Q4 2025 Mineralys Therapeutics Inc Earnings Call

March 12, 2026

Operator 3: Greetings, and welcome to the Mineralys Therapeutics Q4 and full year 2023 conference call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please note this conference is being recorded. I will now turn the conference over to your host, Daniel Ferry of LifeSci Advisors. Please go ahead.

Operator: Greetings, and welcome to the Mineralys Therapeutics Q4 and full year 2023 conference call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please note this conference is being recorded. I will now turn the conference over to your host, Dan Ferry of LifeSci Advisors. Please go ahead.

Speaker #4: A question-and-answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad.

Speaker #4: Please note, this conference is being recorded. I will now turn the conference over to your host, Dan Ferry of LifeSci Advisors. Please go ahead.

Speaker #2: Thank you, operator. I would like to welcome everyone joining us today for our fourth quarter and full year 2025 conference call. This afternoon, after the close of market trading, we issued a release providing our fourth quarter and full year 2025 financial results and business updates.

Daniel Ferry: Thank you, operator. I would like to welcome everyone joining us today for our Q4 and full year 2025 conference call. This afternoon, after the close of market trading, we issued a press release providing our Q4 and full year 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.

Dan Ferry: Thank you, operator. I would like to welcome everyone joining us today for our Q4 and full year 2025 conference call. This afternoon, after the close of market trading, we issued a press release providing our Q4 and full year 2025 financial results and business updates. A replay of today's call will be available on the Investors section of our website approximately one hour after its completion. After our prepared remarks, we will open the call for Q&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.

Speaker #2: A replay of today's call will be available on the Investors section of our website approximately one hour after its completion. After our prepared remarks, we will open the call for Q&A.

Speaker #2: 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.

Speaker #2: 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.

Daniel Ferry: 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 forward-looking statements reflect our opinions only as of today, 12 March 2026. 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.

Dan Ferry: 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 forward-looking statements reflect our opinions only as of today, 12 March 2026. 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.

Speaker #2: Please note that these forward-looking statements reflect our opinions only as of today, March 12, 2026. 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.

Speaker #2: I would now like to turn the call over to Jon Congleton, Chief Executive Officer of Mineralys Therapeutics.

Speaker #3: Thank you, Dan. Good afternoon, everyone, and welcome to our fourth quarter and full year 2025 financial results and corporate update conference call. I'm joined today by Adam Levy, our Chief Financial Officer; Dr. David Rodman, our Chief Medical Officer; and Eric Warren, our Chief Commercial Officer.

Jon Congleton: Thank you, Dan. Good afternoon, everyone, and welcome to our Q4 and full year 2025 financial results and corporate update conference call. I'm joined today by Adam Levy, our Chief Financial Officer, Dr. David Rodman, our Chief Medical Officer, and Eric Warren, our Chief Commercial Officer. I will begin with an overview of the business, our clinical programs and recent milestones, followed by Adam to review our Q4 financial results before we open up the call for your questions. We're pleased to have this opportunity to provide a corporate update as this call comes on the heels of our announcing the FDA's acceptance of the NDA for lorundrostat for the treatment of adult patients with hypertension in combination with other antihypertensive drugs. In connection with the acceptance, the FDA assigned a PDUFA target action date of December 22, 2026.

Speaker #3: I will begin with an overview of the business, our clinical programs, and recent milestones, followed by Adam, who will review our fourth quarter financial results before we open up the call for your questions.

Speaker #3: We're pleased to have this opportunity to provide a corporate update as this call comes on the heels of our announcing the FDA's acceptance of the NDA for Lorunder stat.

Speaker #3: For the treatment of adult patients with hypertension, in combination with other antihypertensive drugs. In connection with the acceptance, the FDA assigned a PDUFA target action date of December 22, 2026.

Speaker #3: This NDA submission followed a successful clinical program, which culminated in the completion of five positive clinical trials that consistently demonstrated clinically meaningful blood pressure reduction, 24-hour control, and a favorable safety profile.

Jon Congleton: This NDA submission followed a successful clinical program which culminated in the completion of 5 positive clinical trials that consistently demonstrated clinically meaningful blood pressure reduction, 24-hour control, and a favorable safety profile. This comprehensive data set has generated broad interest across the medical community, underscoring the significant clinical need in uncontrolled and resistant hypertension and the desire for innovative solutions that help patients meet their blood pressure goals. The NDA includes the positive data from the Launch-HTN and Advance-HTN pivotal trials, as well as the proof of concept trial Explore-CKD and our open-label extension trial, Transform-HTN. Each of these trials demonstrate that lorundrostat maintains a durable and clinically meaningful response across diverse patient populations, a key consideration for its potential as a new treatment for patients with hypertension.

Speaker #3: This comprehensive data set has generated broad interest across the medical community. Underscoring the significant clinical need and uncontrolled and resistant hypertension and the desire for innovative solutions that help patients meet their blood pressure goals.

Speaker #3: The NDA includes the positive data from the launch HTN and advanced HTN pivotal trials, as well as the proof of concept trial Explore CKD and our open label extension trial Transform HTN.

Speaker #3: Each of these trials demonstrate that Lorunder stat maintains a durable and clinically meaningful response across diverse patient populations: a key consideration for its potential as a new treatment for patients with hypertension.

Speaker #3: Uncontrolled and resistant hypertension remain major unmet needs, affecting over 20 million people in the United States, and attributed to nearly 700,000 deaths per year.

Jon Congleton: Uncontrolled and resistant hypertension remain major unmet needs, affecting over 20 million people in the United States and attributed to nearly 700,000 deaths per year. As we have noted previously, roughly 30% of all hypertension patients have dysregulated aldosterone. We are progressively seeing research and updated guidelines that highlight the need to identify and address aldosterone dysregulation in these patients. Our clinical data highlight the differentiated value of targeting aldosterone with an aldosterone synthase inhibitor like lorundrostat, especially when compared to current third and fourth line treatment options.

Speaker #3: As we have noted previously, roughly 30% of all hypertension patients have dysregulated aldosterone. We are progressively seeing research and updated guidelines that highlight the need to identify and address aldosterone dysregulation in these patients.

Speaker #3: Our clinical data highlight the differentiated value of targeting aldosterone with an aldosterone synthase inhibitor like lorundrostat, especially when compared to current third- and fourth-line treatment options.

Speaker #3: To catalyze the successful launch of Lorunder stat, we have begun market access planning and payer engagement to ensure the value proposition of Lorunder stat is understood and appreciated.

Jon Congleton: To catalyze the successful launch of lorundrostat, we have begun market access planning and payer engagement to ensure the value proposition of lorundrostat is understood and appreciated. We have also expanded our medical communications efforts, which will include increased peer-reviewed publications, a larger presence at scientific meetings, and an expanded team of field-based medical science liaisons, which will support broader data dissemination for this potentially transformative therapy. These activities are intended to drive a rapid uptake of lorundrostat and feed into potential partnering opportunities. I would now like to briefly touch on the other development activities we're pursuing to enhance and extend the lorundrostat profile into hypertension with comorbid conditions, which are largely driven by inadequately controlled blood pressure and dysregulated aldosterone. Earlier this week, we issued a press release announcing the top-line results of our exploratory trial, Explore-OSA.

Speaker #3: We have also expanded our medical communications efforts, which will include increased peer-reviewed publications, a larger presence at scientific meetings, and an expanded team of field-based medical science liaisons, which will support broader data dissemination for this potentially transformative therapy.

Speaker #3: These activities are intended to drive a rapid uptake of Lorunder stat and feed into potential partnering opportunities. I would like I would now like to briefly touch on the other development activities we're pursuing to enhance and extend the Lorunder stat profile into hypertension with comorbid conditions.

Speaker #3: These are largely driven by inadequately controlled blood pressure and dysregulated aldosterone. Earlier this week, we issued a press release announcing the top-line results of our exploratory trial, Explore OSA.

Speaker #3: This four-week trial, which enrolled 48 participants, evaluated the safety and efficacy of Lorundestat in participants with moderate to severe obstructive sleep apnea and hypertension.

Jon Congleton: This four-week trial, which enrolled 48 participants, evaluated the safety and efficacy of lorundrostat in participants with moderate to severe obstructive sleep apnea and hypertension. This trial enrolled a high-risk population with an average body mass index of 38, an average apnea-hypopnea index, or AHI, of 48, and baseline systolic blood pressure of 142 mmHg. While lorundrostat did not demonstrate a clinically meaningful difference relative to placebo on the primary endpoint, AHI, the trial did show clinically meaningful reductions in blood pressure and a favorable safety profile in this population with difficult-to-control hypertension. In the pre-planned parallel arm analysis of the first period, the trial demonstrated an 11.1 mmHg blood pressure reduction with lorundrostat and a 1.0 mmHg reduction with placebo at four weeks.

Speaker #3: This trial enrolled a high-risk population with an average body mass index of 38, an average apnea-hypopnea index (AHI) of 48, and a baseline systolic blood pressure of 142 millimeters of mercury.

Speaker #3: While Lorunder stat did not demonstrate a clinically meaningful difference relative to placebo on the primary endpoint, AHI, the trial did show clinically meaningful reductions in blood pressure and a favorable safety profile in this population, with difficult-to-control hypertension.

Speaker #3: In the pre-planned parallel arm analysis of the first period, the trial demonstrated an 11.1 millimeter of mercury blood pressure reduction with Lorundarstat and a 1.0 millimeter mercury reduction with placebo at four weeks.

Speaker #3: There was a 6.2 millimeter mercury placebo-adjusted reduction in blood pressure in the crossover analysis. Lorunder stat demonstrated a favorable safety profile and was well tolerated, with no serum potassium excursions above 5.5 millimoles per liter.

Jon Congleton: There was a 6.2 mm Hg placebo-adjusted reduction in blood pressure in the crossover analysis. Lorundrostat demonstrated a favorable safety profile and was well-tolerated, with no serum potassium excursions above 5.5 mmol/L. Our analysis is ongoing for other endpoints in the trial and will be reported in future publications or medical meetings. Our clinical development strategy has been and will continue to be focused on generating a comprehensive data set that reflects the complexities that physicians face when treating their hypertension patients. We remain focused on fulfilling our mission to develop lorundrostat as a potential best-in-class therapy for patients with uncontrolled or resistant hypertension. We believe the strength of the lorundrostat data generated to date and the significant clinical needs for uncontrolled and resistant hypertension offer substantial opportunity as we prepare for the upcoming milestones.

Speaker #3: Our analysis is ongoing for other endpoints in the trial, and will be reported in future publications or medical meetings. Our clinical development strategy has been and will continue to be focused on generating a comprehensive data set that reflects the complexities that physicians face when treating their hypertension patients.

Speaker #3: We remain focused on fulfilling our mission to develop Lorundestat as a potential best-in-class therapy for patients with uncontrolled or resistant hypertension. We believe the strength of the Lorundestat data generated to date, and the significant clinical needs for uncontrolled and resistant hypertension, offer substantial opportunity as we prepare for the upcoming milestones.

Speaker #3: We are continuing to evaluate further clinical development for lorundostat in comorbidities and other potential indications. We will keep you informed on our progress as appropriate.

Jon Congleton: We're continuing to evaluate further clinical development for lorundrostat in comorbidities and other potential indications. We will keep you informed on our progress as appropriate. I'll now turn the call over to Adam to review our financial results for the Q4 and full year 2025.

Speaker #3: I'll now turn the call over to Adam to review our financial results for the fourth quarter and full year 2025.

Speaker #2: Thank you, John. Good afternoon, everyone. Today, I will discuss select portions of our fourth quarter and full year 2025 financial results. Additional details can be found in our Form 10-K, which will be filed with the SEC today, March 12.

Adam Levy: Thank you, John. Good afternoon, everyone. Today, I will discuss select portions of our Q4 and full year 2025 financial results. Additional details can be found in our Form 10-K, which will be filed with the SEC today, 12 March 2026. We ended the year with cash equivalents, and investments of $656.6 million as of 31 December 2025, compared to $198.2 million as of 31 December 2024. We believe that our cash equivalents, and investments will be sufficient to fund our planned clinical trials and regulatory activities, as well as support corporate operations into 2028. R&D expenses for the year ended 31 December 2025 were $132 million, compared to $168.6 million for the year ended 31 December 2024.

Speaker #2: The end of the year with cash, cash equivalents, and investments of $656.6 million as of December 31st, 2025, compared to $198.2 million as of December 31st, 2024.

Speaker #2: We believe that our cash, cash equivalents, and investments will be sufficient to fund our planned clinical trials and regulatory activities as well as support corporate operations into 2028.

Speaker #2: R&D expenses for the year ended December 31, 2025, were $132 million, compared to $168.6 million for the year ended December 31, 2024. R&D expenses for the quarter ended December 31, 2025, were $24.4 million, compared to $44.6 million for the quarter ended December 31, 2024.

Adam Levy: R&D expenses for the quarter ended December 31, 2025, were $24.4 million compared to $44.6 million for the quarter ended December 31, 2024. The annual decrease in R&D expenses was primarily driven by $49.3 million reduction in preclinical and clinical costs, largely attributable to the conclusion of lorundrostat pivotal program in Q2 2025. The annual decrease was partially offset by increases of $9.9 million in compensation expenses resulting from headcount growth, higher salaries and accrued bonuses, and increased stock-based compensation, as well as $3 million in clinical supply, manufacturing, and regulatory costs. G&A expenses were $38.6 million for the year ended December 31, 2025, compared to $23.8 million for the year ended December 31, 2024.

Speaker #2: The annual decrease in R&D expenses was primarily driven by a $49.3 million reduction in preclinical and clinical costs, largely attributable to the conclusion of the Lorundestat pivotal program in the second quarter of 2025.

Speaker #2: The annual decrease was partially offset by increases of $9.9 million in compensation expenses resulting from headcount growth, higher salaries, and accrued bonuses, and increased stock-based compensation, as well as $3 million in clinical supply, manufacturing, and regulatory costs.

Speaker #2: G&A expenses were $38.6 million for the year ended December 31, 2025, compared to $23.8 million for the year ended December 31, 2024. G&A expenses were $13.9 million for the quarter ended December 31, 2025, compared to $7.2 million for the quarter ended December 31, 2024.

Adam Levy: G&A expenses were $13.9 million for the quarter ended December 31, 2025, compared to $7.2 million for the quarter ended December 31, 2024. The annual increase in G&A expenses was primarily attributable to $8.9 million in higher compensation expense given by headcount growth, higher salaries and accrued bonuses, and increased stock-based compensation. The annual increase was further attributable to $5.3 million in higher professional fees and $0.6 million in other general and administrative expenses. Total other income net was $16 million for the year ended December 31, 2025, compared to $14.6 million for the year ended December 31, 2024.

Speaker #2: The annual increase in G&A expenses was primarily attributable to $8.9 million in higher compensation expense driven by headcount growth, higher salaries, and accrued bonuses, and increased stock-based compensation.

Speaker #2: The annual increase was further attributable to $5.3 million in higher professional fees and $0.6 million in other general and administrative expenses. Total other income, net, was $16.0 million for the year ended December 31, 2025, compared to $14.6 million for the year ended December 31, 2024.

Speaker #2: Total other income, net, was $6.0 million for the quarter ended December 31, 2025, compared to $2.8 million for the quarter ended December 31, 2024.

Adam Levy: Total other income net was $6 million for the quarter ended 31 December 2025, compared to $2.8 million for the quarter ended 31 December 2024. The annual increase was primarily attributable to higher interest earned on investments in money market funds in U.S. Treasuries, resulting from higher average cash balances invested during the year ended 31 December 2025. Net loss was $154.7 million for the year ended 31 December 2025, compared to $177.8 million for the year ended 31 December 2024. Net loss was $32.2 million for the quarter ended 31 December 2025, compared to $48.9 million for the quarter ended 31 December 2024. The annual decrease was primarily attributable to factors impacting our expenses described earlier.

Speaker #2: The annual increase was primarily attributable to higher interest earned on investments in money market funds and U.S. Treasuries, resulting from higher average cash balances invested during the year ended December 31, 2025.

Speaker #2: Net loss was $154.7 million for the year ended December 31, 2025, compared to $177.8 million for the year ended December 31, 2024. Net loss was $32.2 million for the quarter ended December 31, 2025, compared to $48.9 million for the quarter ended December 31, 2024.

Speaker #2: The annual decrease was primarily attributable to factors impacting our expenses described earlier. With that, I will ask the operator to open the call for questions.

Adam Levy: With that, I will ask the operator to open the call for questions. Operator?

Speaker #2: Operator?

Speaker #3: Thank you. We will now be conducting a question-and-answer session. If you would like to ask a question, please press star one on your telephone keypad.

Operator 3: Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press Star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question will come from Michael DiFiore with Evercore ISI.

Operator: Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press Star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question will come from Michael DiFiore with Evercore ISI.

Speaker #3: A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue.

Speaker #3: For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. And our first question will come from Michael DiFiore with Evercore ISI.

Speaker #4: Hi, guys. Thanks so much for taking my question, and congrats on all the continued progress. Two commercial questions for me. Now that the potential launch of Lorundostat is roughly six months behind your direct competitor, what are you hoping to learn from this competitive launch that would optimize the success of Lorundostat's launch?

Michael DiFiore: Hi, guys. Thanks so much for taking my question and congrats on all the continued progress. Two commercial question from me. Now that the potential launch of lorundrostat is roughly six months behind your direct competitor, what are you hoping to learn from this competitive launch that would optimize the success of lorundrostat's launch? Second, could you offer any additional color on the pre-launch payer interactions you've been having? Like, have there been any unexpected changes in anticipated coverage, et cetera? Thank you.

Speaker #4: And second, could you offer any additional color on the pre-launch payer interactions you've been having, like have there been any unexpected changes in anticipated coverage, etc.?

Speaker #4: Thank you.

Speaker #2: Yeah, Mike. Thanks for the questions. We're obviously excited about the timeline we're on now. The day 74 letter giving us the PDUFA date we clearly see a significant market opportunity here with, as we've stated before, about $20 million patients in the United States alone dealing with uncontrolled and resistant hypertension.

Jon Congleton: Yeah, Mike, thanks for the questions. We're obviously excited about the timeline we're on now, the day 74 letter giving us the PDUFA date. We clearly see a significant market opportunity here with, as we've stated before, about 20 million patients in the United States alone dealing with uncontrolled and resistant hypertension. We're obviously aware that AstraZeneca potentially is going to be launching in Q2. I think there'll be some interesting things to identify as far as how they think about pricing, their footprint in the space. Fundamentally, we think this is a large market opportunity. There's certainly room for two novel therapeutics in what I think may be a transformative class overall. We clearly are very bullish on the profile that we've seen with lorundrostat with its best-in-class profile.

Speaker #2: We're obviously aware that AstraZeneca potentially is going to be launching in the second quarter. I think there'll be some interesting things to identify as far as how they think about pricing.

Speaker #2: Their footprint in the space. But fundamentally, we think this is a large market opportunity. There's certainly room for two. Novel therapeutics in what I think may be a transformative class overall.

Speaker #2: We clearly are very bullish on the profile that we've seen with lorundrostat, with its best-in-class profile. As it relates to some of the dialogues that we've had with payers, we continue to feel bullish as it relates to access, particularly where we've targeted lorundrostat's use.

Jon Congleton: As it relates to some of the dialogues that we've had with payers, we continue to feel bullish as it relates to access, particularly where we've targeted lorundrostat's use. That's the third line or later. We think resistant hypertension is the natural opening space, and with experience both from physician standpoint and demand growing into the third line usage. I think it's also important to point out, and I talked about it in my opening remarks, the comprehensive nature of the data set that we've built. When we think about resistant hypertension patients, it's rare that they're isolated to only be dealing with elevated blood pressure. There are so many comorbidities these patients are dealing with. Certainly, that's why we did the Explore-CKD study. It's why we did the Explore-OSA study.

Speaker #2: That's that third line or later. We think resistant hypertension is the natural opening space. And with experience, both from physician standpoint and demand growing into the third line usage, I think it's also important to point out, and I talked about it in my opening remarks, the comprehensive nature of the data set that we've built.

Speaker #2: When we think about resistant hypertension patients, it's rare that they're isolated to only be dealing with elevated blood pressure. There are so many comorbidities these patients are dealing with.

Speaker #2: Certainly, that's why we did the Explore CKD study. It's why we did the Explore OSA study. Even though we did not achieve a benefit on AHI, we know there's significant overlap—over 50% overlap—with resistant hypertension and OSA.

Jon Congleton: Even though we did not achieve a benefit on AHI, we know there's significant overlap, over 50%, with resistant hypertension in OSA. Being able to show the kind of robust, safe benefit we have on blood pressure in this population, we think will have a significant translation into reduced cardiovascular risk for these patients.

Speaker #2: And so, being able to show the kind of robust, safe benefit we have on blood pressure in this population, we think, will have a significant translation into reduced cardiovascular risk for these patients.

Michael DiFiore: Thanks so much.

Speaker #4: Thanks so much.

Speaker #2: Thanks, Mike.

Jon Congleton: Thanks, Mike.

Speaker #3: And our next question comes from Rich Law with Goldman Sachs.

Operator 3: Our next question comes from Richard Law with Goldman Sachs.

Operator: Our next question comes from Rich Law with Goldman Sachs.

Speaker #4: Hey, guys. Congrats on the PDUFA day and getting the NDA accepted. A couple of questions from me. So when you look at the results from the phase two OSA study, do you think the desired limited Lorunder stat's potential to show benefit in the AGI primary endpoint?

Adam Levy: Hey, guys. Congrats on the PDUFA day and getting the NDA accepted. A couple of questions from me. When you look at the results from the Phase 2 OSA study, do you think the design limited lorundrostat's potential to show benefit in the AHI primary endpoint? I mean, the study was much shorter than the historical MRA studies with only four weeks, and you allow CPAP and PAP use. And then the study population was also different from MRA trials. It's not clear to me if the study duration and design really tested lorundrostat's effects one way or the other. How confident are you on the finding and where do you go from here regards to OSA? And then I have a follow-up.

Rich Law: Hey, guys. Congrats on the PDUFA day and getting the NDA accepted. A couple of questions from me. When you look at the results from the phase II OSA study, do you think the design limited lorundrostat's potential to show benefit in the AHI primary endpoint? I mean, the study was much shorter than the historical MRA studies with only four weeks, and you allow CPAP and PAP use. And then the study population was also different from MRA trials. It's not clear to me if the study duration and design really tested lorundrostat's effects one way or the other. How confident are you on the finding and where do you go from here regards to OSA? And then I have a follow-up.

Speaker #4: I mean, the study was much shorter than the historical MRA studies, with only four weeks, and you allowed CPAP and PAP use. And then the study population was also different from MRA trials.

Speaker #4: So it's not clear to me if the study duration and design really tested Lorundestat's effects, one way or the other. How confident are you in the finding?

Speaker #4: And where would you go from here in regards to OSA? And then I have a follow-up.

Speaker #2: Yeah, Rich. Let me give you some opening thoughts and alternatives to Dave. As I noted, the reason we did this study was because we think it's important for the prescribers.

Jon Congleton: Yeah, Rich. Let me give you some opening thoughts, and I'll turn it to Dave. As I noted, you know, the reason we did this study was because we think it's important for the prescribers that are gonna be utilizing lorundrostat to have a clear sense of both efficacy and safety within these complex patients. Being able to show a really robust reduction in BP and doing so safely in these patients that clearly are high risk, particularly the ones that we studied in Explore-OSA with a BMI over 38, with AHI over 48, when severe OSA kicks in above 30, these are patients that have a pretty high cardiovascular risk when you compound that with elevated blood pressure. For us, it was an important study to complete.

Speaker #2: They're going to be utilizing Lorundepstat to have a clear sense of both efficacy and safety within these complex patients. And so, being able to show a really robust reduction in BP and doing so safely in these patients that clearly are high risk—particularly the ones that we studied in Explore OSA, with a BMI over 38, with AHI over 48, when severe OSA is ticked off above 30.

Speaker #2: These are patients that have a pretty high cardiovascular risk when you compound that with elevated blood pressure. So, for us, it was an important study to complete.

Speaker #2: Again, we believe that we're going to be able to operate with our existing label within this population, just given the fact that they have uncontrolled hypertension and elevated cardiovascular risk.

Jon Congleton: Again, we believe that we're gonna be able to operate with our existing label within this population just given the fact that they have uncontrolled hypertension and elevated cardiovascular risk. I'll have Dave talk about some of the design features and his thoughts.

Speaker #2: But I'll have Dave talk about some of the design features and his thoughts.

Speaker #5: Thanks for the question, Rich. Good thoughts. I have a couple of things I want to say. But first of all, directly, was it long enough?

David Rodman: Thanks for the question, Rich. Good thoughts. I have a couple of things I wanna say, but first of all, directly, was it long enough? It's unclear. It could have taken longer than the 4 weeks, but I think there's probably a major interaction between that and the actual study population demographics. In other words, we saw these people were extremely obese. They had extremely high AHIs, close to 50, and their BMIs were 28, with many of them as high as 40.

David Rodman: Thanks for the question, Rich. Good thoughts. I have a couple of things I wanna say, but first of all, directly, was it long enough? It's unclear. It could have taken longer than the four weeks, but I think there's probably a major interaction between that and the actual study population demographics. In other words, we saw these people were extremely obese. They had extremely high AHIs, close to 50, and their BMIs were 28, with many of them as high as 40.

Speaker #5: It's unclear. It could have taken longer than the four weeks. But I think there's probably a major interaction between that and the actual study population demographics.

Speaker #5: In other words, we saw these people were extremely obese. They had extremely high AHIs, close to 50. And their BMIs were 28, with many of them as high as 40.

Speaker #2: 38. 38 on average.

Jon Congleton: 38 on average.

Speaker #5: I'm sorry. Their AHI.

David Rodman: I'm sorry, their AHI.

Speaker #2: AHI was 48, BMI was 38. But please.

Jon Congleton: AHI was 48, BMI of 38. Please.

Speaker #5: Okay, sorry. Thirty-eight. You're right. And so we think the mechanism here, which is—the mechanism is you're fluid overloaded. When you lay down, the fluid goes up into the veins of the neck.

David Rodman: Okay, sorry, 38. You're right. We think the mechanism here, which is the mechanism is you're fluid overloaded. When you lay down, the fluid goes up into the veins of the neck, and that further obstructs the airway. In this population, there's so much extra adipose tissue that it may be that compartment is already obstructing the airway enough just from that structural piece that you wouldn't see any more with decreasing volume. I think the thing to look at going forward, should we wanna answer the question, is take a more representative population similar to the ones that were used in studies like Eplerenone and spironolactone and test it again. I wanna make a different point, if you can just give me a minute, which is this.

Speaker #5: And that further obstructs the airway. In this population, there's so much extra adipose tissue that it may be that that compartment is already obstructing the airway enough just from that structural piece that you wouldn't see any more.

Speaker #5: With decreasing volume. So, I think the thing to look at going forward, should we want to answer the question, is take a more representative population similar to the ones that were used in studies like PARAMOUNT and spironolactone, and test it again.

Speaker #5: But I want to make a different point, if you can just give me a minute, which is this: we did this because we wanted to know about AHI mainly because that's the easier way to register a drug if you want to claim for treatment of OSA.

David Rodman: We did this because we wanted to know about AHI mainly because that's the easier way to register a drug if you wanna claim for treatment of OSA. That's not necessarily our objective. Our objective is to know whether we're gonna have a benefit on long-term outcomes in patients with OSA. The interesting point is, if you make AHI less than 5 with CPAP, it doesn't reduce your blood pressure, and there's no compelling evidence that it makes your long-term cardiovascular outcomes any better. It's really simply a way to look at the regulatory effect. On the other hand, the reduction in blood pressure we saw is comparable to, it predicts rather, and the agency gives you sort of the claim for improved outcomes.

Speaker #5: But that's not necessarily our objective. Our objective is to know whether we're going to have a benefit on long-term outcomes in patients with OSA.

Speaker #5: And the interesting point is if you make AHI less than 5 with CPAP, it doesn't reduce your blood pressure. And there's no compelling evidence that it makes your long-term cardiovascular outcomes any better.

Speaker #5: So, it's really simply a way to look at the regulatory effect. On the other hand, the reduction in blood pressure we saw is comparable to—or predicts, rather.

Speaker #5: And the agency gives you sort of the claim for improved outcomes. And at the 10 millimeters of mercury that we saw in the point estimate analysis, that's been shown to have about a 17% incidence of reduced coronary heart disease, 27% of stroke, and 28% of heart failure.

David Rodman: At the 10 millimeters of mercury that we saw in the point estimate analysis, that's been shown to have about a 17% incidence of reduced coronary heart disease, 27% of stroke, and 28% of heart failure. What we learned here was that we have the potential to be disease-modifying in sleep apnea. As Jon mentioned, we can get to that point with the label we have or we're gonna have already for treatment of uncontrolled resistant hypertension. It's been reported that 80% of these patients have uncontrolled or resistant hypertension. That's the long and the short of it. We don't need to prove it works in AHI 'cause our objective isn't to make a therapy for upper airway obstruction. It's to make a therapy that makes these people live longer, better lives.

Speaker #5: So what we learned here was that we have the potential to be disease-modifying in sleep apnea and, as John mentioned, we can get to that point with the label we have or we're going to have already for treatment of uncontrolled resistant hypertension.

Speaker #5: It's been reported that 80% of these patients have uncontrolled or resistant hypertension. So that's the long and the short of it. We don't need to prove it works in AHI because our objective isn't to make a therapy for upper airway obstruction.

Speaker #5: It's to make a therapy that makes these people live longer, better lives.

Speaker #4: Okay, got it. And then just to kind of go to my second question—I know you guys are still exploring the partnership, but would the PDUFA date now set in December, which is about nine months from now?

Richard Law: Okay, got it. And then, just to kind of, for my second question, I know you guys are still exploring the partnership, but with the PDUFA date now set in December, which is about 9 months from now, can you discuss like what kind of commercial capability have you been building? And how large is that commercial team now, and what commercial hires are you still holding back, while you're continuing to explore the partnership? And then is there any urgency to build a full commercial capability now in case a partnership may not occur until after the PDUFA date? Thank you.

David Rodman: Okay, got it. And then, just to kind of, for my second question, I know you guys are still exploring the partnership, but with the PDUFA date now set in December, which is about 9 months from now, can you discuss like what kind of commercial capability have you been building? And how large is that commercial team now, and what commercial hires are you still holding back, while you're continuing to explore the partnership? And then is there any urgency to build a full commercial capability now in case a partnership may not occur until after the PDUFA date? Thank you.

Speaker #4: Can you discuss what kind of commercial capability you have been building? And how large is that commercial team now? And what commercial hires are you still holding back while you continue to explore the partnership?

Speaker #4: And then, is there any urgency to build a full commercial capability now in case a partnership may not occur until after the PDUFA date?

Speaker #4: Thank you.

Speaker #2: Yeah, thanks, Rich. I'll take you back five years ago. We've always made discrete investment choices that support this molecule and put it in its best position to deliver value for the most appropriate patients possible.

Jon Congleton: Yeah. Thanks, Rich. I'll take you back five years ago. We've always made discrete investment choices that support this molecule and put it in its best position to deliver value for the most appropriate patients possible. Early days, that was CMC, that was clin pharm. Where we're at now is we're making those right investment choices, and we began this late last year, as you're aware, and we're continuing it now to ensure that we're preparing the market. That's why Eric and his team are beginning to have dialogues with payers. It's why we're expanding our medical affairs capabilities from continued data dissemination.

Speaker #2: And so, early days, that was CMC, that was Clint Pharm. Where we're at now is we're making those right investment choices. And we began this late last year, as you're aware.

Speaker #2: We're continuing it. Now, to ensure that we're preparing the market—and so that's why Eric and his team are beginning to have dialogues with payers.

Speaker #2: It's why we're expanding our medical affairs capabilities from continued data dissemination. I mean, we have just a wealth of clinical data that we've accumulated last year, and even as recently as the EXPLORE OSA, that we're going to continue to put into the public forum via medical meetings and publications.

Jon Congleton: I mean, we have just a wealth of clinical data that we've accumulated last year and even as recently as the Explore-OSA that we're gonna continue to put in the public forum via medical meetings and publications. We're expanding our MSL team. I don't wanna give numbers, Rich, other than to say we're continuing to do everything we can to ensure a rapid uptake on the potential approval of lorundrostat for uncontrolled and resistant hypertension. I think fundamentally, that's the right thing for us to do because it also, it becomes very informative and potentially catalyzes those partnering dialogues. We've heard that from potential partners, but we need to make sure that we're continuing to invest in this asset, so upon approval, it does have a rapid uptake and a rapid launch.

Speaker #2: We're expanding our MSL team. I don't want to give numbers, Rich, other than to say we're continuing to do everything we can to ensure a rapid uptake on the potential approval of Lorundestat for uncontrolled and resistant hypertension.

Speaker #2: And I think fundamentally, that's the right thing for us to do because it also becomes very informative and potentially catalyzes those partnering dialogues. And we've heard that from potential partners.

Speaker #2: But we need to make sure that we're continuing to invest in this asset, so upon approval, it does have a rapid uptake and a rapid launch.

Speaker #4: Got it. Thank you.

Rami Katkhuda: Got it. Thank you.

Rich Law: Got it. Thank you.

Speaker #2: Thanks, Rich.

Jon Congleton: Thanks, Rich.

Speaker #1: We'll go next to Seamus Fernandez with Guggenheim Partners.

Operator 3: We'll go next to Seamus Fernandez with Guggenheim Partners.

Operator: We'll go next to Seamus Fernandez with Guggenheim Partners.

Speaker #6: Oh, thanks. So just to follow up on the commercial side of things, can you just help us understand what you believe the number of reps would be to launch the Lorender stat effectively versus AstraZeneca?

Seamus Fernandez: Oh, thanks. Just to follow up on the commercial side of things, can you just help us understand, you know, what you believe the number of reps would be to, you know, launch the lorundrostat effectively versus AstraZeneca? And do you envision having a, you know, sort of differentiated approach to market than Astra? You know, if there is a differentiated approach, what would that be?

Speaker #6: And do you envision having a sort of differentiated approach to market than Astra? If there is a differentiated approach, what would that be?

Speaker #2: Yeah, I don't know that I'll give you a specific number, Seamus, and we're continuing to evaluate that. But as you've heard us say before, when we look at where we've developed this molecule—third line or later—and in the United States, who prescribes there, it's about 60,000 physicians.

Jon Congleton: Yeah, I don't know that I'll give you a specific number, Seamus, and we're continuing to evaluate that. As you've heard us say before, when we look at where we've developed this molecule third line or later, and in the United States, who prescribes there, it's about 60,000 physicians that are responsible for half of the scripts third line or later. That's kind of a broad way to look at the market. I don't wanna give too much on our intended commercial strategy, but I will say that if you look at the comprehensive dataset that we have, Advance-HTN confirmed hypertension. That was the study we did with the Cleveland Clinic. Explore-CKD that looks at hypertension and comorbid chronic kidney disease.

Speaker #2: That are responsible for half of the script, third line or later. So that's kind of a broad way to look at the market. I don't want to give too much on our intended commercial strategy.

Speaker #2: But I will say that if you look at the comprehensive data set that we have advanced HTN confirmed hypertension, that was the study we did with the Cleveland Clinic.

Speaker #2: EXPLORE CKD that looks at hypertension and comorbid chronic kidney disease. And then, if you look at the OSA population, the data that just came out of the EXPLORE OSA—that's going to begin to inform how we think about subsegments of physicians that are treating specific types of hypertension with related comorbidities.

Jon Congleton: If you look at the OSA population, the data that just came out of the Explore-OSA, that's gonna begin to inform how we think about subsegments of physicians that are treating specific types of hypertension with related comorbidities. We'll begin to look at the broad IMS data, but then also in the context of these subsegments that we think can give us rapid uptake within the resistant hypertension population, and then with experience, move rapidly in the third line as well.

Speaker #2: And so, we'll begin to look at the broad IMS data, but then also in the context of these subsegments that we think can give us rapid uptake within the resistant hypertension population.

Speaker #2: And then, with experience, move rapidly into third line as well.

Speaker #6: Great. And then maybe just as a follow-up, is there kind of a timing-related dynamic? How much of a de-risking event—not just for Mineralys, but perhaps for strategics—would you say the availability, the assignment of a PDUFA date actually is, broadly speaking?

Seamus Fernandez: Great. Then maybe just as a follow-up, is there kind of a timing related dynamic? How much of a de-risking event, not just for Mineralys, but perhaps for strategics, would you say the availability, the assignment of a PDUFA date actually is, you know, broadly speaking?

Speaker #2: Yeah. I think each step along this journey there's a level of de-risking and a level of increasing value. That began last year with the readout of advanced and launch.

Jon Congleton: Yeah. I think each step along this journey. There's a level of de-risking and a level of increasing value. That began last year with the readout of Advance and Launch. It continued with the submission of the NDA last year. I think Day 74, both acceptance of and PDUFA date for lorundrostat further de-risks the molecule and brings value nearer term. You know, maybe related to that, when is an ideal time to identify a partnership? I think that these partnerships, they have a life of their own, a timeline of their own. Our goal is to really identify a means to generate the greatest value with lorundrostat, which means getting the molecule in front of the most appropriate patients in the United States and in due course, outside of the United States.

Speaker #2: It continued with the submission of the NDA last year. I think the Day 74, both acceptance of and PDUFA date for Lorendystat, further de-risks the molecule and brings value nearer term.

Speaker #2: Maybe related to that, when is an ideal time to identify a partnership? I think that these partnerships have a life of their own, a timeline of their own.

Speaker #2: Our goal is to really identify a means to generate the greatest value with Lorender stat, which means getting the molecule in front of the most appropriate patients in the United States and in due course outside of the United States.

Speaker #2: So those are all of the things that go into the calculus as we think about maximizing the value of Lorundestad through partnering?

Jon Congleton: Those are all of the things that go into the calculus as we think about maximizing the value of lorundrostat through partnering.

Speaker #6: Great. Thanks so much.

Seamus Fernandez: Great. Thanks so much.

Speaker #2: Thanks, Seamus.

Jon Congleton: Thanks, Seamus.

Speaker #1: And moving next to Jason Gerberry with Bank of America.

Operator 3: Moving next to Jason Gerberry with Bank of America.

Operator: Moving next to Jason Gerberry with Bank of America.

Speaker #7: Hey, guys. Thanks for taking my questions. Just wanted to quickly follow up on the payer access discussions. I think the comment was maybe favorable access with a certain segment of payers.

Jason Gerberry: Hey, guys. Thanks for taking my questions. Just wanted to quickly follow up on the payer access discussions. I think the comment was maybe favorable access with a certain segment of payers. I was wondering if you can expand upon that a little bit and just get a sense of your confidence in breadth of quality coverage, 3L plus, as I guess you've articulated in the past. Then one CFO question here, just from an R&D perspective, thinking about 2026 R&D relative to 2025, should we be thinking about cash burn mitigation effort, or is 2025 a good run rate for the company? Last one for me is just on the OUS regulatory submissions.

Speaker #7: So I was wondering if you can expand upon that a little bit, and just get a sense of your confidence in breadth of quality coverage, 3L-plus, as I guess you've articulated in the past.

Speaker #7: And then, one CFO question here, just from an R&D perspective, but thinking about 2026 R&D relative to 2025—should we be thinking about, I don't know, cash burn mitigation effort, or is 2025 a good run rate for the company?

Speaker #7: And then, last one for me is just on the OUS regulatory submissions. Apologies if I missed this in past commentary from you guys, but is that in any way gated at all by the partnership discussions?

Jason Gerberry: Apologies if I missed this in past commentary from you guys, but is that in any way gated at all by the partnership discussions? Just if you can give us a sense of, you know, when you anticipate the OUS submissions. Thanks.

Speaker #7: If you can give us a sense of when you anticipate the OUS submissions. Thanks.

Speaker #2: Yeah, thanks. Let me maybe give some quick thought on payer, and then I'll have Eric add some additional color. We've done a great deal of research in this area.

Jon Congleton: Yeah, thanks. Let me maybe give some quick thought on payer, and then I'll have Eric add some additional color. We've done a great deal of research in this area. Obviously, it's probably one of the most critical vectors to ensure that we get lorundrostat to the appropriate patients with as few barriers as possible. I think we continue to feel very strong about the value proposition of lorundrostat, the need specifically in the resistant hypertension population. We believe that both the combination of appropriate price and rebate is gonna create that access. Eric, I don't know if you wanna add some additional thoughts. I know your team continues to work aggressively on this.

Speaker #2: Obviously, it's probably one of the most critical vectors to ensure that we get Lorundestat to the appropriate patients with as few barriers as possible.

Speaker #2: I think we continue to feel very strongly about the value proposition of lorundrostat. The need, specifically in the resistant hypertension population, and so we believe that both the combination of appropriate price and rebate is going to create that access.

Speaker #2: But Eric, I don't know if you want to add some additional thoughts. I know your team continues to work aggressively on this.

Speaker #3: Yeah. Yeah. And Jason, I'm just back from a large payer conference in Orlando, PCMA, where the team was engaging Medicare as well as commercial payers.

Eric Warren: Jason, I'm just back from a large payer conference in Orlando PCMA, where the team was engaging Medicare as well as commercial payers. I will say we're on their radar. They're very well aligned with the positioning that Jon spoke of, and we're now in the midst of scheduling these pre-approval information exchange or PIE discussions. We've got a favorable footprint and interaction, you know, kind of cadence with payers.

Speaker #3: I will say we're on their radar. They're very well aligned with the positioning that Jon spoke of. And we're now in the midst of scheduling these pre-approval information exchange, or PIE, discussions.

Speaker #3: So we've got a favorable footprint. And interaction kind of cadence with payers.

Speaker #2: And then Jason, I think to your second question, Adam, do you want to add some thoughts?

Jon Congleton: Jason, I think to your second question, Adam, do you wanna add some thoughts?

Speaker #4: Yeah. So Jason, we have an intended to give guidance on R&D, but I can tell you that in 2025, we're running a number of trials.

Adam Levy: Yeah. Jason, we haven't intended to give guidance on R&D, but I can tell you that in 2025, we're running a number of trials. We had Launch-HTN, Advance-HTN, Explore-CKD for part of that year, Explore-OSA, plus the open-label extension. It was a heavy lift on R&D for us in 2025. When you roll into 2026, we've been wrapping up the costs on the OSA trial. We still have the open-label extension running. There may be other R&D that we decide to do this year, but I would expect that there's less R&D activity in 2026 than we had in our 2025, at least to our current or existing plans. Does that help?

Speaker #4: We had launch HTN, advanced HTN, EXPLORE CKD for part of that year, EXPLORE OSA, plus the open label extension. So it was a heavy lift on R&D for us in 2025.

Speaker #4: When you roll into 2026, we've been wrapping up the costs on the OSA trial. We still have the open label extension running. There may be other R&D that we decide to do this year, but I would expect that there's less R&D activity in 2026 than we had in 2025, at least according to our existing plans.

Speaker #4: Does that help?

Speaker #6: Yep. Thank you.

Eric Warren: Yep. Thank you.

Jason Gerberry: Yep. Thank you.

Speaker #2: And Jason, to your last question, if I recall it right, XUS and how to partnerships play within that. As we've spoken about in the past, our goal is certainly to try to get Lorender stat to as many patients in the United States as well as outside of the United States.

Jon Congleton: Jason, to your last question, if I recall it right, ex-US and how do partnerships play within that? As we've spoken about in the past, our goal is certainly to try to get lorundrostat to as many patients in the United States as well as outside of the United States, as appropriate. We know there are some complexities right now between MFN and tariffs that we're continuing to evaluate. Partnering may play a role in that, and it may play a role, you know, beyond just a co-promotion. This is where co-development becomes an interesting opportunity.

Speaker #2: As appropriate, we know there are some complexities right now between MFN and tariffs that we're continuing to evaluate partnering may play a role in that.

Speaker #2: And it may play a role beyond just a co-promotion. This is where co-development becomes an interesting opportunity. I think David and his team have done such an excellent job of characterizing Lorender stat, not just in hypertension, but in so many of these related comorbidities that that creates an opportunity for us to assess what is the appropriate way to introduce Lorender stat outside of the United States?

Jon Congleton: I think Dave and his team have done such an excellent job of characterizing lorundrostat, not just in hypertension, but in so many of these related comorbidities, that creates an opportunity for us to assess what is the appropriate way to introduce lorundrostat outside of the United States. Is it as a monotherapy? Is it potentially any fixed-dose combination strategy? Those are still things we're evaluating, and once we've made a solid plan relative to that, we'll certainly be communicating that.

Speaker #2: Is it as a monotherapy, as a potential in a fixed-dose combination strategy? Those are still things we're evaluating. And once we've made a solid plan relative to that, we'll certainly be communicating that.

Speaker #6: Yeah. Thanks, John.

Eric Warren: Yeah. Thanks, Jon.

Jason Gerberry: Yeah. Thanks, Jon.

Speaker #2: Thanks, Jason.

Jon Congleton: Thanks, Jason.

Speaker #1: Moving on to Annabelle Samimi with Stifel.

Operator 3: Moving on to Annabel Samimy with Stifel.

Operator: Moving on to Annabel Samimy with Stifel.

Speaker #8: Hi. Thanks for taking my question. Just a little bit more on the commercial side. Maybe you can help—I know it's probably too early to talk about pricing.

Annabel Samimy: Hi. Thanks for taking my question. Just a little bit more on the commercial side. Maybe you can help. I know it's probably too early to talk about pricing, but is there any scenario where the competitor can angle for third line while you're putting yourself in fourth line first? Are you thinking about the possibility of using pricing as a competitive lever? What kind of things do you need to do to get yourself into third line? As a follow-up to that, just with Explore-CKD and Explore-OSA, are you actually seeking to put it in the label as a differentiating feature, or just have the data available for presentation and publication? Thanks.

Speaker #8: But is there any scenario where the competitor can angle for third line while you're putting yourself in fourth line first? Are you thinking about the possibility of using pricing as a competitive lever?

Speaker #8: And what kind of things do you need to do to get yourself into third line? And then as a follow-up to that, just with EXPLORE CKD and EXPLORE OSA, are you actually seeking to put it in the label?

Speaker #8: As a differentiating feature, or just have the data available for presentation and publication? Thanks.

Speaker #2: Yeah, I think it's too early to give you too much specificity on pricing. I can't really speak to where AstraZeneca may go from a pricing, line of treatment approach.

Jon Congleton: Yeah. I think it's too early to give you too much specificity on pricing. I can't really speak to, you know, where AstraZeneca may go from a pricing line of treatment approach. I can tell you as Eric kind of alluded to, and I did in my prior comments, that based on the research we've done with payers right now, the value proposition of lorundrostat certainly resonates fourth line with some payers even third line. I think it's gonna be, as I noted, a beachhead at fourth line. That's clearly where there's unmet need. That's clearly where the value proposition resonates. With experience and demand, I think that begins to open up third line.

Speaker #2: I can tell you, as Eric kind of alluded to—and I did in my prior comments—that based on the research we've done with payers right now, the value proposition of Lorenderstat certainly resonates fourth line with some payers, even third line.

Speaker #2: I think it's going to be as I noted a beachhead at fourth line. That's clearly where there's unmet need. That's clearly where the value proposition resonates.

Speaker #2: And with experience and demand, I think that begins to open up third line. We've talked in the past, Annabelle, that as a guidance or a frame for pricing, we've always directed to probably more of an SGLT2-branded price point, Entresto price point, broadly at a whack.

Jon Congleton: You know, we've talked in the past, Annabel, that as a guidance or a frame for pricing, we've always directed to probably more of a SGLT2 branded price point, Entresto price point, broadly at a WAC, but haven't guided as it relates to rebates. To your second question, as I noted in my prepared remarks, we do anticipate having Explore-CKD as part of the NDA application. That'll be part of a negotiation, what portion of that data may be reflected within the label. We believe that the blood pressure reduction data from Explore-CKD is informative for prescribers, and that'll be part of our positioning from a negotiation standpoint. Explore-OSA was not part of the original NDA application.

Speaker #2: But having guided as it relates to rebates. To your second question, as I noted in my prepared remarks, we do anticipate having EXPLORE CKD as part of the NDA application.

Speaker #2: That'll be part of a negotiation what portion of that data may be reflected within the label. We believe that the blood pressure reduction data from EXPLORE CKD is informative for prescribers.

Speaker #2: And that'll be part of our positioning from a negotiation standpoint. EXPLORE OSA was not part of the original NDA application. It may be part of continued safety updates.

Jon Congleton: That may be part of continued safety updates, but the actual data was not available at the time the NDA submission was made. We do think both of those trials will be very informative to the medical community. We will be using medical meetings, publications, and our medical science liaison team to certainly convey the important messages contained within both of those studies.

Speaker #2: But the actual data was not available at the time the NDA submission was made. But we do think both of those trials will be very informative to the medical community.

Speaker #2: We will be using medical meetings, publications, and our medical science liaison team to certainly convey the important messages contained within both of those studies.

Speaker #8: Okay. And is there any possibility to share other comorbidities you might be interested in exploring that could be particularly impacted by hypertension lowering agents?

Annabel Samimy: Okay. Is there any possibility to share other comorbidities you might be interested in exploring that could be particularly impacted by hypertension lowering agents?

Speaker #2: Yeah, I think I'd go a little bit deeper than hypertension agents. Very specifically, aldosterone-driven conditions. When we talk about 30% of hypertension patients having dysregulated aldosterone, I think, by extension, that goes into other conditions like CKD, like OSA, as David spoke about before, and heart failure.

Jon Congleton: Yeah. I think I'd go a little bit deeper than hypertension agents. Very specifically aldosterone-driven conditions. You know, when we talk about 30% of hypertension patients have dysregulated aldosterone, I think by extension that goes into other conditions. Like CKD, like OSA, as David's spoken about before. Heart failure we've mentioned is a place where clearly aldosterone plays a significant role in the risk profile of those patients. There are some other indications that we've continued to look at that we haven't really spoken about yet. As I said in a previous response to a question, we believe that there are significant opportunities. Some of those are ones that we would pursue on our own. I think some of those others are ones that we've you know, thought about having partnering involvement with.

Speaker #2: We've mentioned this as a place where, clearly, aldosterone plays a significant role in the risk profile of those patients. There are some other indications that we've continued to look at, that we haven't really spoken about yet.

Speaker #2: But as I said in a previous response to a question, we believe that there are significant opportunities. Some of those are ones that we would pursue on our own.

Speaker #2: I think some of those others are ones that we've thought about having partnering involvement with. But yeah, it's clearly at this stage Lorender stat extremely well characterized for what it does to aldosterone and how it safely addresses that.

Jon Congleton: Yeah, it's clearly at this stage, lorundrostat extremely well characterized for what it does to aldosterone, how it safely addresses that, and we think it opens up a lot of other opportunities. As we said in the remarks, as we solidify those development plans, we'll be sure to convey those to the market.

Speaker #2: And we think it opens up a lot of other opportunities. And as we said in the remarks, as we solidify those development plans, we'll be sure to convey those to the market.

Speaker #8: Okay. Thank you.

Rami Katkhuda: Okay. Thank you.

Annabel Samimy: Okay. Thank you.

Speaker #2: Thanks, Annabelle.

Jon Congleton: Thanks, Annabel.

Speaker #1: And our next question will come from Mohit Bansal with Wells Fargo.

Operator 3: Our next question will come from Mohit Bansal with Wells Fargo.

Operator: Our next question will come from Mohit Bansal with Wells Fargo.

Speaker #6: Great, thank you very much for taking my question, and congrats on all the progress. Just one question—just to double-click on the 60,000 prescriber number, John, you mentioned.

David Brown: Great. Thank you very much for taking my question, and congrats on all the progress. Just one question. Just trying to double-click on the 60,000 prescriber number, John, you mentioned. Wondering, like, is this primary care heavy or these are specialists that you would be targeting? And then what sort of role direct-to-consumer marketing type of mechanism could play for a market like this? Thank you.

Mohit Bansal: Great. Thank you very much for taking my question, and congrats on all the progress. Just one question. Just trying to double-click on the 60,000 prescriber number, John, you mentioned. Wondering, like, is this primary care heavy or these are specialists that you would be targeting? And then what sort of role direct-to-consumer marketing type of mechanism could play for a market like this? Thank you.

Speaker #6: Wondering, is this primary care-heavy, or are these specialists that you would be targeting? And then, what sort of role could a direct-to-consumer marketing type of mechanism play for a market like this?

Speaker #6: Thank you.

Speaker #2: Yeah. Mohit, I think it's important that there's two vectors that Eric and his team are looking at. And it's the broad prescriber data that everybody can look at, the IQVIA data.

Jon Congleton: Yeah. Mohit, I think it's important that there's two vectors that Eric and his team are looking at, and it's the broad, you know, prescriber data that everybody can look at, the IQVIA data, and that's where the 60,000 as a broad target comes from. It's about a 60/40 split, primary care specialty, the bulk of the specialty being cardiologists. Then there's another vector that we're looking at, this and that is for those resistant hypertension patients with comorbidities, who's managing those patients? Hypertension and CKD, hypertension and OSA, confirmed hypertension. You know, and even the Black or African American population because we know we have done a considerable job to make sure we have proper representation within our clinical trials.

Speaker #2: And that's where the 60,000 is a broad target comes from. It's about a 60/40 split. Primary care specialty, the bulk of the specialty being cardiologists.

Speaker #2: But then there's another vector that we're looking at this. And that is for those resistant hypertension patients with comorbidities whose managing those patients. So hypertension and CKD, hypertension and OSA, confirmed hypertension.

Speaker #2: And even the Black or African-American population, because we know we have done a considerable job to make sure we have proper representation within our clinical trials.

Speaker #2: And so we're taking the broad macro data from a prescribing standpoint, but also informing that with primary market research to see where are the true targets they can really ensure that we're getting Lorender stat as rapidly to as many appropriate patients as possible.

Jon Congleton: We're taking the broad macro data from a prescribing standpoint, but also informing that with primary market research to see where are the true targets they can really ensure that we're getting lorundrostat as rapidly to as many appropriate patients as possible. I'm sorry, I think you had a second part of your question, Mohit.

Speaker #2: And I'm sorry, I think you had a second part of your question. Mohit?

Speaker #6: Yeah. So yeah, thank you for this. But I was thinking part was more about the direct-to-consumer marketing sort of mechanism. What sort of role it could play for a company like yours?

David Brown: Yeah. Yeah. Thank you for this. Second part was more about the direct-to-consumer marketing sort of mechanism. Like, what sort of role it could play for a company like you, yours.

Mohit Bansal: Yeah. Yeah. Thank you for this. Second part was more about the direct-to-consumer marketing sort of mechanism. Like, what sort of role it could play for a company like you, yours.

Speaker #2: Yeah. I don't know that we're in a position quite yet to talk about the consumer strategy. But obviously, we'll want to be speaking to patients, reiterating the importance of getting their blood pressure under control, seeking different means to do that, whether it's diet, exercise, or therapeutics.

Jon Congleton: Yeah. I don't know that we're in a position quite yet to talk about the consumer strategy, but obviously we'll want to be speaking to patients, reiterating the importance of getting their blood pressure under control, seeking different means to do that, whether it's diet, exercise, or therapeutics, and the benefits specifically of lorundrostat, particularly if they have overlapping comorbidities where we have data that can speak to the opportunity for lorundrostat to help them get to goal and subsequently have hopefully longer lives and better lives.

Speaker #2: And the benefits specifically of lorundrostat, particularly if they have overlapping comorbidities, where we have data that could speak to the opportunity for lorundrostat to help them get to goal and, subsequently, have hopefully longer lives and better lives.

Speaker #6: Very helpful. Thank you.

David Brown: Very helpful. Thank you.

Mohit Bansal: Very helpful. Thank you.

Speaker #2: Thanks, Mohit.

Jon Congleton: Thanks, Mohit.

Speaker #8: We'll go next to Rami Khatkouda with LifeSci Capital.

Operator 3: We'll go next to Rami Katkhuda with LifeSci Capital.

Operator: We'll go next to Rami Katkhuda with LifeSci Capital.

Speaker #9: Hey, guys. Thanks for taking my questions as well. I guess I know it was a small study, but did you observe any differential treatment effects in blood pressure reductions or AHI across any kind of key subgroups in EXPLORE OSA?

Rami Katkhuda: Hey, guys. Thanks for taking my questions as well. I guess I know it was a small study, but did you observe any differential treatment effects in blood pressure reductions or AHI across any kind of key subgroups in Explore-OSA? I guess a particular focus in those receiving and not receiving CPAP. Maybe secondly, I know you touched upon potential future indications. Is the goal to be first in class for those indications, or are they large enough, similar to hypertension, where it doesn't matter?

Speaker #9: And I guess a particular focus in those receiving and not receiving CPAP? And then maybe secondly, I know you touched upon potential future indications.

Speaker #9: Is the goal to be first-in-class for those indications, or are they large enough—similar to hypertension—where it doesn't matter?

Speaker #2: I'll let Dave answer the first part, and then I'll address your second one on other indications, Rami.

Jon Congleton: I'll let Dave answer the first part, and then I'll address your second one on other indications, Rami.

Speaker #10: Thanks, Rami. So we're in the midst of examining deeper into the data. And one of the things we're doing right now is looking at your question of subsets.

David Rodman: Thanks, Rami. We're in the midst of examining deeper into the data, and one of the things we're doing right now is looking at your question of subsets. You're right, it is a small trial, so it will be hypothesis generating more than proving hypotheses, but that's still really useful. We intend to present that kind of analysis at future publications and meeting presentations. Just stay tuned for that. In terms of the CPAP, about a third of the subjects or a quarter were on CPAP, and we didn't see any difference between those groups. Again, they're pretty small numbers, so I don't wanna hang my hat on that.

Speaker #10: You're right, it is a small trial. So it will be hypothesis-generating more than proving hypotheses, but that's still really useful. And we intend to present that kind of analysis at future publications and meeting presentations.

Speaker #10: So just stay tuned for that. In terms of the CPAP, about a third of the subjects or a quarter were on CPAP, and we didn't see any difference between those groups.

Speaker #10: But again, they're pretty small numbers, so I don't want to hang my hat on that.

Speaker #2: Yeah. And Rami, to your follow-up question, as it related to I'll go ahead. Would you repeat it for me one more time? I want to make sure I address it specifically.

Jon Congleton: Yeah. Rami, to your follow-up question as it related to. No, go ahead. Would you repeat it for me one more time? I wanna make sure I address it specifically.

Speaker #9: Yeah. I just wanted to check in and see if those indications, the goal is to be first-in-class there, or could you kind of pursue larger indications?

Rami Katkhuda: Yeah. I just wanted to check in and see if those indications, the goal is to be first in class there, or could you kind of pursue larger indications. I know you mentioned heart failure, where they're large enough to encompass multiple winners here in the ASI class?

Speaker #9: I know you mentioned heart failure, where they're large enough to encompass multiple winners here in the ASI class.

Speaker #2: Yeah. I think what our intent is is to not be a follower. And what do I mean by that? We know that Depogliflozone is going to be generic potentially this year.

Jon Congleton: Yeah. I think what our intent is to not be a follower. What do I mean by that? We know that dapagliflozin is gonna be generic potentially this year. I think some of what's being done with the ASIs tend to be more lifecycle management combined with an SGLT2. I don't know that we're looking to frankly get into that mud fight. I think there's gonna be ample opportunity, and with the data that we have for physicians to use lorundrostat with the SGLT2 of choice if patients have an overlapping comorbidity like CKD with their hypertension. As I noted in a previous response, we know that dysregulated aldosterone plays a significant role across the spectrum of cardiorenal metabolic disorders.

Speaker #2: I think some of what's being done with the ASIs tend to be more lifecycle management combined with an SGLT2. I don't know that we're looking to, frankly, get into that mud fight.

Speaker #2: I think there's going to be ample opportunity and with the data that we have for physicians to use Lorender stat with the SGLT2 of choice.

Speaker #2: If patients have an overlapping comorbidity like CKD with their hypertension, as I noted in a previous response, we know that dysregulated aldosterone plays a significant role across the spectrum of cardiorenal metabolic disorders.

Speaker #2: That's what's informing how we think about where is the white space, where is the opportunity for us to take what we believe to be the best-in-class aldosterone synthase inhibitor and, either alone or in some distinct combinations, bring forward solutions for those patients.

Jon Congleton: That's what's informing how we think about where is the white space, where is the opportunity for us to take what we believe to be the best-in-class aldosterone synthase inhibitor and either alone or in some distinct combinations, bringing forward solutions for those patients.

Speaker #9: Got it. Thank you very much.

Operator 2: Got it. Thank you very much.

Rami Katkhuda: Got it. Thank you very much.

Jon Congleton: Mm-hmm.

Speaker #8: And going next to Dennis Ding with Jefferies.

Operator 3: Going next to Dennis Ding with Jefferies.

Operator: Going next to Dennis Ding with Jefferies.

Speaker #11: Hi. Thank you for taking our questions. This is Georgia Bank on the line for Dennis Ding. Maybe a little bit more on the potential partnerships and if you could talk about what an ideal partnership looks like in terms of capabilities and also creative deal structuring.

Speaker 19: Hi. Thank you for taking our questions. This is Georgia Bank on the line for Dennis Ding. Maybe a little bit more on the potential partnerships and if you could talk about what an ideal partnership looks like in terms of capabilities and also creative deal structuring. Obviously the commercial infrastructure is important, but what other nuances are important to you maybe in terms of R&D funding or bigger indications in payer relationships? I know that you mentioned that there's opportunity in pursuing some indications on your own and others involved, maybe partnering it on. Any color there would be helpful. Thank you.

Georgia Bank: Hi. Thank you for taking our questions. This is Georgia Bank on the line for Dennis Ding. Maybe a little bit more on the potential partnerships and if you could talk about what an ideal partnership looks like in terms of capabilities and also creative deal structuring. Obviously the commercial infrastructure is important, but what other nuances are important to you maybe in terms of R&D funding or bigger indications in payer relationships? I know that you mentioned that there's opportunity in pursuing some indications on your own and others involved, maybe partnering it on. Any color there would be helpful. Thank you.

Speaker #11: Obviously, the commercial infrastructure is important, but what other nuances are important to you? Maybe in terms of R&D funding or bigger indications and payer relationships.

Speaker #11: I know that you mentioned that there's opportunity in pursuing some indications on your own and others involved maybe partnering in on. Any color there would be helpful.

Speaker #11: Thank you.

Speaker #2: Thanks, Georgia. Now, it's a good question, and I will repeat what I've said in the past. We would love to find a partner that sees the opportunity with Lorender stat the way we do.

Jon Congleton: Thanks, Georgia. No, it's a good question, and I'll repeat what I've said in the past. We would love to find a partner that sees the opportunity with lorundrostat the way we do. How is that? That is, with the best-in-class aldosterone synthase inhibitor in the near term generating significant value for patients, for physicians, and for the healthcare community writ large in helping to control uncontrolled and resistant hypertension, but then also more broadly, fully realizing the value of the asset from a development standpoint. Co-development, I'm not gonna talk about what kinda deal structures that would look like, but really, extending the value of lorundrostat beyond hypertension and some of its related comorbidities.

Speaker #2: And how is that? And that is with the best-in-class aldosterone synthase inhibitor in the near term, generating significant value for patients, for physicians, and for the healthcare community writ large, and helping to control uncontrolled and resistant hypertension.

Speaker #2: But then also more broadly, fully realizing the value of the asset from a development standpoint. So co-development, I'm not going to talk about what kind of deal structures that would look like, but really extending the value of Lorender stat beyond hypertension and some of its related comorbidities.

Speaker #2: And then within that becomes addressing the complexity that exists just right now with branded assets that you want to get into the hands of patients outside of the United States.

Jon Congleton: Within that, becomes addressing the complexity that exists just right now with branded assets that you want to get into the hands of patients outside of the United States. It's really what's been informing the dialogues that we've had is finding a partner that thinks more holistically about the opportunity. As we've stated before, lorundrostat has excellent IP out to 2035, patent term extension probably to 2039. There's a significant time period there to fully realize the value of this asset, and bring that value to patients.

Speaker #2: And so it's really what's been informing the dialogues that we've had is finding a partner that thinks more holistically about the opportunity as we've stated before.

Speaker #2: Lorenderstat has excellent IP out to 2035, patent term extension probably to 2039. There's a significant time period there to fully realize the value of this asset and bring that value to patients.

Speaker #8: Got it. Appreciate it. Thank you.

Speaker 19: Got it. Appreciate it. Thank you.

Georgia Bank: Got it. Appreciate it. Thank you.

Speaker #2: Thanks, Georgia.

Jon Congleton: Thanks, Georgia Bank.

Speaker #8: And this concludes our question and answer session. I would like to turn the floor back over to John Congleton for closing comments.

Operator 3: This concludes our question and answer session. I would like to turn the floor back over to Jon Congleton for closing comments.

Operator: This concludes our question and answer session. I would like to turn the floor back over to Jon Congleton for closing comments.

Speaker #2: Thank you, operator. We leave the strength of the clinical results for Lorender stat show the potential benefit for uncontrolled and resistant hypertension and those related comorbidities.

Jon Congleton: Thank you, operator. We believe the strength of the clinical results for lorundrostat show the potential benefit for uncontrolled and resistant hypertension and those related comorbidities. This is an exciting time for our team, the patients with hypertension who may benefit from treatment with lorundrostat, the physicians and researchers that have worked so hard in support of bringing lorundrostat through our clinical trial program, and our shareholders. We look forward to sharing updates with you in the incoming quarters. With that, I'll say thank you, operator, and thank you to everyone for joining us today. We'll now close the call.

Speaker #2: This is an exciting time for our team, the patients with hypertension who may benefit from treatment with Lorenderstat, the physicians and researchers that have worked so hard in support of bringing Lorenderstat through our clinical trial program, and our shareholders.

Speaker #2: We look forward to sharing updates with you in the coming quarters. And with that, I'll say thank you, operator, and thank you to everyone for joining us today.

Speaker #2: We'll now close the call.

Operator 3: Ladies and gentlemen, thank you for your participation. This concludes today's teleconference. You may disconnect your lines and have a wonderful day.

Operator: Ladies and gentlemen, thank you for your participation. This concludes today's teleconference. You may disconnect your lines and have a wonderful day.

Q4 2025 Mineralys Therapeutics Inc Earnings Call

Request a DemoDemo

MLYS

Mineralys

Earnings