Up next, we have Mineralys, and the CEO, Jon Congleton, is going to run us through some slides and some Q&A if we have time. Over to you, Jon. Thank you, Adja. I'd like to first start by saying thank you to Jefferies for the opportunity to provide an update and overview of the Mineralys program and what we're trying to do in our efforts to target aldosterone in the treatment of cardiorenal disorders. Obviously, I'll be making forward-looking statements. So if we think about the opportunity right now, if you, if you're familiar with Lancet's Global Burden of Disease, currently, three of the top eight conditions have an underpinning of hypertension. Those conditions are stroke, CKD, and heart disease. It's important as an industry that we focus on ultra and rare, but it's also critical that we not lose sight of these chronic conditions that are significant burdens globally. We think the obesity epidemic, which is obviously a hot topic right now, is a key and critical driver of some of these conditions as it relates to hypertension, chronic kidney disease, and heart disease. Our lead asset, lorundrostat, is a selective aldosterone synthase inhibitor. This is a class that has been of keen interest to pharma for well over a decade but has had challenges in development because you have to have a selective aldosterone synthase inhibitor that does not inhibit cortisol. We have now evaluated and proven preclinically in phase I and in phase II, that lorundrostat very selectively reduces aldosterone by approximately 70% with once-daily dosing and really an ideal half-life profile. Our proof of concept trial that was recently published in JAMA this past September showed a double-digit reduction in systolic BP, placebo-adjusted, as well as a very well-tolerated safety profile. That has enabled us to move into a pivotal program. We currently have two hypertension studies underway. The first reading out in the second half of 2024, and the larger phase III reading out in the second half of 2025. We will also begin, before the end of this year, a CKD proof of concept trial that will have data read out in Q4 of 2024 or Q1 of 2025. So a great deal of activity with what we think is an exceptionally promising asset. Aldosterone has been known to be implicated in cardiorenal condition for decades. I think what is less appreciated is somewhat the dualistic aspect of aldosterone. It has both the genomic component, which drives volume through the sodium-potassium exchange management, but it also has a non-genomic aspect through the GPR30 that can drive fibrosis, it can drive inflammation. And this becomes a really critical point when you look to interrogate or mediate aldosterone. There are drugs such as spironolactone that have been around since 1959, a very old drug, unfortunately, a bit of an indiscriminate blocker of that mineralocorticoid receptor. But when you block that receptor, invariably you see a concurrent rise in aldosterone, and so that can drive some of the activity that's non-genomic. We frankly think a more intuitive, more precise way to affect aldosterone is through the synthetic pathway. By reducing aldosterone, you reduce both the genomic and non-genomic effects. That has implications, as you see on the slide, in hypertension, in CKD, as well as in heart failure. Now, I talked about the obesity epidemic, and we all know that has implications not only on hypertension, on diabetes, on largely the cardiorenal metabolic syndrome writ large. I think what's underappreciated, beyond the evident obesity epidemic we have, is this rising epidemic in hyperaldosteronism. And there's a clear biologic correlation to this rise from maybe 5%-10% in the '70s and the '80s, to where we may be now at about 25%-30%, pervasive in all hypertension subjects. And there's a clear correlation. As BMI rises, aldosterone increases as well. And there's a great deal of research that goes into that. Let me go back. There's a great deal of research that goes into this shifting systems biology. We're all familiar with the RAAS system, renin-angiotensin-aldosterone, that has historically been the druggable pathway in hypertension. You have ACE inhibitors, you have ARBs, you have beta blockers. But what is occurring in these obese populations that's driving aldosterone is the visceral adipocytes generate hormones or adipokines, such as leptin. Leptin has been found independent of renin to drive aldosterone, and that's why, for us, it's a really critical finding as we continue to interrogate the use of an aldosterone synthase inhibitor within a population that may have obesity and therefore renin-independent hyperaldosteronism. Now, as I alluded to earlier, aldosterone synthase inhibitors have been an interesting target for pharma for well over a decade. Lilly, Merck, Boehringer Ingelheim, and Novartis advanced ASIs, but each in different ways, adjusted those programs. Novartis got the furthest in the clinic. There were four phase II studies that were completed before that drug was actually not shut down, but frankly shifted over to Cushing's disease because it inhibited cortisol sufficiently, that it was stopped for development as a anti-aldosterone agent and a hypertensive and moved into that category. What the authors of those studies pointed out as shortcomings for LCI699 became very instructive for the scientists at Mitsubishi Tanabe, who developed lorundrostat. The selectivity of the Novartis compound was about 3.6 to 1. And that means that it would... It was not very indiscriminate in the inhibition of aldosterone relative to cortisol. There's very tight homology between these two synthetic pathways, and you have to be very selective to just inhibit aldosterone. Lorundrostat is really best in class when it comes to selectivity, with about a 374-to-1 ratio, about 100 times what has been seen with LCI699 in previous clinical work. Baxdrostat is another later generation ASI, has about a 100-to-1 selectivity, and that has shown reasonable data to this point as well. I think one of the really interesting differentiators, and we get asked this question often, what makes your molecule distinct? Certainly, the selectivity is a key component, but so is the half-life. The half-life of lorundrostat is about 10-12 hours, and if you're familiar with aldosterone itself, it follows a very clear diurnal pattern. It surges early in the morning, peaks mid-morning, and then tapers back down to lower levels in the afternoon. A half-life of 10-12 hours that lorundrostat has seems to really nicely match that profile of the aldosterone diurnal pattern, and as you'll see in a moment, we found the QD dosing of this molecule dosed in the morning to really provide robust clinical benefit. So our phase 2 proof of concept study that was published in JAMA in September of this year really consisted of two parts. If you go back to my very first slide, targeting aldosterone, our effort is not just to develop lorundrostat broadly for all hypertension, but is to fundamentally identify where are the responders? Are there indicators of response? Are there tools that we can provide payers and providers that inform who should be on lorundrostat to really get a robust, compelling clinical value? And in that effort, the proof of concept study actually used plasma renin activity as an initial inclusion criterion in part 1. There was a school of thought that we wanted to test that low renin hypertension was indicative of dysregulated or abnormally high aldosterone. And so in that portion of the study, that was a dose range finding, we used PRA above 1, we used systolic blood pressure above 130, and we looked at subjects on 2 or more medications. We did not specifically look at resistant or uncontrolled, because fundamentally, what is critical is the underlying biology, not the number of medications someone is on, which is how we define resistant. So with that as the inclusion criteria, we had subjects go through a 2-week placebo run-in to confirm that they were compliant to their background medication and in fact, still hypertensive. If they were, they were then randomized into one of six arms, placebo or two BID doses, or three QD doses. At about a midpoint of that study, we did an interim analysis, identified 100 mg QD as an effective dose, and began part two of this study. Part two was looking at the other side of the low renin proposition. In other words, in normal to high renin subjects, would this drug work equally well? Once that was identified, that began to enroll as well and had similarity to the dose range finding portion, which is 8-week of duration. The primary endpoint was changed from 8 weeks to baseline in AOBP, that's in-clinic blood pressure measurement. A secondary endpoint was looking at 24-hour ambulatory. So we had both measures to really affirm and confirm the clinical profile that was seen. This is the primary endpoint. And I guess I'll step back. The part A, part B, we saw no difference in response. Whether a subject had low renin, normal, or high renin, lorundrostat worked equally well. The other point I will say is that the 5 doses we tested, 4 were active. So the two BID doses were active, but at the end of the day, as an antihypertensive agent, you wanna focus on once daily dosing, and the 50 and the 100 mg provided the most robust, compelling clinical and safety profile for lorundrostat. What you see here is approximately a 14-mm absolute drop with the 50 mg, about a 10-mm drop, placebo-adjusted. We had a very quiet, well-controlled placebo population in this study, and we saw about an 8-mm placebo-adjusted drop with a 100 mg. That does not, in our mind's eye, represent an inverse dose response. As we looked at the observed values, the 50 and the 100 mg are quite similar. And in fact, if you're familiar with this class of drugs, it has a fairly steep and then plateauing out sigmoidal dose-response curve. We saw that with baxdrostat, we've seen it with our drug as well, and the 50 and the 100 mg are probably on that lower end of the dose response level, and as you'll see in a moment, we're looking to advance both 50 and 100, but titrating through the 50 to get to the 100. We also pre-specified... So we used renin as a marker. Again, how do we identify where aldosterone's driving the condition? Where can we get the best response with lorundrostat? But we also pre-specified subset analysis to further investigate that. We looked at things like age, race, gender, number of background meds. None of those were determinants of enhanced response. The two other elements that we identified were: the presence or absence of a diuretic, and whether somebody's BMI was above or below 30. Now, the BMI piece I will speak to briefly because it's a really critical finding, but I don't want it to be confusing because this is a categorical analysis. So you draw a line at 30, and you say, "What's the response above and below?" That does not mean if you have a BMI of 29, this drug does not work. We presented data, I believe it was at AHA last week, where we actually looked at it. It's a continuous variable. Clearly, what we saw in our data as a subject's BMI rises, and we had patients up to 40 on their BMI, the response becomes even more and more enhanced, and that fits based on the data that I shared earlier. The higher the BMI, the higher the aldosterone. We know from our standpoint that we have a very selective effect of aldosterone synthase inhibitor. So when we find aldosterone, we could see a robust clinical effect. And so that's something we're gonna continue to interrogate in the clinical program. But as you can see here, there's clearly a very robust effect. At the 100 mg, you're looking at 12 mm of mercury, placebo-adjusted drop in, and with the 50, you're looking at almost a 17-mm mercury drop. These are significant reductions that will help patients get to their goal, whether it's 140 in Europe, 130 with comorbidities, or even 120 mm of mercury, which is where I think fundamentally this place, this space will go. We also, excuse me, also found an enhanced response with the presence of a diuretic. Again, that stands to reason. A significant portion of the uncontrolled hypertension that we deal with currently is volume-driven. The diuretics provide a benefit, but not a complete benefit, and certainly, lorundrostat is shown to add, even more value from a blood pressure reduction perspective. The key safety, and it's really an on-target safety finding that needs to be watched with, frankly, mineralocorticoid receptor antagonists, aldosterone synthase inhibitors, ACEs, ARBs, is hyperkalemia. How you're getting to an immediate blood pressure reduction with a genomic aspect of lorundrostat is through the sodium-potassium exchange. So you're excreting more sodium, thus water, reducing blood volume, reducing blood pressure, but you've got to be mindful of the accumulation of potassium, and that's why I think our shorter half-life actually serves us well. What we saw with the 50 and the 100 mg was about a 0.25-0.29 millimole per liter population or mean average change. That's important because that's roughly in line with what you would expect with an ACE inhibitor or an ARB. You also want to look at individual incidence excursions above 5.5. With the 50 mg, a very mild profile, we saw one subject between 5.6 and 6 millimole per liter increase in potassium. We had one subject above 6.5. If you're familiar with the collection measurement of potassium, it's a fickle electrolyte to measure. If you draw blood too quickly, the red blood cells burst and release potassium, so we were constantly retesting to confirm the findings. In the case of the 6.5, upon retest, they were back at baseline, but the timing of the capture was outside of protocol of the 48 hours. So we put it there out of an abundance of caution, but on retest, they were within their baseline figure. The 100 mg, we saw higher excursions in the 5.6-6 range. Again, we think that was on the construct of the proof of concept study. All subjects were started at their randomized dose. The 100 mg for a lot of subjects is frankly an overexposure, and we'll be solving for that in the pivotal program by titrating subjects through the 50-mg QD. Other than that, a very well-tolerated molecule, and that's critical in truly what is an asymptomatic condition. So all of that data became very informative for us as we thought about the lorundrostat pivotal program. We had our end-of-phase 2 meeting with the FDA late in 2022 and began the construct of the pivotal program that's right here the first part of 2023. So it's really constructed of two hypertension studies, one with an N of 300 subjects. That's the Advance study. That's the standardized background med regimen study that I'll talk about in a moment. The Launch study is up to 1,000 subjects. That's on existing background medication. And then the CKD program really has two components to it, a profiling study and a proof of concept. So let me take a moment and talk about the Advance trial, and this is probably gonna be one of the most rigorous hypertension studies completed. There have been a couple of companies, Medtronic, with renal denervation, J&J and Idorsia with aprocitentan, that have done this standardized background regimen. What you do is take subjects who have elevated blood pressure, in this case, over 140 mm of mercury, screen them in, and then take them off of their prescribed background medications that their physician put them on. You standardize them to, in this case, American Heart Association hypertension guideline prescribed treatment at max dose. So we'll have subjects on max dose of olmesartan and a diuretic if they were on 2 medications pre-screen, and if they were on 3, 4, or 5 meds, olmesartan, the diuretic, and max dose of amlodipine. You then follow those subjects for 3 weeks, and then if they remain hypertensive, we randomize. We anticipated that there would be subjects that would, on that type of regimen, get to goal, and that's fine. And what I've told a lot of people about this study is that it's not only going to be informative about lorundrostat, it's going to be informative about the market opportunity we have. I will tell you, three years of working with this lovely company, raising money, if I get a question, it is, "Well, if people just took their drugs, wouldn't they be fine?" And the answer is some, but not all. And I think what is driving a big portion of that is up to 25% of all hypertension subjects probably have dysregulated aldosterone. We do not have enough therapies to address that driver of their condition. This study, I think, is gonna help elucidate that. We're amping up the RAS system from an antihypertensive therapy standpoint. If the RAS system is driving their hypertension, they'll likely get to goal and won't randomize. But if they don't get to goal, I think it will likely enrich for aldosterone-dependent hypertension. And again, when you have an excellent aldosterone synthase inhibitor, that's what you want. And so this study, once subjects are randomized, they will go into either a placebo arm, they'll go into a 50-mg arm, or they will go into a 50-mg arm, where at 4 weeks, we'll measure their blood pressure, we'll look at their electrolytes, and if they've not gotten to goal, and if their potassium and sodium are within range, we will dose escalate to the 100 mg. If they get to goal, we'll keep them at the 50. It's a 12-week duration study. We're looking at 24-hour ambulatory at week 12, relative to baseline is the primary endpoint. We're enrolling up to 300 subjects in that study, and as I said, we began enrollment the first half of 2023, and we're looking at top-line data in the second half of 2024. The larger Launch HTN study, and by the way, the first study, apologies, is in the United States at about 75 sites. Launch HTN is our first global study. It's going to be United States, Europe, Canada, and Australia, up to 1,000 subjects. That study, in several ways, is almost identical to Target, with the exception of we're not using renin as an inclusion criteria, but we are keeping subjects on their background meds. We are enrolling subjects failing to get to goal on 2-5 meds, so we get uncontrolled and resistant hypertension. But we're applying certain learnings from Target HTN to the construct of this study. Just like Advance, the first pivotal study, Launch will have all subjects on a diuretic. So the two to five meds they're on, one of them has to be a diuretic. Because, again, we believe the data that we saw, that there is certainly an additivity in response. And again, I think that helps us to manage this. Oftentimes, when you go from phase II to phase III, you see a drop in efficacy. I think we've actually done a lot of things to make sure that does not happen in the construct and design of these studies. That study will be using in-office AOBP. If you recall or are familiar with our story, we were able to quite well control for the placebo noise in Target-HTN. We saw a 4-mm mercury drop in the placebo group. We'll be applying those same techniques to the measurement of blood pressure in Launch-HTN and the global scale. We're also using. And I took my phone off because it messes up microphones. I usually use it as my show and tell, but we're using. We're partnering with a company called AiCure, and it is basically a way to capture pill consumption on a daily basis. If you're familiar with CinCor, you know they had a study that had difficulty with some sites, with data, with compliance, that led to non-significance of that trial. We didn't see that in ours, and we're making sure we don't by continuing to use technology to confirm compliance, adherence, to not only lorundrostat or placebo, but also the background medications. That study is going to begin enrollment before the end of this year, with top-line data in the second half of 2025. The CKD study is really two forms. One is a CKD profiling study. We're looking at subjects in that portion of the study with eGFR 30-45. We'll be using lower doses, looking at systolic BP, looking at kidney performance, as well as safety aspects such as potassium and sodium. We'll also have a proof of concept study as a part of that, looking at the combination of lorundrostat with dapagliflozin and alone on blood pressure and urinary albumin-creatinine ratio. That study will get underway before the end of this year, and data readout late next year or early 2025. All three of these studies will feed subjects into the open label. They'll have the option to enroll in that. That will also provide long-term safety data for us. Just a real quick construct, where do we see this drug fitting into a crowded generic market? Third line. Just I'll cut right to the chase. We think, and we've done the research, several market research projects with payers and physicians, third line is an ideal open space. It enables the payers to continue to use generics, either ACEs or ARBs, first-line diuretic, second line. But at third line, and with the toolkit we intend to provide, we think we can provide a clear value proposition. Meta-analysis would tell you when you add a third agent, you get about a 5-mm mercury reduction in systolic BP relative to what they're on. We believe we can double that to at least a 10 mm Hg reduction, and we think that kind of value proposition with the toolkit of where to use the drug will certainly give us an opportunity, and that represents up to 20 million subjects. If obesity is really the driving guide, then that's 10 million just in the U.S. that we think are an addressable market for lorundrostat. I've got an amazing team. We have been a lean, agile organization from the start. We're beginning to grow, obviously, as we're getting larger studies, but just an outstanding team that I get the pleasure to work with every day that has generated significant value over the last three years. And just to close it out from a financial standpoint, we currently have $266 million in cash. We have cash through the middle of 2025, and obviously some really interesting data points that'll be reading out in the second half of 2024. I went a bit longer than I thought, but I have 2 minutes and 10 seconds for questions. I'm happy to address just- If anyone has a question, just raise your hand and I'll bring the mic around. If there are none... Nope. Are you looking at fixed-dose combinations or as well as apart from the depth of intervention, but with ACE or ARBs? I think that is certainly something that we're contemplating. We know compliance, pill count is a critical component. These subjects, for the most part, don't just have hypertension. They may have diabetes, they may have CKD, and that's something that we're contemplating, not only within the hypertension space, but even across the spectrum of... You know, as we think about CKD, as we think about down the road, heart failure, doing a polypill approach, not only for the convenience, but potential synergy because of the interplay of aldosterone with other elements driving those conditions. Yeah. Any other questions? Very good. Thank you very much.