Thanks, everyone, for joining us here at Guggenheim's healthcare i nnovation conference. I am here with Mineralys, so Jon Congleton, CEO of Mineralys, joining us. I am Seamus Fernandez, one of the Senior Biopharma Analysts here at Guggenheim. So Jon, we are just weeks away from lorundrostat's December 22 PDUFA date. Before we get into the regulatory and launch details, will you just give us a sense of where the company stands today? What are the most important things to get right over the next couple of months?
Yeah. No, Seamus, thank you. Thanks to Guggenheim team for the invite to the conference. Always very productive and enjoy obviously talking about what we are doing. On the heels of the American Heart Association, where I was this past weekend in Chicago, I get excited about, I think, the focus on hypertension, the focus, frankly, on progressively getting patients to goal, and even sometimes more aggressively, the enthusiasm that we are seeing building around aldosterone as a target and the ASIs.
For us, and we will get into it in more detail, but it is a matter of having all of the key vectors, if you will, so market access, the med ed and dissemination of information around aldosterone and ASIs, the sales team, which we said we have fully in place right now, and all of the back office brand marketing materials ready to roll so that, presuming we have positive news on the action date, we can quickly transition into getting lorundrostat into the hands of physicians and patients in 2027.
Great. Obviously, your commercial background has the company extremely well-prepared for the launch, but how are you thinking about the opportunity for lorundrostat and the ASI class, broadly speaking? It is a market dominated by generics, and there are different approaches that you could take to attacking the category.
Yeah. As you know, I started my career 40 years ago carrying the bag, selling in the hypertension space when all of these generics were branded. A lot of great innovations brought into the space at that time. But if we fast-forward to where we are now, we still have over half of the patients treated are not at goal. Goal progressively comes down. Back when I was a rep, it was 140. It's now 130. There's a lot of argumentation to get down below 120 to really confer the benefits that one would expect on outcomes, which is ultimately what this game's all about. I get asked a lot of questions, and I'm sure you'll ask, difference between baxdrostat and lorundrostat, and those are important distinctions, but I think fundamentally, that's not what this is about.
It's about the 20 million patients who are on two or more meds, cannot get to goal with what's currently available, and a lot of these patients have trialed multiple drugs or have added multiple drugs and are just getting incremental value and not getting aggressively to that goal. From my standpoint, as we think about the introduction of lorundrostat, it is frankly more about juxtaposing lorundrostat's profile to alpha blocker, beta blocker, calcium channel blocker, MRA, because that's where those 20 million patients really need value. Then once a physician is kind of bought into, yes, ASIs are probably where I need to go, then we can talk about some of the distinctions, where there are similarities, where there's differences with baxdrostat. But I think that's where the real opportunity is to really tap into this market.
Got it. There's a lot of, I guess, sort of distinctions as we look at just the growing acceptance of GLP-1s.
There is an impact of GLP-1s on blood pressure that can be seen. Does that have much of an impact on the market opportunity from your perspective, or is that just kind of an incremental tool for physicians at this point?
I think it's going to be a foundational tool, right? The data that we're seeing with the anti-obesity treatments, whether it's single G, double G, triple G, are going to be foundational and a core to the treatment of cardio-kidney metabolic, the CKM disease condition, but they're not the silver bullet, right? What we've seen to date is about a 5MM mercury reduction in blood pressure, mostly across anti-obesity treatments, and frankly, historically, to bariatric, to diet, and exercise. There's certainly some that respond more than that, some that respond less than that. I don't know that it meaningfully cuts into the opportunity for lorundrostat. We've looked at our data and looked very deeply at response relative to BMI, because there's clearly a link, we think, between visceral adiposity and aldosterone and uncontrolled or resistant hypertension.
And frankly, independent of BMI, you're seeing really robust, clinically meaningful reductions with lorundrostat. I don't think one eliminates the need for the other. I could actually see them coexisting well as part of a broader CKM treatment paradigm. And we've had some of our KOLs opine that that's where they see this going, that you're going to need to target obesity with whatever treatment you want, but you also have to really focus on aldosterone as well.
Got it. When we look at just sort of the data itself and the sort of value add of the ASIs, let's obviously focus on lorundrostat-
Right
and the value add that it offers. Just walk us through the data, and really, I think that kind of brings us to the label. What do you hope to see in the label for lorundrostat, and what are the opportunities for differentiation?
Yeah. It's interesting. Three, four years ago, in a dialogue with the agency, Eliza Thompson kind of positioned the label as it's a tool to inform prescribers in how to use the drug, fundamentally. If you think about hypertension in the hands or being treated by a primary care doctor, by a nephrologist, by a cardiologist, they're not just thinking about hypertension, right? There's comorbidities, and I think that's what informed our clinical development program going back four years ago. It's why we did two really distinct pivotal studies, Launch-HTN and Real World. Come as you are with whatever drugs you're on, add lorundrostat, and see the benefit you get. We know we saw a 19 MM absolute, 11.7 MM placebo adjusted in that real-world population. Primary care, that's who they're treating. Cardiologists, on the other hand, tend to really maximize the background treatments.
They follow AHA guidelines as far as treatments they pick. They're going with, for the most part, maximal dose, and so we did that study with the Cleveland Clinic where we took patients off the background meds, maximized an AHA background treatment, followed them for three weeks, and only randomized those that could not get to goal, so truly confirmed. That becomes a really distinct dataset for cardiologists. Then we did our Explore program, CKD, OSA, because again, we're seeing comorbidities of either CKD and/or OSA and/or obesity. The latter study, Explore-OSA, was not part of the label submission, but Explore-CKD was. Each of these three distinct studies, I think, are very informative to the constituents that treat uncontrolled and resistant hypertension. It's what we put into our data package. It's what we put into our label.
It'll be part of the dialogues with the agency as far as which pieces of each of the studies make it into the label. As I look at just kind of a base case assumption, Launch-HTN, I think, is the largest study with an ASI in uncontrolled and resistant hypertension. It shows really meaningful blood pressure reduction, shows a very clear safety profile, and that as a base case in the label, I think, is a strong hand for us to make argumentation for the use of lorundrostat, third line or later, broadly, and a competitive profile relative to baxdrostat specifically.
Got it. When you look at some of the side effects or potential safety issues that can be of concern, what are some of the factors that you think will weigh favorably for lorundrostat in particular, relative to whether it be MRAs or directly versus baxdrostat?
Yeah, I think where we're fortunate is the main adverse events of interest are mechanistically driven, are aligned to what physicians are used to looking for with ACE inhibitors and ARBs and MRAs, and that is the electrolyte changes, so the elevation of potassium, the depletion of sodium, changes in eGFR, and hypotension. Those are the four main ones to look for. I think what we've seen with lorundrostat, given its selectivity, its ideal, what we think is ideal half-life of 10 to 12 hours, you're not compromising efficacy to have really pretty modest changes on electrolytes. The nice thing is, and I've conveyed this to people before, the profile of lorundrostat fits a workflow that physicians have been accustomed to for 40 years, and that was attuned by ACE inhibitors and ARBs.
In other words, you initiate this drug, within two to four weeks, you're going to see the bulk of your blood pressure response. You're going to see changes in electrolytes. You're going to see changes in eGFR. You're going to see symptoms of hypotension. You're going to see those pretty rapidly, and then they stabilize.
We even showed that at AHA this past week and with our open-label Transform-HTN data through 48 weeks. eGFR, Aldo, renin, sodium, potassium, everything stays stable within that first two-week kind of temporal frame. So it fits the workflow for physicians. It's a very modest change. Given our half-life, if you have a patient that does have an extreme response with that on-target effect, you can either reduce dose or just back off and then evaluate, do you do a re-challenge?
Got it. Let's talk a little bit more about the commercialization of the product. What are the choices that you see in market today that AstraZeneca has made to kind of promote Baxfendy? How are you going to kind of approach the market?
Yeah, I think from outside looking in, AstraZeneca in support of Baxfendy is following a path that we are. I think they've looked at the high-volume prescribers, third line or later, and are directing efforts against them. We've identified in the past about 45,000 doctors, plus or minus, that control 40%-50% of the prescribing in that latter line case. What I think has been interesting with the baxdrostat launch data that we've gotten, the prescription-level data, prior to their launch, it was largely primary care, about 60%, 40% cardiology. What we're seeing in the actual scripts is about 55% primary care, about 20%-25% cardiology, and the nephrologists are showing up about 20%, which is a bigger penetration than you would see typically in broad third or fourth line use.
I actually think that's a good thing, a good foretelling sign for us, because I think we've got a really robust dataset and argumentation for nephrologists to use lorundrostat in hypertension overlapping with CKD. So that's part of how we're thinking about making sure we're directing effectively to that nephrology segment as well. But I think that narrow focus on those high-volume prescribers was how we thought about the plan, it's how we continue to think about the plan. It seems to be what's resonating in the early days of what we think is a very strong launch for baxdrostat.
Great. In terms of just there was one kind of important development, I think, that may help you and the team, which is the importance of Medicare.
Can you talk a little bit about the importance of Medicare? I think AstraZeneca talked about not really making the timeline for Medicare formulary inclusion. Is that something that is an opportunity to actually balance out, almost launch availability timelines for lorundrostat and baxdrostat?
Yeah. I got early questions that since AZ missed the bid cycle with baxdrostat, presuming we get approved end of the year, we will miss the bid cycle. Does that mean that for us, 2027 is a wash for Medicare? My answer to that is no. Yes, there are bid cycles, and so from our planning standpoint, 2028 is probably when we would be on full formulary. Medicare has its own flexibility. It could choose to include drugs in formulary at any time, so it could come sooner, but the bid cycle, kind of within a standard rollout, would mean 2028 full formulary. There is clearly an exception pathway to get patients who have Medicare as their insurance, get them access to ASIs. In fact, we are seeing within the current baxdrostat prescription data, about a quarter of all those patients are Medicare.
Even though you are not on formulary, it does not mean that you cannot get access to it. There are a few more hoops you have to walk through, but that is why part of our commercial build includes a PSP and a hub to make sure that we have got staff that are knowledgeable of that space, of that process, that can work with physicians, their office staff, as well as patients, and get them access if a doctor and the patient decide lorundrostat is something they want to pursue.
Okay. Historically, the thought process around launching a drug into a very broad primary care market is that it is spend of $300 million, like right out of the gates, you should just be prepared for it. Hopefully, you can have a great launch. How do we think about that in the context of today's market? There has obviously been a lot of evolution relative to kind of launch spend and expectations.
Yeah.
Without giving guidance for 2027.
Yeah. If you want to, go for it.
Nope, nope. Thanks for the caveat.
Yeah, a couple of things. I come back to hypertension is large, and if you looked at and counted every number of every doc that ever wrote a prescription, it's a big universe. It's also very narrow when you think about how we've positioned this drug, third line or later, when you think about where's the high volume prescribing population, about those 45,000. That suddenly narrows the feet on the street that you need. I've also made the point that launching in 2027 as a small biotech is easier than it would have been 20 years ago, and it's because of all the little devices we have in our pocket and the technology and things like Doximity and OpenEvidence and Facebook.
These are really efficient ways for a small biotech to tap into and build awareness, enthusiasm, and excitement about a molecule beyond just the feet on the street. It's not 20 years ago, it was an army of sales reps to really disseminate information. I think the combination of efficiency of promotional tools that we have available now, coupled with the narrow pool that really drives a big percentage of these latter line treatments, benefits us. Couple that, frankly, with the profile that lorundrostat has. We've talked in the past, if you do a meta-analysis, we're adding the third line agent to a patient that's not a goal, you incrementally get about 5MM of mercury reduction.
Yeah.
We are seeing 19. I mean, these are not just incremental introductions that we are talking about. These are foundational. They are the kind of numbers that get, like we saw on our open-label extension, 56% of the patients to goal who had not been a goal. I think having a narrow target audience, having really efficient, broad dissemination tools that are ready, and having the kind of molecule we have, I think it gives us a nice setup going into a launch in 2027.
There are big differences in individual patient populations. African American patients, Black patients typically can suffer from resistant hypertension. You also have a massive number of patients out there. How has lorundrostat performed in the different patient populations? Is there much differentiation?
Yeah. Early days, we actually, and I am going back to proof of concept. We tried to use renin as a target to identify responders. This drug worked whether you had low, normal, or high renin. We thought there was a signal in obesity. We looked at response relative to BMI. Drug worked great, low, medium, or high BMI. Did a forest plot with Launch-HTN, the largest study in an ASI that we did with lorundrostat. Male, female, race, like you said, whether white or Black African American, Latino, BMI, this drug consistently is left-shifted, no matter how you look at it. For a company that was trying to find the target, the tell was like, "Okay, now what do we do?" It is a really good scenario to have, and physicians see that, and they are really amazed.
Now, that said, there will be, within that third and certainly fourth line, some really specific ones we are going to hone in on. We went to great intent to ensure we had diversity in our study populations. Advance-HTN was 53% Black African American. Launch-HTN was 28%. If you look at some of the prescribing patterns right now, even with baxdrostat, it is very regionalized. We know that rates of uncontrolled and resistant hypertension are overrepresented in the Southeast and the old Rust Belt, if we can still call it that. There is a significant proportion of Black African American patients there. We know they are disproportionately affected by uncontrolled and resistant hypertension. To have that data and go out and speak explicitly to those prescribers is a real benefit for us.
But again, broadly, I think our data just highlights aldosterone is the key that currently is not being properly addressed with any therapeutic out there. Spironolactone is the only one that is out there, and nobody wants to use it.
Got it. Let's talk a little bit about CKD, additional studies that could be conducted. Obviously, AstraZeneca has massive outcomes programs out there. What is the necessity, in your view, of the outcomes programs for lorundrostat versus small additional studies that are supportive or directionally supportive?
Yeah. Outcomes are really interesting. A couple of points on that. One, we will have an outcomes claim at approval. So in 2012, the FDA came out and said, "Any drug that lowers BP will get a statement in their indication that says, 'The reduction of blood pressure is linked to reduced risk of stroke, MI, and cardiovascular events.'" So, that piece is out there. As we go out and do market research physicians, we just ask the question, "How important are outcome studies relative to the fact that we are lowering BP?" It is a rare minority that say, "Well, I would like to see it." Then we ask the question, "Well, do you not believe BP lowers outcome?" It is like, "Well, yeah, I believe that.
I still want to see it." So, there is going to be some value to having the outcomes data, but I think the evidence is pretty irrefutable. Even this weekend at AHA, they looked at 140 versus 120 as a goal, and those at 120, there is about a 20%-27% reduction in risk of CV and stroke outcomes. So, I mean, the data just continues to pound. They get the blood pressure down, you are going to see that benefit. So I do not know that, just to set expectations, you are going to see us come out with a 5,000 or 10,000 patient outcome trial.
But to your point, I think we've done it to date and acknowledged that it's not just hypertension, but there are comorbidities, and adding data around the edges of that to really help us solidify the profile in hypertension is what we're going to continue to do. We did it in OSA. We did it in CKD. We may go deeper in some of those. We may look at some other indications. That's part of what I've got the team really digging into in talking with advisors and looking at the profile of lorundrostat, where do we continue to bolster that profile that we think can be best in class?
Yeah. What would you say, from your perspective, the most underappreciated opportunity for the ASI category and the most underappreciated opportunity for lorundrostat and obviously, by extension, Mineralys?
And by extension what?
Mineralys.
I think just fundamentally tapping into those 20 million patients. It is such a huge market opportunity. It has such a massive impact. We have a saying within the company, my team will shoot me for saying this, but create more better days. I think that's what fundamentally we have an opportunity to do. The linkage of controlling blood pressure and reducing risk of outcome, reducing risk of dialysis, stroke, heart failure, all the implications of that, I think that is, at a purpose humanistic level, what's core for us. That translates significantly into how do we penetrate deeper into those 20 million patients that are not a goal? Yes, we want to look at other indications, but just the job at hand right in front of us is a huge value driver. I think it's underappreciated for this class.
I do think this, and I'll pull baxdrostat into this, I think the ASIs are the right drug at the right time for what is driving a lot of poor outcomes for cardiorenal metabolic patients. By extension, that opportunity for ASI translates for lorundrostat because I think we've got just a fabulous data set to inform prescribers. Then the success we have with lorundrostat as Mineralys just enables us to continue to grow as an organization, look at how we continue to expand the data around lorundrostat, but also look at are there other opportunities for us to bring in and maximize value.
Got it. Just in terms of the cash runway for the company, maybe just help us think about kind of the long-term sort of strategic, how you think about strategic options long-term for Mineralys.
Yeah. We had our earnings call last Wednesday into Q3. We noted we have $625 million in cash. That gets us into 2028, obviously including the launch of the product. We also did a debt facility deal with Pharmakon this past summer for $500 million, pulled $100 million at the time of closing. We have $150 million upon approval, then that leaves $250 million in two different tranches that are somewhat at our discretion and driven by sales achievement. All of that collectively, we feel comfortable supports the launch commercial plan for lorundrostat. Strategically, where do we go? I kind of alluded to it earlier as far as growing lorundrostat by extension grows Mineralys. We're looking at opportunities to drive value within that. We've always talked about partnering will be a part of our story.
We're not going to launch this drug outside of the U.S. on our own. There are complexities with that given MFN, but our goal has always been how do we get lorundrostat to as many people as appropriately as we can without risking, at this point in time, the U.S. marketplace. Strategically, that's going to be an important factor within that, just looking to continue to drive value within all those different levers we have at hand.
Great. Well, definitely exciting times. Going to have several busy months and an extremely busy 2027 ahead. So, exciting times. Jon, thanks so much for joining us here again this year.
You bet. Great to be here, and we'll all have a Merry Christmas.