Mineralys Therapeutics, Inc. (MLYS) Earnings Call Transcript & Summary

There we go. I'll be making forward-looking statements for the course of the day. So as I noted, Mineralys is focused on how do we target aldosterone in cardiorenal metabolic disorders. We do that with our best-in-class selective aldosterone synthase inhibitor lorundrostrat. That's important because we know about 30% of all hypertension patients have some form of dysregulated or elevated aldosterone. This has been shown in several publications. We're seeing a rise in interest and intention to aldosterone through the medical community, through guidelines to really try to diagnose what has been greatly misdiagnosed or underdiagnosed over the last several years. Lorundrostrat, we believe has best-in-class capabilities as an aldosterone synthase inhibitor. We've completed 4 successful trials from our proof of concept to a large registrational study in 2 specialty studies looking at the benefit of lorundrostat and truly confirmed the hypertension as well as hypertension CKD. Those studies have given a very consistent, predictable profile. Within 2 to 4 weeks, you see the bulk of the response from a blood pressure reduction standpoint, as well as the shift in the electrolytes that are beyond target safety signals that you want to see. That effect tends to grow over time, which we think is a very insightful component of the program that we've put in place right now. We've very much been focused not just on the hypertension but hypertension related comorbidities. We know there's significant overlap between hypertension and CKD, hypertension OSA. And that's why we've been doing our Explore programs, which is what we call our proof-of-concept trials in 4 CKD study read out in June, in a very positive benefit on blood pressure safely, but also a benefit on proteinuria as I'll speak about in a minute. And we have an OSA proof-of-concept study, again, looking at the benefit not only on hypertension. But on the symptoms of OSA and very specifically on nighttime BP. As we look at the unmet need, this is within the United States, there's probably about 20 million patients that are failing to get to go on 2 or more medications. That's what's called uncontrolled. If they're on 3 meds and still not a goal and above 3 meds resistant hypertension population, we think there's an increased market opportunity with these comorbidities hypertension-related conditions such as CKD and OSA. We are planning a pre-NDA meeting in Q4 of this year and anticipate the filing in Q4 of 2025 or Q1 of 2026. And so let's talk a little bit more about aldosterone. This is an ancient hormone. It's what controls largely volume through electrolyte management, sodium and potassium. That's the left-hand side of the chart, the genomic aspects is what controls volume. It was really one of the first targets for anti-hypertension drug treatment in 1959, a drug called spironolactone corticoid receptor antagonist to lock the predominant receptor of aldosterone that drives volume control. But there are other mechanisms and other pathways that aldosterone effects and specifically these nongenomic, non-MR pathways, GPR30 is an estrogen receptor drives inflammation, fibrosis and oxidative stress. Why that's important is historically, when you would block aldosterone with an MRA, you actually saw aldosterone increase two to threefold that further procured the other pathways. And so aldosterone is the problem that you're trying to address and aldosterone synthase inhibitor, literally reducing the amount of aldosterone available is an ideal way to affect all the biological pathways. We believe that has been a bit clearly now at this point in uncontrolled and resistant hypertension, chronic kidney disease as well as we think potentially in our failure in vascular and systemic inflammation. If you think about where the medical community is going, it's no longer thinking about treating hypertension as a silo or a heart failure is a silo or CKD is a silo. It's this cardiorenal metabolic syndrome. We're seeing that exclusively pointed out with GLP-1s. I think at the center of this as well is aldosterone and we're beginning to see the signs of that with the data that we generated in uncontrolled and resistant hypertension as well as within proteinuria as we look at OSA. We firmly believe that aldosterone is at the center of this overlap of cardiorenal metabolic syndrome. But I'll step back to hypertension because fundamentally, it's the tip of the spear for so many of these conditions. If you talk to a nephrologist, they will tell you what is paramount for CKD patients is get their blood pressure down. Nothing slows the progression of kidney disease like uncontrolled blood pressure. And we've known for decades that hypertension uncontrolled resistance continues to drive death. 10.8 million lives per year globally are attributed to hypertension and is the leading modifiable risk factor that if you get under control, you can create more days for patients and more better days for patients. And fundamentally, we know that if you lower blood pressure by at least 10 millimeters of mercury, you're going to see a significant risk reduction in all cause of cardiovascular disease, MI in stroke. The data is clear. The data is evident to the point where the FDA has said, if you submit a file for lowering blood pressure, you will get an outcomes client without doing an outcomes trial. The data is that compelling and in controversial. A question we get frequently is, well, if patients just took their drugs, if patients just were on the right drugs, if they were compliant, if we knew how to measure blood pressure, then everybody gets to go on their existing treatments. And the answer through a host of different support points is no. There are some that certainly can. CDC will say that about 50% of patients cannot get to goal. I would say within that, there are some patients that if they were on the right drug at the right dose and were compliant, they can probably get to goal. But we know the prevalence of a parent resistant hypertension at a minimum is about 20%. This is from academic research and we know from our own studies where you optimize background treatment, which is one of the studies we did with Cleveland Clinic, literally taking patients out there back on meds, put them on an American Heart Association prescribed guideline of drug and dose, the smartphone technology to confirm compliance. She used 24-hour ambulatory, which is a gold standard for measuring blood pressure, you're still seeing 30% to 40% of the patients cannot get to goal, even Kaiser that put out a real landmark study and said, here's our very aggressive program. 20% of patients could not get to goal. That's out at 80%, which is a great win, but that still means there's 20% of the population, that's 120 million in the U.S. So there's a significant population that cannot get to goal. Why is that? We frankly think it's aldosterone is the primary culprit here. We know there's a linkage between visceral and deposits, so the obesity epidemic that we have right now. Visceral obesity, those advocate sites can drive aldosterone separate from the adrenal gland. We know that ACE inhibitors and ARBs, about 30% to 40% of patients didn't get to goal on those drugs. We'll have breakthrough, and that's called aldosterone breakthrough. So there is a significant and compelling evidence to support that 30% of these patients have some level of dysregulated aldosterone or elevated aldosterone that is likely causing them to not get to goal because the one drug currently available to do that is spironolactone, concessions and patients do not like to use. So if we look at the lorundrostat clinical data, I'll first step back and look at the molecule itself. I think there are 2 key differentiators within this ASI class. One is selectivity. Aldosterone has best-in-class -- sorry, best-in-class selectivity, which you can see right here. That selectivity relates to the ability to inhibit aldosterone but not affect cortisol. There's [ site homology ] between those 2 synthetic pathways, they're linked evolutionarily. We have best-in-class selectivity for that. But half life maybe the key and true differentiator. The half-life of aldosterone about 10 to 12 hours. Vicadrostat, an ASI by Boehringer Ingelheim has about a 4- to 5-hour half life. The AstraZeneca compound about a 24- to 30-hour half-life. We think that 10- to 12-hour half-life matches the diurnal nature of aldosterone. It begins to rise in the morning peaks mid-morning to noon and then tapers to the rest of the day. We believe that our half-life mirrors that significantly. And I think the data that we've generated to date supports that. Launch-HTN is the largest hypertension study ever completed for an SI. It's over 1,000 subjects. This is the real-world study. This is what will be probably most informative for prescribers because this is how they will use this class of drug. They'll add it on top of existing background meds. They'll use in office blood pressure measurement and what we saw at 6 weeks, which is the primary endpoint, was about a 17-millimeter mercury absolute change in blood pressure, about a 9.1 millimeter mercury placebo and just a change P value, very -- 0.0001. What's interesting about this class of drugs is that as you continue on the compound, the effect persists and, in fact, may grow somewhat. We saw that week 12, a 19-millimeter absolute change at about 11.7 millimeter mercury placebo or 11.6 millimeter placebo adjust to change. I'll take you back to the slide that showed a 10-millimeter mercury reduction can yield anywhere from 18% to 28% improvement in risk profile. This is a 20-millimeter drop almost. And so this is going to be fundamentally shifting the outcomes for a significant number of patients. We also sold about 44% of the patients got to go versus 24 on placebo, which is at week 6. I spoke about the Advance-HTN trial. It's really important to understand the distinction between a parent and confirmed hypertension. A parent is that collection of patients like Launch had. Some of these patients in this study, maybe if they were on the right drug, right dose could have gotten the goal. But again, this is how patients are treated. So this is the reality of the marketplace right now. But board specialist, they may ask the question, well, what about a truly confirmed patient? In other words, they're on the right dose, they're on the right drug. They're truly compliant. You have confirmed the BP with uncontrolled BP with 24-hour ambulatory. This study answers that question. This study is what largely will help given the guidelines, either with AHA in the U.S., European Society in Europe. And again, we saw the similar profile. At 12 weeks, we saw a 15-millimeter mercury drop is with 24-hour ambulatory and 8-millimeter mercury placebo existed change. At week 4, again, it was robust, but we're seeing continued duration of effect persistence have netback improving the effect from week 4 to week 12. Our Explore-CKD study supports how we're looking to introduce this drug. It's not just to provide information on blood pressure and control to prescribers, but about those hypertension related comorbidities. There is significant overlap of the CKD and hypertension OSA and hypertension heart failure and hypertension. And so we're endeavoring to create data they will speak not only the blood pressure or in effect, but also other attributes that are related to hypertension. In this case, or we double-line crossover study, we sell a 9-millimeter mercury reduction in absolute BP, 7.5 placebo adjusted, but these patients also had proteinuria. And we saw a significant benefit on proteinuria reduction, about 31% absolute 25% placebo adjusted. This is a key attribute for prescribers as we go out and do market research. If there is a benefit on proteinuria, you would expect this, you lower BP, you lower rental hyper perfusion, you're going to see a benefit on proteinuria. And this is a surrogate that translates to renal protection promise of lorundrostat. Safety, obviously, is important. This is an asymptomatic condition. This drug is exceptionally well tolerated, very few incidents of serious adverse events relative to placebo. Potassium is the main on-target adverse event to look at. Again, very modest numbers. We saw 0.6% potassium above 6 with lorundrostat and Launch-HTN versus 0.4 with placebo. Advanced-HTN, where you've got a patient that is on max dose ARB, again, very modest impact on potassium and even in Explore-CKD where the eGFR kidney function is much lower, again, a very modest effect on potassium. To put that into context, ACE inhibitors and ARBs that were introduced in the '70s and the '80s or more the '80s are written ubiquitously. They're always the first-line treatment, 85% of all hypertension patients are either on ACE or on ARB and the potassium profile of those 2 compounds looks very similar to what we're seeing with lorundrostat. So I think the combination of the benefit risk profile that we see with lorundrostat is -- hold great promise for these patients as we move forward. I mentioned our OSA study. This is ongoing. We have guided to top line data in the first half. This is an important study because again, there's significant overlap. 70% to 80% of OSA patients have resistant hypertension. Nighttime BP or uncontrolled it BP is really the killer within this population. And so we'll be looking at not only blood pressure AHI, but also a benefit on nighttime blood pressure. And so here is our pipeline to date. Again, a heavy focus on hypertension, but on those hypertension-related comorbidities. Several of these studies Launch, Advance and Explore we think will be informative to the NDA. Again, we have a planned pre-NDA meeting in Q4 of this year. We anticipate filing in Q4 of this year or Q1 of 2026. And so how does that translate that robust clinical data set into a commercial opportunity? This is the United States. We have about 120 million patients dealing with hypertension about half or on treatment, about half of those patients, 30 million get to goal. You have the 30 million that are on treatment, they can get to goal, break into really 3 buckets. The 2 buckets that we're pursuing are patients on 2 meds that are not in goal or those on 3 or more meds. And we know, again, there's significant overlap of hypertension with CKD, hypertension with OSA that we think bolsters the value proposition and helps penetration into that 20 million patient population. Another way to look at this opportunity, this is from IQVIA data. In 2024, there were about 26% of the prescriptions that were new to line. That means patients were starting either first, second, third, fourth, fifth line treatments. When you look at that second bar graph, you see that about 52% of the patients were trying new medications for third line or later. Translate that into -- of the 65 million treated. That means about 8.8 million patients per year are cycling trying something new for third line or later. There's not been innovation in this space meaningful for 25 years, and yet there's cycling of trying to find something to help patients get to goal. And that goal progressively comes down from the medical societies that are out there because it's clearly a link between control BP and better outcomes. I don't have it on this slide, but if you were to look at the 52% of those patients trying to do drugs what those drugs are, it's highly fractured which tells you physicians are dissatisfied with what's currently available. They're having difficulty getting patients goal, and they are in a heavy trial mode, which is ideal for introducing a new class of treatment. We put the profile of Launch and Advance in front of physicians. On the left-hand side of this chart, there's a 95% intent to prescribe. That's based on the efficacy, that's based on the safety. The figure on the right, the 75% came from FirstWord Pharma after our Explore-CKD data came out. And again, that 75% intent to prescribe. It shows the interest in this molecule, the enthusiasm for it and we think creates a significant opportunity. So as I look at the opportunity for introducing, we're under set into the market, that -- our purple is the sweet spot that resistant hypertension, where you have a fracture market, you have heavy churn, which means interest in trying something new, something valuable that will help patients get the goal. But why we are doing the Explore-CKD, why we're doing the Explore-OSA is because there is overlap of hypertension with those conditions. And those data sets allow us to compete, not only just in the resistant hypertension but are those hypertension patients with CKD, the hypertension patients with OSA. And as experience is gained, as physicians have success with this compound, we think there's an opportunity to move earlier lines of treatment, and that is in that 10 million patient population that's uncontrolled. Right now, our cash balance is well situated at the end of Q2. We announced we had $325 million in cash. Last Thursday, we announced the closing of an offering that gained another $270 million net. So we're well positioned to continue to develop this compound prepare the commercial opportunity and look to expand the clinical profile as well. Have a good fortune of working with an exceptional team that over the last 4.5 years has gone from pre-IND to now getting close to an NDA submission for what we think is a transformative medicine that will bring meaningful benefit to millions of patients, not only in the U.S., but also globally. So I appreciate your time. I appreciate your attention, and thank you.

Thank you very much. Thank you for your presence at our conference. Have a good day, everyone.