Mineralys Therapeutics Q2 2024 Earnings Report

Mineralys Therapeutics EPS Results

• Actual EPS: -$0.83
• Consensus EPS: -$0.73
• Beat/Miss: Missed by -$0.10
• One Year Ago EPS: -$0.31

Mineralys Therapeutics Revenue Results

• Actual Revenue: N/A
• Expected Revenue: N/A
• Beat/Miss: N/A
• YoY Revenue Growth: N/A

Mineralys Therapeutics Announcement Details

• Quarter: Q2 2024
• Date: 8/13/2024
• Time: After Market Closes
• Conference Call Date: Tuesday, August 13, 2024
• Conference Call Time: 4:30PM ET

Mineralys Therapeutics (NASDAQ:MLYS), a clinical-stage biopharmaceutical company that develops therapies for the treatment of hypertension and chronic kidney diseases. It clinical-stage product candidate is lorundrostat, a proprietary, orally administered, highly selective aldosterone synthase inhibitor for the treatment of cardiorenal conditions affected by abnormally elevated aldosterone. The company was formerly known as Catalys SC1, Inc. and changed its name to Mineralys Therapeutics, Inc. in May 2020. The company was incorporated in 2019 and is headquartered in Radnor, Pennsylvania.

Mineralys Therapeutics Q2 2024 Earnings Call Transcript

Key Takeaways

• Enrollment is ~90% complete in the pivotal ADVANCE HTN trial, with top-line data now expected in Q1 2025 after FDA alignment on the original 12-week primary endpoint.
• Enrollment in the Phase 3 LAUNCH HTN trial is ahead of schedule, with top-line results anticipated in the second half of 2025 and potential for an accelerated readout.
• The company ended Q2 with $311.1 million in cash, cash equivalents and investments, sufficient to fund planned clinical programs and operations into 2026.
• Net loss widened to $41 million in Q2 2024 from $12.1 million a year earlier, driven by increased R&D spending on pivotal trials and manufacturing activities.
• Enrollment is ramping up in the EXPLORER CKD Phase 2 trial, with top-line data expected in the first half of 2025 to support potential CKD indications.

Presentation

[Operator]

Welcome to the Mineralys Therapeutics second quarter 2024 conference call. At this time, all participants are in a listen-only mode. A question and answer session will follow the presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Dan Ferry of LifeSci Advisors. Please go ahead, sir.

[Dan Ferry, LifeSci Advisors]

Thank you, operator. Good afternoon, everyone, and welcome to our second quarter 2024 conference call. After the close of market trading today, we issued a press release providing our second quarter 2024 financial results and business updates. A replay of today's call will be available on the investors section of our website approximately 1 hour after its completion. After our prepared remarks, we will open up the call for Q&A. Before we begin, I would like to remind everyone that this conference call and webcast will contain forward-looking statements about the company. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified by the cautionary statements contained in today's press release and our SEC filings, including our annual report on Form 10-K and subsequent filings.

[Dan Ferry, LifeSci Advisors]

Please note that these forward-looking statements reflect our opinions only as of today, August thirteenth. Except as required by law, we specifically disclaim any obligation to update or revise these forward-looking statements in light of new information or future events. I would now like to turn the call over to Jon Congleton, Chief Executive Officer of Mineralys Therapeutics. Jon?

[Jon Congleton, CEO at Mineralys Therapeutics]

Thank you, Dan. Good afternoon, everyone, and welcome to our second quarter 2024 financial results and corporate update conference call. I'm joined today by Adam Levy, our Chief Financial Officer, and Dr. David Rodman, our Chief Medical Officer. I'll begin with an overview of the business, our clinical programs, and recent milestones, followed by Adam, who will review our second quarter financial results before we open up the call for your questions. Let me start out by saying that during the first half of the year, we made tremendous progress advancing the development program for our lead asset, lorundrostat.

[Jon Congleton, CEO at Mineralys Therapeutics]

Specifically, we've been steadily moving towards several key milestones for our registration program in hypertension, which is comprised of two pivotal clinical trials titled ADVANCE-HTN and LAUNCH-HTN, an open label extension trial called TRANSFORM-HTN to capture long-term safety and efficacy data, and the proof of concept trial EXPLORER-CKD, evaluating lorundrostat in hypertensive CKD subjects. Enrollment continues to progress in the ADVANCE-HTN trial. As noted previously, this is an extremely rigorous hypertension trial designed to demonstrate the value of lorundrostat when added to standardized, optimized American Heart Association guideline treatment. While we typically do not provide enrollment updates for our clinical trials, we are approximately 90% enrolled in ADVANCE-HTN, and our projections place top-line data readout in the first quarter of 2025. While we're disappointed with the change in top-line data timing, we remain laser-focused on executing the best-in-class trial and ensuring a high-quality data readout.

[Jon Congleton, CEO at Mineralys Therapeutics]

We continue to work with our partners at the Cleveland Clinic to ensure we deliver the most robust data set possible. In addition, we recently met with the FDA and aligned on maintaining the original primary endpoint of the ADVANCE-HTN trial, given that we have already accumulated or accrued substantial trial data. As such, we will maintain the original 12-week time point of change in 24-hour ambulatory systolic blood pressure from baseline for active cohorts versus placebo. We will still collect and analyze all relevant efficacy measures at the 4-week and 12-week time points. This does not impact the timing of the data readout for ADVANCE-HTN. The planned analysis of ADVANCE-HTN trial includes several important subset analysis. Subjects with uncontrolled hypertension, those on baseline regimen of 2 antihypertensives, and resistant hypertension on 3 baseline antihypertensive treatments were separately randomized, allowing us to perform a formal test in each population.

[Jon Congleton, CEO at Mineralys Therapeutics]

This will provide optionality and independent support for each population. We believe that demonstrating efficacy in confirmed resistant hypertension, the area of highest unmet medical need, will be important in positioning lorundrostat for individuals with presumed aldosterone-mediated hypertension, including obesity. We believe positioning lorundrostat as an important option for obese individuals with increased cardiovascular risk due to resistant hypertension will be a straightforward message to prescribers, payers, and patients. In addition, as we accrue more experience and data with lorundrostat, we plan to continue to explore other positive and negative predictive factors using artificial intelligence to expand the precision toolkit for targeting lorundrostat to individuals with uncontrolled and resistant hypertension who are likely to derive long-term clinical benefit. Moving to LAUNCH-HTN, which is our second pivotal trial that was initiated in the fourth quarter of 2023.

[Jon Congleton, CEO at Mineralys Therapeutics]

We are pleased to announce that enrollment in this trial is currently ahead of schedule, and we continue to expect top-line data to be available in the second half of 2025. However, the time to data may accelerate, and we will keep you informed as we move forward. LAUNCH-HTN is a Phase III trial of lorundrostat for the treatment of subjects with uncontrolled or resistant hypertension as add-on therapy, who failed to achieve blood pressure control on their existing prescribed background treatment of 2-5 antihypertensive medications. LAUNCH-HTN will enroll up to approximately 1,000 adult subjects, is designed with the objective of evaluating lorundrostat in a real-world setting when added to a subject's previously prescribed antihypertensive regimen.

[Jon Congleton, CEO at Mineralys Therapeutics]

Subjects who fail to achieve blood pressure control on their prescribed background treatment during the run-in period will be randomized 1 to 2 to 1 to either placebo, once daily 50 milligrams of lorundrostat, or once daily 50 milligrams of lorundrostat, with the option to titrate to 100 milligrams once daily as needed at week 6. The primary endpoint for this trial will be the change in systolic blood pressure, as measured by automated office blood pressure. We believe this endpoint reflects real-world measurements that will be relevant to the primary care provider this trial targets. Subjects from these two trials will be offered the opportunity to roll over into the ongoing open label extension trial called TRANSFORM-HTN.

[Jon Congleton, CEO at Mineralys Therapeutics]

In addition to our pivotal program in hypertension, we are conducting the EXPLORER-CKD Phase II clinical trial for lorundrostat when added to background treatment with SGLT2 inhibitor in patients with uncontrolled or resistant hypertension and Stage 2 to 3b chronic kidney disease. The amended protocol has been implemented and enrollment is ramping up. We anticipate announcing top-line data in the first half of 2025. EXPLORER-CKD is a within-subject comparison trial designed to demonstrate the benefit of lorundrostat in reducing blood pressure and provide supportive evidence for potential benefit on chronic kidney disease on the background of stable SGLT2 inhibitor treatment. This proof of concept trial will enroll approximately 60 subjects with hypertension in Stage 2 to 3b CKD. We look forward to keeping you apprised of the status of the lorundrostat development program over the coming weeks and months.

[Jon Congleton, CEO at Mineralys Therapeutics]

Let me now turn the call over to Adam, who will provide a financial review for the second quarter of 2024.

[Adam Levy, CFO at Mineralys Therapeutics]

Thank you, Jon. Good afternoon, everyone. Today, I will discuss select portions of our second quarter 2024 financial results. Additional details can be found in our Form 10-Q, which was filed with the SEC today. We ended the quarter with cash, cash equivalents, and investments of $311.1 million, compared to $239 million as of December 31, 2023. We believe that our cash, cash equivalents, and investments will be sufficient to allow us to fund our planned clinical trials, as well as support corporate operations into 2026. R&D expenses for the quarter ended June 30, 2024, were $39.3 million, compared to $11.9 million for the same quarter of 2023.

[Adam Levy, CFO at Mineralys Therapeutics]

The increase in R&D expenses was primarily due to increases of $22.8 million in preclinical and clinical costs, driven by the initiation of the lorundrostat pivotal program in the second quarter of 2023, and the EXPLORER CKD trial in the fourth quarter of 2023. $2.6 million in clinical supply, manufacturing, and regulatory costs, $1.7 million in higher compensation expenses resulting from additions to headcount, increases in salaries and accrued bonuses, and increase in stock-based compensation, and $0.3 million in other research and development expenses. G&A expenses were $5.9 million for the quarter ended June 30, 2024, compared to $3.9 million for the same quarter of the prior year.

[Adam Levy, CFO at Mineralys Therapeutics]

The increase in G&A expenses was primarily due to $1.5 million in higher compensation expenses resulting from additions to headcount, increases in salaries and accrued bonuses, and increased stock-based compensation, and $0.5 million in higher professional fees and other administrative expenses. Total other income was $4.2 million for the quarter ended June 30, 2024, compared to $3.6 million for the same quarter of 2023. The increase was primarily attributable to increases in interest earned on our investments in money market funds and US Treasuries. Net loss was $41 million for the quarter ended June 30, 2024, compared to $12.1 million for the same quarter of 2023. The increase was primarily attributable to the factors I described earlier. With that, I will ask the operator to open the call for questions.

[Adam Levy, CFO at Mineralys Therapeutics]

Operator?

[Operator]

Thank you. We will now conduct our question-and-answer session. To ask a question, press star one on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment please, while we pull for questions. Our first question comes from Michael DiFiore with Evercore ISI. Please state your question.

[Michael DiFiore, Evercore ISI]

Hi, guys. Thanks so much for taking my question. Two for me. Just want to get more clarity on why exactly the timelines were extended for ADVANCE-HTN and the CKD trial. And then separately, obviously, you know, the phase 2 ADVANCE-HTN primary endpoint is now back at 12 weeks. The FDA's rationale was just because you had so much accrued data? I wanna clarify that. And now that it's back at 12 weeks, are you concerned that now the waters will be muddied at 12 weeks with the inclusion of patients on 100 milligrams? Thank you.

[Jon Congleton, CEO at Mineralys Therapeutics]

Yeah, Mike. John, good to, good to chat. Glad to have the questions. The first one regarding the timing, when we originally established Q4, I think it was late last year, for guidance on ADVANCE-HTN, at that point in time, we were still earlier in the enrollment, particularly with the protocol amendment. As we've discussed before, the rigor and complexity of ADVANCE-HTN had made it difficult to really try to project when we thought we would see top-line data, as we've spent the last, you know, several months, 6, 7, 8 months since that guidance. And we've obviously gotten further along in the enrollment of the study. The ability to project the time for the top-line data has progressively become easier.

[Jon Congleton, CEO at Mineralys Therapeutics]

As we noted in the press release and in the, the earnings call here, we're at 90% enrolled at this point, so we have high confidence on where we're at currently with enrolled subjects, where we're forecasted to continue to enroll, that we'll have the top-line data in Q1 of 2025. Kind of a similar construct, Mike, with EXPLORER CKD. We announced earlier this year that we were doing a protocol amendment just based on the changing dynamics within the hypertension CKD space and the utilization of SGLT2 inhibitors. We put that protocol in place. It's had the intended effect as far as improving enrollment within that study.

[Jon Congleton, CEO at Mineralys Therapeutics]

As that protocol has gone into effect and we began to enroll subjects, it's been able to give us a clearer sense of timing, and that's why we adjusted the readout for EXPLORER CKD from Q4, Q1 to Q1, Q2. And so that's, that's really what's driven it, is just having more data, more experience with these trials, and to try to give a really clear sense of when we anticipate that top-line data. Before I turn it over to Dave to answer the ADVANCE HTN primary endpoint, any follow-up on that?

[Michael DiFiore, Evercore ISI]

Just, to clarify, too, you said that, you know, the protocol amendment you made now has boosted enrollment as intended. So why wouldn't it? Why was the timelines moved up if enrollment has been enhanced?

[Jon Congleton, CEO at Mineralys Therapeutics]

It's been enhanced relative to what it was, Mike. And we thought there was an opportunity to see that top-line data in Q4 to Q1. While it's been enhanced, it's from our perspective, it's prudent to change that guidance to Q1, Q2 at this point.

[Michael DiFiore, Evercore ISI]

Got it. Okay.

[Jon Congleton, CEO at Mineralys Therapeutics]

Yeah. Dave, do you wanna address Mike's question on the primary?

[David Rodman, CMO at Mineralys Therapeutics]

Hey, Mike, it's David Rodman, and thanks for the question. So the question, just to reiterate, and let me know if I've got it right, is, are we gonna encounter less, more confusion or less clarity, let's say, at 12 weeks because we have some people on 50 milligrams straight through and others who could have their dose increased to 100? Is that your question?

[Michael DiFiore, Evercore ISI]

That's correct. And also wanna clarify, if the FDA's rationale for keeping it at 12 weeks, which is purely because you had so much data already accumulated.

[David Rodman, CMO at Mineralys Therapeutics]

Got it. I'll answer the second one first. The answer to that is yes. It was just simply that we're past halfway enrollment. They just thought, you know, stay the course at that point. So in terms of your other question, it's a good question. We're gonna kind of have our cake and eat it, too, in a sense, because we are gonna do the full analysis at 4 weeks that we proposed, and we're gonna do the 12-week analysis. So we'll have the clarity of the analysis when everybody's on 50 milligrams at 4 weeks, but then the primary is gonna be done at 12 weeks. So the only difference is really when is that primary gonna be done? That's kind of just a p-value question, if you will.

[David Rodman, CMO at Mineralys Therapeutics]

We'll have the clarity at four weeks that'll allow us to have lots of power for subset analyses like obesity, et cetera. We won't really lose anything there, and we'll still have apples to apples between the two trials because of that as well. Did I answer your question?

[Michael DiFiore, Evercore ISI]

Yes, very much. Thanks so much.

[David Rodman, CMO at Mineralys Therapeutics]

Thanks, Mike.

[Operator]

Our next question comes from Richard Law with Goldman Sachs. Please state your question.

[Richard Law, Goldman Sachs]

Hey, guys. Thanks for taking my question. Just following up on that, what patients will be included in the 12-week endpoint analysis for ADVANCE HTN? So will the patients in that 50 to 100 mg cohort, would those be included in the 12-week primary analysis? And also, what is the powering on just that pure 50 mg group alone? And I have a couple more questions.

[David Rodman, CMO at Mineralys Therapeutics]

Good question. So the primary analysis at 12 weeks is a comparison between placebo and each of the active arms. They're, they're not co-primaries, where you have to hit both. They're just dual primaries. And so the way that works is, we'll take everybody who started on 50 and ended on 50, that started on 50 in that second arm, they'll all be essentially treated with 50 milligrams compared to placebo. And then the other arm, if they went up to 100, they're still included in the analysis. So it doesn't matter if they end on 50 or 100. There's a second, so and that's again, versus placebo. So that's for the p values. You'll see 2, 1 for arm 2, 1 for arm 3.

[David Rodman, CMO at Mineralys Therapeutics]

There's also a key thing here, which is what we wanna know is in arm three, the reason we're doing it is if you're a clinician and somebody doesn't respond to 50 milligrams, you think they belong on the drug, and everything else looks good, potassium, everything else. What you wanna know is, can I just double the drug safely and rescue that guy and get him the benefit I think he should accrue? That's, that's a within-subject question, right? You take a person who hasn't responded, give him the drug, and now you say, "Did he get better from that point?" So that's what's gonna happen at 12 weeks. Let me stop there and see if that was responsive to your question.

[Richard Law, Goldman Sachs]

Yeah. So, the patients who are on the 50 to 150 mg arm, so just that titration cohort, can you pull those 50 mg patients who did not get titrated to 100 mg? Can you pull them into the other, like the pure 50 mg cohort, or, or are these patients completely separate, like, separately analyzed by itself?

[David Rodman, CMO at Mineralys Therapeutics]

Yeah, it's a good question. So in terms of 12 weeks, no, you can't pool them. But in terms of the 4-week analysis, absolutely. And so, and we know from the Target-HTN trial that we saw the full benefit by 4 weeks. So we'll also be looking at 4 weeks and 12 weeks in the same people and ask the question, did they maintain the benefit within subjects? And so that'll also be answered. Now, I forgot to answer your powering question, and let me just repeat that. You said, what's our power gonna be for just the 50-milligram arm at 12 weeks? Is that what you were asking?

[Richard Law, Goldman Sachs]

Yeah.

[David Rodman, CMO at Mineralys Therapeutics]

Yeah. So our initial power calculations were designed to have 90% power for to do that. We were looking at, I think, something like maybe a 6 or 7, was it 7, mm Hg difference. So that's where our powering estimates were. You know, obviously at the end, we'll redo that based on a bunch of other things, and it's, you know, the statistics are obviously complicated, but that's the bottom line. 90% power, difference of 7 in each arm.

[Richard Law, Goldman Sachs]

I see. So is the data for that 50-100 mg cohort for the patient who did not get up titrated to a 100 mg, is there any use for that twelve-week data point for those patients?

[David Rodman, CMO at Mineralys Therapeutics]

Yeah, absolutely. So we can do a sensitivity analysis on that, and we will. We can do a pooling analysis, as you suggested. All of those are essentially sort of sensitivity analysis kind of questions. And so, you know, there probably won't be enough power. We could ask, do the people who finish on 50 differ from the people who increase to 100? But there's just so much you can do. But to answer your question, yes, there's gonna be use to them. Those things will be deep in the data, but they'll be available.

[Richard Law, Goldman Sachs]

I think, got it. And then the last set of questions from me is that, do you control or cap the number of patients coming into the study who previously been exposed to MRA or spironolactone? And if not, what proportion of these patients do you expect to be enrolled in the ADVANCE HTN study?

[David Rodman, CMO at Mineralys Therapeutics]

So they all have to wash out of any MRA or an ENaC blocker. On the other hand, they will have a medical history, so if we choose to do so, we could do a look back, but we're not gonna, they can't come in and just switch into the new regimen right off of the MRA. That has to be washed out.

[Richard Law, Goldman Sachs]

Okay, got it.

[David Rodman, CMO at Mineralys Therapeutics]

Great.

[Richard Law, Goldman Sachs]

Thank you.

[David Rodman, CMO at Mineralys Therapeutics]

Thanks, Rich.

[Operator]

Our next question comes from Annabel Samimy with Stifel. Please state your question.

[Annabel Samimy, Stifel]

Hi, thanks for taking my question. Just on the four-week measurement, can you remind us the rationale for wanting to look at the four-week time point in the first place? I just wanna make sure I understand what importance that four-week time point is for you. And I have some follow-ups from that.

[David Rodman, CMO at Mineralys Therapeutics]

Hi, Annabel, it's Dave. So, so your question, just to repeat it so I've got it right, is: What was the rationale for wanting to make the change, or why are we looking at it just from basic principles?

[Annabel Samimy, Stifel]

Well, why were you looking at it for basic principles? Just you had a 40-week endpoint and 12-week endpoint. I'm just curious what the 4-week endpoint measurement was going to give you. Was it-

[David Rodman, CMO at Mineralys Therapeutics]

Right.

[Annabel Samimy, Stifel]

because you want to see how, just for the importance of that endpoint.

[David Rodman, CMO at Mineralys Therapeutics]

So it's a good question. By 4 weeks, you've achieved the maximum benefit, and by having two data points, so baseline, but then 4 weeks and 12 weeks, you manage a lot of issues to answer the question. We think 4 weeks will be the maximum. Is it predictive of 12 weeks? In other words, is there any loss of activity over at least the 12-week time period? Because we only went out to 8 weeks before and didn't see any loss. From a statistical standpoint, it allows you to, let's just say somebody later in the trial, you know, has a problem or whatever, and you stop their drug. As long as we have the 4-week, we do have mechanisms for imputation that can be used.

[David Rodman, CMO at Mineralys Therapeutics]

Now, that's a complicated thing, but as long as they stay in the study, that four-week data point is informative for the modeling. So there's a couple reasons to do it. The third one is the ability to pool the two groups that are replicates up to four weeks. And so you do have, at four weeks, superpower in terms of getting a point estimate.

[Annabel Samimy, Stifel]

Okay. That's, that's helpful. Thank you. And then just a question that we've been grappling with, with some investors. Just can you remind us again, what the difference was in the patients who saw 24-hour blood pressure monitoring benefits and target versus those who did not? And I guess how it could have been that the AOBP measurements overall saw such a strong response while the 24-hour could not. So I just want to try to reconcile those two figures.

[David Rodman, CMO at Mineralys Therapeutics]

If I understand your question, I'm not sure. Let me just say what we saw. So first of all, ABPM, because of the replicate measures every 20 to 30 minutes over the course of the day, you get lots of measurements. So the precision is better when you average it, so the standard deviation is smaller. But remember, a normal person's blood pressure goes down significantly overnight, and so the average blood pressure over the course of 24 hours will be lower with ABPM than the automated office done just in the morning. The same is true of changes then, because you're changing from a lower baseline. So typically, what you'll see is a lower baseline pressure with ABPM and a smaller treatment effect, but a smaller standard deviation. So we saw extremely good concordance between AOBP and ABPM, but there is this systematic difference of smaller numbers.

[David Rodman, CMO at Mineralys Therapeutics]

Now, the other thing that happened, however, is there is this phenomenon of white coat hypertension. In other words, when you get an AOBP, when you come into the clinic at 10:00 A.M., you've got a lot of adrenergic tone because you had to find a parking space, you had to walk up two flights of stairs, you had to wait in the waiting room, et cetera. And so that all goes away with a 24-hour. And so we have this thing where people have hypertension with AOBP, but not with ABPM, and we tend to assume they don't have true hypertension that leads to adverse outcomes, but rather they just have apparent hypertension. Was that the question kind of you were thinking of asking?

[Annabel Samimy, Stifel]

A little bit. I'm just curious. So the ABPM, where you reached statistical significance, was when you reached statistical significance after you removed some outliers of the study. So I'm just trying to understand what those outliers were that made you comfortable that it was a fair assessment. And how do you control for those outliers in this next coming trial so that you don't have some of those divergences?

[David Rodman, CMO at Mineralys Therapeutics]

Yeah, good question. So first of all, those were small trials, n's of 30 with ABPM and all the technical issues with it are extremely challenging to get to statistics. And the, for instance, it was a few patients. There was one patient in particular who, on the office blood pressures, had a 60 millimeter of mercury, I think, increase in blood pressure recorded. In other words, an implausible value. It just can't be accurate. And that's what kind of thing we censored, was just numbers that were just not plausible and not reproduced. So there was only a few. It was really the white coat hypertension, where most of the loss of information from ABPM was the issue.

[Jon Congleton, CEO at Mineralys Therapeutics]

Yeah, and, Annabel, just to add to Dave's point, the distinction between Target-HTN and Advance-HTN in Target-HTN AOBP was part of the randomization rule, not ABPM, and AOBP was the primary endpoint. In this case of Advance-HTN, they have to be hypertensive on the 24-hour ABPM to be randomized. And so that rule or randomization rule itself should eliminate that phenomenon that we saw in Target-HTN.

[Annabel Samimy, Stifel]

Okay, great. Thank you. That's, that's helpful.

[Jon Congleton, CEO at Mineralys Therapeutics]

Yeah.

[Annabel Samimy, Stifel]

Thanks.

[Jon Congleton, CEO at Mineralys Therapeutics]

Yeah. Thanks, Annabel.

[Operator]

Our next question comes from Mohit Bansal with Wells Fargo. Please state your question.

[Mohit Bansal, Wells Fargo]

Great, thank you very much for taking my questions. I have two, but I'll ask one by one. So first question, I'm a little bit confused by the all the talk about advanced HTN and then 12-week thing. If I go back to the launch trial, can you just help us understand what was the confounding issue that probably made FDA to ask you to move to 6 weeks versus 12 weeks? Because the way I see the trial, there are three different arms. There is one 50 milligram, there is there's under 50 milligram moving to 100 milligrams. So you can still compare the 50-milligram arm to the placebo arm. So I'm a little bit confused by the change here. Thank you.

[David Rodman, CMO at Mineralys Therapeutics]

So, it wasn't them telling us what to do. It was us suggesting that it would be better to do it that way. It doesn't have to do with the primary. It didn't matter in that trial, with, as big as it was, if you did the primary at 4 weeks or 12 weeks. It has to do with power for the subset analyses. In other words, because you have two replicate arms, both at 50 milligrams, we can do the independent tests for the primary, each arm versus placebo. But let's say we want to ask a question: Does it matter whether you're African American? Well, we expect maybe 40% of the subjects will be African American, so now you're down to half the sample size.

[David Rodman, CMO at Mineralys Therapeutics]

But by pooling the two, now you get back up to the number, and so you get much more precision to get accurate answers to the subsets. So that's what we went back to the agency with and said, "In this big data set, we want to make sure that we can fully realize the power of the study, and we think for the subsets, we'd be better at six weeks." And basically, this, the decision was, "Okay, if you're going to do that, let's just do the primary at six weeks, too.

[Mohit Bansal, Wells Fargo]

Got it. So that is basically to make sure that you can do the subgroup analysis properly and get the bigger data set here.

[David Rodman, CMO at Mineralys Therapeutics]

It just makes it much more simple and higher productivity. It's, you know, just a good idea.

[Mohit Bansal, Wells Fargo]

Got it. And then I have one more question. So we have seen a couple of readouts from MRAs. So obviously, Novo had some data which was not that successful, but then Bayer had some data in type two diabetes-related CKD, and that was quite successful. So how do you see, like, obviously, different classes, but related, how do you see these two data sets and what do you learn from them, those data sets to inform your own CKD studies?

[David Rodman, CMO at Mineralys Therapeutics]

Well, first of all, MRAs generally are pretty similar. It doesn't matter if it's spironolactone from 1959 or a very new one. The only difference are the steroidal side effects, things like breast development in men and impotence and vaginal bleeding and that kind of stuff. As far as everything else, mechanistically, they're the same. What we observe with the MRAs is almost always you are unable to achieve the maximum therapeutic benefit on something like blood pressure, because you're limited by the on-target increases in potassium and, and also, you know, sodium going down, those kinds of things. For instance, with spironolactone, the maximum efficacious dose is probably 200 milligrams. The conventional dose that's used is 25 milligrams, 50 milligrams by nephrology specialists sometimes. That's different. So we found in our drug, we can go above the maximum efficacious dose.

[David Rodman, CMO at Mineralys Therapeutics]

100 milligrams is the same as 50. So we can safely give 50 milligrams, which is the maximum efficacious dose. So overall, what I would say is the biggest difference that's apparent in the trials we're running is that the benefit-risk, the ability to dose people all the way up to their efficacious dose from getting rid of Aldo, is probably more achievable with an ASI like ours than an MRA. Now, long term, there are a lot of Aldo effects that aren't blood pressure and kidney. They're effects on adipocytes, on insulin sensitivity, on inflammation, on heart and blood vessel fibrosis, and not all of them are mediated through the MR that's blocked by those MRAs. In fact, if you give an MRA, you increase aldosterone by 200 or 300%, and you drive it into these other pathways.

[David Rodman, CMO at Mineralys Therapeutics]

So if you did a longer trial and looked at things like vascular stiffness, maybe even HFpEF, I think eventually they would differentiate, but that's for us, something to define. Once we're in the market for hypertension, we will certainly be looking at that. Those are really the two aspects we would say that look pretty likely to differentiate and show the advantage of ASI over MRA.

[Mohit Bansal, Wells Fargo]

Okay. Thank you very much. Makes sense.

[David Rodman, CMO at Mineralys Therapeutics]

Thanks, Mohit.

[Operator]

Thank you, and a reminder to queue up for a question, press star one. To remove your question, press star two. Our next question comes from Rami Katkhouda with LifeSci Capital. Please state your question.

[Rami Katkhuda, LifeSci Capital]

Hey, guys. Thanks for taking my questions as well. First, I just wanted to make sure that I heard you correctly, in that you'll be able to do a subset analysis of lorundrostat's efficacy in uncontrolled and resistant hypertensive patients in Advance-HTN. I guess, do you expect a difference in efficacy between these populations?

[David Rodman, CMO at Mineralys Therapeutics]

Well, I can answer the first question. So we separately block randomized, uncontrolled, and resistant. In other words, if we have 150 people who are resistant and we have 200 people who are uncontrolled, we'll have 200 uncontrolled placebo and 150 resistant placebo. They're matched in terms of the randomization. And so that means we have full statistical power to do those comparisons, and they're informative. Now, your question of, can I be prophetic and tell you whether it's gonna work better in one or the other? I can't answer that. In the Target-HTN trial, when we asked that question, we didn't see a difference, but let's wait and see on this trial. I don't want to predict.

[Rami Katkhuda, LifeSci Capital]

Fair enough. Then maybe switching to CKD, I guess, given the previous results we saw with Boehringer's ASI, the recent failure with the MRA, is there a threshold of systolic blood pressure reductions that you're looking for in EXPLORER to advance lorundrostat into a larger trial?

[David Rodman, CMO at Mineralys Therapeutics]

For CKD?

[Rami Katkhuda, LifeSci Capital]

Mm-hmm.

[David Rodman, CMO at Mineralys Therapeutics]

So where we think our drug's gonna differentiate is, we made the primary hypertension, and the secondary is gonna be, albuminuria. And the reason for that is, we're gonna be dosing at antihypertensive doses in people who have both a hypertensive component to their CKD and probably also a metabolic syndrome component. And so we believe that by targeting that subpopulation, we will define a niche where our drug can differentiate from other approaches, which are much more a general CKD population. That's why even though it's a crowded field with multiple players, we still think we've probably got the best-in-class ASI, and it has potential in that way.

[Rami Katkhuda, LifeSci Capital]

Got it. And I guess one more, if you don't mind. Can you just remind us of the rationale for using the 25 mg dose instead of 50 mgs in the Explore-CKD study? Is it just hyperkalemia in lower eGFR patients, or is there more to it?

[David Rodman, CMO at Mineralys Therapeutics]

Right. So, it's an abundance of caution at this exploratory stage. We didn't want to take on the hyperkalemia risk. Now, I'll tell you, our nephrology advisors say they're perfectly comfortable using potassium binders, if needed, to get the blood pressure down in these patients. So this is just the first step on the journey, but that's the main reason.

[Rami Katkhuda, LifeSci Capital]

Makes sense. Thanks so much.

[David Rodman, CMO at Mineralys Therapeutics]

Thanks, Rami.

[Operator]

Thank you. There are no further questions at this time. I would like to turn the floor back over to Jon Congleton for closing comments.

[Jon Congleton, CEO at Mineralys Therapeutics]

Thank you, operator, and thank you to everyone for joining us today. We're very excited about the program's progress to date, that we've made in the first half of 2024 and advancing our clinical programs. We remain very enthusiastic about the upcoming milestones for the rest of the year and into 2025. We look forward to updating you as our pivotal program for lorundrostat continues to advance. With that, we will close the call.

[Operator]

Thank you. This concludes today's conference. All parties may disconnect. Have a good day.

Participants

Executives

• Adam Levy, CFO
• David Rodman, CMO
• Jon Congleton, CEO

Analysts

• Annabel Samimy, Stifel
• Dan Ferry, LifeSci Advisors
• Michael DiFiore, Evercore ISI
• Mohit Bansal, Wells Fargo
• Rami Katkhuda, LifeSci Capital
• Richard Law, Goldman Sachs