All right, good afternoon, everyone. It is our pleasure to have you at the Mineralys session this afternoon with CEO Jon Congleton. I guess you all know that Mineralys has had a pretty active year now with a very successful clinical outcome of Launch and Advance. Now you are barreling towards the NDA filing and it looks like all the competitive profiles are out for the ASI class. John, why do you not give us an overview of where Mineralys is right now and we will go into Q and A. Yeah, absolutely. For those that don't know, Mineralys is focused on an aldosterone synthase inhibitor and really targeting cardiorenal metabolic disorders. Hypertension is the lead one, as Annabel said. 2025 is really unique in the context of it's rare that you see a whole new class have two drugs come out with really compelling data sets. In our case, in March, we had the readout from two pivotal studies. One in an optimized, truly confirmed hypertension population, that's Advance-HTN. Launch-HTN was a real world setting. In June, we had a hypertension CKD data set. We've recently seen two data sets out of AstraZeneca with Baxdrostat. I think fundamentally what these data sets are showing us is that we truly do have a significant portion of uncontrolled and resistant hypertension driven by aldosterone. That an ASI is probably going to be the new emergent class to treat these patients, certainly at fourth line and I think in due time in third line. I think now that we've seen all of these data readouts, the dust is kind of settled. I think we're very confident saying we've got best in class molecule to move forward. We're highly confident in the package that we'll be bringing to the FDA. We've gotten the pre-NDA feedback. There were no surprises with that. The open label data that's a key part of that continues to show us a really nice safety signal. Very excited with the success we've had to date. You know, very appreciative of the team that drove that excellent execution and all the participants, physicians and patients in the trials. Great. Now that you're past this clinical portion of it, or partly mostly past the clinical portion of it, I think the big question that most investors have is exactly what is the opportunity? Can you frame it for us? Obviously it's aldosterone specific, but you've shown utility across multiple different populations. How well do you need to specify that population before considering taking an ASI? Yeah, the. So just numerically, these are all U.S. based numbers. Resistant hypertension is about 10 million patients. So that's patients on three or more medications not getting the goal. Typically one of those three or more is a diuretic. Uncontrolled hypertension is patients on two meds not getting the goal. That's about a 10 million population. So we, where we've studied lorundrostat is in that failing to get the goal on two or more. So it's about 20 million patients. We think at launch. The resistant hypertension population is probably where the initial uptake will be. That's where the most difficult to control higher risk populations are. Right now, when you add typically third, fourth line, it's a calcium channel blocker, beta blocker, alpha blocker, you're getting about a 5 millimeter mercury improvement in BP. What we're seeing, absolute change with lorundrostat is 15-19 millimeters, whether it's 24 hour EVPM or in office measurements. Really profound reductions relative to what you can currently get out there. We started our development journey with lorundrostat trying to find indicators of dysregulated aldosterone because the research would say up to 30% of all hypertension patients that are not controlled have elevated dysregulated aldosterone. We looked at plasma renin activity. Could that be a low renin? Could that be a marker? It wasn't. Patients responded whether they had low to high renin. In our proof of concept, we saw a signal that said maybe obesity BMI is a correlate or predictor of response. When we went into the pivotal program, we didn't see that signal. Part of that was so many of these patients, 90% were either overweight or obese in the trial. That signal may have gotten washed. As we looked at, particularly in the large Launch-HTN study, which is a real world study, we had over 1,000 subjects. It's in the publication, a forest plot that looks at young, old, Black, African American or White. High eGFR, low eGFR, no matter how you cut it. Patients were positively responding to lorundrostat. It kind of begs the question, are there signals or is this a, if you're resistant, you should go on lorundrostat because you're going to have a robust response. I think it's a little bit more the latter and I think it speaks to the fact that once you're hypertensive and you're on two, three meds and you're still uncontrolled, the medications you've probably been on, while beneficial, aren't targeting your true underlying cause. It's likely dysregulated aldosterone that needs to be addressed. The profile of lorundrostat fits the current workflow. If you think about right now, you go to your doctor, puts on a cuff, you're hypertensive, they give you a medication, they say, come back in two weeks, measure the blood pressure, do a blood panel for safety. Lorundrostat will fit into that flow because we see about 70% of the reduction in the first two weeks. We see the shift in potassium and sodium, which is the main on-target safety signal to look for within two weeks. It will fit in that flow. It almost becomes the fact that this is working across different subpopulations. Continue what doctors are doing now, and that's empirical treatment as opposed to really trying to target or find indicators of. Do you, don't you have aldosterone? Use it and in all likelihood you'll have some level of response. What I do like about our program, and it is a bit of a juxtaposition to the Baxdrostat program, is we had really strong representation of Black or African American patients in Advance-HTN. We had 53% of the subjects. It was a U.S. study, 53% of the participants were Black or African American. In Launch-HTN, the global study, still 28% were Black or African American. I think that those numbers are significantly higher than what the AstraZeneca program had. Why that's important is that is the highest, one of the highest risk populations as far as intransient, difficult to control blood pressure. They tend not to respond as well to some of the existing armamentariums, such as ACE or ARBs. We have a very robust data set that we could speak specifically to that population, to prescribers that are struggling getting Black or African American patients to their goal, whether it's 130 or 120 with some comorbidities. Okay, great. Just while we've brought up Baxdrostat, why don't you tell us a little bit about how your profile compares to Baxdrostat? What are some of the things that we learned this week that may or may not have been understood? Right. Let's step back and look at the molecules themselves. A really key kind of first gating attribute of an ASI is selectivity for the aldosterone synthetic pathway. The reason that's critical is because it shares about 93% homology with the cortisol synthetic pathway. Some of the first generation early development ASIs were not very selective and so they in fact inhibited both aldosterone and cortisol. That is basically a deal killer. You do not want to have any interruption with the synthesis of cortisol. Lorundrostat has best in class selectivity. It's about 374 to 1 selective aldosterone relative to cortisol. To compare that to Baxdrostat, they're about 101. That's one, that's really the first key component. We've now seen that in our proof of concept study, our two pivotal hypertension studies, our CKD study, that we're seeing anywhere from 45-65% reduction in Aldo and no signal of cortisol inhibition. The other part is then half life. What is the ideal half life? Some of the first generation ASIs had really short half lives and it was posited you need to have a longer half life. When I say short one to two hours, our half life is 10-12 hours. We believe that is ideally suited for the majority of hypertension patients because aldosterone has a clear diurnal pattern. It begins to surge pre wake, peaks mid to late morning, and then tapers off in the afternoon. Our half life mirrors that I think really exquisitely and what that can translate to, maybe less about efficacy, but more about safety. We know the on target safety signals of interest are going to be hyperkalemia and hyponatremia. Having some period of maybe relief of aldosterone inhibition may help modulate the electrolyte balance. Those are some of the distinctions. Baxdrostat by comparison is about 24-30 hours. I think that's maybe a bit of an overshoot and I'll talk about that in a moment. That's the chemical characteristics of the compounds. If we look at the clinical data and we look at like to like studies with all the hazards of comparing across studies, the two big registrational studies are probably the best ones to look at. Launch-HTN was about 1,083 subjects. BaxHTN I think was a little under 800 subjects. Both kept patients on their existing background meds. Both looked at subjects on two or more meds failing to get to goal, one of which had to be a diuretic. Both used in office measurement. Why are those studies important to highlight? Because that's how these drugs will be used in the real world. Physicians tend not to use 24 hour ambulatory as a measurement. They use the in office measure. They keep patients on existing background meds. They want to see how this drug will do for their patients on top of their existing regimen. If we look at those two studies and how the clinical data came out, they're very compelling, both relative to things like renal denervation, Naprosyn 1010, even the angiotensinogen directed therapeutic Zilebesiran. I think that reinforces that aldosterone is the issue for these patients who can't get to goal at that line of therapy. With ASI as kind of being the top of the class for the contemporaneous new innovations, we look across these two studies and we see some similarities. Really where I think it matters most, we're seeing favorability to lorundrostat. The efficacy in BaxHTN absolute blood pressure change was about 15, placebo adjusted about 9.8. For lorundrostat it was 19 absolute and about 11.6 millimeters of mercury, placebo adjusted, quantitatively distinct and favoring lorundrostat. The incidence of hyperkalemia above 5.5 observed was about 11% with Baxdrostat, about 8% with lorundrostat, confirmed above 6 was about 1.1% with BAX and about 0.6. At each incremental important point, lorundrostat had the more favorable profile and is why we believe it's best in class. Now this past weekend there was a study called BAX24 that had 24 hour ambulatory blood pressure measurement as the primary endpoint. In office was a secondary. If we look at in office, the data that was presented is ITT. So it was all the subjects and it looked replicate of what BaxHTN was. 15 millimeter absolute 10 millimeter mercury placebo adjusted hyperkalemia rate again about 12% above 5.5. The challenge with the primary, because that's where I think there was a lot of question is can you even interpret it? Part of that, part of that question is borne out from the fact that subjects who had missing data were just excluded from the analysis. Let me just step back real quick. 24 hour ambulatory means you put a cuff on a patient with a little device on their hip and they wear it for 24 hours. It takes a blood pressure reading three times every hour while you're awake, twice every hour while you're asleep. It is very onerous on a patient. It's very challenging. The cuff has to stay in a certain position to get a good read. Sometimes patients just take it off, sometimes it falls off. Sometimes you lose patients because they discontinued or they had adverse events, and that's acceptable. In the case of Baxdrostat, 24, 15% of the patients did not have a 12 week read. 18% of the Baxdrostat patients either didn't have a baseline or didn't have a 12 week reading. In their analysis they just excluded them. The percentage missing is not the problematic piece. The problematic piece is you have to account for them through imputation. Advance-HTN was a study we did again in an optimized background treatment. So a different patient population, but same measurement tool. And we had about 17% missing data in the 50 mg arm and about 9% in the placebo arm. But in the New England Journal of Medicine presentation and in the ACC presentation, we talked about the imputation that's done to account for that missing data. You don't just exclude it, you have to account for it. And that's why our data, even though we've got missing components, is interpretable because we accounted for it through statistical imputation. There's still, I think, an open question at this point that 24 hours just not interpretable. And so you fall back to what is interpretable. And that was an ITT Office measurement. It looked quite similar to what they saw in Baxdrostat H10. That is why we continue to feel confident at this stage with all of this data available, that lorundrostat is showing the best in class profile. Okay, that was very clear. Thank you. No, I mean, I understand. I'm hoping everyone else does. I apologize. It's more than just you think blood pressure and say no. It's a lot more complex. No, what we're saying is that there is absolutely no comparable measure to the Baxdrostat data that they presented, nor would it be an acceptable endpoint from the FDA because they didn't do the imputations. I mean, it could be acceptable, but they have to do the imputation as it was presented would not be accepted by the FDA. Right. Maybe that's the simplest way to say it. You have got to account for the missing data. Yeah. Okay. So generally speaking, both products are approvable in the market, have a good set of data. How should we think about the place that these drugs are going to be used? You've done studies both on uncontrolled and responsive or resistant rather. Do you go after the resistant population first? How do you get into the uncontrolled population? Where do you think this is best placed? In the marketplace? Yeah, I think where it's best placed is that third line position. Now, where it will be first place is probably resistant. The third line being uncontrolled. Exactly. We've done some pretty significant market research, particularly after Baxdrostat HTN physician and payer research and there's a clear interest and motivation to utilize this drug in resistant certainly. Also in that third line position for uncontrolled, I don't think the payers, you know, so much of this is predicated on the clinical profile which is established now and robust and then now it's around price and rebate and you can kind of toggle that with payers. Presuming that that is in an acceptable range, then I do not believe there'll be significant utilization management barriers to access to at least lorundrostat. I think this class at the third line or later, I think fourth line is probably the natural landing place because there's not been a lot of innovation, there's not been a lot of change in prescribing for 20-25 years. If there's a place where there's maybe a really more open minded, open arm to new innovation, it's probably in that fourth line resistant population. Our models have shown share penetration for the class is greatest in fourth line initially. I think that's where the trial, the usage will be and with success, meaning safe, robust reduction in bp, then I think you'll see an audience of prescribers willing to move earlier in the treatment paradigm and that means third line for that uncontrolled population. I think that 10 million patient population gets unlocked first and then I think that second 10 million gets unlocked fairly quickly afterwards. I'm not talking years in the making of that, but the natural trial space is going to be the resistant hypertension population. Okay, but what moves it from resistant into uncontrolled? What do you have to do to move into that category? I think we've each got the data at this point. I think it's really a matter of comfort and I don't, I think the access with the payers will not be necessarily restricted to a line of therapy. Again that's going to be dependent upon price and rebate strategy that informs what kind of step edit you have. Most of the research we have done says that physicians will be required to step through two lines of therapy. That means including diuretic, or two lines of antihypertensive. Exactly. So it could be an ARB and a calcium channel blocker. I think based on the clinical data we've generated, and I would say Z probably would have the same view because it's what they included in their pivotal program. We think the use of a diuretic with this class of drugs, there's a synergy there. You'd want to have a diuretic as a part of it. What I think really incentive, what drives use and uncontrolled is going to be that experience of the prescribers in the most difficult to treat patients. I think the benefit risk in a resistant population is probably gonna be more open for physicians initially. When they see that there's minimal risk of adverse effects and a really positive benefit on BP reduction, that kind of experience with patients is gonna reinforce wanting to use it earlier. Now, going earlier than third line. I don't know if that is something that we haven't really modeled that because I think fundamentally this class of drugs again works best with a diuretic. We know this class of drugs, by lowering aldosterone, raises renin. You'll probably want an ACE inhibitor or an ARB on board to counteract that rise in renin. I think the ideal triplet in due course is going to be some form of RAS inhibitor as ARB, diuretic, and an ASI. Got it. Just one other question with regard to fourth line therapy. Once you're on that many drugs, what happens to compliance in the real world? And does that sort of mask what your real utility or real efficacy is going to be? We know progressively in any category, the more pills you add on, the more you have a risk of compliance and adherence to a regimental. I think in this case, when you're getting to that fourth line, you have two motivated population. You have a prescriber that wants to get that patient to goal, and you have a patient that at that point, if they've tried three meds, they know they have an issue, they want to get it under control. You have those two forces working. I think the key for an ASI, and I'll say this broadly for the class, is I think their adherence compliance is going to be much better than like spironolactone, which is currently recommended. Fourth line, it's a mineralocorticoid receptor antagonist. It blocks the effects of aldosterone rather than lowering it. I've looked at the IQVIA data, the spironolactone compliance data is about the worst of any of the hypertension class drugs because of a mix of hyperkalemia and just off target effects. I think that's, you know, it's a real world consideration, but I think it's something that the tolerability and safety profile of lorundrostat can overcome that. Okay, got it. So you're coming into, you're gonna be filing at the end of the year, but you're coming into 12 month safety data end of year, beginning of 2026. Are we gonna be seeing that 12 month safety data ahead of the filing, or and if so, what are we to expect? Are you looking at more efficacy endpoints only? Safety, what exactly should we be looking for? Yeah, we're looking at all the metrics. After the 12 week placebo-controlled, all patients from Advance and Launch and even Explore-CKD went into this big omnibus open label safety trial. It's not just safety. We are looking at efficacy. In the case of the CKD patients, we'll continue to look at eGFR and proteinuria. In the case of the hypertension population, we'll be looking at blood pressure measurements up to 52 weeks and beyond. We're supportive of keeping these participants in these trials who committed their time, giving them access to lorundrostat up to the point of launch. We'll have data even beyond the 12 month. I would not anticipate seeing a publication of the open label extension until all subjects are through 52 weeks. Now for the NDA, we don't have to wait for that time point. In other words, we did an interim cut when we felt like we had enough data to characterize the long term safety to put into the NDA. About 120 days post that submission date, there's something called a safety update where we can update the file with safety data. At that point in time, we may have all of the subjects through 52 weeks and at that point we'll lock that portion of the study and plan to get that out in publication, in manuscript or to Congress. It is open label data. I can share with you that we continue to be very comfortable with the safety profile that we're seeing. We're also comfortable with the persistence of response as far as blood pressure control beyond just that 12 week window. We will be looking to get that published and I think that'll be an important part of the data. I think there's another, if I can real quick, another subset of data within that. AstraZeneca has published it for Baxdrostat and Baxhtn. We have it in our open label. We saw the same phenomenon that's called the randomized treatment withdrawal, which means after a certain period of exposure in the open label arm, subjects get randomized to either placebo or to stay on drug. It's a requirement from the FDA. In their mind's eye, it shows. All right, you lowered blood pressure on the drug. What happens without the drug? Does BP go back up? It does go up, but not as much as you would see with such a spironolactone, an ACE or an ARB, where when you pull the drug away, BP goes back to baseline. There's something about an ASI that is doing a shift in the underlying systems biology of aldosterone, where aldosterone levels, even off drug, continue to stay suppressed relative to baseline and BP is slow to come back up. That's actually a really compelling, interesting finding. It goes to your question about compliance adherence with this class of drugs. After a fairly short period of, you know, 12 weeks, maybe 24 weeks, even if you miss a dose, you're not going to see a rebound in your BP. You're going to have control. We're still going to recommend take the drug daily, but if you miss a dose, you're not going to lose control. All of that data will be something we'll be sharing in 2026 at Congresses and in publications. Okay, great. You also have CKD data, as you mentioned, and you're doing a study in OSA. I guess two questions. One, why? Give us the specific reasons why you're doing studies in each of these different areas? How are you going to leverage the data for the label? Is it just for the label? Is it for a completely different indication? Is it just for a safety perspective? Maybe you can just help us understand that. Yeah, the why is simply an acknowledgement that these patients don't just have hypertension. Hypertension, we know, leads to stroke, heart disease, kidney disease, can exacerbate all of these different conditions. There is so much overlap like CKD. Two thirds of all CKD patients have hypertension. 70%-80% of all resistant hypertension patients, or 78% of all resistant hypertension patients, I believe, have some form of OSA. There is an intermingling of hypertension with all of these comorbidities. As we went out and talked to physicians in the market and said, all right, what are key attributes for us to show you about lorundrostat, obviously, number one is BP reduction, number two is safety. Quickly behind that are some of these comorbidities, like is there a benefit on proteinuria? May there be a benefit on the cardiovascular risk or even the symptoms of OSA? Doing the Explore-CKD study, where we saw a 30% reduction in UACR albuminuria at four weeks, is an important part of the profile of lorundrostat for those prescribers. In the case of that one, Explore-CKD, that one is also going to inform the label. In other words, the pivotal studies went down to an eGFR or kidney function of 45. That study goes down to 30. That will be part of the label package that we will put in front of the FDA. Will we get the proteinuria data in the label? That is part of the discussions we will have with them. We certainly believe the effect on blood pressure in that population will be a part of that label. We have another study in hypertension OSA that will read out in Q1 of next year that will not be in time for the label. Again, that is going to be another data point that speaks to some of these comorbidities that these uncontrolled and resistant hypertension patients deal with. It'll be part of the message, either through medical affairs or through promotion, that we'll be able to share with physicians about the benefit of lorundrostat, primarily for education. OSA is, and I think each of them do what I described, but they also de-risk maybe future development. If we want to contemplate going into CKD, if we want to contemplate going into OSA as standalone indications, we've now de-risked those with those data sets. Okay, great. I guess we have to take it to commercialization. Obviously, you're Mineralys going up against AstraZeneca, which is the deep pockets, broad infrastructure already in a very relevant population. How should we think about that and what are your inclinations towards partnership? Yeah, I mean, I've said it before. We're very open to finding the right partnership structure. That makes sense from a value generation standpoint. I will step back. This is a broad population. I mean, it's 120 million people in the United States with hypertension, 60 million treated. Again, we're looking at that 10 million resistant, 10 million uncontrolled, 20 million writ large. As we look at IQVIA data, the top 50% of the prescriptions for that third line or later prescribing is about 60,000 docs so we're not looking at a partner that needs to bring thousand reps. This is still as big and maybe broad of a market as it is. It's targeted in who's actually prescribing where you would want to be at launch with this drug. We can be selective, make sure that we're picking the right partner that sees the molecule and the opportunity the way that we want. From a broader standpoint, global partnership is compelling to me because it includes potential co development opportunities and not just solve a share of voice issue in the United States. There are a lot of different constructs we're looking at. Again I look at all the data that we have and feel very comfortable. I have best in class molecule now how do I make sure that I've got appropriate share of voice and commercial footprint against that and what is the. Rate limiting step to completing that? Just getting the right terms or I. Think getting the right deal construct that would include terms. I think we have shown through the course of 2025 the real value here, the unmet need, the opportunity. Having a best in class molecule, we do not have to go begging for a partner. We want to find the right partner that we think can really make a difference. Because I can show a path of us keeping this molecule on our own and driving it. Even as formidable as AZ can seem, there is a path to generating value on the go. It alone I do not know that we can maximize that value going along. You're prepared to do it? I think we have to be mindful of doing it and how do we do it efficiently. Again, it's a consideration as we think about the partners, the economics on our own, the economics with the partner, and where the real value driver is great. I guess we'll stop there because you have the cash to do it. We're well positioned right now for that. Excellent. Thank you very much Annabel. Thank you. Appreciate the time.