Great. Thank you very much for joining us today. My name is Mohit Bansal. I'm one of the Biopharma Analysts here at Wells Fargo, and we have Jon, so Jon Congleton with us. Sorry if I mis-speak. No worries. The CEO of Mineralys. We do not have Adam, but he's definitely listening somewhere. Yeah. But thank you very much for joining us today. Yeah. I appreciate the invite. Awesome. So maybe, like, for those who are new to the story, can you just talk a little bit about the company and then what you are, what you're doing, and then, what is the investment case in the company? Yeah, happy to do it. And like I said, appreciate the opportunity to share the story. So Mineralys was formed, really in the summer of 2020, shortly after we licensed our lead asset, lorundrostat, from Mitsubishi Tanabe. Mitsubishi Tanabe had discovered and developed the compound through phase I. We were able to license and basically build Mineralys around that. You know, our focus is really deeply on the role that aldosterone plays in cardiorenal metabolic diseases. Hypertension is a natural, kind of indication to go after as a small biotech, particularly with the proof of concept study that we did. It enables us to do dose range finding, look at safety profile, look at the initial efficacy signals. We completed that study in 2022, with really compelling data, that obviously we pivoted from into the pivotal development program that we could talk about a little bit, later on. You know, for me, the overarching need within this space, and this is coming from a person that started my career 38 years ago, carrying the bag in hypertension, is the fact that we haven't solved this issue yet. I actually was in London last weekend for the European Society of Cardiology meeting, and the ESC and the WHO have done a lot of joint, analysis about the continuing unmet need. We know there's over a billion people globally that have hypertension. We know that, you know, roughly half are treated, and of those, only half get to goal. These are massive numbers, and we know that hypertension is a precursor to CKD, to stroke, to heart disease, which continue to be three of the top eight reasons for global QALY and DALY accumulation. The work's not done here. And most importantly, what we think is driving the hypertension and the related comorbidities is the obesity epidemic and the shifting biology underlying that, specifically aldosterone. We believe that about 25% of all hypertension patients have dysregulated aldosterone. The treatment armamentarium in hypertension, while it's generic, is really limited in what you can do to directly address aldosterone. Spironolactone, which frankly is just not used, certainly in the U.S., it's about 2% market share. So we need better alternatives to address this growing epidemic, if you will, of dysregulated aldosterone to not only help patients reduce their blood pressure, but get to the goal that we know will have an impact on long-term outcomes. So for those who, I hear a lot of questions around MRAs versus, can you just help us understand the difference between MRA and ASI, aldosterone synthase inhibitors? What is the difference? Because, I mean, whenever you see a failure of MRA, there's a retest, but it's probably not a retest. So can you just talk a little bit about that? Yeah. The ASIs are really going to the root of the problem. And so an aldosterone synthase inhibitor, by definition, is inhibiting that synthetic pathway for aldosterone production. And what we've seen is roughly 70% reduction in plasma aldosterone with our 50 and 100 milligram dose. The issue with ASIs historically, because they had been in, you know, big pharma pipelines going back to maybe 15 years, has been selectivity. Because there's very tight homology between the aldosterone pathway and synthetic pathway and the cortisol synthetic pathway, about 93%. And if you're not selective for that aldosterone pathway, what happens is you inhibit both, and clearly you don't want to inhibit cortisol. That's basically the end of a program. Fast-forward to where we are with lorundrostat, we've got best-in-class selectivity, about 374-1. So from the preclinical work we've done, the phase I to phase II, we're very comfortable that we can get robust reduction of aldosterone without inhibition of cortisol and do that safely from an electrolyte profile standpoint. So the ASI class and lorundrostat specifically very exquisitely reduces aldosterone, whereas an MRA, by definition, it's a mineralocorticoid receptor antagonist. So that MR, the mineralocorticoid receptor, is where aldosterone has one of its pathways, largely to impact extrarenal activity. So it's the management of sodium and potassium. If aldosterone's elevated, you retain more sodium, you retain more water, it increases blood volume, blood pressure. Correct. An MRA can block that effect. Lowering aldosterone will reduce that effect. The interesting thing with the MRAs is there's a compensatory mechanism. When you block the receptor, you actually see an increase in aldosterone. In the case of spironolactone, which is a really indiscriminate blocker, it's about a two to threefold increase in plasma aldosterone concentration. Where that becomes a problem is aldosterone has other biologic pathways and other receptors that it interrogates, such as GPR30, that drives oxidative stress, inflammation, and fibrosis. Again, we think the more elegant way to address aldosterone when you've identified it as the cause of an underlying condition is to go to the root cause, and that is reduce the amount through the synthetic inhibition. Got it. That completely makes sense. So thank you for that. So to that extent, I mean, the Novo trial, what happened with that trial that has no read through for? Yeah, we don't know a lot about that. You know, if we go back to BLOCK-CKD, which was the phase II study that KBP executed, what we saw in that data was what we typically see with an MRA, that as you increase the dose, you see a greater reduction in BP, but you tend to see a greater increase in hyperkalemia. Right. You know, what we heard from Novo, who had acquired the asset, was in the futility analysis at that 12.5 milligram dose, I believe, that they stopped it at that point. We know in that phase two study, going from 12.5- 25 increased efficacy, but increased hyperkalemia. They may have seen an incidence of hyperkalemia or lack of effect that, you know, crossed the threshold for them that made them stop it. That is a little bit of an inherent characteristic of an MRA that I don't know that we've seen with the ASIs from either our data or the baxdrostat data, that you're compromised on dose and efficacy because of the constraint of hyperkalemia. Got it, so coming back to your own trial, so, I mean, with the Advance trial, there is a specific design element which is different from Launch and other trials. So like you have a standardized background regimen. Can you talk a little bit about that? And what is the thought process behind this, and could it introduce any risk in terms of efficacy readout? So. Yeah, we've benefited from a partnership with the Cleveland Clinic, one of the world's leading cardiovascular research groups, as far as thinking about the design, the construct, and even some of the site education for our pivotal studies, both Advance and Launch-HTN. As we were speaking with them, not only about you know, putting together a package that would be NDA enabling, but also what would be important to bring to the market, what would enable us to get into hypertension guidelines, we really leaned into one of the studies having a standardized background. And so just very quickly, with Advance-HTN, subjects have to have a systolic BP above 140 millimeters of mercury on in-office measurement. If they have that, then we take them off their existing meds, and we put them onto an American Heart Association prescribed treatment regimen. If they're on two drugs at screening, they get olmesartan at high dose, 40 milligrams, and a diuretic, either indapamide or hydrochlorothiazide, again, in high dose. If they were on three to five meds, they're given the ARB and the diuretic, but also amlodipine and calcium channel blocker at 10 milligrams. So what we've effectively done is kind of reset and put them on best drug, best dose. We then use smartphone technology to confirm daily compliance. They literally have to film themselves taking the medications. It goes to the cloud. That information goes to the site, the CRO and us, and we actively call patients if they're missing doses. We give them three weeks on that optimized treatment regimen, and then give them a twenty-four-hour blood pressure monitor to confirm, are they still hypertensive? And if they are, then we randomize. So it's a very rigorous construct, but what it fundamentally does, and it, t his is how it addresses risk from our standpoint, is it doesn't eliminate, but it certainly mitigates white coat hypertension, masked hypertension, any false read related to lack of compliance. So what we're randomizing into Advance-HTN, this twelve-week study, are truly uncontrolled or truly resistant hypertension patients. Now, the question is, have we created a really tough data set of patients, you know, that are recalcitrant or very difficult to treat? I don't know if that's the case. I think what one way to think about it and how we do is, when you've done a high-dose ARB, a high-dose diuretic, high-dose calcium channel blocker, you've hit a lot of the pathways that drive hypertension, but you've not addressed aldosterone. We may actually be enriching for an aldosterone-dependent form of hypertension within this population, and if that's the case, we're very confident with what lorundrostat can do to aldosterone. So again, we need to execute the study. We need to get the top-line data and anticipate the results we see. But from what we saw in Target-HTN, and given the fact that we saw about an eight to ten millimeters of mercury reduction in that proof of concept without everyone on a diuretic, and now everyone will be on a diuretic, we're fairly confident that we'll see that replicate efficacy measure hit with an Advance-HTN. Can you remind us again, because those who were on diuretic in the initial trial, they had better benefit on systolic blood pressure. Why would that be? What are the synergies there? You know, there's two thoughts to that. One is that volume overload plays a significant role in hypertension. A lot of the available agents that physicians have right now are focused more on the vasoconstrictive side. So ACEs, ARBs, beta- blockers predominantly are on that side. Calcium channel blockers kind of have a benefit on both sides, but really, the only currently available agents for volume are either a diuretic, an MRA. Mm-hmm. or a sodium channel blocker, and the latter two really are not used to great effect. So we knew that a diuretic would help address the volume side, and the fact that the diuretic actually works on a different part of the kidney. Right. We anticipated there may be some level of synergy there, and that's why we pre-specified that analysis. Got it. Got it. So of course, when we see the data from Advance trial, we'll see the top-line efficacy data, but what else would you look in terms of subgroup point of view and all? First of all, we're looking at a lot of different measures. We have really loaded, not only created great rigor in this study, but we've loaded it with data. So we're the primary endpoint is the twenty-four-hour ambulatory. That's really considered the gold standard. You typically see a placebo response with 24 hour ambulatory of about plus or minus one millimeter of mercury. Mm-hmm. Put that into context, in our proof of concept study, the office based placebo effect is about four millimeters of mercury. We know with CinCor, they saw nine, and then they saw 16 in their failed study. So that really helps, again, manage some of that operational risk. We're also doing the in-office measurement and doing the technique we did in Target-HTN to help quiet the background noise. And we're doing in-home measurement as well, which ironically, the home measurement is about as good as 24 hour ambulatory as far as quieting out placebo. So we'll have a lot of different ways to look at blood pressure. And then from a subset analysis, we're gonna continue to dig into some of the findings that we had within Target-HTN, specifically the correlation to BMI. So that's certainly going to be a pre-specified analysis. We wanna look at, is there a differential effect if you're on two meds or on three meds? Or are you uncontrolled, or are you truly resistant? As well as a host of other metrics, things like ethnicity, that we wanna continue to interrogate that. You know, we had about 39% African American in our proof of concept study. I think we'll be tracking to what, a range similar to that within the pivotal program, and that's a critical piece of information. That is well beyond what you typically see in these studies and certainly addresses an at-risk community. We're also looking at a host of markers. We'll be looking at things like UACR within the study, even though proteinuria is not part of the inclusion criteria. We know some of these patients will be proteinuria. We'll be looking at eGFR, we'll be looking at cardiac markers. So this study is gonna give us a wealth of information, not only about lorundrostat and blood pressure, but also, the related cardiorenal benefits that it could have. But these are not, I mean, these patients are not sick enough to have high proteinuria, at least? They're not. They're not. Their hypertension is the gate for it, but again, we know that there's a huge overlap between hypertension and CKD, and so there will be some patients that'll be considered proteinuria, and some that'll be borderline. The bottom line is we'll have the measure and see what kind of benefit we see with lorundrostat. Got it. Very helpful. Maybe, let's just touch upon the Launch trial, and then I think you had some discussion with the FDA, and then there were some changes in terms of where they want you to measure the primary endpoint. So can you talk a little bit about that and the reasons behind that? Yeah. Yeah, it was really a collaborative discussion. It wasn't so much something that they wanted. We were talking about our desire not only to look at the ITT, but also to really do deep dives- Right -in the subset analysis. And through the course of that discussion, landed on the six-week time point as kind of an ideal for the primary endpoint, because it allows us to pool the 50 milligram arm. So just very quickly, Launch- HTN, we keep subjects on their background, existing medications, and then we randomized one of three arms, either placebo, fifty milligrams through the course of the trial or 50 milligrams through six weeks, at which point, those that are not responding and whose safety measures, like potassium, sodium, are in a safe range, we uptitrate to a 100. Mm-hmm. With that six-week time point, we're able to pool both 50 arms because no one's been titrated up yet. That study is also randomized one to two to one, so we'll have roughly 750 patients on the 50 milligrams compared to 250 on placebo. So it really gives us superpower on the primary endpoint, but it also enables us to do some of those deep dives with pretty robust statistical power on the subset analysis, like the BMI. We got very comfortable with moving to that six-week time point, frankly, because we were comfortable in that being the titration point, because we saw in Target-HTN, at week two, you see about 70% - 80% of the clinical effect on blood pressure reduction. At week four, we feel like we'll see the vast majority of it. And so week six is a very appropriate time to do that cut. I don't think we'll be leaving any efficacy in quotes on the table. Mm-hmm. But we are still capturing the 12-week data. Right. That will be a key secondary endpoint, and if there is residual benefit, we'll be seeing that in the secondaries. There are some questions regarding this. One is that, obviously, is that, do we know what% of patients might need something more than 50 milligram, based on the prior data? No, we don't have that information yet. That would, you know, kind of effectively be unblinding. Mm. The reason that we chose to do the titration of the 100 milligrams, when, b ecause when you look at Target- HTN, the 50 and the 100 look fairly similar. Right. It's an interesting phenomenon with the ASIs. They have this very tight sigmoidal dose-response. Mm-hmm. We saw it with baxdrostat with their 1-2 milligrams. We saw it with lorundrostat at 50 and 100. As we dug in, though, we knew there was some variability of exposure and thus clinical response to lorundrostat, and we think that there are some patients who may be on the lower exposure side, on the 50, that may have additional benefit they could derive from the 100 milligrams. And so that's where that 12-week analysis will be interesting to see. Right. As we think about not only the reduction of blood pressure, but frankly, getting the goal, which is kind of the end game here, I don't know if I'd expect to see a difference in blood pressure reduction between those two arms, including the 100 milligram titration. Mm. But the percent that get to goal may be slightly favorable in the 100 milligram arm- Got it -because you're capturing those that, from an exposure standpoint, did not respond. Got it. So, I mean, on that point, I mean, so basically, you, you probably lose a little bit because some patients are not getting to that level or, or goal level, but at the same time, probably the powering increases because you have more patients on the treatment arm, because you are pooling these two arms together. So net-net, do you see this as a, like, probably from a trial success point of view, where do you, where do you stand on that? I think the net-net is probably more in the subset analysis. I mean, Launch is 1,000 patients. Our power at a 7 millimeter mercury placebo adjustment was, like, 95%. Right. I think going to week six, it takes it up to 98. So for the top line endpoint, this was a super powered study. I think it really helps enable the subset analysis that, again, fits into our overall thesis of how do we identify and target responders. Got it. And there is some, like, I mean, again, there is another ASI. CinCor had one, which is now AstraZeneca, and, of course, Boehringer has something. So how do you see the competitive landscape evolving over the next few years? Yeah, I think the. You know, we've heard the drumbeat for aldosterone increase over the last several years at medical conferences. I think part of it's driven by the renewed interest from a targeting standpoint with ASIs as well as MRAs. You know, there's a lot of different ways to look at the competitive landscape. First is just the molecules themselves. Again, we feel like we've got best in class based on selectivity, half-life of 10- 12 hours that really matches the diurnal nature of aldosterone. And things as simple as hepatic metabolism. You know, when you get into a CKD population with lower and lower eGFRs, we don't have to worry about adjusting dose because of kidney impairment. So from a molecular standpoint, I feel very confident in some of the competitive advantages we're gonna have. I think developmentally, we have always been a little bit distinct, certainly from CinCor, and I think what AZ has picked up from them as far as our effort, is not just to broadly develop this drug for hypertension, but to really identify what are predictors of response. We don't have time for me to get into how we're applying AI to our pivotal program to really help further inform, what we call our toolkit, that we can take out to the payers and physicians to help really guide their treatment and selection of patients. But I think that targeted approach is a bit differently, and then, you know, looking at what BI is doing, I think they're largely focused on combining with their SGLT2 and dapagliflozin in CKD and heart failure. AstraZeneca is doing both independent, just baxdrostat for hypertension, as well as adding it to dapagliflozin. So I'm emboldened by where the field's going, the interest in aldosterone and feel very comfortable with how the Mineralys is going to be able to stand up relative to those other two. How do you think about some of the longer acting ASIs? So I think, like, not longer acting, I think, like, I think there was a partnership. Roche had a partnership with one of those SI RNA approaches, right? So was it Alnylam and Roche? Um- The partnership- -for, angiotensinogen? Yeah. Yeah, zilebesiran. So yeah, some of the longer acting versions, so. Yeah, I mean, I think, you know, if we step back broadly, we've gone twenty-five years without a lot of innovation in this space. Right. And so now we've got angiotensin directed therapies from Ionis and Alnylam. We've got endothelin receptor antagonists from Idorsia. You've got newer MRAs, even though the Novo one hit futility, you've got ASIs. So for me, that renaissance, you know, really, I think values the unmet need within this space, but I think there's distinct approaches to it. In the case of angiotensinogen directed therapies like zilebesiran, I don't know that I view them as competitors, because they're really looking at the RAS system. They're- Right -to a degree, like a long-acting ACE or ARB. Right. The data that we've seen kind of reflects that. From our standpoint, we're almost looking at the opposite of that. You know, when renin is not driving aldosterone, but there's other factors like obesity. So again, I applaud the efforts and innovation. I think it just elevates the noise around the need within this space, but I think fundamentally, they're going after a different population than we would. So another area that you are exploring is, chronic kidney diseases- Mm-hmm -with the Explore trial. So can you talk a little bit about that? And what do you want to see from this trial? Yeah. The, if you look at the macro data, probably about 70% of all CKD patients have hypertension concurrently. As we go out and talk to physicians about, attributes that are important to them for an antihypertensive, it's always reducing blood pressure, number one, doing so safely, number two, but always in that next three, four, five range is having a benefit on proteinuria, because there is such a significant overlap. So for us, this study does two purposes: One, it helps bolster the profile from a hypertension standpoint by developing that proteinuria data. And two, it'll help inform how we think about next steps in the development of the program. But from a market standpoint, we know that's a bit of a wide space, a drug that can really give you both benefits in one drug, and that is a reduction in proteinuria and a reduction in blood pressure. The SGLT2s have been absolute, wonder drugs within CKD. I'll be that bold. I mean, they've rapidly become standard of care. Okay B ecause they have a great reduction in urinary albumin-creatinine ratio, urinary protein, creatinine ratio. But they don't have much of an effect on blood pressure, about two to three millimeters of mercury. And so being able to come in and provide a benefit both on blood pressure and they then safely reduce urinary albumin and protein, we think is a significant benefit for the hypertension profile, but also then for informing how we would think about moving forward in CKD itself. Our expectations. Now, we've lowered the dose going into that study. We're using 25 milligrams once a day, and we're doing that on the basis of what we saw in Target- HTN. We tested 12.5 BID. You know that's an active dose for us. This drug is predominantly driven by AUC, so the 25 QD, we feel very confident in, showing an effect on blood pressure, which is the primary endpoint of that study. As well as within four weeks, time point, being able to show a benefit as it relates to, urinary albumin-creatinine ratio. Got it. Got it. I mean, so, in terms of, so, I mean, Boehringer also showed their data for CKD. Mm-hmm. So what do you learn from that? I think the albuminuria reduction was pretty significant there, so, like, what is your take on that data so far? Yeah, I think. A couple things we learned, one was on the risk profile. I think that was a well-received study, and it was well-conducted, showed really nice response to their ASI. So I think it de-risks our program, from a, you know, data standpoint, knowing what we know about our molecule and what we're beginning to learn about BI's molecule. I think it was interesting to see their primary endpoint, I think they showed about a 39% reduction in UACR at one of their doses. One of the other secondary endpoints, and it's typically so in a CKD study, is percent of subjects with a 30% reduction. Theirs was a 12-week study, so I think if, you know, we see something at four weeks in that 25%-30% range. Mm-hmm You know, that maybe would be expected, but, you know, time will tell. We'll execute the study, and I think fundamentally what we're looking for is to have a safe effect on both BP and urinary albumin-creatinine ratio. Where do you think these GLP-1 fit in there? Because the GLP-1s you are seeing. Where don't they fit in? That's true, right? But. No, I. You know, more seriously, you know, coming out of the ESC this past weekend, you know, the ACC earlier this spring, the GLP-1s are having a significant impact. Mm-hmm And, you know, well beyond weight loss. But the benefit that we're seeing from a cardiorenal standpoint, risk standpoint, I'm not overly surprised by it, right? Right. We've known for decades, you lose weight, everything gets better. Right. Now, there may be some other properties I know they're trying to tease out, that they may provide some of that, that may be the reason they're seeing the cardiorenal benefit. From our standpoint, we think that, you know, an aldosterone-directed therapy is gonna be part of an obesity plus world. Right. You know, what we've seen as relates to cardiovascular risk reduction, a 20% reduction, well, that was eight, went down to 6.5%. There's still residual risk. Right. When we look at blood pressure from the data presented thus far, it's a 6-7 millimeters of mercury reduction, which is good, but it's still... That's not the end game. Right. The endgame is goal. And so from our standpoint, I mean, an ASI like lorundrostat can happily coexist with GLP-1 treatment. And particularly given the fact that historically, I think the medical community thought about you treat hypertension, you treat CKD, you treat heart failure, you treat heart disease, all as independent elements. And now what you're seeing in the medical community is this embrace of cardiorenal metabolic syndrome, that these things are all linked, and for good cause. Right And aldosterone's at the center of that. We know that aldosterone plays a role in CKD. We saw that not only with BI's drug, but with finerenone's data. We know that it plays a role in heart failure, spironolactone is used there, and we know from our own studies that it plays a role in hypertension. So being able to normalize aldosterone levels, we think is gonna have a benefit across that spectrum. Got it. I have one question for Adam, but I'll ask you the cash run question. Yeah, no, cash at our August earnings call, we announced Q2 financials, $311 million in cash and cash equivalents on hand. That basically gives us cash to complete all the clinical programs we have underway right now and into 2026 for cash. So, feel very comfortable with that and our ability to execute on the plan relative to that cash. Awesome. One last question. Sure. Fast-forward one year, September 2025. We are here. I hope you are here, and I'll ask this question, if I ask the question that what would make you look back, one year back and then say, "This was a great year? The table's really set for us in 2025. We have a great deal of very compelling data coming out. We have Advance- HTN queued up for Q1 of 2025. We have the Explore- CKD study queued up for the H1 of 2025. We have the Launch- HTN queued up for the H2 of 2025. There's just gonna be a host of data points that we're gonna be able to bring forward. That package collectively, you know, knock wood, it all plays out as we anticipate, could be indeed enabling. Mm-hmm. So, for us, if, you know, sitting here next year- Mm-hmm -looking back, it will be the successful outcome of those trials that we've been working tirelessly on in 2023 and 2024. You're going to be very busy. Yeah. We are. Yeah. It's my team. They're the ones driving all the value, so. Thank you. Yeah. No, on that high note, thank you very much for coming here. Yeah, Mohit. Thank you. Appreciate it. Always good to chat with you.