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5 days ago
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RESTEM to Present at the 2025 BIO International Convention
MIAMI, June 03, 2025 (GLOBE NEWSWIRE) -- RESTEM – a clinical-stage biotechnology company that develops off-the-shelf, next-generation cell therapies designed to modulate the immune system, today announced that Andres Isaias, its Chief Executive Officer, will present at the upcoming 2025 BIO International Convention taking place in Boston, MA from June 16 – 19, 2025. BIO International Convention Format: Corporate presentation and one-on-one meetings Presentation Date and Time: June 18, 2025, at 1:45 PM in Room 153A Location: Boston Convention & Exhibition Center, Boston, MA To register for the conference and schedule a one-on-one meeting with RESTEM's management, please visit About RESTEM RESTEM is a leading clinical-stage biotechnology company focused on developing off-the-shelf, next-generation cell therapies designed to modulate the immune system. Leveraging our proprietary products, robust clinical development expertise, and cutting-edge-manufacturing capabilities, we advance two potentially groundbreaking programs, Restem-L, our umbilical cord lining stem cells (ULSCs) program for auto-immune diseases and our natural killer cell (NK) therapeutics targeting senescence and age-associated disorders. Our therapies are intended to treat a broad range of disabling diseases and are designed to improve patient outcomes, as well as overall health and wellness. RESTEM is headquartered in Miami, Florida. For more information, please visit and follow us on X and LinkedIn. Investor Contact Daniel Ferry LifeSci Advisors +1.617.430.7576 daniel@ Media Contact Nelson CabautanRestem Group, Inc. +1.800.490.0924 ncabatuan@ in to access your portfolio
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13-05-2025
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Q1 2025 Mineralys Therapeutics Inc Earnings Call
Daniel Ferry; Investor Relations; LifeSci Advisors Jon Congleton; Chief Executive Officer, Director; Mineralys Therapeutics Inc David Rodman; Chief Medical Officer; Mineralys Therapeutics Inc Adam Levy; Chief Financial Officer, Company Secretary; Mineralys Therapeutics Inc Michael DiFiore; Analyst; Evercore Jin Law; Analyst; Goldman Sachs Seamus Fernandez; Analyst; Guggenheim Securities Rami Katkhuda; Analyst; LifeSci Capital Operator Good afternoon, ladies and gentlemen, and welcome to the Mineralys' first-quarter 2025 earnings conference call. (Operator Instructions) This call is being recorded on Monday, May 12, 2025. I would now like to turn the conference over to Dan Ferry. Please go ahead. Daniel Ferry Thank you, operator. We'd like to welcome everyone joining us today for our first quarter 2025 conference call. Earlier this afternoon, we issued a press release providing our first quarter 2025 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 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. Please note that these statements reflect our opinions only as of today, May 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 Jon Congleton, Chief Executive Officer of Mineralys Therapeutics. Jon Congleton Thank you, Dan. Good afternoon, everyone, and welcome to our first quarter 2025 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, 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. This has been an exciting past few months for Mineralys as our team delivered on several clinical milestones to make significant progress across our entitlement pipeline. The most highly anticipated of these accomplishments was the simultaneous announcement of positive top line data from the pivotal trials Launch-HTN in Advance-HTN, which is understand 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 Emery efficacy end points 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 Cardiology's ACC '25 meeting. The Launch-HTN data has been accepted for a late-breaking presentation at the European Society of Hypertension on May 24 with a planned future publication. Each of these exciting outcomes helps to underscore the strength of these clinical data and the potentially transformative nature of a to help people achieve their blood pressure goal and potentially reduce their cardiovascular risk. The positive efficacy, safety and tolerability data from these 2 pivotal trials, along with the data from our Target-HTN Phase II trial of lorundrostat are key elements of our planned new drug application to the FDA. We continue to believe that this regulated aldosterone is not adequately addressed with currently available RAS directed therapeutics, including mineral corticoid receptor antagonist. These results we have seen with lorundrostat reinforce the need for a new Aldostero-directed therapeutic approach. The Transform-HTN open-label extension trial is evaluating the safety and efficacy of lorundrostat long-term use will be an important aspect of lorundrostat's profile and a critical component of our new drug application. We anticipate discussing the results from the Advance, Launch, Target and Transform HTN trials as well as the Explore-CKD trial with the FDA at a pre-NDA meeting in the fourth quarter of 2025, during which forward for an NDA submission and potential approval of lorundrostat. We look forward to providing updates on this program throughout the remainder of 2025. We're very optimistic about the interest physicians have on lorundrostat 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 from lorundrostat are the data we collected in a survey fielded in March, which evaluated the data from the Launch-HTN and Advance-HTN trials with cardiologists and primary care physicians. The results from that survey showed if lorundrostat is approved, 95% of the physicians are likely to prescribe lorundrostat broadly for hypertension and specifically in the third and fourth line position. This intent to prescribe is based on the health care professionals interpretation of the efficacy data relative to what they currently have available for uncontrolled and resistant hypertension as well as lorundrostat 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 con 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 lorundrostat profile in hypertension subjects with comorbid conditions, largely driven by inadequately controlled blood pressure in dysregulated aldosterone. We've made steady progress with both trials since the beginning of 2025, and anticipate announcing top line data from Explore-CKD trial later this quarter. We're also pleased to announce the appointment of Eric Warren as Chief Commercial Officer. Eric brings approximately [30] 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 & Company where we went on to hold commercial positions of increasing responsibility for almost 2 decades. In addition, Eric has held commercial leadership roles at Sanofi and Nabriva and was most recently the Chief Commercial Officer of the Therapeutics. As the Chief Commercial Officer of Mineralys will lead our commercial strategy as we prepare for the potential FDA approval of lorundrostat and support our partnering ambitions in the U.S. and ex U.S. markets. In March, we completed a public equity financing that raised gross proceeds of approximately $201.2 million 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 Thank you, Jon, and good afternoon, everybody. As Jon 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 III Launch-HTN trial, which randomized 1,083 subjects in North America and Europe who had failed to achieve the U.S. guidelines specified blood pressure targets despite having been provided on multidrug 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, installed 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 6, the primary end point, the 50-milligram once daily lorundrostat arm demonstrated a 9.1-millimeter of mercury placebo-adjusted reduction in systolic blood pressure, and a 16.9 meter mercury reduction in observed systolic blood pressure. At week 12, the reduction in systolic BP was maintained with the point estimate being greater than that observed at week 6. 11.7 millimeters of mercury and 19 millimeters of mercury for placebo-adjusted and observed changes, respectively. Reductions in blood pressure and this magnitude is linked to significant reduction in overall cardiovascular risk and the incidence of major adverse cardiovascular events. The Launch-HTN trial confirmed 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 potential measurement over 6 millimole per liter in the Launch-HTN trial in (inaudible) milligram arm was 1.1% in placebo in active and 0.7% in placebo. The prespecified rate, excluding falsely elevated or factitious hyperkalemia was comparable to placebo with the demonstrated incidences being 0.6% and 0.4%, respectively. While quantitative comparisons between different clinical trials are difficult, the incidence of moderate or severe hyperkalemia of approximately one-half of 1% compares quite favorably with most prior reports of mineralocoid receptor antagonist tested in a similar clinical context. The Launch-HTN global pivotal trial is the largest aldosterone on synthase inhibitor trial reported to date and the benefit of risk profile compares quite favorably with previously reported smaller trials of the 3 other aldosterone synthase inhibitors that have been tested in hypertensive individuals. Now turning to the Advance-HTN trial. Here, we tested the effect of lorundrostat in the clinical context and hypertension intensive individuals who are the most refractory to current standard of care, and often referred to hypertension specialists. The trial used highly rigorous criteria for enrollment and randomized -- randomization designed to mirror best practice care provided in the most advanced hypertension referral centers, maximization of conventional best practice 2 and 3 drug treatment regimens along with active monitoring of compliance, we're used to document and confirm the existence of uncontrolled or resistant hypertension. The results from the trial in the 50-milligram once-daily lorundrostat 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 24-hour ambulatory blood pressure were observed at the prespecified 12-week visit. Lorundrostat demonstrated a favorable safety and tolerability profile with modest on-target changes in serum potassium, sodium and EGFR and a low discontinuation rate. 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, Dr. Lu Lasan, in a late-breaking session at the American College of Cardiology's ACC '25 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 6 millimole per liter in the 50-milligram arm was 2.1%. 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 6 millimole per liter has an acceptable benefit risk profile appropriate for the use in these patients. Okay. Now turning to our other programs, Explore-CKD and Explore-OSA Phase II proof-of-concept trials. Both of these trials are designed to provide data that augments the anti-type pretensive protocol of lorundrostat by profiling the an efficacy of lorundrostat in these 2 special populations of hypertensive individuals. During the first quarter, we announced the completion of enrollment in the Explore-CKD Phase II 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 milligrams 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. This is another area with great unmet medical 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 4-week treatment period relative to that seen in a 4-week placebo treatment period in the same individuals. The key mechanism of kidney damage in hypertensive nephropathy is elevated blood pressure glomerular hyper perfusion, scarring and reduction of the number of glomeruli available to filter the blood. Changing prutinuria 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 and rather than changing proteinuria may be a more useful outcome measure for a Phase II trial in this population. In the first quarter of 2025, we announced initiation of the Explorer-OSA Phase II trial to evaluate the effect of lorundrostat in treatment of moderate to severe obstructive sleep apnea, blood pressure increases significantly as arterial oxygenation falls during upper airway obstruction at night. By dosing lorundostated bedtime, we believe we will suppress the majority of aldosterone produced during sleep, while maintaining 24-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. 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 hypertensive nephropathy, for which normalizing aldosterone production may result in meaningful clinical benefits. I'll now turn the call over to Adam to review our financial results for the first quarter of 2025. Adam Levy Thank you, Dave. Good afternoon, everyone. Today, I will discuss elect portions of our first quarter 2025 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 $343 million as of March 31, 2025, compared to $198.2 million as of December 31, 2024. 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&D expenses for the quarter ended March 31, 2025, were $37.9 million, compared to $30.8 million for the quarter ended March 31, 2024. The increase in R&D expenses was primarily due to increases of $4.8 million in preclinical and preclinical costs and $2.8 million in compensation expense resulting from additions to headcount, increases in salaries and accrued bonuses and increased stock-based compensation, partially offset by $0.5 million in lower clinical supply, manufacturing and regulatory costs. G&A expenses were $6.6 million for the quarter ended March 31, 2025, compared to $4.6 million for the quarter ended March 31, 2024. The increase in G&A expenses was primarily due to $1.2 million of compensation expense resulting from additions to headcount, increase in accrued bonuses and increased stock-based compensation and $0.7 million in higher professional fees. Total other income net was $2.2 million for the quarter ended March 31, 2025, compared to $3.9 million for the quarter ended March 31, 2024. The decrease was primarily attributable to decreased interest earned on our investments in money market funds and U.S. treasuries. Net loss was $42.2 million for the quarter ended March 31, 2025, compared to $31.5 million for the quarter ended March 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 (Operator Instructions) Michael DiFiore, Evercore. Michael DiFiore 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 largesat will improve their blood pressure. So I guess the question is, will it be the max level of Grade 2 hyperkalemia that would be acceptable if lorundrostat were to yield a high single-digit placebo-adjusted SBP reduction? And then I have a follow-up. Jon Congleton Yes, Mike, just quick response. So I don't know that we categorized what would be an acceptable level. I think what's key and critical is we talk to specialists and our advisers 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 tend to be predominantly nephrologists are more comfortable with higher level of capacity meetings 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 to be production with lorundrostat, they may reduce the dose of ACE or arm. So the take with us is within export, you get a clear sense of the safety, characterize the efficacy with this drug and knowing the full well, they're 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 Got it. That's helpful. And my final question is like despite cadrostats, shorter half-life and lesser selectivity for aldosterone synthase inhibition relative to rent. It still showed a high single-digit percent SBP reduction over 14 weeks in their Phase II CKD trial. So I guess, should we expect similar efficacy and safety with lorundrostat? Jon Congleton Yes, Mike, I 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 lorundrostat has been well characterized now with 3 successful studies from Target-HTN, Advance and Launch. But it's too early to hedge what we'd anticipate seeing, but I would anticipate certainly a clinically meaningful reduction and then we'll see how the data evolves as far for those other hemodynamic characteristics. Operator Richard Law, Goldman Sachs. Jin Law Great. And congrats on the process from me as well. So a couple of questions from me. Can you discuss how the overall, like the Explore-CKD study fit in the strategy for were submission with Launch and Advance. My understanding is that the study is important to provide clinical support for patients below EGFR 45. 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 Yes, Rich, thanks for the question. We're certainly excited about the benefit risk profile that's emerged now with lorundrostat with the successful completion of the Advance study and the Launch study, seeing double-digit reduction in BP with a really acceptable safety tolerability profile. The submission of the renters NDA will be inclusive of all 3 of those studies, as I noted, as well as the transform open-label extension, and Explore-CKD will be a component of that. Really, the biggest driver of Explore-CKD was related to informed blood pressure response in subjects with an EGFR down to 30 as well as going with a lower dose of 25 milligrams QD. And so it will be a component. I think it's going to be part of the totality of evidence of 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 what we have in the dialogue with the agency on. Jin Law Great. Fantastic. And then -- so we saw in the New England Journal publication that the patients who have the potassium levels greater than 6 have a much lower average eGFR compared to the rest of the population. What is -- I mean, in your view, like what is the typical EGFR between like such study population in EXPLORE CKD study and dosed in a general hypertension study, like the 1 in your pivotal study program. like BI, the CKD study is that a good benchmark in terms of patient population? Or is this a different population from that? Jon Congleton Rich, 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? Jin Law Yes. So in your New England Journal publication, patients who have the higher potassium levels greater than 6, 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 Explore-CKD study, compared to the Advance and Launch? And like what would be a good benchmark terms of the type of patient that would -- that -- in terms of the eGFR level, for your CKD study? Jon Congleton All right. Thanks, Rich. I appreciate that. Yes, I think that's why we're doing the Explore-CKD study. We know the eGFR, eGFR launch was higher than that in advance. Advance was a more high-risk population truly uncontrolled, truly confirmed resistant hypertension. They had a lower eGFR. I think you're alluding to what Luke shared at the ACC about the subjects above 6 had a mean of about 58. As far as how tight is the correlation between eGFR and risk and hypercare, I think we need more data and more evidence, but it's part of why we're doing the Explore-CKD trial. Looking at subjects going down to an eGFR 30. We know they have the risk of potential more challenges in managing electrolyze that's why we're testing the 25-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 Rich, good question. And how are you doing -- the -- 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 good incidents. It was a little bit lower and they had it. In this trial, what we're really looking for those individuals who are in that 30 to 45 range, maybe on the lower side and saying, what happens to them. Not that 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 Jon said, back off on the art 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 an outer as we do about means in that trial. Jin Law Got it. Very helpful. And then just one last question. Similar to Explore-CKD, do you expect to include data from the Explore-OSA in your found package? Jon Congleton I think, Rich, it's 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 what or would that not be included in the discussions with the FDA. Operator Seamus Fernandez, Guggenheim. Seamus Fernandez Great. So Jon, I think on the last discussion call, you mentioned that as many as 47,000 physicians could actually be appropriate for promotion in the uncontrolled and resistant hypertension opportunity. And then you also at ACC emphasized that the opportunity may sit a little bit more initially in the sort of 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? And 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? Jon Congleton Yes. The 47,000, Rich, those that maybe hadn't heard before. So we did a significant project about a year ago with IQVIA with about [1 million] prescription claims within that. And when you basically narrowed down, where does 50% of the prescribing come from for third line or later priming, 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 from our standpoint, there's a very efficient commercial model, particularly with kind of clinical profile that runestat has now demonstrated to go out and target the 47,000 prescribers and generate significant value. But as we've talked about in the past, partnering for us is inclusive of U.S., but certainly global, looking for partners they can help optimize the opportunity of lorundrostat U.S. because we have no intentions of creating Mineralys commercial entities stand-alone outside of United States. So finding a partner can help maximize that opportunity ex U.S. but then really fully tap into the opportunity in the United States as well. And that would basically mean some level of overall 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 lorundrostat, 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. 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 to more med shows the value of an atosteron-directed treatment that physicians are going to want to work, 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 Great. And maybe just one follow-up. Can you just remind us what gating factors are to sort of finalizing and filing the NDA specifically? Jon Congleton Yes, happy to do that. First and foremost, recently very pleased with the benefit risk profile that we continue to see with this molecule. Now with the 2 active portions of the pivotal program completed. As we've stated before, the unlabeled extension is a critical aspect of that. If you think about when the last subjects enrolled and launched in advance that was at the end of October last year, we would anticipate also just completing the 52-week open label by Q1 of next year. Now we don't need to have all of those subjects to enable the filing. But we need the -- certainly, a majority of those subjects through 52 weeks before we'd be comfortable with the NDA. But that's part of what we'll have a dialogue with the FDA in Q4, as we've discussed in the pre-IND meeting. And so it will be both the pit programs for Advance and Launch will be part of the target data, the Explore-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. Operator Tim Anderson, Bank of America. This is Alice on for Tim. I just want to check, can you hear me okay? Jon Congleton Yes, we can. 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 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 Baxters at for data? And then I have a follow-up. Jon Congleton Sure. So to date, we haven't given updates on our partnering discussion, 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. Okay. And then as to the economy references a $5 billion peak sales for baxdrostat. I'm curious how are you thinking that you can best leverage a partner in order to realize this sort of potential with lorundrostat. For example, does it involve developing fixed dose combinations or other indications and things like that? Jon Congleton Yes. Thanks, Alex. There's clearly great deal of unmet need in this space. We're focused exquisitely right now in hypertension, but we know there's utility for an ideal aldosterone-directed treatment beyond that. That's why we're looking at the adjacencies because there's such an overlap in all of these card renal metabolic syndromes that have either hypertension or diabetes kind of at the central point. And so 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. But moving from hypertension into adjacencies, such substructive 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 a commercial perspective. But -- for those that have a shared vision, it also could be development partnerships as well. Looking at some of these adjacent areas, such as heart figure or CKD. Again, we know that aldosterone plays a role across the spectrum, and having what we believe to be a leading ASI gives us significant opportunity to tap into that value. Operator Annabel Samimy, Stifel. This is Jed on for Annabel. I have two questions. First is -- at what point do you think that guideline -- hypertension guidelines would in start including Launch and added HTN data? Is there any possibility that it could be updated before you guys would theoretically launch? Jon Congleton Yes, 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 -- it's a fair question. That's why we went to the what we did in Advance-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 does the profile physicians could expect? And how would guideline committees inform their communication and their constituents. Got it. And my other question is related to Explore-CKD. What do you think is the primary if you're looking for here? Are you looking for safety in the CKD population with concomitant drugs, inhibitors and ARBs? And then do you expect efficacy to generally be in the line of what you saw in -- or are there some nuances with that patient population that we should know? Jon Congleton Yes. I'll just reiterate what Dave had said with a profiling the study like the 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 3 studies to date. That's what we would anticipate to see in this population, and then providing additional information about the 25-milligram QD dose. Operator Mohit Bansal, Wells Fargo. This is Fatima on for Mohit. And congrats on all the recent progress. So on the hypertension readout, you've previously mentioned plans for subgroup Can you elaborate on those plans for which subgroups you're focused on and the time line for presentation of that data? And can you talk about how it could potentially help physicians select patients for lorundrostat? And if it could also influence placement of lorundrostat into treatment guidelines? Jon Congleton Yes, thank you for the question. As you know, we've to prespecify analysis of populations that may be unique responders to lorundrostat. You saw some of that data within the Advance-HTN, ACC as well as Nigam presentation and publications, respectively. I would anticipate seeing something similar with Launch-HTN. I think to date, what we've seen and it's frankly beneficial for prescribers, whether failing to achieve goal on 2 meds or 3 meds on controller resistant hypertension, you're seeing a pretty profound reduction in regardless of gender, age, race, number of background medications. And so it creates a predictable response that physicians can anticipate when using lorundrostat. We're going to 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 a multitude of subsets. And then on the OSA trial, how are you thinking about this 4-week endpoint? How it aligns with expected time lines for improvements in the hypoxia index and nocturnal blood pressure? And what magnitude of action would you consider to be clinically meaningful and also competitive in the context of the data reported with GLPs, for example? David Rodman Really good questions. Let me try to take those one at a time. So the first question was 4 weeks. What might we see? So as far as APMEA popular 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 water, the fluid shifts up. It's called roster cattle redistribution into your upper body and neck. That benefit is accrued within a few weeks. And so by 4 weeks, we would expect to see the benefit on Apnea Hypopnea Index. As you know, around a 50% reduction has been seen with the Lilly study similar with the APMEA 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. So let me just say something. Treating at the FDA hypopnea index is important, but the main risk for adverse outcomes is this extreme burst 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-1-second measurements -- 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 Hyponea Index and patient reported performance metrics are the current guidance from the agency for approval. So we're going down both of those paths. This is on 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 hypoxia 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 will be reporting them. And I think that will be really an important milestone in studying this disease. Operator Rami Katkhuda, LifeSci Capital. Rami Katkhuda I guess I just wanted to confirm a statement that Dr. Robin made that patients with hypertensive nephropathy may have more modest levels of proteinuria. I guess, is the patient population in Explore-CKD similar to that of the Bohringer study? Or are there other key differences in enrollment criteria? And I guess is that 37% placebo-adjusted UACR reduction with monotherapy a fair bar here? David Rodman 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 you -- 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 will not be the majority in this trial. So a different subset and it's actually a different subset of CKD. These people have scarring of their external part of their -- the 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 globe live at our left. 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 clinic 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's a highly safe and effective drug for uncontrolled and resistant hypertension. Now we're starting to go to the very high unmet need subpopulations, which right now is we consider to be hypertensive for nephropathy and OSA. Jon Congleton And Rami, just to add to that, the distinctions between the studies. I think the baseline is like BP in that study was low that is our inclusion criteria. So to Dave's point, we really are retreating the with GFR hypertension -- think that does create a distinct population between the two studies. Operator There are no further questions at this time. I would hand over the call to Jon Congleton for closing remarks. Please go ahead. Jon Congleton Thank you, operator. Mineralys 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 20 million patients in the U.S. alone. Our Launch in Advanced studies reinforce the differentiated clinical profile of lorundrostat 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. Thank you all. Thank you for joining for joining us today. And with that, we'll close the call. Thank you, everyone. Operator Ladies and gentlemen, this concludes today's conference call. 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Globe and Mail
24-04-2025
- Business
- Globe and Mail
X4 Pharmaceuticals to Report First-Quarter 2025 Financial Results and Host Conference Call and Webcast on May 1, 2025
BOSTON, April 24, 2025 (GLOBE NEWSWIRE) -- X4 Pharmaceuticals (Nasdaq: XFOR), a company driven to improve the lives of people with rare diseases of the immune system, today announced that it will report financial results for the first quarter ended March 31, 2025 and provide corporate updates on Thursday, May 1, 2025. The company will host a conference call and webcast on the same day at 8:30 a.m. EDT. The conference call can be accessed by dialing 1-800-343-4849 from the United States or 1-203-518-9848 internationally, followed by the conference ID: X4PHARMA. The live webcast will be accessible through the investor relations section of X4 Pharmaceuticals' website at Following the conclusion of the call, a webcast replay will be available on the website. About X4 Pharmaceuticals X4 is delivering progress for patients by developing and commercializing innovative therapies for those with rare diseases of the immune system and significant unmet needs. Leveraging expertise in CXCR4 and immune system biology, X4 has successfully developed mavorixafor, an orally available CXCR4 antagonist that is currently being marketed in the U.S. as XOLREMDI® in its first indication. The company is also evaluating additional uses of mavorixafor and is conducting a global, pivotal Phase 3 clinical trial (4WARD) in people with certain chronic neutropenic disorders. X4 is headquartered in Boston, Massachusetts. For more information, please visit Investor Contact: Daniel Ferry Managing Director, LifeSci Advisors daniel@ (617) 430-7576 X4 Media Contact: Rhiannon Jeselonis Ten Bridge Communications rhiannon@
Yahoo
27-03-2025
- Business
- Yahoo
CorMedix (CRMD) Q4 2024 Earnings Call Transcript
CorMedix (NASDAQ: CRMD)Q4 2024 Earnings CallMar 25, 2025, 8:30 a.m. ET Prepared Remarks Questions and Answers Call ParticipantsOperator Good day, and welcome to the CorMedix Inc. fourth-quarter and full-year 2024 financial results conference call. All participants will be in listen-only mode. [Operator instructions] Please note, today's event is being recorded. I would now like to turn the conference over to Dan Ferry with LifeSci Advisors. Please go ahead. Daniel Ferry -- Investor Relations Good morning, and welcome to the CorMedix fourth-quarter and full-year 2024 earnings conference call. Leading the call today is Joe Todisco, chief executive officer of CorMedix. And he is joined by Dr. Matt David, executive vice president and CFO; Beth Zelnick Kaufman EVP and chief legal and compliance officer; Liz Hurlburt, EVP and chief clinical strategy and operations officer; and Erin Mistry, EVP and chief commercial officer. Before we begin, I would like to remind everyone that during the call, management may make what are known as forward-looking statements within the meaning set forth in the Private Securities Litigation Reform Act of 1995. These statements are statements other than statements of historical fact regarding management's expectations, beliefs, goals, and plans about the company's prospects and future financial position. Actual results may differ materially from the estimates and projections on which these statements are based due to a variety of important factors, including the risks and uncertainties described in greater detail in CorMedix' filings with the SEC, which are available free of charge at the SEC's website or upon request from CorMedix. CorMedix may not actually achieve the goals or plans described in these forward-looking statements. 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GAAP to non-GAAP financial reconciliations and supplemental financial information are provided in CorMedix' earnings release and the current report on Form 8-K filed with the SEC. This information is available on the Investor Relations section of the CorMedix Website. At this time, it is now my pleasure to turn the call over to Joe Todisco, chief executive officer of CorMedix. Joe, please go ahead. Joe Todisco -- Chief Executive Officer Thank you, Dan. Good morning, everyone, and thank you for joining us on this call. Having completed our initial partial year of commercial launch of DefenCath, I'm incredibly proud of the team's efforts and pleased with the commercial results thus far. The fourth quarter saw continued growth with both existing as well as new customers in the outpatient segment which was the primary driver of our strong revenue and profit results for both Q4 and full year 2024. Net revenue for the fourth quarter and full year were 31.2 million and 43.5 million respectively, both of which exceeded Wall Street consensus prior to our pre-announcement on January 7th. The fourth quarter was also the first profitable commercial quarter in the company's history, with net income of $13.5 million and adjusted EBITDA of $15.3 million. Fourth-quarter results were driven by strong uptake among patients at U.S. Renal Care, ramping implementation at our mid-size customers, IRC and DCI, as well as utilization by other small outpatient dialysis customers. As we announced back in early January, we began the first quarter of 2025 with more than $25 million of purchase orders in hand from existing customers for first-quarter delivery. While we are not going to provide full-year revenue guidance at this time, we currently estimate that net revenue from existing purchasing customers for the first six months of 2025 should be in the range of $50 million to $60 million with more than 33 million expected in the first quarter. DefenCath net selling price has been fairly stable throughout the first three quarters of outpatient commercialization. However, we do expect to begin to see some net price erosion beginning in the second quarter of 2025. With respect to patient growth opportunities, there is still some potential for new patients with existing outpatient customers. However, to a large extent, our ability to grow patient volumes significantly in the back part of 2025 will be contingent upon the timing of purchasing and scale of implementation by our contracted large dialysis organization customer. Prior to year-end, we met with our contracted LDO customer who communicated to CorMedix that DefenCath implementation was pushed into 2025 due to operational resource constraints. Over the course of February and early March, we have had multiple meetings with this customer, provided significant requested information around resources available at CoreMedix to assist with training and the implementation of DefenCath, and we remain hopeful the customer will begin ordering and commence utilization prior to mid-year. Turning to the inpatient segment. We have started to see utilization increase at a handful of larger hospitals, and we are hopeful to increase penetration as we move throughout 2025. Back in January, we announced a change to our inpatient commercialization strategy, whereby we reorganized our field team covering outpatient and inpatient customers. This process is now complete as we are partnering with Syneos Health to build a dedicated inpatient field team that is highly experienced in the hospital formulary process and the launch of first-in-class products in this setting of care. We also recently announced a partnership with WSI to provide marketing and promotional resources for DefenCath, specifically to facilities operated by the Veterans Administration. I am happy to announce that the new inpatient team is nearly fully staffed and is expected to be active in the field in the next four to five weeks. The team contracted through WSI has already commenced promotional activities to VA facilities. While we do not currently report inpatient sales as a separate segment, we do expect to see meaningful growth in this setting of care by the end of 2025 with an increased contribution to overall revenue and earnings in 2026 and beyond. Focusing now on our clinical developments, we are in the process of beginning our Phase 3 clinical study for the reduction of central line-associated bloodstream infections or, CLBSIs, in patients receiving total parenteral nutrition, or TPN, through a central venous catheter. We began site selection in February and expect to begin patient enrollment for the study in the second quarter of this year. As we communicated previously, this is a 12-month study in less than 150 patients, and we are targeting completion of the study and submission of a new drug application to FDA by the end of 2026. We recently submitted to FDA an application for orphan drug status for this indication and are awaiting FDA's determination of eligibility. The company's goal for TPN is to obtain FDA approval for an expanded use of our taurolidine and heparin catheter lock solution in the late 2027 to early 2028 time frame. And we estimate annual peak sales potential in this indication to be in the range of $150 million to $200 million. We'll provide investors with updates on progress in this important area of unmet need as we move forward. During our previous earnings call, we also discussed three additional clinical initiatives, all having either commenced in 2024 or expected to begin in 2025. The most meaningful of the three from a data value standpoint is our real-world evidence study, which we are running in cooperation with our study partner, U.S. Renal Care. Our hope with this study in which we expect to evaluate outcomes of more than 2,000 patients over 24 months would be to generate real-world evidence around the impact of DefenCath utilization on cost-of-patient care, infection rates, hospitalizations, mortality, and multiple other metrics such as lost share time and CRBSI-related antibiotic use. Data collection for this study has already commenced. In addition to our adult TPN and real-world evidence studies, we will also be commencing a study in pediatric hemodialysis in 2025. This will be a relatively small study spread over several years as we expect patient enrollment to be a challenge given an extremely small patient population and the need for very personalized protocols for these ultra vulnerable patients. This pediatric study is a post-marketing requirement under the Pediatric Research Equity Act by the FDA, and we have FDA's concurrence on the final study protocol. We currently expect patient enrollment to begin in the third quarter of 2025, and we expect this study to span three to five years. Lastly, in addition to our other clinical initiatives, we have commenced an expanded access program for high-risk populations, including but not limited to pediatric TPN, peritoneal dialysis patients with refractory peritonitis, and neutropenic oncology patients utilizing a CVC. These high-risk patients are those that have exhausted other infection-prevention methods and, unfortunately, remain at significant risk for comorbidities and mortality. We are fielding a high number of requests for participation in this expanded access program and currently expect patients to be dosed under this program in the second quarter of this year. I would now like to turn the call over to Matt to discuss the company's fourth-quarter and full-year financial results and financial position. Matt? Matt David -- Executive Vice President, Chief Financial Officer Thanks, Joe, and good morning, everyone. I am pleased to be here today to provide an overview of our fourth-quarter and full-year 2024 financial results as well as an update on CorMedix' cash position. The company has filed its annual report on Form 10-K for the year ended December 31st, 2024. I urge you to read the information contained in the report for a more complete discussion of our financial results. With respect to our fourth quarter of 2024 financial results, our net revenue for the fourth quarter of 2024 amounted to 31.2 million. CorMedix achieved profitability in the fourth quarter as our net income was 13.5 million, or $0.22 per share, compared with the net loss of 14.8 million or $0.26 per share in the fourth quarter of 2023. The net income recognized in 2024 was driven by the profits associated with net sales of the DefenCath following the product's launch in 2024. Operating expenses in the fourth quarter of 2024 increased 9% to 17.1 million, compared with 15.7 million in the fourth quarter of 2023. The increase was driven by higher selling and marketing and G&A expenses offset by a decrease in R&D. R&D expenses decreased by 26% to 1.7 million, driven by the approval of DefenCath. CorMedix is now reporting selling and marketing expense and general and administrative expense as separate line items. On an apples-to-apples basis, S&M expense increased 1% to 8.3 million in the fourth quarter of 2024 compared with 8.2 million in the fourth quarter of '23. G&A expense increased 36% to 7.1 million in the fourth quarter of 2024 versus 5.2 million in the fourth quarter of 2023. The increase in S&M expense was attributable primarily to increased marketing efforts and new personnel inclusive of our field sales organization and support for the commercial launch of DefenCath. The increase in G&A expense was primarily due to increases in personnel costs in preparation for support activities related to our commercial launch. With respect to our full-year 2024 financial results, total net revenue during 2024 amounted to 43.5 million. This marks the first full year CorMedix is reporting net revenue since launching DefenCath in spring-summer of 2024. Total operating expenses during the full year 2024 amounted to 62.6 million, compared with 49 million in 2023, an increase of 28%. R&D expense decreased 70% to 3.9 million, driven primarily by the approval of DefenCath. Selling and marketing expense increased 59% to 28.7 million, compared with full year 2023, and G&A expense increased 69% to 30 million, compared with 2023. The increases in S&M and G&A were driven primarily by new personnel and costs to support the commercial launch of DefenCath. We recorded net cash used in operations during 2024 of 50.6 million, compared with net cash used in operations of 38.4 million in 2023. The increase is primarily driven by an increase in trade receivables and inventories, offset by a net increase in the change of accrued expenses and accounts payable and a decreased net loss. The company has cash and cash equivalents of 51.7 million as of December 31st, 2024. Based on accounts receivable collection throughout first quarter of 2025 and, to a lesser extent, proceeds from ATM issuance, we anticipate completing first quarter of 2025 with at least 75 million in cash and cash equivalents. As described in our January 7th release, we are guiding to 2025 cash operating expenses of approximately 72 million to 78 million. The increase over 2024 spending levels is expected to be primarily driven by an increase in R&D spending on clinical initiatives. I will now turn the call back over to Joe for closing remarks. Joe? Joe Todisco -- Chief Executive Officer Thanks, Matt. CorMedix is working diligently on all fronts to increase our existing customer base as well as expand the use of DefenCath to new therapeutic indications. I appreciate everyone's continued support and CorMedix, and I'm happy to take Thank you. We will now begin the question-and-answer session. [Operator instructions] At this time, we'll pause for just a moment to assemble our roster. And today's first question comes from Roanna Ruiz with Leerink Partners. Please go ahead. Roanna Ruiz -- Analyst Hey, good morning, everybody. So, I did have a question about the Syneos Health partnership and your build-out of the inpatient sales team. What are your first steps for this team once they're fully launched? And do you have any color on what the ramp might look like in the inpatient setting for DefenCath over time? Joe Todisco -- Chief Executive Officer Well, look, let me -- I'll comment on the inpatient kind of ramp, and then I'll let Erin and Liz comment a little bit on -- on the team and its deployment. So, you know, obviously, we were a little bit slow at the gate on the inpatient side last year. That's not unusual for -- for this setting of care or for these types of launches. It takes quite a while to -- to work through P&T processes. I am pleased with what we've seen in the first quarter. I know we -- as I said, we don't report anything from a -- from a separate segment standpoint on the inpatient side. But right now, for the first quarter, inpatient is looking to be about 3% of unit volume and 4% to 5% of dollars. So, I feel pretty good about that trend. Inpatient as a as a total is 10% of the unit volume of the overall market opportunity. So, if we can, you know, move toward there, right, as we get into 2026, I think that's certainly a target that we'd like to try to achieve. We're at the process of -- of just finally completing the staffing of the last two to three roles, right, to fill out the team completely. Training is near complete, and we're hope to have them out in the field in the next four to five weeks. Erin, do you want to comment anything beyond that? Erin Mistry -- Executive Vice President and Chief Commercial Officer Sure, I think that just what we plan for them to do right out of the gate is to focus on the large academic medical centers. Similar as before, they're not starting from scratch. These hospitals either have -- going through the P&T process now, or they have already ordered DefenCath. And so, we're just making sure that they've got the support they need and the ramp to order more. And we're also aligning them closely with VA medical centers that are typically in the same territory or region. Roanna Ruiz -- Analyst Got it. Thanks. And second one for me. I noticed on the call you talked about net price erosion starting in 2Q. Could you just elaborate a bit on the degree of the erosion? Could it flow into some of the subsequent quarters as well? Joe Todisco -- Chief Executive Officer Yeah, thanks, Roann. I think it'd be good to comment on the guidance we gave first and kind of what it means, right? So, you know, I know it's unusual to -- to guide for a partial part of the year, but the way we're kind of looking at it or the way I think investors should look at it is, the 50 million to 60 million range is really, I guess, what you would think of as our base business, right? In terms of the customers that we're -- that we're really buying by year-end and then you know into the early part of the first quarter, certainly to the extent we bring in either new customers -- obviously new customers, there's upside, right, from those numbers. If -- certainly, if our LDO customer starts buying in the second quarter, right, that there's upside in those numbers. Now, when we talk about price erosion, it's -- I'm not going to -- I don't know if I can give you an exact percentage, but the way in which we're thinking about it is our agreements with customers and the way that we're currently priced, there are, let's say, discounts and rebates off of government ASP. And government ASP has remained kind of stable, right? It starts out at whack during TDAPA, and then it adjusts for the first quarter. I think it was down only 1% from -- from what it was the prior quarter. Next quarter is still -- second quarter, going to be fairly stable. The third quarter, you know, it should come down a little bit, but we're going to have to or we're expecting to take a shelf stock adjustment at the end of the second quarter, right, as we move into third. And what we don't really have a handle on right now is exactly how much inventory will be in the channel by the end of the second quarter. So, that's something that we're still working through, and that kind of factors into the range that we gave for revenue from existing -- you know, what we'll call the existing base business over the -- over the first part of the year. Roanna Ruiz -- Analyst Got it. Helpful. Thanks. Joe Todisco -- Chief Executive Officer Thanks. Operator Thank you. And our next question today comes from Jason Butler, Citizens JMP. Please go ahead. Jason Butler -- Analyst Hi. Thanks for taking the question, and congrats on the progress in the quarter. Joe, can you maybe just give us some more color about the process that the contracted LDO is going through and your interactions that kind of just reinforce your confidence that they will begin ordering in the next couple of months, next few months? Joe Todisco -- Chief Executive Officer Thanks, Jason. Look, I think what I can say at this point in time is we're being as supportive as we can possibly be. We've had a lot of information requests come from them, right, specifically around support services we could provide for training, for reimbursement. And we're making our staff available to them kind of across the board. So, I -- you know, as I said, we're hopeful that we'll stick with the original kind of plan or communicated timeline of implementation by mid-year, but that's really all I have to go on at this point in time. Jason Butler -- Analyst OK, helpful. And then just from in terms of the magnitude of use within the LDO, has that number remained consistent throughout your dialogue with them? Joe Todisco -- Chief Executive Officer Yeah. Look, they haven't -- they haven't given us any indication right now that that number -- or they're going to deviate from that number. But we do know they're looking at implementation. I think there's -- there's a possibility that number could be higher. There's a possibility that number could be lower. Right. I think what we're trying to do right now, as I said, is make all the resources of CorMedix available to them and, hopefully, accelerate the rollout, both in terms of speed and scale. Jason Butler -- Analyst Great. And then just a second one for me. In terms of potential new customers, obviously, there's the other LDO. Could you give us an update there? But beyond that, are there other smaller providers that, potentially, could come online in the second half of the year? Thanks. Joe Todisco -- Chief Executive Officer Yeah, thanks. Look, with respect to the other LDO, obviously, we remain in communication with them. We've -- we've provided them additional information. I think, candidly, we haven't moved the needle there as much as we would have liked to over the past couple of months. We are still working there, call it top-down, right, through the senior level of management. We've also started to work their bottom-up, right? These -- a lot of these large [Inaudible] operators, they have joint venture-owned entities where the JV partner has some decision-making authority. So, we've started to work through some of those joint venture organizations that have expressed an interest in DefenCath. And we're hopeful to kind of make inroads there over the next two to three months. On the small side, you know, yes, right, there's -- you know, there are a lot of -- I guess first, I'd say we are shipping to a number of small customers where we don't talk about them specifically. You know, some may have 10 -- you know, 10 dialysis centers. Some might have 20, but in addition to some health systems that have 10 to 25 hospitals. But yes, that's absolutely part of our focus over the next -- part of 2025 to build inroads with those smaller customers and to increase ordering size and frequency. Jason Butler -- Analyst OK, great. Thank you for taking the questions. Operator Thank you. And our next question today comes from Gregory Renza with RBC Capital Markets. Please go ahead. Anish Nikhanj -- Analyst Hi, guys, it's Anish on for Greg. Congrats on all the progress, and thanks for taking our questions. Just a couple from us. First, just on TDAPA. How should we be thinking about patient applicability, and what are your thoughts and trends in coverage such as Medicare Advantage over the next two to three years? And second, what are the key levers you look to pull to maximize uptake of DefenCath to ensure the best possible post-TDAPA add-on adjustment? Thanks so much. Joe Todisco -- Chief Executive Officer Thanks, Anish. Look, I think with respect to TDAPA, I'm not sure what you meant by applicability, but in terms of what we're seeing -- I'll start out with what we're seeing from Medicare Advantage now, right? So, when we look at our payer claims, we launched the product in mid 2024 in the outpatient setting. And initially, 100% of claims were fee for service, right, because it's the Medicare Advantage. There was a little bit of a lag in picking up TDAPA. And as we move toward the back part of last year, we started to see the trend going toward Medicare Advantage. I think we closed out last year with about 25% or 30% of our claims being Medicare Advantage through this first part of the first quarter, 40% of our claims are Medicare Advantage and other payers, and 60% are fee for service. Som that's certainly the trend we want to see. When you look at the broader ESRD market, 80% to 85% of it is Medicare. And within Medicare, half of it is fee for service and half is Medicare Advantage. We do see the Medicare Advantage market share of Medicare growing over time. We do think it ultimately will become 70% of ESRD patients, and we do see that as a good opportunity for CorMedix. So, what we're doing to better prepare ourselves, call it for the out years of the TDAPA and beyond, is the real-world evidence study that we're running in collaboration with U.S. Renal Care, right? A lot of that data and, you know, specifically around the pharmacoeconomic benefits of DefenCath is what we'd like to utilize as part of a direct contract negotiation with the MA plans for -- for separate and more sustainable reimbursement. Did I address the second question as well, Anish? Anish Nikhanj -- Analyst Yes, that's very helpful. Thank you. Joe Todisco -- Chief Executive Officer OK, all right. Operator Thank you. And our next question comes from Les Sulewski with Truist Securities. Please go ahead. Jeevan Larson -- Truist Securities -- Analyst Hey, this is Jeevan On for Les. Thanks for taking our questions. We recently saw the news on FDA's acknowledgment of bloodline shortages that might impact hemodialysis procedures. Can you provide any commentary if this has any impact on utilization or uptake of DefenCath? Thank you. Joe Todisco -- Chief Executive Officer Yeah. Hi, thanks, Jeevan. No, it's not -- it's not likely to have any impact, but I'll let Liz explain why. Liz Hurlburt -- Executive Vice President, Clinical and Medical Affairs Yeah. So, thanks for the question. The good news is that there are two equivalent alternative manufacturers for this. So, hemodialysis isn't going to stop. I think that the dialysis providers feel pretty good about that, but I don't anticipate any impact to DefenCath utilization with this. It's simply a manufacturing challenge that can be addressed with alternatives. Jeevan Larson -- Truist Securities -- Analyst OK, great. Then just a quick second one from me. Can you provide any updates on the status of DefenCath manufacturing capacity? Has there been any readjustments needed or challenges to filling the open purchase orders due Q1? Thank you. Joe Todisco -- Chief Executive Officer I'm sorry, Jeevan. Was that -- was that question around inventory availability? Jeevan Larson -- Truist Securities -- Analyst Yeah, yeah. Joe Todisco -- Chief Executive Officer OK. Jeevan Larson -- Truist Securities -- Analyst Just your capacity there and any challenges in filling the 25 million open purchase -- Joe Todisco -- Chief Executive Officer No, no. We have more than a year's worth of finished dosage on hand at our current run rate. We're well situated. Jeevan Larson -- Truist Securities -- Analyst Great. Thank you. Operator Thank you. And our next question comes from Serge Belanger with Needham and Company. Please go ahead. John Todaro -- Analyst Hi. Good morning. This is John on for Serge today. Thanks for taking our questions. First, if you just quickly give us the current business mix between the various MDOs that you have on board. Obviously, U.S. Renal Care has been your -- has been your anchor thus far. And secondly, in terms of the expectations for the TPN program, are these patients going to be similar to those that were enrolled in the LOCK-IT trial in terms of CRBSI susceptibility? Joe Todisco -- Chief Executive Officer All right. Thanks, John. I'll -- in a minute, I'll let Liz comment on the study design for TPN. From a business mix standpoint, I think we have exact percentages in the -- in the 10-K for where we closed out last year. Obviously, U.S. Renal Care still remains more than -- more than 80% of orders through that period. It is -- it is coming down. Beyond that, I don't think we're going to be providing specific customer specific guidance, but we'll reevaluate as we go forward. Do you want to comment on the study design on TPN? Liz Hurlburt -- Executive Vice President, Clinical and Medical Affairs Sure. So, our Nutriguard study, which is our Phase 3 randomized double-blind, two-arm study, which is looking at the efficacy and safety of DefenCath for adult patients receiving TPN, is really focused on those that have had a CLBSI in the last 12 months. We know that patients that have had a CLBSI are at higher risk to have another one. They have an average infection rate of 20% to 25%. So, similar to dialysis patients in the sense that they are very vulnerable to infection and they may be immunocompromised for a multitude of reasons, right -- that's why they're probably on TPN. But unlike dialysis, these are folks that access their catheter on a daily basis, not three times a week like you would see in hemodialysis. Does that answer your question? John Todaro -- Analyst Yeah, that's great. Thank you very much. Operator Thank you. And this concludes the audio question-and-answer session. I'd like to turn the conference back over to Dan Ferry from LifeSci Advisors for written questions. Daniel Ferry -- Investor Relations Thank you, operator. We do have some written questions from the audience. The first will be: Did the change in CMMI, which is the Center for Medicare and Medicaid Innovation, did that policy impact patient uptake in the first quarter? Joe Todisco -- Chief Executive Officer OK, thanks, Dan. And I think -- I think what you're referring to is the policy change that took place back in November that removed or the patients that participate in a kidney care entity, the benchmarks, they excluded to TDAPA from the benchmark. So, they were now allowed to accept TDAPA payments and not be penalized. I think at the time, we guided -- we did expect a patient lift of somewhere around 15% to 20%. You know, we did see that throughout the first quarter, certainly, with U.S. Renal care that we saw lift in patient numbers as a result of that. And I think overall, I think it's important for innovative products in general, right? It was somewhat of a of a headwind that, thankfully, CMS eliminated. Daniel Ferry -- Investor Relations OK, great. I have another one here. Proposed changes from the new administration have certainly caused volatility in the sector. Have you seen anything in these announcements that you see as a risk or possibly an opportunity? Joe Todisco -- Chief Executive Officer Yeah. Look, I know there's a lot of trepidation from investors right now, certainly in the biotech segment, because of the new administration and potential tariffs on pharmaceuticals. I think the way we're looking at it specific to DefenCath is definitely more -- more of an opportunity. And I think I would divide it probably in a couple of buckets. I think if you're looking at the situation through the lens of let's say DOGE, right, and kind of taking cost out of government spend, I think DefenCath is something that fits you know very well with that agenda, right? So, the government spends over $3 billion a year between inpatient and outpatient derived CRBSIs in the hemodialysis space. You know, if we can replicate our clinical result in a real-world setting, we have the opportunity to offset a large amount of that spend. You know, if -- second, I think if you're looking at it through the lens of, let's say, make America healthy again, right, type thing -- we -- I think we also fit pretty well, right, with that type of mindset where if we are able to have, again, replicate our clinical results in a real-world setting and have that type of impact on infections, a byproduct of that is you're reducing hospitalizations from those infections. You'd ultimately be reducing antibiotic use that would result from those infections. I think both of which fit pretty well within that initiative. I think more broadly for this administration though, I think we do get -- just because it's a change of administration, not because of who the administration is, I think there is the ability to look at either past decisions through a new lens or new legislative initiatives. And certainly, there's a lot of I think momentum right now on a bipartisan basis for, hopefully, TDAPA reform. I think -- TDAPA was a really good start. I think it's -- we've done OK, but I think everybody recognizes from a long-term standpoint that it certainly could be better in terms of incentivizing innovation, reimbursing providers for utilizing that innovation. And we do know that there's a bill that's hopefully making its way through Congress, and hopefully, it'll be proposed before the end of this year. And if not, hopefully, CMS through rulemaking can make some more positive adjustments. But I think, you know, for us, in our situation specifically, I think we see a lot of opportunity. Daniel Ferry -- Investor Relations Great. Thank you for that, Joe. I have another one here that's a bit more on the commercial side of things. What resources does CorMedix have available to help providers with processing reimbursement? Joe Todisco -- Chief Executive Officer That's a good question. Yeah. So, we've set up a third-party hub, specifically to help the providers themselves navigate claims. And, Erin, do you want to -- it's through a third party. Erin, do you want to comment on how that's set up? Erin Mistry -- Executive Vice President and Chief Commercial Officer Sure. So, third-party prospectus, and they work directly with both us and our customers across inpatient and outpatient settings. They have a couple of main focus areas. One of those is benefits verification for patients and then they have very specific billing and coding expertise to make sure that claims are submitted correctly for TDAPA, for example, on the outpatient side and NTAP on the inpatient side as well as the J codes. And then they also can navigate any payer policies or complex state Medicaid challenges that we may run into. Daniel Ferry -- Investor Relations OK, great. Thanks, Erin. It looks like we have one final one here. And I think you touched on this earlier, Joe. But if signing an agreement or a currently contracted LDO requires greater capacity, what is your RAM time? And how does CorMedix -- how is CorMedix situated from a raw material standpoint? Joe Todisco -- Chief Executive Officer OK, thanks. So, I guess that goes back to inventory. So, I think we divide it into a couple of buckets. I said before from a finished dosage standpoint, I think we're in pretty good shape based on the current run rate and the anticipated ramp that we kind of built into our LE, right, for -- for the -- what we expected the LDO customer to do. Now, if they wanted to ramp significantly beyond that, our ability to pivot is pretty good, right? I don't think our ramp time is more than a handful of months. We have more than enough raw material on hand between, let's say, heparin and taurolidine API, you know, to cover that ramp over a year. Turnaround time on heparin API is not significant. Turnaround time on taurolidine API is a bit longer, but we have several -- several lots on order that would be delivered in the back part of the year. So, really, we've got two finished-dosage contract manufacturers. One of them is definitely underutilized. So, we have finished dosage capacity we can pivot to. And I think it's a matter of a handful of months to be able -- to be able to ramp. Daniel Ferry -- Investor Relations That's great. Thank you so much, Joe. Operator, this concludes the written question portion of the call. You may now close. Operator [Operator signoff] Duration: 0 minutes Daniel Ferry -- Investor Relations Joe Todisco -- Chief Executive Officer Matt David -- Executive Vice President, Chief Financial Officer Roanna Ruiz -- Analyst Erin Mistry -- Executive Vice President and Chief Commercial Officer Jason Butler -- Analyst Anish Nikhanj -- Analyst Jeevan Larson -- Truist Securities -- Analyst Liz Hurlburt -- Executive Vice President, Clinical and Medical Affairs John Todaro -- Analyst Dan Ferry -- Investor Relations More CRMD analysis All earnings call transcripts This article is a transcript of this conference call produced for The Motley Fool. While we strive for our Foolish Best, there may be errors, omissions, or inaccuracies in this transcript. As with all our articles, The Motley Fool does not assume any responsibility for your use of this content, and we strongly encourage you to do your own research, including listening to the call yourself and reading the company's SEC filings. Please see our Terms and Conditions for additional details, including our Obligatory Capitalized Disclaimers of Liability. The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy. CorMedix (CRMD) Q4 2024 Earnings Call Transcript was originally published by The Motley Fool Sign in to access your portfolio
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13-02-2025
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Q4 2024 Mineralys Therapeutics Inc Earnings Call
Daniel Ferry; Investor Relations; LifeSci Advisors Jon Congleton; Chief Executive Officer, Director; Mineralys Therapeutics Inc David Rodman; Chief Medical Officer; Mineralys Therapeutics Inc Adam Levy; Chief Financial Officer, Chief Business Officer; Mineralys Therapeutics Inc Michael DiFiore; Analyst; Evercore ISI Richard Law; Analyst; Goldman Sachs Annabel Samimy; Analyst; Stifel Europe Seamus Fernandez; Analyst; Guggenheim Securities LLC Mohit Bansal; Analyst; Wells Fargo Securities, LLC Rami Katkhuda; Analyst; LifeSci Capital, LLC Matthew Caufield; Analyst; H.C. Wainwright Operator Good morning, ladies and gentlemen, and welcome to the Mineralys fourth quarter and fourth year 2024 earnings conference call. (operator instructions) Also note that this call is being recorded on Wednesday, February 12, 2025. And I would like to turn the conference over to Dan Ferry of Lifesci Advisors. Please go ahead, sir. Daniel Ferry Thank you, operator.I would like to welcome everyone joining us today for our fourth quarter and full year 2024 conference call. Earlier this morning, we issued a press release providing our fourth quarter and full year 2024 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 up the call for Q& 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 10K and subsequent note that these forward-looking statements reflect our opinions only as of today, February 12, 2025, 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 Congleton, Chief Executive Officer of Mineralys Therapeutics. Jon Congleton Thank you, morning, everyone and welcome to our 4th quarter in full year 2024 financial results and corporate 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. Then Dave will discuss our clinical programs and recent milestones. Then Adam will review our fourth quarter financial results before we open up the call for your looking back over the past year, it was a tremendous period for the company. I'm very proud of the work our team has done in executing and supporting our clinical strategy of targeting this regulated or elevated aldosterone in patients with uncontrolled and resistant data for Advance-HTN will be available this coming March and Launch-HTN will be available mid-1st half of this year. We also have our exploratory programs evaluating lore that in hypertension and chronic kidney disease, as well as hypertension and obstructive sleep apnea. Our purpose at Mineralys is to create more healthy days for people dealing with cardio renal metabolic disorders, and the trial readouts we have this year will evaluate the potential of lorundrostat to deliver on that first of the two ongoing pivotal trials is the Advance-HTN trial that is evaluating the efficacy and safety of lorundrostat for the treatment of uncontrolled or resistant hypertension when used as an add-on therapy to a standardized background treatment of two or three antihypertensive medications. The trial enrolled 285 subjects and the rigor of the standardized American Heart Association recommended background regimen. It was designed to ensure only subjects who were enrolled had confirmed uncontrolled or confirmed resistant noted, we anticipate announcing the top line data for this trial next month. The second pivotal trial is Launch-HTN with 1,083 subjects enrolled and is designed to be confirmatory to our Target-HTN proof of concept objective is to evaluate the benefit risk of lorundrostat in a real world setting when added to a subject's previously prescribed regimen of two to five antihypertensive medications, one of which must be a diuretic. As previously guided, we anticipate top line data in the mid-1st half of this year. Upon completion of the treatment phase in the advanced HTN and launch HTN trials, participating subjects were offered the opportunity to enter the transform HTN Open label extension we await the announcement of these pivotal topline data, I invite everyone to revisit the KOL event we held last quarter. An archived webcast is available on the investor relations section of our website. This discussion focused on the unmet medical need and uncontrolled and resistant hypertension. The long-term impact of uncontrolled blood pressure and insights into the treatment of hypertension from these leaders in cardiovascular addition, during the event, the KOLs gave their perspectives on our highly selective aldosterone synthase inhibitor, lorundrostat as a new therapy and its potential to change the current treatment provide more color on our clinical pipeline and recent milestones, I will now turn the call over to David Rodman Thank you, John, and good morning, everybody. Picking up from where John just left off discussing the KOL event we just had last quarter, I agree that there were a lot of great topics clinicians did an excellent job of highlighting the need for innovation, and there was agreement that targeting aldosterone would address an important gap in the current antihypertensive also agreed that a confirmation of the favorable safety and blood pressure reduction of 8 millimeters to 10 millimeters of mercury we saw in the target HTN trial would be transformative for patients. Over the next few months, we look forward to sharing the data with you for the lorundrostat from both the Advance-HTN trial and Launch-HTN trials. We're excited about the potential of lorundrostat to demonstrate a meaningful benefit in patients with uncontrolled or resistant hypertension. I would like to echo John's appreciation for the work of the Mineralys team as well as the investigators and patients in both trials to advance the hypertension development recently had some exciting news around the rest of our clinical program, including the Explore-CKD and Explore-OSA Phase 2 proof of concept trials. Both of these trials are designed to provide data that augments the anti-hypertensive profile of the lorundrostat while also providing insight into the potential benefit in reducing overall cardiovascular week we announced that enrollment was completed in the Explore-CKD phase 2 trial. This trial is evaluating the efficacy and safety of lorundrostat for the treatment of hypertension in subjects with an eGFR as low as 30 and Albuminuria, despite having received stable treatment with an ACEi inhibitor or an ARB, as well as an SGLT2 and associated hypertensive nephropathy is a leading cause of kidney damage alone and in combination with other obesity associated comorbidities. This is another area with great unmet medical need where aldosterone synthase inhibition with lorundrostat has the potential for transformative benefit to patients. We look forward to announcing top line data from the trial in the 2nd quarter of January we announced our plans for the initiation of the Explore-OSA phase 2 trial to evaluate the effect of lorundrostat in the treatment of moderate to severe obstructive sleep apnea. During the night, blood pressure increases significantly during each hypoxic episode. This leads to resistant nocturnal hypertension that is underdiagnosed and lacks a specific therapy. We are using a novel approach in this trial to measure blood pressure continuously with each heartbeat during addition, we anticipate that dosing or lorundrostat at bedtime will maximize aldosterone suppression during the period that it is being driven by hypoxia while still providing daytime blood pressure control and the favorable safety profile achieved with once daily dosing of is estimated that 60% to 85% of patients with OSA have resistant hypertension. Establishing the benefit risk of lorundrostat in treating these patients could lead to the development of lorundrostat as a unique small molecule treatment for the adverse respiratory and cardiovascular manifestations of obstructive sleep are very excited about our programs that are designed to evaluate the value of the scat and the associated milestones expected in the first half of this year. I will now turn the call over to Adam to review our financial results for the quarter and the full year. Adam Levy Thank you, Dave. Good morning, everyone. Today I will discuss select portions of our fourth quarter 2024 financial results. Additional details can be found in our Form 10k, which will be filed with the SEC today, February entered the quarter with cash equivalents, and investments of $198.2 million as of December 31, 2024, compared to $239 million as of December 31, 2023. We believe that our current cash equivalents, and investments will be sufficient to fund our planned clinical studies as well as support corporate operations through the first quarter of 2026. R&D expenses for the year ended December 31, 2024, were $168.6 million compared to $70.4 million for the year end of December 31, 2023. R&D expenses for the quarter end of December 31, 2024, were $44.6 million compared to $23.7 million for the quarter end of December 31, annual increase in R&D expenses was primarily due to increases of $88.7 million in pre-clinical and clinical costs driven by the initiation of the lorundrostat pivotal program in the second quarter of 2023. $10.6 million in clinical supply, manufacturing, and regulatory costs. $7 million in higher compensation expense resulting from additions to headcount, increases in salaries, and accrued bonuses, and increased stock-based compensation, and $0.9 million in other research and development expenses, partially offset by a decrease of $9 million in licensing fees associated with development milestone payments in 2023 that did not recur in 2024.G&A expenses were $23.8 million for the year end of December 31, 2024, compared to $14.3 million for the year end of December 31, 2023. G&A expenses were $7.2 million for the quarter end of December 31, 2024, compared to $4 million for the quarter end of December 31, 2023. The annual increase in G&A expenses was primarily due to $6.6 million in higher compensation expenses resulting from additions to headcount, increases in salaries and incurred bonuses, and increased stock-based compensation. $2.6 million in higher professional fees and $0.3 million in higher other administrative other income net was $14.6 million for the year ended December 31, 2024, compared to $12.8 million for the year ended December 31, 2023. Total other income net was $2.8 million for the quarter end of December 31, 2024, compared to $3.3 million for the quarter ended December 31, 2023. The annual increase was primarily attributable to increased interest earned on the company's investments in money market funds in US loss was $177.8 million for the year ended December 30, 2024, compared to $71.9 million for the year ended December 31, 2023. That loss was $48.9 million for the quarter end of December 31, 2024, compared to $24.4 million for the quarter end of December 31, 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. Operator. Operator Thank you, sir. (Operator Instructions)First, we will hear from Michael DiFiore at Evercore ISI. Please go ahead, Michael. Michael DiFiore Hey guys, thanks so much for taking my questions and congrats on all the products, the progress. A couple for me, I guess a hypertension question in the phase two target trial when the when the QC analysis was performed on the 50 mg QD group. You took out two additional patients that had improbable readings, leaving 12 valuable patients that were truly hypertension. This seems like a very small end to extrapolate to the larger pivotal study. So I guess my question, my first question is what gives you confidence that the SBP reduction seen in these 12 patients, and these 12 patients can be extrapolated to phase 3, and then I have two follow ups. Jon Congleton Yeah, Mike, thanks for the call. I appreciate it. From our standpoint is we looked at both the in-office measurement as well as the 24 hour ambulatory and as you noted. When we looked at the 24 hour ambulatory, we had some subjects that actually had baseline blood pressure below goal, and so that confounded the findings a bit, but as we looked at the totality of the evidence for the 50 QD, the 100 QD, even the 25 BID looked at the exposure response, we got very Comfortable that the 50 mg QD provided what we believe is the ideal benefit risk as far as reduction in blood pressure, as well as benefit from a safety tolerability standpoint. So obviously as we moved the 50 mg into the pivotal program, it showed our confidence in that dose to provide 24-hour blood pressure control. Michael DiFiore Got it. Very helpful. And then just two files for me, one on the OSA trial, one on the CKD trial. For the OSA trial, will improvement in the apnea hypotony index after four weeks be primarily due to fluid volume reduction, or would nongenomic antifibrotic effects equally contribute over that time period? And my final question is, For the CKD trial, for the SGLT2 naive patients who start their SGLT2 for the first time in the trial, to what extent may that confound SBP and or eGFR you. David Rodman Okay, why don't I take that one. This is Dave Brodman. Thanks for the call, for the questions, and so I'm going to take the The first of those two questions, which was an OSA oh wait a minute, did you want me to do, yeah, so the OSA question and your question there was about the apnea hypoxia index and what the mechanism is. So, as first of all that when you in two small trials with both spironolactone and eplerenone. The apnea hypoxia index was reduced on a pretty short-term study like two weeks to four weeks by 50%, which is pretty dramatic. We anticipate being at least as good as that with our mechanism and it may be mediated by both the decrease in MR activation and nongenomic effects. But when we look at the mechanism with MR, it's volume other words, there's something called rostrocaudal redistribution of fluid. These patients will have edema in their legs. When they lay down, that fluid will redistribute horizontally and caudally towards the head and their neck, which is already obstructed with usually with fat tissue, will then become even more obstructed. So you're right, that mechanism's volume and the combination of a diuretic plus lorundrostat should dramatically decrease that you asked about non-genomic effects. The answer there is yes, but not fibrosis. It's inflammation most likely. So if there is a contribution, it'll be related to the genomic effects on inflammation, but also the effects on oxygen radical production in small vessels, which is that answer that question? Michael DiFiore Yes, it you. David Rodman Now SGLT2 inhibitor, we know that SGLT2 inhibitors in combination with an ASI do have some theoretical and practical advantages. I would say one of them is those are modest anti-hypertensive drugs, and it's possible that there will be some additivity between the two mechanisms. In addition, there is some loss of potassium that you have with the SGLT2 inhibitor. The three weeks as the run-in period in this trial is sufficiently long for most of those effects to already be manifest by the time that we start the addition, it's a crossover study where the in the first period, the placebo people will have that same effect. So, it's built in that we can assess exactly the effect that you are discussing, know what it is, and have a sensitivity analysis to address that possibility. Michael DiFiore Very you. Jon Congleton Thanks bye. Operator Thank question will be from Rich Law at Goldman Sachs. Please go ahead, Rich. Richard Law Hey guys, good morning. Yeah, a couple of questions for me. Given your guidance for events and launch, read our timelines overlap with each other. Is there more refined guidance now, on your base case of when, each of those will be presented? First, can we assume that events will go first before launch, or is there a chance that both can go together? And then I'll follow up with that. Jon Congleton Yeah, Rich, thanks for the question. As we noted in our opening remarks, we're continuing to guide Advance-HTN for March and Launch-HTN for mid first half of this year. Richard Law Okay, got it. And then for events, I know you potentially could present that twice, one for like a top line webinar and one at ACC. Do you see something similar for Launch? Jon Congleton Yeah, we're certainly excited about the acceptance of the late breaking abstract for lorundrostat in the Advance-HTN trial at the upcoming ACC meeting, depending upon when we get the top line results, we'll either do a corporate announcement in conjunction with that, or if we have the results sooner than that, we would anticipate doing a corporate top line announcement, as to launch. I think it's too early to opine on what the communications would look like with that trial. Richard Law Got it. And then, one final question. So the advanced trial actively tracks and enforce adherence of the treatment, but what do you expect for the compliance for patients wearing the ABPM device for that whole 24-hour period? Like, have you seen any issues of patients like taking off the device for a long period of time that could affect results? And then our patients like required not to do certain activities while wearing the device like like exercise or stuff like that. Jon Congleton Yeah, I'm glad that the team made the choice with Target-HTN to not only do the in-office measurement but the 24-hour ambulatory. It gave us as a team experience with the device, with the vendor. We're working with the same vendor and technology and Advance-HTN, so we've got that past experience as far as. How to use that device, how to teach and train sites and subjects on proper technique with do allow subjects when they either exercise or bathe to have breaks from that their compliance or QC requirements with the 24-hour ambulatory where we have to get a certain percentage of the, I think it's roughly 70 measurements over a 24-hour we're very confident that we have sites and subjects well trained for that, and the experience that our team has in working with that device gives us high comfort in the data and the quality of the data that we're going to get from that. And that's why we chose 24-hour ambulatory, which, as is the gold standard, and in a trial as rigorous as Advance-HTN where we are optimizing treatment, optimizing dose, optimizing compliance, using the gold standard. Really gives us, I think, a high quality data set, particularly relative to what's been done with new innovations in this space and what's being done with other had one? David Rodman Yeah, hey Rich, that's a great question. It's key to have as much good data from the primary as you never have it perfect with ABPM. But we went through the QC and the procedures as a root cause for losing data in the first trial, and we identified several ways to improve retention of informative data from those studies. We did lots of work on statistics and we're confident that we're going to have more than adequate good quality data to have the power that we imputed when we designed the size of the trial. Richard Law Great. And then just to follow up on that, is there any, what's the plan for like any missing data if patients take off the device and then for like say a couple of hours and then what's the plan for that? David Rodman Rich, that was part of the root cause analysis. We've got that built into the algorithms. We went over it with the FDA they approve it. Richard Law Okay, thank you so much. Jon Congleton Thanks, Rich. Operator Next question will be from Charlie Yang at Bank of America. Please go ahead, Charlie. Hi, this is Alice on for you for taking our just on the upcoming pivotal readouts, what are your latest expectations around safety and tolerability? Where do you hope to differentiate most versus typical MRAs? And even if efficacy were to be slightly less than MRAs, for example, wouldn't a cleaner drug still be a commercial winner?Thank you. Jon Congleton Yeah, thanks for the question. I think it's important to continue to distinguish the aldosterone synthase inhibitor class from the mineralocorticoid receptor antagonist. The MRAs block the effect of aldosterone at one of the biological pathways that aldosterone affects, and that's the mineralocorticoid receptor. aldosterone synthase inhibitors, however, go to the root cause of the problem and actually reduce the amount of plasma benefit of that is not only how aldosterone can be its effects mitigated at the mineralocorticoid receptor, but also at other pathways such as GPR30 that affects fibrosis, inflammation, and oxidative stress. So as such, the adverse events that are attributable, particularly for sperm lactone on blockade of MRAs, such as the androgenic effects such as gynecomastia and fertility issues with women. Something we don't see with this class of drugs.I think it's also fairly well accepted that the mineralocorticoid receptor antagonists seem to have a compromised tradeoff that as you push those to get to efficacy, you invariably see a push in our perspective, we think there's a more modest impact on potassium with an aldosterone and synthase inhibitor. It's something that was exhibited in Target-HTN. And so, we'll continue to evaluate that in the pivot program, but we believe that is the key distinguishing factor relative to the MRAs. I'll have Dave at a thought as well. David Rodman Yeah, so we, obviously everyone thinks about this a lot. I want to point out something about just the trial designs. When you say how are we going to compare to say MRA, as far as I know, no one's ever done a trial like our advanced trial. As rigorously to deliver the data we're going to have with advance. In other words, we're looking at confirmed you failed on two or three drugs at maximum doses. You took the drug and then we used 24-hour ambulatory to prove there is no benchmark. If you, the Launch trial is the closest thing to a benchmark, and so what I encourage you to do is look at these trials as they stand alone. These will be, especially the Advanced trial, but also Launch definitive establishment of the point estimate for how good these drugs are. Thank you. Operator Thank will be Annabelle Sammy at Stifel. Please go ahead. Annabel Samimy Hi, thanks for taking my questions. Just to put things in perspective again, can you remind us what coverage payers could give you if you hit in specific ranges like, 7 to 9, 8 to10 over 10, as you did, just in the various subpopulations. So can you help us frame how payers are going to look at the different responses and where they can position you within the treatment paradigm, and then I have a follow up. Jon Congleton Yeah, Annabelle, thanks for the have to date completed four separate payer research projects in the United States and feel very bullish about our ability to get access for lorundrostat and particularly in our targeted approach. We have basically put forward a base case of an 8 millimeter to 10 millimeter mercury improvement that's well tolerated. And typically fourth line, we think that's a space we can own. So in that resistant population, particularly as Dave highlighted with the prior answer with Advance-HTN, frankly being one of the most rigorous, if not most rigorous study ever done, that kind of data set we believe based on the research gives us an opportunity to really own the resistant hypertension space. And then as we look at third line, and this is what we put in front of payers as well, when we bring forward a patient type or an endo phenotype of a responder such as those with a BMI over 30, so that more targeted approach that is viewed favorably by payers as well with that 8 millimeter to 10 millimeter mercury improvement. Now all of this obviously [Nel] is going to be based the pricing and the rebate strategy within that, but just that clinical profile has resonated with the payers in that resistant population and targeted third line. Annabel Samimy Okay, and then I guess can you remind us the proportion of the population that are, truly The 3rd, 4th line population, how does each of those different, I guess, how does that position change your opportunity within the different populations that you have? Jon Congleton Yeah, it's, I think the resistant populations, so those failing on 3 or more with the diuretic is a little bit more easy to Quantify it it's typically seen as about 10% to 15% of the treated population, so roughly 7.5 million to 10 million subjects are in that resistant hypertension that would be third line, so failing on two or more is a little bit difficult to triangulate to with the data, but ballpark we view that population is about 10 million as well. So collectively between those that are failing on two or those that are failing on three or more, it's roughly, 15 million to 20 million, I would say as an addressable market. Annabel Samimy Okay, great. All right, thank you, that was great helpful. Jon Congleton Thanks Annabelle. Operator Next question will be from Seamus Fernandez at Guggenheim. Please go ahead. Seamus Fernandez Hi, it's Colleen on for Seamus. Thanks for taking our question. Could you just talk a little bit of where you view the threshold for hyperkalemia rates in Advance and Launch, and what needs to be shown there to be differentiated in the clinic, and then just how would you expect the addition of diuretics, required in every patient to impact the rates for what we saw on Target? Jon Congleton Thanks, done a, as I said, a significant amount of pay research. We've also done a significant amount of physician research over the last several years.5% or less is what we've always tested as a rate of hyperkalemia as part of a base case, and I think that's viewed as favorable by the physicians that we've done the research with. As you may recall, we saw about a 3.6% rate in your point, there is a belief that the use of a diuretic can be potassium wasting, so could offset the modest rise that we know we see with aldosterone synthase inhibitors. We saw that with lorundrostat, saw that with Baxdrostat, and on par with what you typically see with an ACE inhibitor. Or an ARB that have been used safely for decades at this I think that'll be an interesting addition to the pivotal program where all subjects in both studies are on a diuretic and in Target-HTN where we saw that modest impact, only half of the subjects were on a diuretic because it wasn't required for protocol. Let me have Dave add a comment on top of that, Colleen. David Rodman Yeah, I'm going to give you a clinician perspective, and we hear this all the is about benefit risk. The FDA has told us that it's not p-values. It's nothing. It's really what's the benefit and what's the risk. And what that means is the bigger the blood pressure response, the more tolerance there is for changes like potassium and what that means for us is that we are looking at you ask about the thiazides, they lower potassium, ensuring that people are taking their thiazides improves benefit risk both by increasing the response and decreasing the potassium. So think about it that way. It's benefit risk for the worst patients, the ones with CKD. The clinicians uniformly say we have great potassium binders. What we don't have are great antihypertensives, and so they're willing to tolerate almost any level of hyperkalemia and just treat it to get the maximum blood pressure response to lorundrostat is the feedback we thank you. Operator Thank question will be from Mohit Bansal at Wells Fargo. Please go ahead. Mohit Bansal Great, thank you very much for taking my questions. So like I have a couple of questions, so I'll start with first, do you think we'll see meaningful differences in the placebo adjusted results in terms of ABPM versus AOBP?And then like how do you think this, whatever, office reader, reading is for from advanced STN could read to Launch-HTN where office reading is the, is the primary endpoint, and I want to follow up. Jon Congleton Hey Mohit, I got your first question. Can you repeat your second one though? I'm sorry, there was a little bit of a breakup in the line. Mohit Bansal Sorry about that. So, what I'm saying is that, so from Advance-HTN, whatever you see in office blood pressure reduction, how much you could read that for what is the read across for Launch-HTN because Launch-HTN has AOBP as the primary endpoint. Jon Congleton Yeah, I, okay, thank you for clarifying that. What we saw in Target-HTN was about a four millimeter mercury change in the in-office measurement and in the 24 hour ambulatory, about a one millimeter to two millimeter mercury placebo change, so fairly tight concordance. I think it's a tribute to the team, the work they did to. Aligned to the AHA recommended best practices in measuring blood pressure, we've applied those same techniques for in-office measurement for both Advanced as well as Launch. I'd hate to opine on, are we going to see a replication of that? What's the read through from Advanced to Launch?There are different studies, but it's the same technology, the same technique, the training that we've done with the sites. So it's difficult to, project what it could be. I just think the team has, made the right choices as far as technology and technique that was validated and Target-HTN and that's what we're applying in Advance and Launch. Mohit Bansal No, fair enough. That's helpful. And then the second part is that how are you thinking about the nighttime coverage with lorundrostat? The reason I'm asking is because half life is shorter here. So do you think the timing of the dose could impact the ABPM measure more than the AOBP here? Jon Congleton Yeah, let me, I'll have Dave give a comment to this. I think it's important to reiterate that we think the 10 to 12 hour half-life of lorundrostat is actually ideal for, as Dave articulated earlier, the benefit risk of an ASI in the treatment of hypertension.I'll reiterate that in Target-HTN where we saw that 8 to 10 millimeter mercury drop in in office measurement, that blood pressure measurement was in the morning at [drop] before that day's dose. So we have strong confidence in the 24 hour coverage of the lorundrostat with that 10 to 12 hour half-life. We also think it provides the ideal mix of efficacy and safety, particularly the on-target component, which is potassium and Dave, do you want to add some thoughts on top of that? David Rodman Well, I can just add a little bit, as John know from Novartis, and I was there that a 4 hour half-life isn't long enough. We also believe that leaving a window that recapitulates normal circadian rhythm when [aldo] does go up pre-arousal is the best way to try to treat it, restore the normal rhythm. We have 100% by our healthy volunteer study, suppression of [aldo]. With our drug we can adjust how long that 100% lasts. And so just to reiterate that last point for John, we tune that so that it's 100% for until you go to sleep essentially and that it slowly comes up to only 30% of pre-treatment baseline, which is 70% suppression and then goes back down to zero again after the morning dose. We just think that's Science based on what we know about circadian rhythm and it's the most appropriate way to treat this disorder. Mohit Bansal you very much for this. Appreciate. Jon Congleton Thanks, Mohit. Operator Next question will be from Rami Katkhuda at LifeSci Capital. Please go ahead. Rami Katkhuda Good morning, guys. Thanks for taking my questions. Maybe going off a previous one, do you expect to delt in the treatment effects observed with lorundrostat in the pivotal studies, just given the slight difference between trials and the fact that patients in advance are potentially enriched with aldosterone-driven hypertension, then I have a follow up. Jon Congleton Yeah, Ray, thanks for the question. I think it's hard to predict, the response in advance, the response in launch and a differential. There are different studies as you've heard Dave articulate, I think the interesting aspect of Advance is that we have a truly confirmed uncontrolled or resistant hypertension population. On the one hand, that may be a more rigorous, challenging population to treat. On the other, it may be somewhat enriched for an aldosterone dependent form of is largely confirmatory to what we saw or what we designed and Target-HTN with the exception of all subjects and Launch, you're going to be on the diuretic, and we know there was a favorable synergy as far as more enhanced response there, so. It's difficult to predict across these two trials, we're just excited about the design of these two, I think they address key aspects of the market. Advance being as rigorous as it is really built for the specialists that are dealing with the difficult to treat patients. It's also the kind of study that gives us the opportunity to be included in the hypertension guidelines and then launches the real world setting of what the primary care physicians are going to be doing with the run that should we be able to bring it into the marketplace. Rami Katkhuda Got it. Makes sense. And then a recent paper detailed that [BI's] aldosterone synthase inhibitor has a half life of 4 to 6 hours, which is lower than what we've seen with lorundrostat and Baxdrostat, I guess. Does this affect how you view their CKD data at all and render stats, I guess overall positioning in that population. David Rodman Well, that's a very good question, and it is reminiscent of what happened with LCI699 Osilodrostat, which is pretty much the same half-life. And if you read the papers that were written, it was recommended that a longer half-life would be required to develop a maximally efficacious dose. We agree with that. We are targeting in CKD the subset of patients who mainly have not enough control of their blood pressure, which is damaging their glomeruli, scarring them every day and driving the deterioration in eGFR. If you don't treat that adequately, get it down to gold, you will continue to have progression of the at least with our drug, with our tunable suppression in that disease. And you'll remember we're testing 25 mg in that group, although it can be escalated in the real world. We have an optimum way to do that. I don't want to comment on somebody else's drug in their program. They probably know more than I do, but we like our approach. We also like the fact that we can add it on to an SGLT2 of choice, which we think may also be an advantage when you're mainly going after the hypertension. And not using the combination for the metabolic syndrome component mainly. Jon Congleton Awesome thanks so Operator Next question will be from Matthew Caufield at H.C. Wainwright. Please go ahead. Matthew Caufield Hi, thank you. Good morning, guys, and thanks for the updates this morning. So kind of changing gears considering obstructive sleep apnea, can you speak a bit more to the mechanism expectations for ASI benefit for those patients and then any read through from the current pivotal developments? Thanks again. David Rodman So let me address that in two ways. So there are two potential benefits at this stage, near term, we're focused on the fact that these patients have 60% to 85% resistant hypertension, and on top of that, it's not being diagnosed or treated because it's at night. And goal there is to look at the aldosterone dependent mechanism, which is right in the sweet spot for our hypertension program. What happens in these people, and it's often men and only postmenopausal women, is what's driving the [aldo] is the hypoxia. Remember, we say 15 apneas per hour. Think about that. Every 4 minutes. You're unable to move oxygen from your airway down into your lungs. Your body responds to that with a stress response that drives aldosterone. And so that's the mechanism for why they have such exceptionally high incidence of, dying in their sleep, arrhythmias like ventricular and atrial arrhythmias, etc. So that mechanism is directly targeted by our drug. It's part of the theory for dosing the drug for that indication at night. Even though you're trying to go after the hypertension primarily, it's a better way to do it and still get that window in our opinion. Now, the OSA, the airway obstruction itself, well, we know you can treat that with CPAP. It's not a treatment people love. And if you don't use it six hours a day, you get essentially almost no benefit on either blood pressure or survival. And so again, by adding our drug in, and we're going to study it during a two day period off the CPAP, you will get potentially additive benefits from the fact of the mechanisms I told you before occurred to you before, which is primarily fluid shift and secondarily probably some inflammation. Matthew Caufield Very helpful. Thanks a. Jon Congleton Lot Matt. Operator And at this time we have no other questions registered, so I would like to turn the call back over to John for closing remarks. Jon Congleton Thank you, operator, and thank you to everyone for joining us today. We're very excited about the progress we made in 2024 and thus far in 2025 in advancing our clinical programs, and we remain enthusiastic about the upcoming data milestones planned for the first half of 2025. We look forward to keeping you updated. With that, we will close the call. Operator Thank you, sir. Ladies and gentlemen, this does indeed conclude your conference call for today. 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