Conference Transcript - MLYS 2026-06-03

Dennis Deng, Analyst — Jefferies

Welcome to day one of the Jefferies Healthcare Conference. My name is Dennis Deng, biotech analyst here at Jefferies. I have the pleasure of having CEO John Congleton and also CFO Adam Levy here with us from Mineralis Therapeutics. And I'm going to turn it over to you, Adam, to give a brief overview around what happened this morning and then the rest of the presentation.

Adam Levy, CFO

Thank you, Dennis. I'll go through a recap of the news from this morning and then turn it over to John to talk about the business we'll be making some forward-looking statements today so there were three transactions that we announced this morning we had the opportunity to repurchase our royalties from Tanabe we paid 200 million up front and there's a hundred million in additional potential commercial milestones these are the royalties if people remember were mid single digits escalating up to 10% pro forma for the purchase will have a hundred million in new commercial milestones and 165 million from the existing commercial milestones of which 10 million were related to a potential second indication and the royalties are completely extinguished in parallel with that we raised 150 million in equity and we secured a 500 million dollar debt facility with pharmacon of which a hundred million was funded at closing and we have an additional 400 million available to us in certain tranches the next available tranche will be at FDA approval for 150 million and then there'll be 250 million in committed capital that we have the ability to draw our discussion over the next several years triggered by the achievement of certain sales milestones the interest rate is floating it's so far plus five and a half percent and the credit facility can be prepaid at any time at our discretion with subject to prepayment fees with that I'll turn it

Jon Congleton, CEO

over to John thanks Adam obviously very excited about the news I'll add one point to what Adam made based on the cash cash equivalents from the financing and what we had on hand plus the debt facility with all tranches pulled in with our current plan we're fully funded for the commercialization so obviously very excited about that enabling what we've been focused on here we go targeting aldosterone as it relates to cardiorenal and metabolic disorders lorunder stat for those of you that don't know the story is a highly selective aldosterone synthase inhibitor that's relevant because in the united states and globally we think that about 30 percent of all uncontrolled and resistant hypertension patients have some form of dysregulated or elevated aldosterone over the last five years we have demonstrated that lorunder stat once daily provides 24-hour control of that blood pressure extends benefit to subjects with ckd which i'll talk about in a moment and has shown a benefit in reducing blood pressure blood pressure in patients that are both obese and have OSA that reduction in BP we think is one of the biggest drivers of potential CV risk benefit there are 20 million patients in the United States I'll break that down in a moment with uncontrolled and resistant hypertension and there's significant overlap of comorbidities such as CKD and OSA which we think will create opportunities for lorundrostat. We filed the NDA late last year. We notified the market in March that the file was accepted and we had received a PDUFA date of December 22, 2026. So the role of aldosterone has been fairly well established as far as the genomic effects. This is what controls fluid volume in the system, electrolyte, shift, sodium, and potassium. What I think is growing to be appreciated are the non-genomic effects of aldosterone and how it can drive fibrosis oxidative stress and inflammation. Aldosterone in the dysregulated state can then be a driver of not only uncontrolled and resistant hypertension but also chronic kidney disease, heart failure, and vascular inflammation. Why this is relevant is we have demonstrated at this point clearly that lorunder stat has a significant benefit on uncontrolled and resistant hypertension we've shown signals of benefit as it relates to CKD but given the fact that aldosterone sits at the nexus of all of these cardio renal metabolic disorders we believe that lorunder stat has the utility to provide benefit across a host of disease indications for those of you that haven't met me I started my career in 1986 selling cardism in the hypertension space at that time hypertension uncontrolled hypertension was one of the leading drivers of cardio renal disease mortality loss of quality of life unfortunately 40 years later that has not changed uncontrolled and resistant hypertension continue to be one of the leading global modifiable risk factors and that leads to morbidity and mortality and in fact there's been significant evidence that demonstrates just a 10 millimeter mercury reduction in systolic BP can lead to significant reduction in CV risk and stroke and heart failure to the tune of anywhere from 13 to 28 percent as you'll see with lorunder stat we're looking at absolute changes in the neighborhood of 15 to 19 millimeters of mercury and thus we think will translate significantly into benefit for patients and so to kind of recap that if you think about the opportunity for lorunder stat anywhere from 20 to 40 percent of patients who are treated fail to get to their prescribed goal part of that challenge is the goal is progressively coming down 30 40 years ago it's 140 millimeters of mercury systolic now it's 130 and in some cases with comorbidities it's 120 millimeters of mercury that is part of the challenge in patients actually getting to goal because we haven't had true innovation in this space and yet the goal continues to come down. There's needs for new alternatives to help patients achieve those goals. Aldosterone, we do believe, is a culprit, and there's different drivers of that. We've known for, I think, decades that ACE inhibitors and ARBs can get patients to go, but about 30 to 40 percent of them, after six to 12 months, have what's called aldosterone breakthrough. They begin to lose control of their blood pressure with the ACE and the ARB because aldosterone breaks through that inhibition further upstream in the RAS system. The other element of research that has become evident is the linkage between visceral adiposity and aldosterone production. We're all very much aware of the obesity epidemic. What's I think less appreciated is the hidden epidemic of dysregulated aldosterone that we believe based on literature is linked to the obesity epidemic. And so let's talk a little bit about lorandrostat clinical efficacy and safety as I said we've spent the last five years executing five studies really demonstrating the best-in-class potential of this molecule but let's start with lorandrostat itself there are two elements that we believe are critical for an aldosterone synthase inhibitor to provide once daily efficacy and safety appropriately one is the half-life lorandrostat has a half-life of 10 to 12 hours in our proof of concept trial, we looked at both BID and QD and found that once daily dosing provides the proper balance of efficacy and safety, provides 24-hour control. It matches very nicely the diurnal pattern of aldosterone, which tends to begin to surge in the pre-wake hours, peak late morning, taper in the afternoon. Selectivity is another key element. There There were first-generation aldosterone synthase inhibitors that lacked selectivity for aldosterone relative to cortisol and inhibited both of those hormones. This is obviously something you don't want to achieve with an aldosterone synthase inhibitor. With lorundrostat, relative to baxterostat and vicodrostat, we see best-in-class selectivity by about a factor of 2 to 1 or 4 to 1 with a 374 to 1 ratio of selectivity. so on the basis of that we moved into a very robust clinical program what you're seeing here are four studies that I think speak very eloquently to the distinct populations of uncontrolled and resistant hypertension the slide the table on the left is launch HTM this is a real world study it's the largest trial ever done with an ASI in hypertension we saw very robust meaningful reductions as early as six weeks of about 16 and almost 17 millimeters of mercury 9.1 placebo adjusted at week 12 we saw a 19 millimeter absolute reduction 11.6 millimeter mercury placebo adjusted I think it's important to point out that within this study 44 percent of these patients got to gold versus 24 percent at week six this is a critical point if you think back to the number of patients that are failing to get to their goal the benefits of seeing these kind of reductions this will translate into significant cardiorenal risk reduction for these patients additionally within this trial there were about 28% of this population that were black or african-american we know that's a high-risk population and we saw a similar benefit across to all racial and ethnic groups advanced HTN is a study that we did in partnership with the Cleveland Clinic this is likely the most rigorous hypertension study ever completed we did a three-week run-in period where we took patients off their existing background treatments put them on an optimized AHA prescribed treatment regimen we use smartphone technology to confirm adherence on a daily basis and only subjects after three weeks that had failed to achieve their goal were randomized over that 12-week period we saw a 15.4 millimeter mercury absolute reduction and a 7.9 millimeter mercury placebo adjusted reduction and in this study again we use 24-hour ambulatory that confirmed the 24-hour control for this population 41% of the patients achieved goal in this rigorous confirmed population versus 18% on placebo at week four and I'm very proud of again how we ensured that we had diverse representation with this within this trial 53% of the study participants were black or african-american in the study again providing evidence for prescribers in a very difficult to control and high-risk population in support of these two pivotal trials we also conducted two proof-of-concept studies we call these the explore programs explore CKD looked at subjects with an EGFR down to 30 the prior two studies went down to an EGFR of 45 in this study population crossover design we saw about a seven and a half millimeter mercury placebo adjusted reduction just at four weeks we also saw a concurrent reduction of 31 percent in UAC are which is a surrogate or a marker for renal protection and so feel very confident that for nephrologists specifically who are treating a hypertensive nephropathy they're not only going to be able to get control of the patient's blood pressure, but also see a benefit on their kidney function. ExploreOSA was a study where we were exploring the benefit of reducing aldosterone with lorundrostat to see if there's a benefit on the apnea hypopnea index, as well as looking at blood pressure reduction. We did not see a demonstrated benefit on AHI in this population. It was a very severe population. I think the average BMI was 37 to 38. The average AHI was 48, and severe cutoff is 30. So this was a very affected population, but happy to see yet again, and as anticipated, a robust reduction in clinically meaningful reduction in systolic BP at just four weeks. And again, frankly, this is the biggest driver of cardiovascular risk for these patients. I say that because we know with CPAP you can reduce AHI, but you do not see an alteration in that patient's cardiovascular risk profile. From a safety standpoint, the ASIs are kind of a prototypical RAS inhibitor pathway, so you want to look at electrolytes. You want to look at things like change in EGFR. Very pleased with what we've seen to date with the potassium profile specifically. In the largest trial launch HTN, we only saw 0.6% of the patients have a confirmed hyperclemia event. In advanced H10, it was a little bit higher, 2.1%, but again, very low. And this is an important finding for prescribers, specifically cardiologists. These patients were on nearly the highest dose of Olmosartin, a very potent ARB. And in advanced H10 with Lorundrostat, we've demonstrated that you can achieve dual RAS inhibition with two different mechanisms and do so safely. Explore CKD, again, we went to a lower EGFR. We used a 25 milligram dose once daily. We know that these patients are renal impaired. They can have more difficulty in controlling their electrolytes. And again, saw a very modest change in hyperkalemia of 5%. And then in Explore OSA, we saw no patients with a potassium noted above 6.0 millimoles per liter. So very well tolerated. But to give you some context for these numbers, I think it's important to look at the predominant class of drugs that are used right now in treating hypertension and that is ACE inhibitors and ARBs. About 85% of all treated patients are on one or the other. These affect the RAS pathway further upstream. This is data from a meta-analysis and what you would typically see in large populations is hyperkalemia rates in the 1 to 3% with ACEs and ARBs. And, again, looking at both our real-world study launch and in our very confirmed, rigorously ran trial advance right within the goalposts of what's currently being prescribed. So we feel very confident that the efficacy is well matched with the safety with Lorunderstat that will help with adoption for physicians. I will add, from a workflow standpoint, and I think that's the beauty of the aldosterone synthase inhibitors, They fit very well into the current practice of treating hypertension. What I mean by that is if a physician chooses to use lorundrostat, they'll get a blood panel, they'll check potassium, sodium, they'll get an EGFR measurement, as well as blood pressure, start the patient on that, and then in two, four weeks, bring them back, check their blood pressure, and then within that short period of time, you'll see the shift in electrolytes, and they can comfortably modify and periodically check on those patients going forward, presuming all are within safe zones. And so that brings me to where our pipeline is right now. We've completed advanced HCN, launch HCN. Target HCN was our proof of concept study that I referred to earlier. Both advanced and launch were key components of our NDA that we submitted last year, as well as the Explore CKD. The Explore OSA study was completed post. The submission of the NDA. So it was not included some of the safety data may be in the 120 day update we do have Our transform HTN study continuing to progress. It's our open label extension trail. That's an omnibus open label extension That includes patients from advanced launch and explore CKD. That's an important data set. We anticipate publishing information from that omnibus open label extension later this year or into next year and so there's a significant commercial opportunity here and again as I said I started my career in this space and saw the transformation of cardiorenal conditions because of calcium channel blockers selective beta blockers ACE inhibitors and eventually ARBs unfortunately we have not seen innovation in this space for quite some time and yes it's a completely genericized market I have the gray here to show that I saw it when saw the brands when they launched but they're all generic now but the the problem is we have not solved this problem whether it's the 20 40 percent that we try to triangulate on for those patients on two or more meds that are not a goal fundamentally the prescriber base feels they're missing something and I think fundamentally what it is is an effective safe and easy to tolerate aldosterone directed treatment the only thing at physicians disposal right now is spironolactone a mineral corticoid receptor antagonist that was launched in 1959 has significant off-target effects and is limited by its safety profile if you push the dose so from my standpoint this market opportunity is immense it's needed clearly we will see a benefit to patients on their cardiorenal risk profiles as we progress but in the United States alone there are 120 million patients with hypertension about 60 million of them are treated about half roughly are at goal the other half that are not goal about 20 million are on two or more meds we believe that's the addressable market we believe that's where the opportunity is and it's not just a belief it's what we've seen in the market data that we've we've done we've spoken to physicians whether their primary care cardiology nephrology and chronology we've obviously had a lot of interactions with payers payers are open to creating access for innovation within that third line or later space they know the cost they know the implications of uncontrolled blood pressure and so that 20 million is an ideal target for us and there's significant overlap these are patients that have had uncontrolled and resistant hypertension potentially for decades and they're now beginning to see the implications of that whether that's CKD whether it's OSA whether it's cardiovascular implications and so that's why we continue to use our Explorer programs to not only show the benefit on controlling blood pressure but also on those related comorbidities so this is a little bit of a complicated slide but I think it gives a really good picture of the market dynamics or what's actually going on in the treatment of hypertension right now this is an IQ via data set it's from 2024 it is the total movement of scripts for that year for the ICD-10 code of treating hypertension said another way there are 65 million patients that either got a new or an existing treatment or a prescription filled in 2024 26 percent of those were new to line that means a patient either it was the first time so a first line treatment or it was the third treatment added or fourth and so on if we go to that middle bar about 52 percent of the patients were either getting for the first time a third line treatment or a fourth line or later treatment I will remind you in 2024 we were at no innovation in this space and yet you see a highly activated market and highly dissatisfied market physicians have not given up they've not become nihilistic neither have patients they're continuing to try new things and it's it fits the empiric approach that has been the path for hypertension for 40 years adding new agents trying to incrementally move the patient closer to their goal and so for me as I look at these 65 million patients fully a quarter of those getting new line half of those being third liner later that's about 8.8 million patients just in 2024 that we're trying new but old treatments and so the introduction of a truly innovative approach such as lorunder stat I think has a grand opportunity to really tap into that churn that exists within this market and hopefully pull some of these patients out of that continued trial pathway and get to their goal effectively and the intent and interest is there we did this CERMO survey last spring after we had the launch in advance date and we just asked what what is your intent to prescribe show them the profile of lorunder stat and 95% of the physicians said likely to very likely to try lorunder stat again I think that speaks to their interest in having innovation having new approaches to treating these patients for the Explorer CKD we did the same thing 75% intent to prescribe when the Bax HTN data came out we basically put the Bax HTN data blinded as to what the drug was we put our launch HTN data blinded to what it was put it in front of physicians and did a forced selection there was no middle ground you couldn't say like them both so pick one and there was two to preference for lorunder stat and I think that's based on the efficacy and safety that we see within launch HTN in those real-world uncontrolled and resistant hypertension patients and so as we think about the market opportunity and how you could enter this space fourth line is the beachhead low-hanging fruit whatever you want to call it I didn't share it in the IQ via data because it gets too complicated but if you look at the fourth line and what's actually prescribed there is no mechanism that has more than about 12% share I envision the wheel of fortune wheel that just spends the doctor just spinning and just picking something trying something it's not directed it's not targeting what fundamentally these patients on three or more meds probably are dealing with and that's dysregulated aldosterone and so that fourth line is an optimized space again based on the payer research that we've done with a non-specialty tier price point we believe access is going to be completely enabled for these patients again they are high cost to the health care system and thus innovation is going to be accepted in this space we built a data set that speaks very exquisitely to this population advanced HTN is the confirmed uncontrolled and resistant hypertension population this is the group that cardiologists are dealing with they are the ones that most likely are optimizing treatment of existing antihypertensives and yet still cannot get patients to goal the hypertensive nephropathy for those patients with below one gram of protein as a marker of their nephropathy explore CKD will be very informative for those physicians and then the uncontrolled patients that are complicated by OSA and obesity clearly a lot of our studies cover that because I think on average our BMI is above 30 but Explorer OSA spoke very eloquently to those patients that have comorbid OSA and the kind of benefit you could expect on blood pressure control now that does not mean that we're not going to effort to third line utilization as well I think those patients that are on two meds not a goal with complications and comorbidities we'll be building the use case for but I think this is very much a market where you build from the fourth line and then move earlier into treatment and tap into what is collectively about 20 million subjects overall. And so bringing that to conclusion, this is our financial summary as of Q1. Obviously, we'll be updating this with our Q2 based on the announcement today. but as of q1 we had 646 million in cash and 83 million shares of common stock outstanding i am grateful and benefit from working with some outstanding leaders that have helped us move lorunder stat from a phase one asset about five years ago to an asset under review that holds the potential to address the needs of 20 million subjects hypertension patients here in the united States we're obviously also looking at pathways to get lorunderstat to subjects outside of the United States as well but certainly I'm pleased with how we've advanced the program to date and on the cusp of introducing what we believe is a drug that can create more better days for patients going forward so I thank you for your time and your attention perfect thank you so much