CKD, which we refer to as Explorer-CKD. This is the fourth positive clinical trial of lorundrostat that we have completed in uncontrolled and resistant hypertension subjects, which of course also include the two pivotal trials, Advance HTN and Launch HTN, as well as the proof of concept and dose range finding trial, Target HTN. All four trials have successfully demonstrated the meaningful and consistent efficacy, safety, and tolerability profile of lorundrostat, a novel, highly selective aldosterone synthase inhibitor. Explorer CKD was the first trial of lorundrostat designed to assess the safety and efficacy in a population of patients with uncontrolled hypertension, a lower mean eGFR than our previous studies, and the presence of proteinuria. Given the significant correlation of uncontrolled hypertension and worsening kidney function, we believe this is an important area of unmet need that lorundrostat could provide benefit beyond blood pressure. In the case of this trial, reducing urine albumin creatinine ratio, or UACR, a proven surrogate of improved renal function. I'm pleased to inform you that our blood pressure benefit, evaluated after only four weeks and with the 25 mg once-daily dosing, was clinically meaningful and consistent with the reductions we have seen in both Launch HTN and Advance HTN. While it is challenging to compare across clinical trials, I'm equally pleased to let you know the benefit on UACR reduction was comparable to what has been seen in recent trials of both baxdrostat and aldosterone synthase inhibitor, and finerenone, a mineralocorticoid receptor antagonist. The Explorer CKD data for lorundrostat demonstrates the value of aldosterone synthase inhibition in cardiorenal disorders and the benefit of targeting aldosterone therapeutically. In this trial, focused on a renally compromised population, no new safety signals were observed, and the rate of hyperkalemia was similar to that demonstrated with ASIs and MRAs when added to an SGLT2 inhibitor and either ACE inhibitor or ARB background treatment. I'm grateful to the participating trial investigators and subjects for their enthusiasm and commitment to the development program for lorundrostat. I want to thank the Mineralys team for their dedication and hard work, which has allowed us to get to this point in the development of lorundrostat. As I stated following the readout from our two pivotal studies, we believe lorundrostat is well positioned to be the best-in-class aldosterone synthase inhibitor for the treatment of uncontrolled and resistant hypertension. Our clinical program for lorundrostat provides a broad spectrum of insights to inform prescribers treating patients who are failing to achieve their blood pressure goal. Launch-HDN provides data that will be especially useful for the general practitioner looking to add lorundrostat to a patient's existing background treatment. Advance-HDN provides data that will be especially useful for the specialist who, in spite of optimizing background treatment, is searching for a new option to help their patients further reduce their blood pressure. Explorer-CKD now provides data for specialists who need an alternative means to control blood pressure in a renally compromised patient, balanced with a manageable safety profile with the hope of slowing their kidney disease progression. Our open-label extension Transform-HDN will provide physicians and patients data that will demonstrate the safety and efficacy of long-term chronic use of lorundrostat. Lastly, our ongoing Explorer-OSA trial continues to enroll and will provide valuable information on nighttime blood pressure, OSA symptoms, and cardiovascular risk. To provide more information on the Explorer-CKD study, I will now turn the call over to Dave Rodman, our CMO, to walk you through the study design and detailed results. Dave? Thanks, Jon, and good morning. This slide has all of the details of the trial and will be posted on our corporate website. I'm going to point out a few of the most important aspects of the design. The Explorer-CKD study was, in essence, a special population profiling study in a particularly relevant subpopulation with evidence of chronic kidney disease. Chronic kidney disease is a syndrome resulting from several root causes. A common mechanism in diseases like obesity, diabetes, and uncontrolled hypertension is inappropriate aldosterone production. For that reason, we felt it was important to provide prescribers with guidance for use in individuals with CKD, especially those with reduced eGFR and proteinuria. We used a 25 mg dose of lorundrostat to provide information using a lower starting dose of lorundrostat rather than the 50 mg dose that was highly efficacious in our prior studies of uncontrolled and resistant hypertension in individuals with eGFR in excess of 45. In the EXPLORER CKD trial, subjects had an eGFR as low as 30 and albuminuria levels between 200 and 5,000 mgs per gram. These subjects also had to be on an SGLT2 inhibitor for inclusion. If they were not, they were started on dapagliflozin in a run-in period of 2 weeks. This allowed us to evaluate the benefit of lorundrostat on top of standard of care. To provide the most precise comparison between placebo and active treatment in the most efficient way, we used a double-blind placebo-controlled crossover design. Subjects were randomized to either placebo or 25 mgs of lorundrostat at the beginning of the first four-week treatment period. Then all subjects went through a four-week washout period, and finally, they were treated with the other intervention. Those on lorundrostat switched to placebo, and those on placebo were switched to lorundrostat. Importantly, we confirmed that the four-week washout was sufficient for return of BP and UACR to baseline values before initiation of the second four-week treatment period. The study population had a mean age of 65. 69% were male, 66% were white, and 17% were Black or African American, and 76% were diabetic. The subjects at baseline had a mean systolic blood pressure of 149 mm of mercury, an eGFR of 55, and a UACR of 516 mgs per gram. Using the waist-to-hip ratio, all subjects had either a moderate or a severe risk profile related to excess visceral fat. All subjects were using an ACE or an ARB, and 56% were taking an SGLT2 inhibitor at screening. As noted, those not using an SGLT2 inhibitor were started on dapagliflozin at the beginning of the two-week run-in period. The changes in blood pressure and proteinuria that we observed are related only to the contribution of lorundrostat on top of the SGLT2 inhibitor, rather than that that might be observed if both were started simultaneously, as is the case with a fixed dose combination. The primary outcome measure was change in systolic blood pressure measured by automated office blood pressure at week four of the treatment period, compared to that at week four in the placebo treatment period. Similar to results in our prior trials, there was a clinically meaningful reduction in systolic blood pressure measured by the automated office BP technique. The primary endpoint confirmed the efficacy of the 25 mg dose, with an absolute reduction in systolic blood pressure of 9.3 mm of mercury and a placebo-adjusted reduction at week four of 7.5 mm of mercury with a p-value of 0.002. I will remind you that in our pivotal Launch HDN and Advance HDN trials, a further reduction in systolic blood pressure was observed between 6 and 4 weeks, respectively, and the end of the study at 12 weeks. While we did not measure blood pressure beyond four weeks of active treatment in Explorer CKD, all subjects were offered the option to roll over into a 25 mg once-daily open-label extension, with most accepting. We plan to evaluate the durability of the response at later time points in that trial. In obesity, diabetes, and other aldosterone-associated forms of CKD, reduction in proteinuria, quantified by urine albumin-to-creatinine ratio, or UACR, is a useful surrogate for renal protection and amelioration of decline in renal function. There was a 31% reduction in spot urine UACR, with a p-value of 0.0001. We believe that the benefits on UACR are representative of what one might anticipate if lorundrostat was added to standard of care treatment with SGLT2 inhibitor in the setting of uncontrolled hypertension and comorbid CKD. An equally important objective of EXPLORER CKD was to characterize the safety of lorundrostat in individuals with CKD, especially those with reduced eGFR. For level setting, the mean randomization eGFR in the three trials was 90 in the Launch HTN trial, 72 in the Advance HTN trial, and 55 in the Explorer CKD trial. Only two subjects out of 58 discontinued the lorundrostat. In this trial, adverse events of special interest were hyperkalemia, hyponatremia, excessive reduction in eGFR, hypotension, and hypocortisolism. Hypotension and abnormalities in cortisol were not seen, and there was only one subject with hyponatremia. The most important safety parameter when targeting aldosterone is change in serum potassium, especially so in individuals with reduced kidney function. At the group mean level, the increase in serum potassium in the Explorer CKD trial was 0.5 millimole per liter, between 0.42 millimole per liter in the Launch HTN trial and 0.61 millimole per liter in the Advance HTN trial. As this table shows, the cumulative incidence of hyperkalemia was 7 of 58 subjects, or 12.1%, with serum potassium above 5.5 millimole per liter. Of those 7, 3, or 5.2%, were above 6 millimole per liter, and 1 of those, or 1.7%, was above 6.5 millimole per liter. Of the 3 with serum potassium greater than 6, only 1 subject had the lorundrostat treatment discontinued. A second subject had the lorundrostat dose reduced to 12.5 mgs per day. The third subject had the elevated potassium noted at the four-week visit and then entered the washout period. In all cases, the serum potassium was reversible without any clinically significant changes in EKG or necessity for hospitalization or monitoring. These values compare favorably to prior published trials of other ASIs and appear to be manageable in the context of CKD. As this bar graph shows, only modest changes in mean eGFR, typical of RAS pathway inhibitors, were observed. One subject discontinued the lorundrostat due to low eGFR alone, and a second due to a combination of low eGFR and elevated serum potassium, as noted in the prior slide. You can see on the table that there were six subjects who were identified as having an adverse event of special interest, AESI, related to reduction in kidney function by the investigator, two of whom discontinued the lorundrostat. Five subjects had an AESI due to hyperkalemia. As previously noted, three of these subjects had serum potassium above 6, of whom one had the lorundrostat discontinued, one had dose reduced, and one was monitored into the open label. Two had serum potassium between 5.1 and 5.5 millimole, which was above the normal range, but did not reach the protocol-defined threshold for hyperkalemia. In summary, EXPLORER CKD demonstrated robust reduction in systolic blood pressure in subjects with comorbid CKD associated with uncontrolled hypertension treated with 25 mgs of lorundrostat once daily. In addition to the reduction in blood pressure, there was a 31% reduction in spot UACR, indicative of renal protective properties. We believe that the safety profile, including the incidence of elevated potassium and low discontinuation rate of 3.4%, is acceptable and in line with other aldosterone-directed treatments for this patient population and was well tolerated. In combination with our prior pivotal trials and dose range finding information from our Healthy Volunteer and TARGET HTN trials, the results of these successful trials will constitute the core of our planned new drug application. We believe that the consistent findings of a favorable benefit risk profile, not only in otherwise healthy hypertensive individuals, but also individuals with CKD, will provide an excellent basis for a solid NDA submission. I will now turn the call over to Dr. Matt Weir, who can provide his thoughts. Thank you very much, Dr. Rodman, and good morning, everybody. You know, we've learned a lot about treating hypertension and kidney disease in the last 10 years or so. Many new opportunities for clinical therapeutics have come along. Despite the advantages of so many of the newer drugs in facilitating antiproteinuric responses, there still is a major unmet need in better control of blood pressure. We've also learned that even people with CKD can have problems with excess aldosterone effect, thus requiring some form of clinical therapeutics to target aldosterone in addition to other commonly used therapies. The ability to lower blood pressure remains paramount in people with chronic kidney disease. It is essential, as the filters of the kidney like to operate at approximately one-half to two-thirds of systemic blood pressure. Thus, if they are exposed to higher levels of blood pressure, they can be damaged by the higher levels of pressure. This leads to increasing albumin in the urine and then a relentless progression to end-stage kidney disease. Thus, lowering blood pressure remains critically important. It's interesting that we're appreciating now the importance of targeting aldosterone more effectively now in medicine. We've certainly seen recent clinical trials showing improvements in cardiorenal outcomes. This, I think, is a step in the right direction. We also know that there may be better ways of targeting aldosterone. An aldosterone synthase inhibitor actually limits the production of aldosterone, whereas a receptor antagonist, although blocking the receptor, may lead to a rebound increase in serum aldosterone levels, which potentially could have off-target effects on other vascular tissues and target organs. There may be a better opportunity here, and this is being fervently studied. The other issue, obviously, is tolerability. People with chronic kidney disease need multiple medications. Unfortunately, if they cause side effects, this can lead to issues of noncompliance. Thus, it's critical for an asymptomatic disease process to remain, obviously, without symptoms in the course of its treatment. Thus, I think it's important to mention that one of the advantages of this new aldosterone synthase inhibitor is that it's very well tolerated. The modest changes in serum potassium that occur are observed with other forms of renin-angiotensin system blockade, such as with an ACE inhibitor or an angiotensin receptor blocker or with mineralocorticoid receptor antagonist. Routine surveillance can be helpful in eliminating any concern about changes in serum potassium levels, which are to be expected. Of course, the importance of monitoring serum potassium is critical, but so is the opportunity to better control blood pressure and limit cardiorenal disease progression. This new therapy, I think, will be helpful in that regard because the modest changes in serum potassium can be easily monitored and obviously dealt with either with potassium binders, adjustment in diuretics, or adjustment in dose. The other interesting point here is that the lowest dose was used and provided a robust opportunity to facilitate better blood pressure reduction in these patients, along with reductions in albuminuria. I think, again, the shorter half-life of this drug will obviously allow an opportunity for rapid reversal if there are concerns about changes in potassium, the excellent side effect profile, and of course, the most important thing, lowering blood pressure and of course, the observed reductions in urinary albumin excretion on top of appropriate guideline-based medical therapy for people with chronic kidney disease. I hope that puts it into perspective for you and to appreciate the opportunities here. I'll turn it back over to Mr. Congleton now. Thank you, Dr. Weir. Really appreciate your time, expertise, and insight to frame the new thinking in managing hypertension and comorbid CKD. The lorundrostat program has achieved several milestones over the past few months with positive clinical data announced from three clinical trials. The data from Launch HTN are highly informative for the treatment of real-world hypertension patients. Advance HTN and now EXPLORER CKD address the specific needs of more difficult-to-treat patients that are in need of innovative solutions, as Matt described, to help reduce their blood pressure. In the case of EXPLORER CKD, we also have a clearer sense of the additive benefit of lorundrostat when added to standard of care SGLT2 inhibitors in the presence of hypertension and comorbid CKD. Lorundrostat has demonstrated a consistent clinical efficacy and safety profile now in a spectrum of hypertension patients. We look forward to further expanding the profile of lorundrostat with the Explorer-OSA and Transform-HDN trials. As previously stated, we plan to meet with the FDA at a pre-NDA meeting in the fourth quarter of 2025 in advance of our anticipated NDA filing for the approval of lorundrostat. We continue to work on commercial preparation and our partnering activities with these new data to ensure that we can maximize the value of this novel, best-in-class, and potential first-to-market aldosterone synthase inhibitor, lorundrostat. We're very excited about these new clinical data, and we look forward to your questions. With that, I'll ask the operator to open the call for questions. Thank you. We'll now be conducting a question-and-answer session. If you'd like to ask a question at this time, please press Star one from your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press Star two if you'd like to withdraw your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the Star keys. One moment, please, while we poll for the first question. Thank you. Our first question today is from the line of Michael DiFiore with Evercore ISI. Please proceed with your question. Hey, guys. Thanks so much for taking my question, and congrats on the data. I guess two for me. This first question is for Dr. Weir. Just curious to see if you would expect higher rates of hyperkalemia with longer durations of follow-up. A quick follow-up to that question would be, what would be the maximum acceptable rate of hyperkalemia for this patient population? I have a follow-up to that. Those are excellent questions. Believe it or not, the body has really very capable ways of maintaining potassium homeostasis even at higher levels. There is no concern, at least that has been observed in other clinical trials with mineralocorticoid receptor antagonists or other ASIs, to suggest that there is an accruing increase in serum potassium over time. That is not to be expected. I think what you see within the first two, maybe three weeks, is what you're going to see in total. I don't think there's going to be a problem there. Again, now that we have effective strategies for mitigating hyperkalemia, certainly with the newer potassium binders and even adjustments in diuretics if need be, I don't think that's going to be an overall concern. Obviously, people with chronic kidney disease have such a substantial increased risk for both cardiac and kidney progression disease risk. It's important that we have opportunities to control their serum potassiums over the long haul in an effective manner. I think the beauty of these therapies is that they will not lead to, shall we say, higher accruing levels of potassium over time unless something bad happens to the patient for another reason, taking a nonsteroidal anti-inflammatory drug, having acute kidney injury, something like that. With regard to, I guess, what your second question had to do with the dose, was that the question? Yeah. I guess for any drug that would treat this patient population, what would be the maximum acceptable level of grade? Oh, risk of, yeah. I mean, basically, what you see is what you get, which is comparable to what I've seen with other therapies as well that alter the renin-angiotensin-aldosterone system. These are very acceptable changes with a very small percentage of patients who would have to stop the drug. Again, in these trials, remember, the people who had the events that required cessation were able to stop it. In the real world, you could certainly give a potassium binder, for example, and maintain current therapy. It would be my supposition, and what I've learned in clinical practice over many years is that there are very effective ways of mitigating potential problems with potassium so that the very vast majority of patients can be treated with guideline-based medical therapy. I think only a very small percentage of patients would run into problems here. The tolerability profile is excellent, which also is very helpful for a long-term therapy. Right, right. No, that's very helpful, Dr. Weir. And one final follow-up, if I may. Kind of a similar question with the reduction observed in eGFR. I guess, how variable was the change among patients? And has eGFR stabilized at four weeks? Can we expect further declines in eGFR over time? Yeah. The eGFR changes are very modest, maybe on the order of 10%. This is related to blood pressure reduction. You are absolutely going to see a change in GFR with blood pressure reduction because you are lowering pressure in the kidney's filters, which is absolutely essential for long-term kidney protection. A 10% change is modest when you consider it is added on top of an ACE or an ARB and an SGLT2 inhibitor. Remember that the changes that we see with ACE inhibitors and ARBs can often be up to 30%. This is a very modest change. What I think is more important is not the subtle change in GFR, but more importantly, the reduction in albuminuria and the reduction in blood pressure. We have no reason to believe that the initial drop would alter the rate of progression of kidney disease in an adverse way. If anything, it will be beneficial. Matt, if I could add to that. Let me add one other comment just on top of Matt's. I think the eGFR reduction, completely agree with everything Matt said. I think it's also important to point out it's a pretty consistent reduction across all three of the trials, Launch, Advance, and Explorer. It continues to be a really consistent profile that we're seeing with lorundrostat across these unique patient populations. Thanks for the questions. Appreciate it. Thanks, guys. Congrats again. Yep. Our next questions are from the line of Richard Law with Goldman Sachs. Please just use your questions. Hey, guys. This is Paxton on for Rich. Quick question about the UACR responses you saw. I think that in some of the competitor studies, we've seen a longer endpoint of 14 weeks from the Vycodrostat study. I guess, how long do you anticipate that you would also see a similar deepening of response had the study been extended out beyond four weeks? Also, were there any markers that you were able to identify as being predictive of outsized responses? I have a quick follow-up. Yeah. I mean. I'll send that over to Dave. Hey, Matt. All right. That's fine. Let me have Dave address that one. Dave? Thanks, Paxton. Good questions. As we mentioned, these people rolled over into an open-label extension. Rather than being prophetic, we'll have those data. We have no reason to suspect we won't see the same patterns. That's typically what our experts have suggested as well, that this will accrue over time as there's healing of the parts of the kidney that are responsible for holding onto the protein, etc. Your second question, part of that question was, remind me. Go ahead, Paxton. You said you had a second follow-up. Yeah. I guess just about the predictors of response as well, if there's anything you're looking at with this study or that you've seen already from the data. Yeah. As you can imagine, there are a lot of data that remain to be evaluated and reported. We're going to be doing that in subsequent presentations and publications. I don't have any more to comment on that except that we've looked at a lot of things and we'll be continuing to look at them. I got it. And then just the final one was just, how do you think about future development going forward in CKD? And then maybe just a little bit of commentary again on how the FDA will interpret these results and how they'll be used to support the NDA filing. Yeah. Paxton, thanks for that. I think in the past, we've discussed the fact that our current plans don't include doing a CKD study standalone. That's part of a potential partnering dialogue as we move forward with the program. This study was really critical for a couple of reasons. As we look at the hypertension profile for lorundrostat and look at attributes that prescribing physicians like Dr. Weir consider, blood pressure reduction, doing so safely, doing so with a well-tolerated profile are critical, but having a benefit on proteinuria is seen as a key attribute as well. This data really bolsters the hypertension profile from a standalone perspective. I think we've guided in the past that we anticipate including the EXPLORER CKD data into our NDA package, how that will be referred to in the label. That'll be a part of our negotiations with the FDA. Clearly, we've now shown a benefit in a population with eGFR as low as 30, showing a very safe, well-tolerated reduction in BP and a clear benefit on a marker of renal protection, UACR. Great. Thanks for that again. Thanks, Paxton. Our next question is from the line of Seamus Fernandez with Guggenheim Partners. Please proceed with your questions. Oh, great. Thanks for the questions. Maybe just from a bigger picture perspective, when you look at—and this is for the doctor on the call—when you look at the kind of competitive profiles of other agents and category, how are the MRAs and the ASIs really differentiating? Do you see them sort of behaving very similarly within the class category? Just hoping to get a better understanding of how within CKD these products would potentially differentiate. The second question is related. Do you feel it's more important from an overall perspective to really manage the hypertension earlier such that the data that we've generated or that Mineralys has generated with lorundrostat is actually more important to really get after the hypertension sooner and earlier? Do you want me to address CMS? Yeah. Sure. Yeah. Go for it, Matt. Absolutely. Blood pressure control is paramount. As I said before, sooner is always better. I mean, the longer your blood pressure remains uncontrolled, the more you're losing nephrons or kidney filters over time, which is obviously not a good thing. I think there are mechanistic differences between ASIs and MRAs, which I outlined, which theoretically may offer a better opportunity for the control of vascular disease. That remains to be studied further in mechanistic studies. I also think the tolerability profile between MRA and ASI may be, again, a decided advantage for being able to use these drugs more commonly in people with various forms of heart and kidney disease. Great. Maybe just a question for the team. In terms of the background therapies that were utilized in the study, we know that SGLT2s were on board. In terms of other therapies that are starting to kind of make their way into whether it be CKD or other forms of kidney disease or disorders, was there any representation of other therapies, whether it be GLP-1s that can impact blood pressure? Just wanted to get a better sense of the background rates. Maybe I missed it on the slide, so I apologize if that's an overlapping question. The last question is just, in terms of initiating new profiling studies or additional indications, are there opportunities beyond OSA that you see going forward? Thanks. Yeah. A couple of things on the background therapies. What we shared in the slide deck was all subjects were on an ACE or an ARB. A significant portion came in on an SGLT2, but those that were not were ran in on an SGLT2, specifically dapagliflozin. Future publications and medical conference, we'll get into any additional. I think those are the main and important background treatments these subjects were on. Your other question around other profiling studies, we're certainly excited about the OSA program from a profiling standpoint with nighttime BP in a resistant population with OSA. It has a clear linkage to reduce cardiovascular risks. That's a study that's underway. As far as future studies moving forward, that's something that we'll evaluate and contemplate. We certainly look at this EXPLORER CKD study as the first time that we've shown lorundrostat having a benefit on a hypertension-related comorbidity, in this case, chronic kidney disease. I think that, frankly, de-risked some of those other adjacencies. Certainly, hypertension plays a significant role in heart disease, as you heard Matt refer to, and very specifically in heart failure and HFpEF. I think there's a lot of utility with a molecule like lorundrostat that continues to show a very beneficial profile and now extending beyond hypertension into those related comorbidities. It is something we'll continue to contemplate. As those plans evolve, we'll be sure to update the investment community. Great. Thanks, guys. And congrats again. Thanks, CMS. Our next questions are from the line of Tim Anderson with Bank of America. Please proceed with your questions. Hi. Good morning. This is Susan on for Tim. I have a couple of questions. Has lorundrostat already been studied in combination with potassium binders? If yes, what do we know about how potassium binders might impact the efficacy and tolerability of lorundrostat? If not, given that we know hyperkalemia is a known side effect of this drug class, why would not adding hyperkalemia-lowering drugs be part of a trial protocol going forward? Yeah. Let me answer the first part. Yeah. Matt, let me answer the first part. I was going to turn it over to you. The first part of your question, Susan, it has not been studied with the potassium binders. Matt, I'll have you answer the question. Would you anticipate an impact on efficacy? Yeah. I've been quite experienced over the years with the research on potassium binders. There's been no evidence of an interaction with any of the cardiorenal protective therapies, for the most part. Again, it is recommended, for example, with the patiromer to be separated three hours from other drugs, for the sodium zirconium, 2 hours. And to be honest with you, there are very few drugs that were actually in the development programs that were studied because in the development programs, they got everything simultaneously. There were very few drugs which were affected by simultaneous administration. The likelihood that a potassium binder would affect the efficacy, safety, and tolerability of ASI is, I would say, at best, remote. The idea of prophylaxis, that is certainly a conversation point. The potassium binders were approved to treat hyperkalemia but not to facilitate enabling. You hate to add drugs that may not be needed. I certainly would say if I had a patient with uncontrolled hypertension, for example, who had a potassium of 5.5, where I wanted to add an aldosterone-blocking therapy, I think that would be a situation where I think it would definitely be indicated to do that. I would say, quite honestly, that does not happen very often. To do a study on a very unusual circumstance, I think, would be a waste of a lot of effort. I hope that answers your question. It does. Thank you. Thanks, Matt. Next questions are from the line of Mohit Vansal with Wells Fargo. Please proceed with your questions. Great. Thank you very much for taking my questions and congratulations. I have a couple of questions. Number one, Jon, I know you talked about this before, but this is actually a trial where even the 25mg dose looks like it has very meaningful blood pressure reduction. How do you think about FDA willing to put 25 mg as well on the label? I mean, FDA seems to be liking the lowest possible dose, which is effective. How do you think about that possibility? The other question is for Dr. Weir. In the real world, given the known risk of hyperkalemia and your prior comment that it happens quite early, how would you think about monitoring these patients for potassium levels? How often? For how long in the beginning of the treatment? Thank you. Yeah. Mohit, let me maybe answer your first question, and Matt, I'll turn it over to you for the monitoring of K. We're obviously very excited with the results that we've seen across the entire program with the 25 and with the 50 mg. The way we view it is it provides flexibility for physicians. Mohit, you know that we've always tried to move with this focus on safety. It's why we use the 25 mgs in this population that has a lower mean eGFR. The 50 mgs has shown really excellent efficacy as well as safety in the LAUNCH HTN and ADVANCE HTN trials. From our standpoint, I think having the 25 and the 50, once-daily dosing of lorundrostat provides flexibility to prescribers. It'll be part of the dialogue that we'll have with the agency. I won't opine on how it'll be represented in the label, but as I noted, all three of these studies will be a part of the NDA package and part of our discussions with the FDA. We're certainly just excited about the overall efficacy, safety, and tolerability profile, and now with the flexibility of 2 different doses. Matt, you want to address Mohit's question about monitoring potassium and the frequency? Sure. I mean, every patient's a little bit different depending on their compliance, their diet, their kidney function. Typically, when I start an ACE and ARB, an MRA, and I would say the same would be true if I added on an ASI, I'll check the serum potassium in approximately two to three weeks. If it looks okay, I'll probably wait another couple of months or two. If it's stable, then I just go to routine laboratory monitoring based on their level of kidney function and number of medications they're on. It's not out of the ordinary that what we've done with any of the drugs that we utilize to abrogate the effects of the renin-angiotensin aldosterone system. Again, it is important to emphasize that blocking the effects of angiotensin II and aldosterone has been shown to be a disease-modifying therapy, which is very important in limiting cardiorenal progression. Again, more often than not, these therapies tend to raise serum potassium levels by about 0.5 milliequivalents per liter, more or less, but variable depending on the patient. I mean, we're aware of that, and we do our best to monitor them and to be able to use guideline-based medical therapy. Great. Thank you. Thanks, Mohit. The next questions are from the line of Rami Katkhuda with LifeSci Capital. Please proceed with your questions. Hey, guys. Congrats on the update, and thanks for taking my questions as well. I guess, has the team had the chance to analyze whether there's a correlation between the magnitude of blood pressure reduction or hyperkalemia rates based on a patient's eGFR? And then secondly, in patients with potassium increases, how quickly did you see levels kind of normalize during the washout period in the study as well? A good question. Let me take the second one first. That was the washout, how quickly? We watched them for 4 weeks. We get blood at two weeks. By 2 weeks, most of the blood pressure and electrolyte renal changes have reverted back to baseline. By four weeks, they all have. Now, the first part of your question, though, was the relationship between blood pressure, the eGFR, and potassium. Just so I got that straight, can you repeat the question so I'm sure I answered the right question? Yeah. Basically, is there any correlation between blood pressure reduction or hyperkalemia rates in a patient's eGFR? Do you see higher rates of hyperkalemia in the bucket of patients with lower eGFR? Is there a correlation on the efficacy front as well? Gotcha. In this study, you could have an eGFR of 30 and up, and we had the full spectrum. Subjects who had eGFRs in the 30s tended to be the ones who had the greater increase in potassium, although it was not invariable that way. That is what you would expect. As far as the blood pressure responses, they were the same regardless of where the eGFR started, to the extent that you can make a conjecture about that. Got it. Thank you very much. Thanks, Rami. The next question is from the line of Dennis Ding with Jefferies. Please proceed with your questions. Hi. Good morning. Thanks for taking our questions. I just had 1. Number 1, can you talk about the slope of the eGFR curves through week four for lorundrostat relative to placebo? I think there's going to be larger eGFR declines relative to placebo early on, but then the slope changes over time as the body adapts. Do you have any color there? As you're thinking about future studies, should we expect the declines to get better for lorundrostat beyond four weeks relative to placebo? My second question is just around commercialization strategy and how you're thinking about what you're looking for in a partner. What sort of capabilities are you looking for outside of the obvious, which is for the partner to have a large cardiovascular sales force? Are you also looking for R&D capabilities, etc.? Thanks so much. Thanks for the questions. I'm going to answer the first one first. The first question was, what was the slope of the effect of lorundrostat on the change in eGFR? What we're looking at early on is the perfusion difference. In other words, you lower blood pressure, and you see the eGFR change. That happens rather quickly. There are some secondary effects that you might see over time related to blood vessels changing. It might decrease a little bit more. All of those things are indices of benefit, and they tend to stabilize. In trials that look at this over longer periods of time, what happens is that initial reduction in pressure levels out. Certainly, in the first few months, it levels out and stays pretty flat. By 12 months, in most cases, the placebo group, which actually has a little bit higher eGFR, crosses. You lose function. By about 12 months, the placebo group is starting to have worse eGFR than the treatment group. In general, the treatment group will remain relatively flat beyond that, and the placebo group will continue to lose kidney function. In a four-week trial, most of those things will not be observed. In longer trials where you are looking at progression, you will see what I mentioned. Understood. Dennis, to your question on commercialization, we've guided in the past that certainly partnering is going to be a part of the Mineralys story. From a commercialization standpoint, ex-U.S., certainly we have no intention of launching the drug outside of the U.S. on our own. We'd be looking for potential partners to handle the ex-U.S. From the U.S. standpoint, there's a clear concentration of prescribers. About 50% of the volume of third-line or later prescribing is within about 47,000 physicians. That's a footprint that Mineralys could effectively drive forward with these excellent results for lorundrostat and really provide benefit for patients. In the U.S., we know there's an opportunity even beyond that. We'd be looking at a partner that potentially has a cardiovascular-focused franchise, but really a generalist franchise that could augment the commercial footprint and really maximize the value of the drug in the U.S.. We've also guided to, in the past, finding a partner beyond commercial alignment, but also sees the real value in lorundrostat as a transformative agent in cardiorenal metabolic disorders. We've talked about now how we're seeing a benefit in hypertension-related CKD. OSA is going to be the next engine that we look at. We believe this drug could have value within cardiovascular disease or heart failure. Finding a partner that is aligned with how we see the value and vision of this asset from a developmental standpoint would be an interesting component of partnering dialogues as well. Perfect. That's really helpful. Thank you. Thanks, Dennis. Thank you. This now concludes our question-and-answer session. I'd like to turn the floor back over to Jon Congleton for closing comments. Thank you, Operator. I also want to thank Dr. Matt Weir. I know he's got a busy practice there. It's not all research. I think he's heading off to meet with patients. So Matt, thank you for your time today. I really appreciate it. I know the callers today or the listeners today value that as well. I also want to thank everyone for joining us today. We're very excited about the data announced and the overall progress we've made in advance in our clinical programs. We look forward to keeping you apprised of future progress. With that said, we'll close the call for today. This will conclude today's conference. Let me disconnect your lines at this time. Thank you for your participation. Have a wonderful day.