Hi, everyone. Good afternoon. It's our pleasure to host Mineralys this afternoon with CFO Adam Levy. Mineralys has clearly had a very successful clinical outcome to its pivotal program for lorundrostat in hyperaldosteronism-driven, uncontrolled and resistant hypertension. Now we're approaching the 12-month data, and shortly after filing and preparation, shortly we'll have the filing, and then we'll have preparations for commercial launch. So, Adam, maybe...
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Can someone mute their line, please? Clearly had a very successful clinical outcome to its pivotal program for—sorry, I've got a weird echo. Anyway, we are approaching commercial launch, and Adam, maybe you can go into an overview very quickly of the lorundrostat profile, and I'll then open up for Q&A, and we can talk a little bit more about the commercial aspects here.
Yeah, absolutely. Thanks, Annabel, and I hope the echo's gone. We've been developing an aldosterone synthase inhibitor. We have pivotal data now, and we're moving towards an FDA filing. The lorundrostat's initial indication is in hypertension. We're interested in comorbidities. We've run a trial in chronic kidney disease, with hypertension, and we just announced this morning that we've completed enrollment in a trial for subjects with obstructive sleep apnea and hypertension, and that trial's expected to read out in the first quarter of next year.
Excellent. Let's start speaking about lorundrostat and its activities. It works broadly across populations, whether it be female, obese, or just overweight, age, race. The data at the most recent medical conference detailed numerically how the responses were. I guess, were you all surprised by that given that this is so aldosterone-specific? What how does that help you as far as how you target the market?
We've known for some time that about 30% of all hypertension patients have some form of elevated or dysregulated aldosterone. The data we're seeing now really confirms the prevalence of aldosterone in patients with uncontrolled or resistant hypertension, and maybe more importantly, the magnitude of the reduction that we've seen with lorundrostat relative to other third or fourth-line treatments, whether they're existing or new treatments, really confirms that targeting aldosterone is critical to how patients achieve their blood pressure goal.
Got it. When you think about how you're going to approach the market, are you just going to go straight to broad access, third, fourth line? I guess maybe you want to frame how you approach the market, though.
Our aspiration really is to start with fourth-line. We've run our trials with subjects with third- and fourth-line subjects, and we've seen great responses in both people who failed to achieve their goal with two backgrounds or with three or more backgrounds. The initial thought is to go into fourth-line, and then over time expand into third-line.
Okay. Got it. Are you going to need, I guess, guideline changes to be able to target fourth-line very readily? Do you think that's going to be you driving the effort, or are the guideline changes evolving in parallel to the regulatory review as well as, like, ready commercial preparations?
If you look at guidelines versus what the standard of treatment is, people follow guidelines in the initial line. First line would be typically an ACE or an ARB, second line a diuretic, third line likely calcium channel blocker, and when you get to fourth line, it's been a real mixture of what people tend to use. To say you would need a change in guidelines to be successful, I think that would be an overstatement, but certainly it'll be helpful, and we're working very closely with key opinion leaders on guideline inclusion for lorundrostat. The Advance-HTN data set we believe will be really helpful because of how rigorous it was. We took all the subjects off their background meds and put them on standardized, optimized guideline-directed treatment, and we measured compliance.
That trial should be very helpful because it really confirmed uncontrolled or resistant population, and we think that getting included as a fourth-line agent in guidelines will be very achievable, and then possibly in third line as an alternative. When you think about what the guidelines will be, our expectation is it would be around use of an aldosterone synthase inhibitor or use of the class versus just talking about lorundrostat, but it's too early to tell exactly what it'll look like.
Okay. Is there any argument to bring it earlier into third-line, given that you'd looked at patients who were, you know, on top of two treatments?
Certainly, we saw substantial benefit for the participants in the trial on the background of two therapies. Certainly, third line, we believe the trial supports strong evidence that it could be helpful for patients. Over time, we think that it will migrate to third line, but for now we feel very comfortable looking at it as fourth line. If you look at the patient populations, there's about 10 million potential patients with resistant hypertension that could be a target for lorundrostat, and then probably another 10 million in third line.
Okay. Got it. Sorry, say that again?
I was going to point out that that's in the U.S.
Okay. Got it. I guess the next data point we'll see on lorundrostat will be the 12-month safety and presumably some more efficacy. What do you expect here? Are you going to provide any further efficacy maintenance data, or do you expect any additional incidences of hyperkalemia, or is that something that just occurs early on? Like, what kind of data set do we see here?
Yeah. We don't anticipate additional, you know, the hyperkalemia or stuff over time. We think that the effect often occurs early and stabilizes. We are excited about the data we're capturing, though, and we plan to share that data with the FDA in the NDA submission, and then also publish it and get it out in scientific conferences over time. We also, as I mentioned, anticipate having the EXPLORE OSA trial data as well in the first quarter. There's a lot of additional data and analyses that are coming.
Okay. Is that all going to be part of the package, including some color on OSA, or is OSA a completely different indication that you're looking at?
For the initial NDA filing, we probably won't have the OSA data included, but we'll definitely be sharing it with the FDA. It's a distinct indication in the sense that we're including OSA, but OSA and hypertension have strong overlap, and these subjects are people with OSA and hypertension as comorbidities in the trial.
Okay. Got it. I guess maybe we can talk about the most recent piece of information, which was the phase III data on Baxdrostat. I mean, competitively, the data numerically favored lorundrostat, but for all intent and purpose, they're pretty comparable. Why do you think the outsized reaction here? I mean, I have my theories, that it was just complete fear factor that there would be something that's more competitive, from you, but maybe we can hear your take on how Mineralys viewed that data, you know, some of the feedback that you received from the medical community, and now how you approach the market, given the profiles that you both have.
Regarding the stock price reaction, I think it's pretty justified based on the value proposition for lorundrostat. I wouldn't describe it as an outsized reaction. I think that there were investors who may have been on the sidelines waiting to see what the competitive landscape looks like, and the question got answered at ESC with Baxdrostat showing a 15.7 ml absolute change or 9.8 ml placebo versus 19.1/11.6 for lorundrostat. I would say the Baxdrostat data was good. It supports the class. I think that you're seeing a real understanding of what aldosterone is doing driving this disease, and if we take a look at together the data that you saw for lorundrostat and Baxdrostat, it's very differentiated versus what you've seen with other methodologies that are either existing or new. I think it's a real positive for the class.
As far as positioning of lorundrostat, we feel really good about what lorundrostat was able to demonstrate in the trials we had, and we think that it'll be a huge benefit for patients if it's approved and available.
Maybe I used the wrong word saying outsized. I would just say it was a very exciting reaction, let's just say, as opposed to an outsized, wrong descriptor. I apologize for that, but yes, it was indicative of about the number of people who are waiting on the sidelines to see what the competitive landscape, sort of how it's shaped up to be. I guess one of the questions, and maybe this is getting into the weeds a little bit, but there was, they've often, if you can say counter-detailing at this point, again, I might be using the wrong word, but they did tout the benefit of a longer half-life, and that didn't seem to help them much. In fact, maybe it gave them just an edge more hyperkalemia. It's clear that specificity, your specificity is good.
What can we make of the components of counter-detailing that may be thrown your way? Do you think that there's anything more that they can say about this, or do you think that they're going to now back off from arguments about we have a better profile, we have a longer half-life, maybe we have better coverage, et cetera? How should we think about the counter-detailing in the marketplace?
It's hard for me to predict what another company will say, but I can talk about what we've seen with lorundrostat. We've had four successful clinical trials where we measured blood pressure 24 hours after the dose, right before the next dose. What we're measuring is the 24-hour control, and like we saw in LAUNCH HTN, placebo-adjusted 11.6 compared to 9.8 for Baxdrostat. We feel like lorundrostat stacks up really well, and the question's really been asked and answered on 24-hour control. Some of the other things that we've heard or seen, I mean, there's, you know, I don't, I think the data really speaks for itself.
Yeah. Okay. The one thing that Baxdrostat has over you is the deep pockets of AstraZeneca. You know, obviously they have infrastructure, they're in the CKD space, they have access to a population that is most likely to have hypertension. How do you compete in this space? Are you seeking a partnership at this point? You know, have you had incoming conversations or incoming inquiries about this now that all the cards are sort of turned over for this conversation? How has that activity sort of picked up?
Yeah, I think we've been pretty open about talking about our discussions and thoughts around partnering, and we really think that, you know, this is not something ex-U.S. that Mineralys would do on our own, and then in the U.S. as well, we've been very interested in the opportunity to partner and do something that maximizes the opportunity for lorundrostat to get paid to patients and optimizes the value for shareholders. We continue to have those conversations. There's, we think, a pent-up demand for novel treatments in hypertension and cardiovascular conditions in general from potential partners, and we, you know, this is a large population of patients who suffer from uncontrolled or resistant hypertension, but the base of third-line and later subscribers or prescribers is relatively focused. About 60,000 physicians make up the top five deciles of prescribers.
It is a manageable sort of commercial organization that you would need to get in front of these physicians, but I think that it would be, you know, something that we could do better with a partner, and we fully, you know, embrace that.
Got it. I mean, I will argue that there have been several successful launches by small companies, and these were possibly in markets that didn't have other options or other players. What would it take for you to launch this independently? I imagine that you have thought about this, and given that you have a concentrated number of physicians who target that third, who prescribe in the third, fourth line. If you had to think about an independent launch of this and marketing of this, what kind of infrastructure are we talking about here?
Yeah. I don't want to get into sort of number of reps necessarily, but if you think about doing the math on, say, if you were targeting those 60,000 physicians that I mentioned, it's a manageable field force of reps, and the footprint that we would need to effectively move forward with the results we've seen is not out of the question, although we still think that working with a partner would make a lot of sense. We recently did a survey, with the AZ data and ours on a no-name basis, and two-thirds of the physicians that we surveyed said that they would prefer lorundrostat over Baxdrostat.
I think we're coming in with a nice profile, and there certainly is an opportunity, and if you think about the valuation of where we are versus the opportunity with the 10,000 - 20,000 target patients that you could get access to, I think the opportunity is substantial.
Yeah. Great. Okay. I did want to touch on the other indications, CKD and OSA, obviously. These are being developed not necessarily for an actual label in CKD or in sleep apnea, but more, I guess maybe I'm coloring this incorrectly, but more as painting a more holistic picture of who the potential populations can be. For example, CKD, you want data there to establish a guideline for physicians who have a hypertensive patient with CKD, but not necessarily for the CKD patient, or not necessarily for a sleep specialist to treat hypertension, but for a hypertensive patient, a cardiologist who's treating a hypertensive patient who has OSA to know that they can treat that patient safely. How should we be thinking about these additional indications? I know we touched on it earlier, but maybe how far are you going to take it through development?
There is a lot of overlap, as you mentioned, between OSA, CKD, and hypertension. When we did the CKD trial, we wanted to have an opportunity to evaluate lorundrostat in subjects who had lower kidney function. We went down to an eGFR of 30 in that trial. When we are able to launch lorundrostat, then we'll be able to talk about the impact that we've had on those subjects that had the lower eGFR. That's not to say that we're going to run a standalone CKD trial on our own. It would be large, time-consuming, expensive, but we think that we've been able to address an opportunity in that group of subjects with lower kidney function by doing the trial that we did and then bringing that to the FDA and potentially into the label.
With OSA, we are running our phase II trial now, and I think it really depends on what the results are, how we would move forward. Sleep apnea is something that's really common in hypertension patients. It is an area of real interest for us, and I think we'll have to see where we come out on that phase II before we talk about what the next steps are. When we think about the launch for lorundrostat, the initial population is resistant hypertension, and moving out and expanding from there would be our aspiration.
Okay. Any other logical areas that you can investigate with hypertension that we should think about, and how you can sort of develop this product?
Heart failure is of real interest with aldosterone synthase inhibitors, and some of the markers and data that we're going to get from the EXPLORE OSA trial may inform future work in that area.
Got it. Okay. One last question, as we're kind of running out of time. Obviously, while we are in a conference that's the topic is comorbidities relating to obesity, and one of the overriding comments that we've had from KOLs is that they're really able to see meaningful reductions in blood pressure with only 5% weight loss. How do you think about the opportunity? I know there's like tens of millions of hypertensive patients, but how do you think about your opportunity as we see greater use of GLP-1s, incretins, weight loss that obviously many people can get to 5% weight loss, and what that target population can be if you run any kind of numbers to see how that might impact the overall TAM for your product?
The data on blood pressure reduction and weight loss has been known for decades. Diet and exercise, bariatric surgery, other means like that will get your blood pressure down to some extent. GLP-1 usage has provided reductions in blood pressure for the high weight loss responders. Maybe it'll be sufficient. There's a significant portion that will need further assistance to achieve their desired weight and to ensure the CV risk reduction. With this high prevalence of elevated aldosterone in hypertensive patients that you see, it's about 30% across hypertension. We think there's still a significant opportunity for an ASI like lorundrostat.
Okay. Great. We are out of time, so we're going to leave it at that. Thank you for taking the time today, and I'm glad to have you, and it's going to be an exciting next six to 12 months for sure.
For sure. Thanks, Annabel. Appreciate it.
All right. Take care.