Mineralys Therapeutics Q1 2025 Earnings Call Transcript

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Provided by Quartr
May 12, 2025

Key Takeaways

  • Successful Phase 3 trial results from LAUNCH HTN and ADVANCE HTN showing statistically significant, clinically meaningful reductions in systolic blood pressure and a favorable safety/tolerability profile.
  • Publication of detailed ADVANCE HTN results in the New England Journal of Medicine and late‐breaking presentations at ACC and ESH highlight the potential of lorundrostat in uncontrolled and resistant hypertension.
  • A pre-NDA meeting with the FDA is planned for Q4 2025 to review data from pivotal and proof-of-concept trials (LAUNCH, ADVANCE, TARGET HTN, TRANSFORM HTN, EXPLORER CKD), aiming to define the path for an NDA submission.
  • Completed a public equity financing raising approximately $201 million and ended Q1 with $343 million in cash, cash equivalents, and investments, providing operational runway into 2027.
  • First quarter R&D and G&A expenses increased due to higher clinical development costs and headcount additions, leading to a net loss of $42.2 million versus $31.5 million in Q1 2024.
AI Generated. May Contain Errors.
Earnings Conference Call
Mineralys Therapeutics Q1 2025
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Operator

Good afternoon, ladies and gentlemen, and welcome to the Minauralis First Quarter twenty twenty five Earnings Conference Call. At this time, all lines are in listen only mode. Following the presentation, we will conduct a question and answer session. If at any time during this call you require immediate assistance, please press 0 for the operator. This call is being recorded on Monday, 05/12/2025.

Operator

I would now like to turn the conference over to Dan Ferry. Please go ahead.

Dan Ferry
Managing Director at LifeSci Advisors, LLC

Thank you, operator. We'd like to welcome everyone joining us today for our first quarter twenty twenty five conference call. Earlier this afternoon, we issued a press release providing our first quarter twenty twenty five financial results and business updates. A replay of today's call will be available on the Investors section of our website approximately one hour after its completion. After our prepared remarks, we will open the call for Q and A.

Dan Ferry
Managing Director at LifeSci Advisors, LLC

Before we begin, I would like to remind everyone that 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 ks and subsequent filings. Please note that these forward looking statements reflect our opinions only as of today, 05/12/2025, and as 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 John Collison, Chief Executive Officer of Mineralis Therapeutics.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Thank you, Dan. Good afternoon, everyone, and welcome to our first quarter twenty twenty five financial results and corporate update conference call. I'm joined today by Adam Levy, our Chief Financial Officer, and Doctor. David Rodman, our Chief Medical Officer. I'll begin with an overview of the business, then Dave will discuss our clinical programs and recent milestones, followed by Adam to review our first quarter financial results before we open up the call for your questions.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

This has been an exciting past few months for Mineralis as our team delivered on several clinical milestones to make significant progress across our entire development pipeline. The most highly anticipated of these accomplishments was the simultaneous announcement of positive top line data from the pivotal trials launch HTN and advanced HTN, which evaluated lorundarcet in uncontrolled and resistant hypertension subjects. We were pleased to announce in March that both trials successfully achieved statistical significance and were clinically meaningful in their primary efficacy endpoints, and demonstrated a favorable safety and tolerability profile. Detailed results from the ADVANCE HTN trial were also published in the New England Journal of Medicine, and presented in a late breaking presentation at the American College of Cardiology's ACC twenty five meeting. The launch HTN data has been accepted for a late breaking presentation at the European Society of Hypertension meeting on May 24, with a planned future publication.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Each of these exciting outcomes helps to underscore the strength of these clinical data, and the potentially transformative nature of lorundestat to help people achieve their blood pressure goal, and potentially reduce their cardiovascular risk. The positive efficacy, safety, and tolerability data from these two pivotal trials, along with the data from our target HTN phase two trial of lorundestat are key elements of our planned new drug application to the FDA. We continue to believe that dysregulated aldosterone is not adequately addressed with the currently available RAS directed therapeutics, including mineralocorticoid receptor antagonists. These results we have seen with lorundrostat reinforce the need for a new aldosterone directed therapeutic approach. The TRANSFORM HT in open label extension trial is evaluating the safety and efficacy of lorundrostat long term use, which will be an important aspect of lorandostatin's profile and a critical component of our new drug application.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

We anticipate discussing the results from the ADVANCE, LAUNCH, TARGET and TRANSFORM HTN trials, as well as the EXPLORER CKD trial with the FDA at a pre NDA meeting in the fourth quarter of twenty twenty five, during which we expect to define the path forward for an NDA submission and potential approval of lorunderstat. We look forward to providing updates on this program throughout the remainder of 2025. We're very optimistic about the interest physicians have in lorunderstat's overall clinical profile based on the pivotal data, especially given the double digit absolute reduction in systolic blood pressure. Supporting our excitement around the market opportunity for lorundestat are the data we collected in a survey fielded in March, which evaluated the data from the launch HTN and advanced HTN trials with cardiologists and primary care physicians. The results from that survey showed if lorundrostat is approved, ninety five percent of the physicians are likely to prescribe lorundocet broadly for hypertension, and specifically in the third and fourth line position.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

This intent to prescribe is based on the healthcare professional's interpretation of the efficacy data relative to what they currently have available for uncontrolled and resistant hypertension, as well as lorunderstat safety and tolerability profile. The overall results speak to the desire for innovative solutions that physicians want in their treatment armamentarium to address uncontrolled and resistant hypertension. Our two ongoing proof of concept trials address advanced chronic kidney disease, specifically those with uncontrolled hypertension, as well as obstructive sleep apnea with nocturnal hypertension. These trials are designed to enhance and extend the lorandostatin profile in hypertension subjects with comorbid conditions, largely driven by inadequately controlled blood pressure and dysregulated aldosterone. We've made steady progress with both trials since the beginning of twenty twenty five, and anticipate announcing top line data from EXPLORER CKD trial later this quarter.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

We're also pleased to announce the appointment of Eric Warren as Chief Commercial Officer. Eric brings approximately thirty years of experience in the pharmaceutical industry, during which he has developed a breadth of commercial and partnering expertise, focusing primarily on cardiometabolic and acute care medicine. He started his career as a pharmacist and then joined Merck and Company, where he went on to hold commercial positions of increasing responsibility for almost two decades. In addition, Eric has held commercial leadership roles at Sanofi and Abreva, and was most recently the Chief Commercial Officer at Asperion Therapeutics. As the Chief Commercial Officer at Mineralis, he'll lead our commercial strategy as we prepare for the potential FDA approval of lorundestat and support our partnering ambitions in The US and ex US markets.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

In March, we completed a public equity financing that raised gross proceeds of approximately 201,200,000.0 before deducting fees and expenses. This financing contributed meaningfully to the strength of our balance sheet. Now to provide more color on our clinical pipeline and recent milestones, I'll turn the call over to Dave.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

Thank you, John, and good afternoon, everybody. As John mentioned, our team has been had an exciting few months with the advancement of our clinical programs. I'll start by summarizing the top line results of the pivotal Phase three launch HTN trial, which randomized ten eighty three subjects in North America and Europe who had failed to achieve The US guidelines specified blood pressure targets, despite having been prescribed a multi drug antihypertensive regimen. The trial which tested lorundrostat in a real world clinical context met its primary and secondary endpoints with highly statistically significant, clinically meaningful placebo adjusted reduction in systolic blood pressure, as well as in the observed change in blood pressure that is conventionally used by prescribing physicians to assess response to antihypertensive therapy. At week six, the primary endpoint, the fifty milligram once daily lorunderstat arm demonstrated 9.1 millimeter of mercury placebo adjusted reduction in systolic blood pressure, and a 16.9 millimeter mercury reduction in observed systolic blood pressure.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

At week twelve, the reduction in systolic BP was maintained, with the point estimate being greater than that observed at week six. Eleven point seven millimeters of mercury and 19 millimeters of mercury for placebo adjusted and observed changes respectively. Reductions in blood pressure of this magnitude have been linked to significant reduction in overall cardiovascular risk in the incidence of major adverse cardiovascular events. The LAUNCH HTN trial confirmed the expected modest on target increase in serum potassium that accompanies the therapeutic benefit in individuals with inadequately controlled hypertension, as well as an overall safe and well tolerated profile. The incidence of any potassium measurement over six millimoles per liter in the launch HTN trial in the fifty milligram arm was one point one percent in placebo, inactive and zero point seven percent in placebo.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

The pre specified rate, excluding falsely elevated or factitious hyperkalemia, was comparable to placebo with the demonstrated incidences being zero point six percent and zero point four percent respectively. While quantitative comparisons between different clinical trials are difficult, the incidence of moderate or severe hyperkalemia of approximately one half of one percent compares quite favorably with most prior reports of mineralocoid receptor antagonists tested in a similar clinical context. The launch HTN global pivotal trial is the largest aldosterone synthase inhibitor trial reported to date, And the benefit risk profile compares quite favorably with previously reported smaller trials of the three other aldosterone synthase inhibitors that have been tested in hypertensive individuals. Now turning to the ADVANCE HDN trial. Here we tested the effect of lorongestat in the clinical context of hypertension sensitive individuals who are the most refractory to current standard of care, and often referred to hypertension specialists.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

The trial used highly rigorous criteria for enrollment and randomization designed to mirror best practice care provided in the most advanced hypertension referral centers. Maximization of conventional best practice two and three drug treatment regimens, along with active monitoring of compliance, were used to document and confirm the existence of uncontrolled or resistant hypertension. The results from the trial in the fifty milligram once daily lorundestat arm were highly statistically significant. The 7.9 millimeter mercury reduction in placebo adjusted systolic blood pressure and 15.4 millimeter mercury reduction in observed systolic blood pressure measured by twenty four hour ambulatory blood pressure were observed at the pre specified twelve week visit. Larundrostat demonstrated a favorable safety and tolerability profile with modest on target changes in serum potassium, sodium, and eGFR, and a low discontinuation rate.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

This trial was designed and conducted in partnership with the Comprehensive Hypertension Center at the Cleveland Clinic and their C5 research team. Results were presented by the co director of the Cleveland Clinic Hypertension Clinic, Doctor. Luke Laffin, in a late breaking session at the American College of Cardiology's ACC twenty five meeting and published in the New England Journal of Medicine on May 8. As was reported in the New England Journal of Medicine paper, the ADVANCE HTN trial per protocol confirmed incidence of hyperkalemia over six millimole per liter in the fifty milligram arm was two point one percent. Given the high dose of olmesartan, a potent long acting arm, which also elevates serum potassium, we feel that this incidence of serum potassium greater than six millimole per liter has an acceptable benefitrisk profile appropriate for the use in these patients.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

Okay, now turning to our other programs, EXPLOR CKD and EXPLOR OSA phase two proof of concept trials. Both of these trials are designed to provide data that augments the antihypertensive protocol of lorundrostat by profiling the safety and efficacy of lorundrostat in these two special populations of hypertensive individuals. During the first quarter, we announced the completion of enrollment in the EXPLORER CKD phase two trial. This trial evaluates the safety and efficacy of lorundrostat for treatment of hypertension in subjects with an eGFR from 30 to 90 and at least 200 of UACR despite receiving stable treatment with an ACE inhibitor or an ARB, as well as an SGLT2 inhibitor. Hypertension and associated hypertensive nephropathy is a leading cause of kidney damage alone and in combination with other obesity associated comorbidities.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

This is another area with great unmet medical need where aldosterone synthase inhibition with lorundrostat has the potential for transformative benefit to patients. In this trial, the primary outcome measure is change in systolic blood pressure during a four week treatment period relative to that seen in a four week placebo treatment period in the same individuals. The key mechanism of kidney damage in hypertensive nephropathy is elevated blood pressure induced glomerular hyperperfusion, scarring, and reduction of the number of glomeruli available to filter the blood. Change in proteinuria is being assessed in this trial as well. In contrast to CKD due to diabetes and metabolic syndrome, where proteinuria is a useful surrogate endpoint, individuals with predominant hypertensive nephropathy tend to have modest levels of proteinuria, Change in blood pressure, along with acute physiological reduction in eGFR, rather than change in proteinuria, may be a more useful outcome measure for a Phase two trial in this population.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

In the first quarter of twenty twenty five, we announced initiation of the EXPLORER OSA Phase two trial to evaluate the effect of lorundrostat in the treatment of moderate to severe obstructive sleep apnea. Blood pressure increases significantly as arterial oxygenation falls during upper airway obstruction at night. By dosing lorundostat at bedtime, we believe we will suppress the majority of aldosterone produced during sleep while maintaining twenty four hour blood pressure control. Episodes of nocturnal hypertension are underdiagnosed and lack a demonstrated highly effective treatment. The current treatment armamentarium is limited to weight loss and the use of positive airway pressure.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

We believe that neither is sufficiently effective at minimizing the impact of OSA on major adverse clinical outcomes. In summary, we have now demonstrated the clinically meaningful benefit risk profile of lorundrostat in individuals with aldosterone mediated hypertension. We are focused both on moving lorundrostat towards an NDA submission, as well as exploring its use in prevalent comorbidities such as OSA and hypertensive nephropathy, for which normalizing aldosterone production may result in meaningful clinical benefit. I'll now turn the call over to Adam to review our financial results for the first quarter of twenty twenty five.

Adam Levy
Adam Levy
CFO at Mineralys Therapeutics

Thank you, Dave. Good afternoon, everyone. Today I will discuss select portions of our first quarter twenty twenty five financial results. Additional details can be found in our Form 10 Q, which will be filed with the SEC today, May 12. We ended the quarter with cash, cash equivalents and investments of three forty three million dollars as of 03/31/2025, compared to $198,200,000 as of 12/31/2024.

Adam Levy
Adam Levy
CFO at Mineralys Therapeutics

We believe that our current cash, cash equivalents and investments will be sufficient to fund our planned clinical trials and regulatory activities, as well as support corporate operations into 2027. R and D expenses for the quarter ended 03/31/2025 were $37,900,000 compared to $30,800,000 for the quarter ended 03/31/2024. The increase in R and D expenses was primarily due to increases of $4,800,000 in preclinical and clinical costs, and $2,800,000 in compensation expense resulting from additions to headcount, increases in salaries and accrued bonuses, and increased stock based compensation, partially offset by $500,000 in lower clinical supply, manufacturing, and regulatory costs. G and A expenses were $6,600,000 for the quarter ended 03/31/2025, compared to $4,600,000 for the quarter ended 03/31/2024. The increase in G and A expenses was primarily due to $1,200,000 in higher compensation expense resulting from additions to headcount, increases in salaries and accrued bonuses, and increased stock based compensation, and $700,000 in higher professional fees.

Adam Levy
Adam Levy
CFO at Mineralys Therapeutics

Total other income net was $2,200,000 for the quarter ended 03/31/2025 compared to $3,900,000 for the quarter ended 03/31/2024. The decrease was primarily attributable to decreased interest earned on our investments in money market funds and US treasuries. Net loss was $42,200,000 for the quarter ended 03/31/2025 compared to $31,500,000 for the quarter ended 03/31/2024. The increase was primarily attributable to the factors impacting the company's expenses described above. With that, I'll ask the operator to open the call for questions. Operator?

Operator

Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press 1 on your touch tone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press 2.

Operator

Your first question comes from Michael DeFury of Evercore. Your line is already open.

Michael Difiore
Managing Director at Evercore

Hey guys, thanks for taking my question and congrats on all the progress. Just two for me. With regards to the CKD trial, in the past you said that these patients are so sick that physicians will readily accept some level of hyperkalemia if it means that lorundestat will improve their blood pressure. So I guess my question is, what would be the max level of grade two hyperkalemia that would be acceptable if lorundestat were to yield a high single digit placebo adjusted SBP reduction? And then I have a follow-up.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Yes, Mike, just quick response. I don't know that we've categorized what would be an acceptable level. I think what's key and critical is we talk to specialists and our advisors who are treating these patients with hypertension and more advanced kidney disease. They're really looking at providing a benefit to the BP, as well as relieving or improving the kidney function overall. I think these specialists, which tend to be predominantly nephrologists, are more comfortable with higher level of potassium readings within these patients. They have a means to manage that. They've got tools to use that. They're also more likely to modulate other background treatments. In other words, if they're getting the BP reduction with lorundrostat, they may reduce the dose of ACE or ARB.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

So I think the key takeaway for us is with an X4CKD, get a clear sense of the safety, characterize the efficacy with this drug, and knowing full well that providing the benefit on both BP as well as kidney function in these subjects is what the specialists who are treating these patients predominantly are looking for.

Michael Difiore
Managing Director at Evercore

Got it. That's helpful. And my final question is like, despite by cadrostat shorter half life and lesser selectivity for aldosterone synthase inhibition relative to lorundrostat, it still showed high single digit percent SBP reduction over fourteen weeks in their Phase two CKD trial. So I guess, we expect similar efficacy and safety with lorundestat?

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Yeah, Mike, think it's too hard to hedge what we expect to see. I think we would anticipate seeing the clinically meaningful reduction in BP. I think the profile for lorundestat has been well characterized now with three successful studies from target HTN advanced and launch. But it's too early to hedge what we do anticipate seeing, but I would anticipate certainly a clinically meaningful reduction. And then we'll see how the data unfolds as far as for those other human dynamic characteristics.

Michael Difiore
Managing Director at Evercore

I see. Thank you.

Operator

Your next question comes from Richard Law of Goldman Sachs. Your line is already open.

Richard Law
Richard Law
Analyst at Goldman Sachs

Great. Thank you so much and congrats on the progress from me as well. So a couple of questions for me. Can you discuss how the overall the EXPLORER CKD study fit in the strategy for regulatory submission with launch in advance? My understanding is that this study is important to provide clinical support for patients below EGFR 45.

Richard Law
Richard Law
Analyst at Goldman Sachs

And it will be great to hear your latest thinking on this and if that has evolved. And I have a follow-up.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Yeah, Rich, thanks for the question. We're certainly excited about the benefit risk profile that's emerged now with lorenostat with the successful completion of the advanced study and the launch study seeing double digit reduction in BP with a really acceptable safety tolerability profile. The submission of the lorenostat NDA will be inclusive of all three of those studies, as I noted, as well as the TRANSFORM open label extension and EXPLORER CKD will be a component of that. Really the biggest driver of EXPLORER CKD was really to inform the blood pressure response in subjects with an eGFR down to 30, as well as going with a lower dose of twenty five milligrams QD. And so it will be a component.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

I think it's going to be part of the totality of evidence lorundrostat that will go into the NDA. I don't know if I could opine at this point as far as the specific language that will be included in the label from EXPLORER, but it's certainly a part of the total package we'll be having the dialogue with the agency on.

Richard Law
Richard Law
Analyst at Goldman Sachs

Great, fantastic. And then, so we saw in the New England Journal publication that the patient who have the potassium levels greater than six have a much lower average eGFR compared to the rest of the population. What is, I mean, in your view, like, is the typical eGFR delta between like such study population in EXPLORER CKD study and those in the general hypertension study, like the one in your pivotal study program? Like it's BI, the CKD study, is that a good benchmark in terms of patient population or is it a population from that?

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Rich, and I'm sorry to do this. Can you rephrase your question? I just want to make sure I'm answering what you're looking for.

Richard Law
Richard Law
Analyst at Goldman Sachs

Yeah, so in your New England Journal publication, the patients who have the higher potassium levels greater than six millimole, they all have like lower than average eGFR compared to the rest of the population. So the question here is that, how do we think about sort of the differences between the eGFR in your EXPLORER CKD study compared to the advanced and launch? And it's like, what would be a good benchmark in terms of the type of patient that in terms of the EGFR level for CKD study.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

All right, thanks, Rich. I appreciate that. Yeah, I think it's why we're doing the EXPLORER CKD study. We know the EGFR, mean EGFR and launch was higher than that in ADVANCE. ADVANCE was obviously a more high risk population, truly uncontrolled, truly confirmed resistant hypertension.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

They had lower eGFR. I think you're alluding to what Luke shared at the ACC about the subjects above six had a mean of about a 58. As far as how tight is the correlation between eGFR and risk of hyperkalemia, I think we need more data and more evidence, but it's part of why we're doing the EXPLORER CKD trial. Looking at subjects going down to an EGFR 30, we know they have the risk of potential more challenges in managing electrolytes is why we're testing the twenty five milligram QD that we believe is an effective dose of lorundrostat. But as far as the correlation, I think that's something that will continue to unfold. Dave, if you've got some additional thoughts, please.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

Hey, Rich, good question. And how are you doing? When you talk about studies like this, the outliers are in some ways more important than the means, right? So the mean was above 60, say for the people who didn't have any of an incidence, it was a little bit lower and they had it. In this trial, what we're really looking for are those individuals who are in that 30 to 45 range, maybe on the lower side and saying, What happens to them?

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

None of this is an issue other than giving guidance to clinicians for who to keep an eye on, and probably who to give a potassium binder if needed. Or as John said, back off on the ARB and see if you can maintain the same blood pressure. So it's a guidance, it's what we call a special population profiling study. And we anticipate looking just as much at outliers as we do about means in that trial.

Richard Law
Richard Law
Analyst at Goldman Sachs

Got it. Very helpful. And then just one last question. Similar expect to include data from the EXPLORER OSA in your filing package?

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Think, Rich, it's a fair question. I think it's too early to opine on that. We haven't guided on top line data. We're excited about that study to address a significant unmet need within that resistant hypertension OSA population. But it's too early to comment whether would that not be included in the discussions with the FDA.

Richard Law
Richard Law
Analyst at Goldman Sachs

Great, thank you.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Thanks, Rich.

Operator

Your next question comes from Seamus Fernandez of Guggenheim. Your line is already open.

Seamus Fernandez
Senior Managing Director at Guggenheim Partners

Great. Thank you for the questions, So, John, I think on the last discussion call, mentioned that as many as 47,000 physicians could actually be appropriate for promotion in the uncontrolled and resistant hypertension opportunity. I think you also at ACC emphasized that the opportunity may sit a little bit more initially in the fourth line hypertension opportunity. Can you just help us understand how does the sort of intersection of that broad physician base intersect with your view of the needs of a partner in that context? What are you really looking for in the context of either a partner or something perhaps more strategic or an opportunity to actually start advancing the opportunity to promote on your own? Thanks.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

The 47,000 Rich, for those that maybe hadn't heard before. So we did a significant project about a year ago with IQVIA with about 1,600,000,000 prescription claims within that. And when you basically narrow down, where does 50% of the prescribing come from for third line or later prescribing, there's about 47,000 doctors that account for about half of that prescribing and a significant portion of the influence on the other 50%. And so from our standpoint, there's a very efficient commercial model, particularly with kind of clinical profile that Lunderstat has now demonstrated, to go out and target those 47,000 prescribers and generate significant value. But as we've talked about in the past, partnering for us is inclusive of US, but certainly global.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Looking for partners that could help maximize the opportunity of lorenderstat ex US because we have no intentions of creating mineralis commercial entities standalone outside of The United States. Finding partners that can help maximize that opportunity ex US, but then really fully tap in to the opportunity in The United States as well. And that would basically mean, some level of overlap maybe with the targeted physicians that we've talked about, but certainly coverage of those outside of those 47,000 that we target. And in fact, that target may be a little bit smaller as we think about an initial launch of lorendroset, fourth line is probably going to be the ideal place to go. That's where there's minimal benefit with existing treatments beyond aldosterone directed therapeutics.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

We know spironolactone is thought to be valuable there, but it's greatly underutilized. I think our clinical program to date where we've targeted those subjects failing to get to goal on two or more meds shows the value of an aldosterone directed treatment that physicians are going to want to work with, that patients are going to want to take and persist with. So we think there's significant opportunity there. We think we could tap into a significant portion of those prescribers, but having a partner clearly is going to help us maximize the value of the asset in The United States.

Seamus Fernandez
Senior Managing Director at Guggenheim Partners

Great, and maybe just one follow-up. Can you just remind us what the gating factors are to sort of finalizing and filing the NDA specifically? Thanks.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Yeah, happy to do that. First and foremost, we're obviously very pleased with the benefit risk profile that we continue to see with this molecule. Now with the two active portions of the pivotal program completed, as we've stated before, the open label extension is a critical aspect of that. If you think about when the last subjects enrolled and launched in advance, that was at the October, we would anticipate all subjects completing the fifty two week open label by Q1 of next year. Now we don't need to have all of those subjects to enable a filing, but we need the certainly a majority of those subjects through fifty two weeks before we'd be comfortable with the NDA.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

But that's part of what we'll have a dialogue with the FDA in Q4, as we've discussed in the pre NDA meeting. And so it'll be both the pivotal programs for advance and launch, it'll be part of the target data, the EXPLORER CKD data, and then a portion of that open label extension will be informative for that pre NDA meeting that will then have better guidance for timing of an NDA submission.

Seamus Fernandez
Senior Managing Director at Guggenheim Partners

All right, great. Thanks guys and congrats.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Thanks Seamus.

Operator

Your next question comes from Tim Anderson of Bank of America. Your line is already open.

Alice Nettleton
Alice Nettleton
VP - US Pharmaceutical & Biotechnology Equity Research at Bank of America

Hi, this is Alice on for Tim. Thank you for taking our questions. I just want to check. Can you hear me okay?

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Yes, we can.

Alice Nettleton
Alice Nettleton
VP - US Pharmaceutical & Biotechnology Equity Research at Bank of America

Okay, perfect. Just following on from Seamus' questions on partnering, could you talk about any early discussions you may have had so far and what are the limiting factors that a partner may be looking for? So we're going to have the full data from launch and the top line from the CKD study very soon. But do potential partners need to wait for the outcome of the pre NDA meeting, for example, as well as the AstraZeneca Bactrim set full data? And then I have a follow-up.

Adam Levy
Adam Levy
CFO at Mineralys Therapeutics

Sure, so to date we haven't given updates on our partnering discussions, but we do continue to believe that a partner or multiple partners will be a part of our story and we'll keep you updated as appropriate.

Alice Nettleton
Alice Nettleton
VP - US Pharmaceutical & Biotechnology Equity Research at Bank of America

Okay, thank you. And then AstraZeneca commonly references a $5,000,000,000 peak sales for Bactristat. I'm curious how are you thinking that you can best leverage a partner in order to realize this sort of potential with lorindostrat? For example, does it involve developing fixed dose combinations or other indications and things like that? Thank you.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Yeah, thanks, Alice. There's clearly a great deal of unmet need in this space. We were focused exquisitely right now on hypertension, but we know there's utility for an ideal aldosterone directed treatment beyond that. It's why we're looking at the adjacencies because there's such an overlap in all of these cardio renal metabolic syndromes that have either hypertension or diabetes kind of at the central point. And so for us, we think there is significant unmet need, there's significant value to provide to patients to help reduce their BP, which is the leading modifiable risk factor for cardiovascular risk.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

But moving from hypertension into adjacencies such as obstructive sleep apnea, hypertensive nephropathy, as you heard Dave speak about, we think basically generate significant value for us. As we have partnering dialogues, as I've spoken about in the past, part of that is partnering from commercial perspective. But for those that have a shared vision, also could be development partnerships as well. Looking at some of these adjacent areas, such as heart failure or CKD. Again, we know that aldosterone plays a role across this spectrum, And having what we believe to be a leading ASI gives us significant opportunity to tap into that value.

Alice Nettleton
Alice Nettleton
VP - US Pharmaceutical & Biotechnology Equity Research at Bank of America

Thank you very much.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Thank you.

Operator

Your next question comes from Annabel Samimy of Stifel. Your line is already open.

Jayed Momin
Jayed Momin
Biopharma Equity Research Associate at Stifel Financial Corp

Hi, guys. This is Jayed on for Annabel. Thanks for taking our questions. I have two questions. First is, at what point do you think that guidelines, hypertension guidelines would start including launch and advanced HTN data?

Jayed Momin
Jayed Momin
Biopharma Equity Research Associate at Stifel Financial Corp

Is there any possibility that it could be updated before you guys would theoretically launch?

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Yeah, I appreciate the question. I don't know that we can opine on when the timing will be specifically. I think we can only look at historical precedents. And I think the various guideline committees when faced with new valued innovations have been responsive to try to guide their constituents on how they should think about and integrate these new innovations into their treatment paradigm. So it's too early to opine, but it's a fair question.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

That's why we went to the effort we did in advanced HTN, because I think it fundamentally addresses the kind of questions that these guideline committees wish to have. And that is not only in maybe an existing background treatment, but when you get to truly high risk patients like we tested in advance, what is the profile physicians could expect and how would guideline committees inform their communication to their constituents.

Jayed Momin
Jayed Momin
Biopharma Equity Research Associate at Stifel Financial Corp

Got it. Thank you for that. My other question is related to explore CKD. What do you think is the primary thing that you're looking for here? Are you looking for safety in the CKD population with concomitant drugs like SGO2 inhibitors and ARBs?

Jayed Momin
Jayed Momin
Biopharma Equity Research Associate at Stifel Financial Corp

And then do you expect efficacy to generally be in the line of what you saw in launch and event, or are there some nuances with that patient population that we should know?

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Yeah, I'll just reiterate what Dave had said with a profiling study like this. Safety is a key element of the analysis and what we expect from a clinical benefit standpoint would be clinically meaningful reduction in blood pressure. I think that's been well characterized in the three studies to date. That's what we would anticipate to see in this population. And then providing additional information about the twenty five milligram QD dose.

Jayed Momin
Jayed Momin
Biopharma Equity Research Associate at Stifel Financial Corp

Great, thanks. That's all I had.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Thank you.

Operator

Your next question comes from Mohit Bansal of Wells Fargo. Your line is already open.

Sadia Rahman
Sadia Rahman
Vice President, Biopharma Equity Research at Wells Fargo

Hi. This is Fahdi Rahman on for Mohit. Thanks for taking the questions, and congrats on all the recent progress. So, on the hypertension readouts, you previously mentioned plans for subgroup analyses. Can you elaborate on those plans for which subgroups you're focused on and the timeline for presentation of that data?

Sadia Rahman
Sadia Rahman
Vice President, Biopharma Equity Research at Wells Fargo

And And can you talk about how it could potentially help physicians select patients for lorandostatin and if it could also influence placement of lorandostatin into treatment guidelines?

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Yes, I do thank you for the question. As you know, we've efforted to pre specify analysis of populations that may be unique responders to lorundersat. You saw some of that data within the advanced HTN ACC as well as NEGEN presentation and publications respectively. Would anticipate seeing something similar with launch HTN. I think to date what we've seen and it's frankly beneficial for a prescriber is whether failing to achieve goal on two meds or three meds, one controlled or resistant hypertension, you're seeing a pretty profound reduction in BP regardless of gender, age, race, number of background medications.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

And so it creates a predictable response that physicians can anticipate when using lorundrostat. We're gonna continue to investigate and dive into the data. I mean, what we've shared to date has been very informative about the value from a clinical reduction and safety standpoint. But there's a great deal of data we're going to continue to dig into within launch and advance and eventually explore CKD to really continue to further inform, all right, what is the ideal population to respond to this drug? But to date, we've seen great responses across multitude of subsets of patients.

Sadia Rahman
Sadia Rahman
Vice President, Biopharma Equity Research at Wells Fargo

Great, thanks. And then on the OSA trial, how are you thinking about this four week endpoint? How it aligns with expected timelines for improvements in the apnea hypoxia index and in nocturnal blood pressure? And what magnitude of AHI reduction would you consider to be clinically meaningful and also competitive in the context of the data reported with GLP-1s, for example?

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

Really good questions. Let me try to take those one at a time. So the first question was four weeks, what might we see? So as far as apnea hypopnea index, the primary mechanism through which our drug will work is the diuretic effect and reducing the amount of salt and water overload, because when you lay down at night, the excess salt and water, the fluid shifts up, it's called rostrocodile redistribution into your upper body and neck. That benefit is accrued within a few weeks.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

And so by four weeks, we would expect to see the benefit on apnea hypopnea index. As you know, around a fifty percent reduction has been seen with the Lilly study, with the APNIMED study of a different mechanism. We're powered down to about 30%, and these are small trials. So we would ultimately be observing where we are in that range. But let me just say something.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

Treating the apnea hypopnea index is important, but the main risk for adverse outcomes is this extreme bursts of hypertension, these spikes that you see at night when those things happen. And we're going to be doing the first trial using sub one second measurements, beat to beat blood pressure over the course of an entire night. So we'll be able to look at how well does this drug actually reduce the risk for adverse clinical outcomes. In many ways, that's a more important endpoint. However, apnea hypopnea index and patient reported performance metrics are the current guidance from the agency for approval.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

So we're going down both of those paths. This is an antihypertensive drug, and it's a sodium depleter. We expect to see benefits on both, but both are going to be meaningful. So I can't tell you for sure if apnea hypopaxia index is 30, but we see a terrific impact on nighttime blood pressure, maybe restoration, nighttime dipping, we'll be the only ones with those data at that point, and we'll be reporting them. And I think that will be really an important milestone in studying this disease.

Sadia Rahman
Sadia Rahman
Vice President, Biopharma Equity Research at Wells Fargo

Great, appreciate the context. Thank you.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Thanks, Sajja.

Operator

Your next question comes from Rami Kakuta of LifeSci Capital. Your line is already open.

Rami Katkhuda
Senior Equity Research Analyst at LifeSci Capital, LLC

Hey, guys. Thank you for taking our questions as well. I guess I just wanted to confirm a statement that Doctor. Robin made that patients with hypertensive nephropathy may have more modest levels of proteinuria. I guess is the patient population in EXPLORER CKD similar to that of the Bowringer study?

Rami Katkhuda
Senior Equity Research Analyst at LifeSci Capital, LLC

Or are there other key differences in enrollment criteria? And I guess is that thirty seven percent placebo adjusted UACR reduction with monotherapy vikadrostat a fair bar here?

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

Okay, those are good questions. And if we think about this, and this has happened in other diseases, chronic kidney disease is a syndrome, right? It can be autoimmune and you want to use an anti IgA, which has been very effective. If it's in the context of obesity and diabetes, it's from metabolic syndrome, and that is the one that's associated with a fair amount of proteinuria, even nephrotic syndrome, which is an extreme of that. What we're looking at, some of these patients may have high levels of proteinuria, but we anticipate that that will not be the majority in this trial.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

So it will be a different subset. And it's actually a different subset of CKD. These people have scarring of their external part of their cortex of their kidney, loss of these glomeruli from this water hammer effect of the pounding of blood pressure. For these people, getting their blood pressure down to 125 or 130 is not all they need. They need lower blood pressures than those to truly protect the glomeruli that are left.

David Rodman
David Rodman
Chief Medical Officer at Mineralys Therapeutics

And so we're going to be looking at that and continuing to explore the possibility of differentiating on that basis as we get into this chronic kidney disease space. It's not our primary objective per se, because we are going after hypertension broadly. We're now since we've proven that it's a highly safe and effective drug for uncontrolled and resistant hypertension. Now we're starting to go to the very high unmet needs subpopulations, which right now is we consider to be hypertensive form of nephropathy and OSA.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

And Rami, just to add to that, the distinctions between the studies, I think the baseline systolic BP in that study was below what is our inclusion criteria. So to Dave's point, we really are recruiting those with low eGFR and hypertension. And I think that does create a distinct population between the two studies.

Rami Katkhuda
Senior Equity Research Analyst at LifeSci Capital, LLC

Got it. That makes a lot of sense. Thank you.

Operator

There are no further questions at this time. I would hand over the call to John Congleton for closing remarks. Please go ahead.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Yeah, thank you, operator. Mineralis Therapeutics, we're committed to improving the lives of patients with cardiorenal metabolic diseases. Uncontrolled and resistant hypertension are significant unmet medical needs impacting more than twenty million patients in The US alone. Our launch and advanced studies reinforce the differentiated clinical profile of lorundarstat versus agents that are typically used in the third and fourth line treatment positions, and the quantitative research that we've done supports the commercial potential. We're excited for key upcoming milestones and look forward to sharing updates with you in the coming quarters.

Jon Congleton
Jon Congleton
CEO at Mineralys Therapeutics

Thank you all. Thank you for joining us today. And with that, we'll close the call. Have a good day, everyone.

Operator

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation, and you may now disconnect.

Executives
Analysts
    • Dan Ferry
      Managing Director at LifeSci Advisors, LLC
    • Michael Difiore
      Managing Director at Evercore
    • Richard Law
      Analyst at Goldman Sachs
    • Seamus Fernandez
      Senior Managing Director at Guggenheim Partners
    • Alice Nettleton
      VP - US Pharmaceutical & Biotechnology Equity Research at Bank of America
    • Jayed Momin
      Biopharma Equity Research Associate at Stifel Financial Corp
    • Sadia Rahman
      Vice President, Biopharma Equity Research at Wells Fargo
    • Rami Katkhuda
      Senior Equity Research Analyst at LifeSci Capital, LLC
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