Q2 2025 Mineralys Therapeutics Inc Earnings Call

Speaker #1: Good evening and welcome to the Minerals Second Quarter 2025 earnings call. At this time, all participants are in a listen-only mode. Any questions and answers session will follow the formal presentation.

Operator: Greetings and welcome to the Mineralis second quarter 2025 earnings 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, please press star zero on your telephone keypad. It is now my pleasure to introduce your host, Dan Ferry of LifeStyle Advisors. Thank you. You may begin.

Speaker #1: If anyone should require operator assistance, please press star zero on your telephone keypad. It is now my pleasure to introduce your host, Dan Ferry of LifeSight Advisors.

Speaker #1: Thank you. You may begin.

Speaker #2: Thank you, operator. I would like to welcome everyone joining us today for our second quarter 2025 conference call. Earlier this afternoon, we issued a press release providing our second quarter 2025 financial results and business updates.

Dan Ferry: Thank you, operator. I would like to welcome everyone joining us today for our second quarter 2025 conference call. Earlier this afternoon, we issued a press release providing our second quarter 2025 financial results and business updates. A replay of today's call will be available on the investor 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. These forward-looking statements are qualified by the cautionary statements contained in today's press release and our FCC filings, including our annual report on Form 10-K and subsequent filings.

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 a 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.

Speaker #2: Please note that these forward-looking statements reflect our opinions only as of today, August 12, 2025. Acceptance required by law; we specifically disclaim any obligation to update or revise these forward-looking statements in light of new information or future events.

Dan Ferry: Please note that these forward-looking statements reflect our opinions only as of today, August 12th, 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 Jon Congleton, Chief Executive Officer of Mineralis Therapeutics.

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

Speaker #3: Thank you, Dan. Good afternoon, everyone, and welcome to our second quarter 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 second quarter 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 second quarter financial results before we open the call for your questions. We're proud to be leading the way in the development of aldosterone synthase inhibitors, or ASIs, for the treatment of hypertension and comorbid cardiorenal conditions such as chronic kidney disease, or CKD, and obstructive sleep apnea, or OSA. Earlier this year, we became the first company to announce pivotal data for an ASI with the readouts from Launch HTN and Advance HTN.

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

Speaker #3: We're proud to be leading the way in the development of aldosterone synthase inhibitors, or ASIs, for the treatment of hypertension and comorbid cardiorenal conditions such as chronic kidney disease, or CKD, and obstructive sleep apnea, or OSA.

Speaker #3: Earlier this year, we became the first company to announce pivotal data for an ASI with a readouts from LaunchH10, and AdvanceH10. These results have since been presented at leading scientific conferences, and published in the New England Journal of Medicine, and the Journal of the American Medical Association.

Jon Congleton: These results have since been presented at leading scientific conferences and published in the New England Journal of Medicine and the Journal of the American Medical Association. The clinically meaningful and sustained reductions in systolic blood pressure demonstrated with Lorandrostat have generated broad interest across the medical community, underscoring the unmet need, the desire for innovation in the management of hypertension, and the commercial potential of Lorandrstat. To better understand how our data could translate into clinical use, we surveyed approximately 300 cardiologists and primary care physicians. The key takeaway from that survey was that 95% of these practicing clinicians indicated that based on the data from Launch HTN and Advance HTN trials, if Lorandrstat is approved, they would likely prescribe it broadly for patients with uncontrolled or resistant hypertension, specifically third line or later.

Speaker #3: The clinically meaningful and sustained reductions in systolic blood pressure demonstrated with more understanding and generated broad interest across the medical community. Underscoring the unmet needs, the desire for innovation in the management of hypertension, and the commercial potential of lower understanding.

Speaker #3: To better understand how our data could translate into clinical use, we surveyed approximately 300 cardiologists and primary care physicians. The key takeaway from that survey was that 95% of these practicing clinicians indicated that based on the data from LaunchH10 and AdvanceH10 trials, if lower understanding is approved, they would likely prescribe it broadly for patients with uncontrolled or resistant hypertension.

Speaker #3: Specifically, third-liner later. This intent to prescribe was based on the differentiated efficacy and safety profile which truly set lower understanding apart from agents typically used in the third-liner or later treatment position.

Jon Congleton: This intent to prescribe was based on the differentiated efficacy and safety profile, which truly set Lorandrstat apart from agents typically used in the third line or later treatment position. We've also completed a project with IQVIA, and it showed nearly 9 million patients in 2024 started new treatments in the third line or later position. These data are reflective of the dissatisfaction in the market and the challenges physicians face in addressing uncontrolled hypertension. Both of these data sets speak to the strong need and demand for innovative solutions that physicians want in their treatment armamentarium to address uncontrolled and resistant hypertension. Uncontrolled and resistant hypertension are significant unmet medical needs, impacting more than 20 million patients in the United States and directly contributing to adverse cardiorenal risk.

Speaker #3: We've also completed a project with IQVIA, and it showed that nearly 9 million patients in 2024 started new treatments in the third-line or later position. These data are reflective of the dissatisfaction in the market and the challenges physicians face in addressing uncontrolled hypertension.

Speaker #3: Both of these data sets speak to the strong need and demand for innovative solutions that physicians want in their treatment armamentarium, to address uncontrolled and resistant hypertension.

Speaker #3: Uncontrolled and resistant hypertension are significant unmet medical needs impacting more than 20 million patients in the United States and directly contributing to adverse cardiorenal risk.

Speaker #3: Our clinical results reinforce the differentiated clinical impact of targeting aldosterone with an ASI like lower understanding, as compared to the current standard of care used in third and fourth-liner treatment positions.

Jon Congleton: Our clinical results reinforce the differentiated clinical impact of targeting aldosterone with an ASI like Lorandrstat as compared to the current standard of care used in third and fourth line treatment positions. We are continuing to focus our pre-commercial efforts on market access and payer value assessment for this novel treatment. We've expanded our medical communications team to disseminate the data we're developing on Lorandrstat via publications, medical conferences, and field-based medical science liaisons. These are critical efforts for pre-launch readiness to generate awareness, interest, and enthusiasm for Lorandrstat. I would now like to briefly touch on the other development activities we're pursuing to enhance and extend the Lorandrstat profile on hypertension with comorbid conditions, which are largely driven by inadequately controlled blood pressure and dysregulated aldosterone.

Speaker #3: We are continuing to focus our pre-commercial efforts on market access and payer value assessment for this novel treatment. We have expanded our medical communications team to disseminate the data we're developing on lower understanding, via publications, medical conferences, and field-based medical science liaisons.

Speaker #3: These are critical efforts for pre-launch readiness to generate awareness, interest, and enthusiasm for lower understanding. I would now like to briefly touch on the other development activities we're pursuing to enhance and extend the lower understanding profile in hypertension with comorbid conditions.

Speaker #3: Which are largely driven by inadequately controlled blood pressure and dysregulated aldosterone. Our focus on and rationale behind making reduction in blood pressure the primary outcome measure in the explorer CKD trial, was the central role of uncontrolled blood pressure and chronic kidney disease progression.

Jon Congleton: Our focus on and rationale behind making reduction in blood pressure the primary outcome measure in the EXPLORE CKD trial was the central role of uncontrolled blood pressure in chronic kidney disease progression. Lorandrstat demonstrated a clinically meaningful reduction in systolic blood pressure in this trial. The key secondary outcome measure of reduction of UACR, an accepted surrogate for renal protection, was also highly significant and comparable in magnitude to that observed in trials of VicoDurostat and Phenergan when combined with an SGLT2 inhibitor. It should be noted that all participants in EXPLORE CKD were treated with Lorandrstat while on a stable therapeutic dose of SGLT2 inhibitor, most commonly Dapagliflozin.

Speaker #3: Lower understanding demonstrated a clinically meaningful reduction on systolic blood pressure in this trial. The key secondary outcome measure of reduction of UACR and accepted surrogate for renal protection was also highly significant and comparable in magnitude to that observed in trials of Vicodur stat, and Finarone, when combined with an SGLT2 inhibitor.

Speaker #3: It should be noted that all participants in explorer CKD were treated with lower understanding while on a stable therapeutic dose of SGLT2 inhibitor, most commonly dapagliflozin.

Speaker #3: Immediately after the release of these data, first word pharma surveyed 133 healthcare professionals, and confirmed that these data were clinically meaningful. With 77% of the surveyed healthcare professionals indicating they would consider prescribing lower understanding to CKD patients uncontrolled on either ACE inhibitor or ARB with an SGLT2 inhibitor.

Jon Congleton: Immediately after the release of these data, First Word Pharma surveyed 133 healthcare professionals and confirmed that these data were clinically meaningful, with 77% of the surveyed healthcare professionals indicating they would consider prescribing Lorandrstat to CKD patients uncontrolled on either ACE inhibitor or ARB with an SGLT2 inhibitor. The rationale for our EXPLORE OSA trial relates to the substantial portion of patients with obesity and resistant hypertension who also have OSA, which is often undiagnosed and untreated. A majority of OSA patients have uncontrolled or resistant hypertension, as well as elevated nighttime blood pressure and hypoxia, which are drivers of major adverse cardiovascular events, including death. Prior small studies of mineralocorticoid receptor antagonists or adrenalectomy patients demonstrated an approximate 50% reduction in AHI, which is the primary registration endpoint.

Speaker #3: The rationale for our explorer OSA trial, relates to the substantial portion of patients with obesity and resistant hypertension who also have OSA. Which is often undiagnosed and untreated.

Speaker #3: A majority of OSA patients have uncontrolled or resistant hypertension, as well as elevated nighttime blood pressure and a hypoxia, which are drivers of major adverse cardiovascular events including death.

Speaker #3: Prior small studies of mineralocorticoid receptor antagonists or adrenalectomy patients demonstrated an approximate 50% reduction in AHI, which is the primary registration endpoint. Explorer OSA is powered for the AHI primary outcome measure and will also test the effect of lower understanding on nighttime blood pressure using both 24-hour ABPM as well as a novel measurement of continuous blood pressure.

Jon Congleton: EXPLORE OSA is powered for the AHI primary outcome measure and will also test the effect of Lorandrstat on nighttime blood pressure using both 24-hour ABPM as well as a novel measurement of continuous blood pressure. We have clearly demonstrated that Lorandrstat, dosed once daily in the morning, is a highly effective antihypertensive. Given the contribution of nighttime aldosterone production in OSA patients, the EXPLORE OSA trial will be evaluating Lorandrstat dosing at night, the effects on nighttime blood pressure, and 24-hour blood pressure control. Based on the rate of enrollment in EXPLORE OSA, we anticipate having top-line data in the first half of 2026. The next step in providing Lorandrstat to the millions of patients who could benefit from its clinical profile is its regulatory approval. We have a pre-NDA meeting with the FDA scheduled to take place in the fourth quarter of 2025.

Speaker #3: We have clearly demonstrated that lower understanding dosed once daily in the morning is a highly effective antihypertensive. Given the contribution of nighttime aldosterone production in OSA patients, the explorer OSA trial will be evaluating lower understanding dosing at night, the effects on nighttime blood pressure, and 24-hour blood pressure control.

Speaker #3: Based on the rate of enrollment in explorer OSA, we anticipate having top line data in the first half of 2026. The next step in providing lower understanding to the millions of patients who could benefit from its clinical profile is its regulatory approval.

Speaker #3: We have a pre-indeem meeting with the FDA scheduled to take place in the fourth quarter of 2025. In summary, we have now demonstrated the clinically meaningful benefit risk profile of lower understanding in individuals with uncontrolled or resistant hypertension in four clinical trials.

Jon Congleton: In summary, we have now demonstrated the clinically meaningful benefit-risk profile of Lorandrstat in individuals with uncontrolled or resistant hypertension in four clinical trials. We continue to evaluate Lorandrstat's use in prevalent comorbidities of hypertension, such as OSA and CKD, for which normalizing aldosterone production may result in meaningful clinical benefit. I will now turn the call over to Adam to review our financial results for the second quarter of 2025.

Speaker #3: We continue to evaluate lower understanding's use, and prevalent comorbidities of hypertension, such as OSA and CKD. For which normalizing aldosterone production may result in meaningful clinical benefit.

Speaker #3: I will now turn the call over to Adam to review our financial results for the second quarter of 2025.

Speaker #4: Thank you, Jon. Good afternoon, everyone. Today, I will discuss select portions of our second quarter 2025 financial results. Additional details can be found in our Form 10-Q, which will be filed with the SEC later today, August 12.

Adam Levy: Thank you, Jon. Good afternoon, everyone. Today, I will discuss select portions of our second quarter 2025 financial results. Additional details can be found in our Form 10-Q, which will be filed with the FCC later today, August 12th. We ended the quarter with cash, cash equivalents, and investments of $324.9 million as of June 30th, 2025, compared to $198.2 million as of December 31st, 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 June 30th, 2025 were $38.3 million, compared to $39.3 million for the quarter ended June 30th, 2024.

Speaker #4: We ended the quarter with cash, cash equivalents, and investments of $324.9 million as of June 30, 2025, compared to $198.2 million as of December 31, 2024.

Speaker #4: 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.

Speaker #4: R&D expenses for the quarter ended June 30th, 2025, were $38.3 million, compared to $39.3 million for the quarter ended June 30th, 2024. The decrease in R&D expenses was primarily due to a decrease of $4.5 million in preclinical and clinical costs driven by the conclusion of the lower understanding pivotal program in the second quarter of 2025, partially offset by increases of $2.7 million in higher compensation expense resulting from additions to headcount, increases in salaries, and accrued bonuses, and increased stock-based compensation, and $0.8 million in higher clinical supply manufacturing, regulatory, and other costs.

Adam Levy: The decrease in R&D expenses was primarily due to a decrease of $4.5 million in preclinical and clinical costs driven by the conclusion of the Lorandrstat pivotal program in the second quarter of 2025, partially offset by increases of $2.7 million in higher compensation expense resulting from additions to headcount, increases in salaries and accrued bonuses, and increased stock-based compensation, and $0.8 million in higher clinical supply, manufacturing, regulatory, and other costs. G&A expenses were $8.5 million for the quarter ended June 30th, 2025, compared to $5.9 million for the quarter ended June 30th, 2024. The increase in G&A expenses was primarily due to $1.9 million in higher compensation expense resulting from additions to headcount, increases in salaries and accrued bonuses, and increased stock-based compensation, $0.6 million in higher professional fees, and $0.1 million in other administrative expenses.

Speaker #4: G&A A expenses were $8.5 million for the quarter ended June 30th, 2025, compared to $5.9 million for the quarter ended June 30th, 2024. The increase in G&A expenses was primarily due to $1.9 million in higher compensation expense resulting from additions to headcount, increases in salaries, and accrued bonuses, and increased stock-based compensation, $0.6 million in higher professional fees, and $0.1 million in other administrative expenses.

Speaker #4: Total other income net was $3.5 million for the quarter ended June 30th, 2025, compared to $4.2 million for the quarter ended June 30th, 2024.

Adam Levy: Total other income net was $3.5 million for the quarter ended June 30th, 2025, compared to $4.2 million for the quarter ended June 30th, 2024. The decrease was primarily attributable to decreased interest earned on investments in money market bonds and US Treasuries as a result of lower average cash balance invested during the three months ended June 30th, 2025. Net loss was $43.3 million for the quarter ended June 30th, 2025, compared to $41 million for the quarter ended June 30th, 2024. The increase was primarily attributable to the factors impacting the company's expenses described earlier. With that, I'll ask the operator to open the call for questions. Operator?

Speaker #4: The decrease was primarily attributable to decreased interest earned on investments in money market funds and U.S. Treasuries as a result of lower average cash balance.

Speaker #4: The invested amount during the three months ended June 30, 2025. Net loss was $43.3 million for the quarter ended June 30, 2025, compared to $41 million for the quarter ended June 30, 2024.

Speaker #4: The increase was primarily attributable to the factors impacting the company's expenses described earlier. With that, I'll ask the operator to open the call for questions.

Speaker #4: Operator?

Speaker #1: Thank you. We will now be conducting a question and answer session. If you'd 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.

Operator: Thank you. We will now be conducting a question and answer session. If you'd 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 to remove yourself from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, while we pull for questions. And our first question comes from the line of Michael DeFiore with Evercore ISI. Please proceed with your question.

Speaker #1: You may press star two to remove yourself from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.

Speaker #1: One moment, please, while we pull for questions. And our first question comes from the line of Michael D. Fiore with Evercore ISI. Please proceed with your question.

Speaker #5: Hi, guys. Thanks so much for taking my questions, and congrats on all the progress. I have two questions. One question that we get a lot recently is AstraZeneca's full Phase 3 VaxHTM data that will be coming up later at ESC shortly.

Speaker 5: Hi guys, thanks so much for taking my questions and congrats on all the progress. Two from me. One question that we get a lot recently is AstraZeneca's full phase three batch HTN data that will be coming up later at ESC shortly. My question is, any thoughts on how different grade one and grade two hyperkalemia rates would need to be in order for physicians to consider Lorandrstat more or less safe? And my follow-up question is too, it's separate, if there's any, if there's been any updates on partnership discussions and initiatives. Thank you.

Speaker #5: My question is, any thoughts on how different grade one and grade two hyperkalemia rates would need to be in order for physicians to consider lower understanding more or less safe?

Speaker #5: And my follow-up questions too, it's separate. If there's been any updates on partnership discussions and initiatives. Thank you.

Speaker #4: Yeah, Mike, thanks

Jon Congleton: Yeah, Mike, thanks for the call. I appreciate it. To your first question, it's tough for me to opine on, you know, what AZ's data may look like, what that may translate to from a potassium level and differentiation. I, you know, we feel very confident in the package that we've developed over the last four and a half years and certainly just in the last six months with the readout of Launch HTN, Advance HTN, and EXPLORE CKD. I think we very well characterized the efficacy of this drug and the safety of this drug in a spectrum of patients, and that was by design.

Speaker #3: for the call. I appreciate it. To your first question, it's tough for me to opine on, you know, what AZ's data may look like, what that may translate to from a potassium level in differentiation.

Speaker #3: You know, we feel very confident in the package that we've developed over the last four and a half years, and certainly just in the last six months with the readout of LaunchH10, AdvanceH10, and Explorer CKD.

Speaker #3: I think we very well characterized the efficacy of this drug, the safety of this drug, and the spectrum of patients. And that was by design.

Speaker #3: LaunchH10, I think, is the the perfect trial to really look at where this drug is going to be used in the vast majority of patients on top of an existing background treatment that while not optimizes is how physicians in the real world, are prescribing antihypertensives.

Jon Congleton: Launch HTN, I think, is the perfect trial to really look at where this drug is going to be used in the vast majority of patients on top of an existing background treatment that, while not optimized, is how physicians in the real world are prescribing antihypertensives. And we know with Lorandrstat, we saw an 11.7, 11.6 millimeter mercury placebo-adjusted change, 19 millimeter absolute, and frankly, ACE inhibitor ARB level rates of hyperkalemia both 6 millimoles per liter of 0.6% of the patients. So very well characterized, really robust clinical benefit coupled with a very favorable safety profile that I know you've seen the survey that we've done that I referenced in the prepared remarks. 95% of physicians deemed it as likely, or very likely, to prescribe if they get access to it if the drug gets approved.

Speaker #3: And we know with lower understanding we saw an 11.7, 11.6 millimeter mercury placebo-adjusted change, 19 millimeter absolute, and frankly, ACE inhibitor ARB level rates of hyperkalemia both, six millimoles per liter of 0.6% of the patients.

Speaker #3: So very well characterized, really robust clinical benefit, coupled with, a very favorable safety profile that I know you've seen the the survey that we've done that I referenced in the prepared remarks, 95% of physicians deemed it as likely or very likely to prescribe if they get access to it, if the drug gets approved.

Speaker #3: And so we'll have to see the data, Mike, from VaxH10 because there are so many things that go into that. You know, what are the patient demographics?

Jon Congleton: And so it's, well, we'll have to see the data, Mike, from batch HTN because there's so many things that go into that. You know, what are the patient demographics? How are they measuring potassium? You know, what's confirmed? What's observed? Just we need to get to the data. It's a fair question, but it's hard to opine on. As far as partnering dialogues, as we've alluded to in the past, you know, we're very interested in partnering, certainly ex-US, where we don't have intention of commercializing Lorandrstat on our own, but even in the United States. And you know, the intent in the United States is how can we extend the reach to as many physicians to impact as many patients as possible that we think ultimately can maximize the value of Lorandrstat, which we think can be significant in the management of uncontrolled and resistant hypertension.

Speaker #3: How are they measuring potassium? You know, what's confirmed? What's observed? Just we need to get to the data. It's a fair question, but it's hard to opine on.

Speaker #3: As far as partnering dialogues, we've alluded to in the past, you know, we're very interested in partnering, certainly outside the U.S., where we don't have intention of commercializing lower understanding on our own, but even in the United States.

Speaker #3: And, you know, the intent in the United States is how can we extend the reach to as many physicians to impact as many patients as possible that we think ultimately can maximize the value of lower understanding, which we think can be significant in the management of uncontrolled and resistant hypertension.

Speaker #1: Got Got it. Thanks very much.

Speaker 5: Got it. Thanks very much.

Speaker #3: Thanks, Mike.

Jon Congleton: Thanks, Mike.

Speaker #1: Thank you. Our next question comes from the line of Rich Law with Goldman Sachs. Please proceed with your question.

Operator: Thank you. Our next question comes from the line of Rich Law with Goldman Sachs. Please proceed with your question.

Speaker #6: The first is that when you think about lower understanding outside hypertension, do you see any opportunity for lower understanding to combine with other drugs besides SGLT2 inhibitors in CKD?

Speaker 5: The first is that when you think about Lorandrstat outside hypertension, do you see any opportunity for Lorandrstat to combine with other drugs besides SGLT2 inhibitors in CKD? And then I have a follow-up.

Speaker #6: And then I have a follow-up.

Speaker #3: Rich, are you saying specific to CKD?

Jon Congleton: Rich, are you saying specific to CKD?

Speaker #6: No, just anything outside hypertension and maybe outside, like, like SGLT2. Is there, any other disease areas or indications that you see potential combination strategy with lower understanding?

Speaker 5: No, just anything outside hypertension and maybe outside like SGLT2. Is there any other disease areas or indications that you see potential combination strategy with Lorandrstat?

Speaker #3: Yeah, I think the what we've seen to date with, you know, four successful trials is that aldosterone in and of itself is a significant driver, not only of hypertension, but the related comorbidities, right?

Jon Congleton: Yeah, I think what we've seen to date with, you know, four successful trials is that aldosterone in and of itself is a significant driver not only of hypertension, but the related comorbidities, right? We know hypertension drives CKD. We know it drives heart failure. We know it drives and is a component of OSA. And in the four studies that we've done, you know, we're seeing robust response. You know, if you think about it relative to just for hypertension, what other agents like alpha blockers, beta blockers, renal denervation, endothelin receptor antagonists, you're seeing really compelling clinical benefit with Lorandrstat, which I think speaks to the molecule, but it also speaks to the unmet need in dysregulated aldosterone. I think that extends by definition into these related comorbidities. So hypertension and CKD, hypertension and OSA.

Speaker #3: We know hypertension drives CKD. We know it drives heart failure. We know it drives and is a component of OSA. And in the four studies that we've done, you know, we're seeing robust response.

Speaker #3: you know, if you think about a relative to just for hypertension, what other agents like alpha blockers, beta blockers, renal denervation, endothelial receptor antagonists, you're seeing really compelling clinical benefit with lower understanding, which I think speaks to the molecule, but it also speaks to the unmet need in dysregulated aldosterone.

Speaker #3: I think that extends by definition into these related comorbidities. So hypertension and CKD, hypertension and OSA, I think given the small molecule nature of lower understanding, there are some interesting fixed dose combinations that we've contemplated.

Jon Congleton: I think given the small molecule nature of Lorandrstat, there are some interesting fixed dose combinations that we've contemplated. I can't really get into that at this point in time. But I would say that fixed dose combinations, their acceptance is varied by region. I think in Europe, you tend to see an inclination to use fixed dose combinations more frequently than in the United States. I think in the United States, there's actually more of an inclination to keep drugs as separate treatments to allow physicians to manage dose.

Speaker #3: I can't really get into that at this point in time, but I would say that fixed-dose combinations, their acceptance varied by reach, and I think in Europe you tend to see an inclination to use fixed-dose combinations more frequently than in the United States.

Speaker #3: I think in the United States, there's actually more of an inclination to keep drugs as separate treatments to allow physicians to manage dose. And I think that's where it becomes interesting, Rich, specifically the CKD, the dynamics that will be occurring with the SGLT2 market over the next several years with the introduction of likely generics.

Jon Congleton: And I think that's where it becomes interesting, Rich, specifically the CKD, the dynamics that will be occurring with the SGLT2 market over the next several years with the introduction of likely generics, with SGLT2s quickly becoming standard of care in the treatment of CKD, and with the potential launch timing of Lorandrstat for hypertension, and with the data that we've collected to date in hypertension and CKD, there may not be a need for a fixed dose combination to meet the needs of the patients with Lorandrstat being able to address the aldosterone aspect of the condition, and as has been seen quickly adoption of the SGLT2s standard of care in that population.

Speaker #3: with SGLT2s quickly becoming standard of care, and the treatment of CKD, and with the potential launch timing of lower understanding for hypertension, and with the data that we've collected to date on hypertension and CKD, there may not be a need for a fixed dose combination to meet the needs of the patients, with lower understanding being able to address the aldosterone, aspect of the condition, and, as has been seen quickly adoption of the SGLT2 standard of care in that population.

Speaker #1: Okay, got it.

Speaker 5: Okay, got it. And then, so kind of going back to your previous discussion on the batch data at ESC, under what scenarios would you think that that readout could negatively affect your discussions with potential partners or the outlook for Lorandrstat? And also, do you think that most partners that you've been talking to see both of these drugs to be likely similar because they have the same MOA, or do you think that they're looking for like a best-in-class drug over the other?

Speaker #6: And then, kind of going back to your previous discussion on the Vax data at ESC, under what scenarios would you think that that readout could negatively affect your discussions with potential partners or the outlook for lower understanding?

Speaker #6: And also, do you think that most, you know, partners that you've been talking to see both of these drugs to be likely similar because they have the same MOA, or do you think that they're looking for like a best-in-class drug over the other?

Speaker #3: Yeah, it's again hard to opine on what may be seen with the Vaxtrostat data. I'll go to what we do know. At this point, we know four successful trials have a very well-characterized and beneficial clinical profile with lower understanding.

Jon Congleton: Yeah, again, it's hard to opine on what may be seen with the batch stat data. I'll go to what we do know, and we know at this point, four successful trials have very well characterized and beneficial clinical profile with Lorandrstat that based on the unmet need in the marketplace, I think stands to generate significant value for patients and commercial value for shareholders. And so that's what we're focused on. As to the placement of or the availability of two ASIs, I think we've always said there's certainly room for two within this marketplace. We happen to think that Lorandrstat has a distinct offering as it relates to its selectivity and its half-life and the spectrum of data we've generated within the clinical development program.

Speaker #3: That based on the unmet need in the marketplace, I think stands to generate significant value for patients and commercial value for shareholders. And so that's where we're focused on.

Speaker #3: As to the placement of or the availability of two ASIs, I think we've always said there's certainly room for two within this marketplace. We happen to think that lower understanding has a distinct offering as it relates to its selectivity, and it's half-life, and the spectrum of data we generated within the clinical development program.

Speaker #3: But with 20 million patients failing to get the goal on two or more meds, we think there's significant opportunity for more than just one player in this space.

Jon Congleton: But with 20 million patients failing to get the goal on two or more meds, we think there's significant opportunity for more than just one player in this space.

Speaker #6: Got it. That makes sense. But I mean, any comment on potential partners looking— I mean, seeing these drugs to be similar versus, you know, there could be a best-in-class or there's no such thing?

Speaker 5: Got it. That makes sense. But I mean, any comment on potential partners looking, I mean, seeing these drugs to be similar versus, you know, there could be a best-in-class or there's no such a thing?

Speaker #3: No, it's hard to get into specifics on that, Rich. But we remain confident in the value of lower understanding.

Jon Congleton: No, it's hard to get into specifics on that, Rich, but we remain confident in the value of Lorandrstat.

Speaker #6: Okay, got it. And thank you.

Speaker 5: Okay, got it. And thank you.

Speaker #3: Yeah, thanks, Rich.

Jon Congleton: Yeah, thanks, Rich.

Speaker #1: Thank you. Our next question comes from the line of Seamus Fernandez with Guggenheim Partners. Please proceed with your question.

Operator: Thank you. Our next question comes from the line of Seamus Fernandez with Guggenheim Partners. Please proceed with your question.

Speaker #7: Oh, thanks for the question. So a couple of quick ones here. You know, just in terms of drug-drug interactions and anything that could, you know, impact an outside assessment of lower understanding, would you guys maybe just help us understand the cited PPI drug-drug interaction?

Dan Ferry: Oh, thanks for the question. So, a couple of quick ones here. You know, just in terms of drug-drug interactions and anything that could, you know, impact an outside assessment of Lorandrstat, would you guys maybe just help us understand the cited PPI drug-drug interaction, you know, that you called out in your 2023 10-K? I think this is a very minor issue, but just wanted to confirm some of the details that you have around the PPI utilization in your trials, as well as just kind of what your market research shows in terms of the frequency of use there, if there are any limitations at all. And then the second question really comes down to this sort of 24-hour profile. One of the things that AstraZeneca does cite is the prospect of potentially being differentiated, you know, in terms of the half-life.

Speaker #7: You know that you called out in your 2023 10-K. I think this is a very minor issue, but I just wanted to confirm some of the details that you have around the PPI utilization.

Speaker #7: In your trials, as well as just kind of what your market research shows in terms of the frequency of use there, if there are any limitations at all.

Speaker #7: And then the second question really comes down to the sort of 24-hour profile. One of the things that AstraZeneca does cite is the prospect of potentially being differentiated, you know, in terms of the half-life. Just interested to know how you guys think about the profile of lower understanding from a 24-hour perspective.

Dan Ferry: Just interested to know how you guys think about the profile of Lorandrstat from a 24-hour perspective and what you might be hoping to see in your OSA study as well as those data emerge later this year. Thanks.

Speaker #7: And what you might be hoping to see in your OSA study as well as those data emerge later this year. Thanks.

Speaker #3: Great, thanks, Seamus. From a for the first part of the question, the PPI from the research that we've done, PPI use is in about 10% of adults, maybe about 15% in older adults, for both our launch and AdvanceH10 study.

Jon Congleton: Great. Thanks, Seamus. From the first part of the question, the PPI, from the research that we've done, PPI use is in about 10% of adults, maybe about 15% in older adults. For both our Launch and Advance HTN study, we allowed PPI use three times per week. We recommended, if people could, to go on an H2 antagonist dosed in the evening, whereas Lorandrstat was dosed in the morning. The reason for that is Lorandrstat is a basic salt, requires a level of acidity for full bioavailability. So the question is not one, Seamus, of safety. It's about exposure and ensuring coverage of that patient's blood pressure. Now, as you're aware, the 50 milligram is the intended target starting dose. We have shown in EXPLORE CKD that the 25 milligrams is active. From the EXPLORE CKD, we saw about a 7.5 millimeter mercury placebo-adjusted change at four weeks.

Speaker #3: We allowed PPI use three times per week. We recommended, if people could, to go on an H2 antagonist. Dosed in the evening, whereas lower understanding was dosed in the morning.

Speaker #3: The reason for that is lower understanding: a basic salt requires a level of acidity for full bioavailability. So the question is not one of safety.

Speaker #3: It's about exposure and ensuring coverage of that patient's blood pressure. Now, as you're aware, the 50 milligram dose is the intended target starting dose. We have shown in Explorer CKD that the 25 milligram dose is active.

Speaker #3: From the Explorer CKD, we saw about a seven and a half millimeter mercury placebo-adjusted change at four weeks. And so we believe the 25 milligram is clearly an active dose.

Jon Congleton: And so we believe the 25 milligram is clearly an active dose. And so if somebody's on 50, they have to be on a chronic PPI. We would just suggest that the physician monitor their blood pressure, and if they feel they're losing some level of blood pressure control, double the dose. But again, within the two pivotal studies, we allowed periodic use of that and clearly saw robust clinical benefit. To your second question about 24-hour profile, I've heard that before. I would say after four clinical studies where we measure the in-office blood pressure the same way, and that is in the morning at trough before that day's dose, we're very confident in the 24-hour blood pressure control that we provide for patients.

Speaker #3: And so if somebody's on 50, they have to be on a chronic PPI, we would just suggest that the physician monitor their blood pressure.

Speaker #3: And if they feel they're losing some level of blood pressure control, double the dose. But again, within the two pivotal studies, we allowed periodic use of that and clearly saw robust clinical benefit.

Speaker #3: To your second question about the 24-hour profile, I've heard that before. I would say after four clinical studies where we measure the in-office blood pressure the same way—and that is in the morning at trough before that day's dose—we're very confident in the 24-hour blood pressure control that we provide for patients.

Speaker #3: So, looking at LaunchH10 with an 11.6 millimeter mercury placebo-adjusted change, 19 absolute, to Advance that had almost an 8 millimeter mercury placebo-adjusted and 15.5 millimeter mercury absolute, those were all done in the morning.

Jon Congleton: So looking at Launch HTN with 11.6 millimeter mercury placebo-adjusted change 19 absolute to Advance that had almost 8 millimeter mercury placebo-adjusted and 15.5 millimeter mercury absolute, those were all done in the morning, and the Advance was a 24-hour so we clearly see that. And the numbers that I explained for EXPLORE CKD, the same thing. Morning measurement at trough, so we're very confident in the 24-hour control.

Speaker #3: And the Advance was the 24-hour, so we clearly see that and the numbers that I explained for Explorer CKD the same thing. Morning measurement, at trough, so we're very confident the 24-hour control.

Speaker #4: And just a question on OSA.

Dan Ferry: And just a question on OSA. You know, timing for OSA and what you might be hoping to see in that data set.

Speaker #3: You know, timing for OSA and what you you might be hoping to see in that dataset. Yeah, the as we said, I'm sorry for missing that.

Jon Congleton: Yeah, the, as we said, and sorry for missing that, as we said in the prepared remarks, there are interesting, albeit small studies that show with a mineralocorticoid receptor antagonist or a unilateral adrenalectomy that you see improvement of AHI, frankly, in that 50% reduction of event range. And so the reason we're doing this study, on the one hand, is that we feel that aldosterone plays a role clearly in OSA, but also the need to address nighttime BP, which we don't believe current treatments like GLP-1s and CPAP do as effectively as patients require. And so that's why we're doing this study right now. That's why AHI is the primary endpoint, which is the registrational endpoint that could inform further clinical development for the program. As far as opining on what the blood pressure reduction will be, it's hard to say.

Speaker #3: As we said in the prepared remarks, there are interesting, albeit small studies that show with the mineral corticoid receptor antagonist or, you know, a unilateral adrenalectomy, that you see improvement of AHI frankly in that 50% reduction of event range.

Speaker #3: It's the reason we're doing this study on the one hand is that we feel that aldosterone plays a role clearly in OSA, but also the need to address nighttime BP, which we don't believe current treatments like GLP-1s and CPAP do as effectively as patients require.

Speaker #3: And so that's why we're doing this study right now. That's why AHI is the primary endpoint, which is the registration endpoint, that could inform further clinical development for the program.

Speaker #3: As far as opining on what the blood pressure reduction will be, it's hard to say. The nighttime dosing as I said in the prepared remarks is intended to really target the aldosterone surge that we believe is related to those OSA symptoms during the evening hour.

Jon Congleton: The nighttime dosing, as I said in the prepared remarks, is intended to really target the aldosterone surge that we believe is related to those OSA symptoms during the evening hour. And so we're really trying to match Lorandrstat to the time of production of more aldosterone.

Speaker #3: And so we're really trying to match lower understanding to the time of production of more aldosterone.

Speaker #6: Great, super helpful. Thanks so much.

Dan Ferry: Great. Super helpful. Thanks so much.

Speaker #3: Sure.

Speaker #1: Thank you. Our next question comes from the line of Tim Anderson with Bank of America. Please proceed with your question.

Jon Congleton: Sure.

Operator: Thank you. Our next question comes from the line of Tim Anderson with Bank of America. Please proceed with your question.

Speaker #8: Thank you. This is Alice on for Tim. Our question, first question is, what percentage of payers do you foresee putting in a step edit i.e. requiring patients to fail spironolactone before granting access to an ASI?

Speaker 6: Thank you. This is Alice on for Tim. Our question, first question is, what percentage of payers do you foresee putting in a step edit, i.e., requiring patients to fail spironolactone before granting access to an ASI? And then the second question is, if there has been any apprehension by potential partners to partner with you, what are the things that they would like more clarity on, or what is the biggest debate? Thank you.

Speaker #8: And then the second question is, if there has been any apprehension by potential partners to partner with you what other things that they would like more clarity on or what is the biggest debate?

Speaker #8: Thank you.

Speaker #3: Yeah, Alice, thank you for your questions. Let me take the second one, and I'll turn it over to Eric for your first one. As to any dialogues with prospective partners, we really haven't gotten into specifics on that.

Jon Congleton: Yeah, Alice, thank you for your questions. Let me take the second one, and I'll turn it over to Eric for your first one. As to any dialogues with prospective partners, we really haven't gotten into specifics on that. Again, I'll just pivot to the unmet need within this space, which we think is significant, coupled with the clinical profile that we've developed with the four studies to date that we think can be significant as far as addressing that unmet need. As regards to the payers, I'll let Eric provide the answer.

Speaker #3: Again, I'll just pivot to the unmet need within this space, which we think is significant. Coupled with the clinical profile that we've developed with the four studies to date that we think can be significant as far as addressing the unmet need.

Speaker #3: As regards to the payers I'll let Eric provide some insight.

Speaker #4: Yeah, sure. Yeah, hi, Alice. Thanks for the question. So we do not anticipate a step through spironolactone. In fact, that's something that we specifically asked payers during market research.

Adam Levy: Yeah, sure. Yeah. Hi, Alex. Thanks for the question. So we do not anticipate a step through spironolactone. In fact, that's something that we specifically ask payers during market research. The reason that they don't or they won't put us through spironolactone is A, about a 2% share in the hypertensive market for spironolactone, and then B, very significant AEs that even the payers recognize. Instead, what's likely to happen is the payers will step us through two generic classics, which then create an electronic step-by-edit, which is easily navigatable through the cloud. So that's our ultimate goal, is to make sure that utilization management criteria are relatively modest, prescriber-friendly, and that we ultimately optimize the net price.

Speaker #4: The reason that they don't or they won't put us through spironolactone is A, about a 2% share in the hypertensive market for spironolactone. And then B, very significant AEs that even the payers recognize.

Speaker #4: Instead, what's likely to happen is the payers will step us through two generic classes, which then creates an electronic step edit that is easily navigable through the cloud.

Speaker #4: So that's our ultimate goal is to make sure that utilization management criteria are relatively modest. Prescriber-friendly, and that we ultimately optimize the net price.

Speaker #8: Thank you very much.

Speaker 6: Thank you very much.

Speaker #3: You're welcome, Alice.

Adam Levy: You're welcome.

Jon Congleton: Thanks, Alice.

Speaker #1: Thank you. Our next question comes from the line of Annabelle Samimi with STIFL. Please proceed with your question.

Operator: Thank you. Our next question comes from the line of Annabelle Samimi with Stifel. Please proceed with your question.

Speaker #9: Hey, this is Diane on for Annabelle. Thanks for taking our question. So we've got a couple. The first one is around you guys you know are shifting into a commercial mindset.

Speaker 7: Hey, this is Diane on for Annabelle. Thanks for taking our questions. So we've got a couple. The first one is around, you guys, you know, are shifting into a commercial mindset. Have you laid out the strategy of how you will enter this market? Who's going to be the initial target audience? And how will you stage the launch given the size of the company and what kind of reach you can have?

Speaker #9: Have you laid out the strategy of how you will enter this market? Who's going to be the initial target audience? And how will you face the launch?

Speaker #9: Given the size of the company and what kind of reach you can have?

Speaker #3: Yeah, I'll go ahead and take that question. I think it's too early to get into, you know, the commercial strategy, staging, and targeting.

Jon Congleton: Yeah, I'll go ahead and take that question. I think it's too early to get into, you know, the commercial strategy, staging, targeting. As I noted in the prepared remarks, I think the big focus right now is really on two vectors. One is just the payer strategy and the value proposition based on the clinical data that we've generated to date. And then the second is really using medical affairs to ensure that we're disseminating the data that we've generated to date through conferences, publications, and a growing, albeit small, but growing medical science liaison group. And the intent there is really to grow the awareness, excitement, and enthusiasm for Lorandrstat.

Speaker #3: As I noted in the prepared remarks, I think the big focus right now is really on two factors. One is just the the payer strategy and the value proposition based on the clinical data that we generated to date.

Speaker #3: And then the second is really using medical affairs to ensure that we're disseminating the data that we generated to date through conferences, publications, in a growing, albeit small, but growing medical science liaison group.

Speaker #3: And the intent there is really to grow the awareness, excitement, and enthusiasm for lower understanding.

Speaker #9: Thanks, Diane. I've got one more here. How are you preparing for the pre-MBA meeting with the FDA? You've been pretty collaborative with the Cleveland Clinic, and you also had a lot of comprehensive data in your clinical trials.

Speaker 7: Thanks. I've got one more here. How are you preparing for the pre-MBA meeting with the FDA? You've been pretty collaborative with the Cleveland Clinic, and you also had a lot of comprehensive data in your clinical trials. What expectations do you have going to the meeting? What kind of questions do you expect the FDA might have?

Speaker #9: What expectations do you have going to the meeting? What kind of questions do you expect the FDA might have?

Speaker #3: So So we're we're confident in the data package that we've put together, and that you know predates or goes back to the end of phase two meeting.

Jon Congleton: So we're confident in the data package that we've put together, and that, you know, predates or goes back to the end of phase two meeting where we had the target HTN data laid out, the intended clinical development program, the purpose behind that, as well as, as you're well aware, all the other elements from CMC to non-clinical. So we're confident in the package that we've put together and the comprehensive nature of it. I think the intent for the FDA when they review any new drug is it well characterized across distinct populations. And we believe with Launch HTN being an existing background, Advance HTN being truly optimized, and EXPLORE CKD looking at subjects with hypertension and lower EGFR that we have a fairly comprehensive package going into those discussions with the FDA.

Speaker #3: Where we had the target HTN data. Laid out the the intended clinical development program, the purpose behind that, as well as as you're well aware, all the other elements from CMC to non-clinical.

Speaker #3: So we're confident in the package that we've put together. And the comprehensive nature of it. I think the intent for the FDA when they review any new drug is, is it well characterized across distinct populations?

Speaker #3: And we believe with LaunchH10 being the existing background, AdvanceH10 being truly optimized, and Explorer CKD looking at subjects with hypertension and lower EGFR that we have a fairly comprehensive package.

Speaker #3: Going into those discussions with the FDA.

Speaker #9: Great. I'm sorry, I do have one more quick one. Just regarding Vaxtrostat, I know their data hasn't been published, but they did reach their goal.

Speaker 7: Great. I'm sorry. I do have one more quick one. This is regarding batch of that. I know their data hasn't been published, but they did reach their goal. Is there, can you talk to them about any kind of counter-detailing messaging that may be starting?

Speaker #9: Is there can you talk to us about any kind of counter detailing messaging that may be starting?

Speaker #3: No, I think we'll wait and see what their their study shows, what the data shows. You know, we're we're believers as a company that aldosterone is a significant unaddressed target right now in the treatment of not only hypertension, but related comorbidities.

Jon Congleton: No, I think we'll wait and see what their study shows, what the data shows. You know, we're believers as a company that aldosterone is a significant unaddressed target right now in the treatment of not only hypertension, but related comorbidities. We would anticipate seeing positive data as they've alluded to what that data is going to be as far as the magnitude of effect, the safety profile. I just, I think it's far, far too early for us to even opine. We need to see the data and, again, look at the construct of the study, the patient disposition, background meds, how they were doing measurements before we could begin to juxtapose their data relative to ours, which is always a challenge across trials.

Speaker #3: We would anticipate seeing positive data as they've alluded to what that data is going to be as far as the magnitude of effect, the safety profile.

Speaker #3: I just I think it's far, far too early for us to even opine. We need to see the data and again, look at the construct of the study, the patient disposition, background meds, how they were doing measurements.

Speaker #3: Before we could begin to juxtapose their data relative to ours, which is always a challenge across trials.

Speaker #9: Thank you so much.

Speaker 7: Thank you so much.

Speaker #1: Thank you. Our next question comes from the line of Rami Kathouda with LifeSci Capital. Please proceed with your question.

Operator: Thank you. Our next question comes from the line of Lami Kathuda with LifeSci Capital. Please proceed with your question.

Speaker #10: Hey, guys. Thanks for taking my questions as well. Two quick ones for me. First, has AstraZeneca noted whether they're taking the average of three blood pressure readings similar to the Syncro Phase 2 studies, or are they taking a similar approach to what you guys did in Launch and Advance?

Speaker 5: Hey guys, thanks for taking my questions as well. Two quick ones for me. First, has AstraZeneca noted whether they're taking the average of three blood pressure readings similar to the Syncrophase II studies, or are they taking a similar approach to what you guys did in Launch and Advance? And I guess how could that influence placebo response rates at the end of the day?

Speaker #10: And I guess how could that influence placebo response rates at the end of the day?

Speaker #3: Yeah, Rami, the only thing I know, and it's from clinical trials, is that it's attended. But I don't know how many measurements they're taking and what they're doing with those measurements.

Jon Congleton: Yeah, Rami, I don't, the only thing I know, and it's from CLIN trials, is that it's attended, but I don't know how many measurements they're taking and what they're doing with those measurements. As you're aware, we've followed the guidelines from the American Heart Association on best practices and do unattended measurements with those automated devices, take five measurements and average the last two. So from our standpoint, that practice has paid off as far as helping us control the noise of placebo. I'm not sure what kind of strategies or operational plans that AZ has put in place to try to manage the placebo noise that, you know, was a bit of an issue with previous BaxterStat trials, specifically Halo.

Speaker #3: You know, as you're aware, we've followed the guidelines from the American Heart Association on best practices and do unattended measurements with those automated devices.

Speaker #3: Take five measurements, and the average of the the last two. So from our standpoint, that practice has paid off as far as helping us control the noise of placebo.

Speaker #3: I'm not sure what kind of strategies or operational plans that AZ has put in place to try to manage the placebo noise that you know was a bit of an issue with previous Vaxtrostat trials, specifically Halo.

Speaker #10: Got it. And then I know it's a bit of a race to become the first ASI on the market. Has the FDA specified what percentage of patients need to complete 52 weeks of treatment with lower understanding before you can ultimately file an NDA?

Speaker 5: Got it. And then I know it's a bit of a race to become the first ASI on the market. Has the FDA specified what percentage of patients need to complete 52 weeks of treatment with Lorandrstat before you can ultimately file an NDA?

Speaker #3: No, they don't give specific guidance to that, Rami. It's in consultation with the consultants, which we've got some of the top consultants I think in the world helping us with this.

Jon Congleton: No, they don't give specific guidance to that, Rami. It's in consultation with the consultants, which we've got some of the top consultants, I think, in the world helping us with this. It's just making sure that we have what we feel to be an appropriate amount of the safety data for the FDA to begin their review and then not overload that submission with a 120-day safety update.

Speaker #3: It's just making sure that we have what we feel to be an appropriate amount of the safety data for the FDA to begin their review.

Speaker #3: And then not overload that submission with a 120-day safety update.

Speaker #10: Makes sense. Thanks again.

Speaker 5: Makes sense. Thanks again.

Speaker #3: Thank you.

Jon Congleton: Thank you.

Speaker #1: Thank you. Our next question comes from the line of Mohit Bansal with Wells Fargo. Please proceed with your question.

Operator: Thank you. Our next question comes from the line of Mohit Basil with Wells Fargo. Please proceed with your question.

Speaker #8: Hi, this is Fadia Rahman on for Mohit. Thanks for the questions. How did the Vaxtrostat data any trial design differences that you'd highlight for Launch compared with VaxH10?

Speaker 6: Hi, this is Adi Rahman on for Mohit. Thanks for the questions. For ahead of the batch of that data, any trial design differences that you'd highlight for Launch compared with batch HTN that could contribute to differences in either the efficacy or on the safety side? And would you expect differences on the hyperkalemia rates to be driven more by trial design aspects or by pharmacokinetics of these drugs, for example, the half-life differences?

Speaker #8: That could contribute to differences in either the efficacy or on the safety side? And would you expect differences on a hyperkalemia rates to be driven more by trial design aspects or by pharmacokinetics of these drugs, for example, the half-life differences?

Speaker #3: Yeah, I think the you know as the VaxH10 data becomes available, I think if you think about the breadth of our program, the most comparable study is probably LaunchH10.

Jon Congleton: Yeah, I think the, you know, as the batch HTN data becomes available, I think if you think about the breadth of our program, the most comparable study is probably Launch HTN. The commonalities are both studies are looking at subjects failing to get to go on two or more meds. It's using in-office blood pressure measurement. A diuretic must be part of the background treatment. But beyond that, it's hard to opine on what else they may be doing within that study. You know, and to your secondary question to how that may or may not impact from a design standpoint, rates of hyperkalemia, again, it depends upon how they characterize it, how they capture it, how they go from observed to confirmed. So it's just difficult from a design standpoint for me to give a view on that.

Speaker #3: The commonalities are both studies are looking at subjects failing to get the goal on two or more meds. It's usually an in-office blood pressure measurement.

Speaker #3: A diuretic must be part of the background treatment. But beyond that, it's hard to opine on what else they may be doing within that study.

Speaker #3: You know, and to your secondary question how that may or may not impact from a design standpoint, rates of hyperkalemia, again, it depends upon how they characterize it, how they capture it.

Speaker #3: How they go from observed to confirmed. So it's just difficult, from a design standpoint, for me to give a view on that. You know, the pharmacokinetics specifically, the selectivity and the half-life, we know is distinct from lower understanding.

Jon Congleton: You know, the pharmacokinetics, specifically the selectivity and the half-life, we know is distinct from Lorandrstat. Our selectivity is about four times more selective for aldosterone than cortisol. The half-life of 10 to 12 hours, we believe, is kind of ideal, mirroring the diurnal nature of elevated aldosterone. Theirs is 25 to 30 hours. It'll be interesting, and I think that's one of the things that we're interested to see is just how does that all translate into their clinical profile. But it's hard to opine ahead of actually seeing the data.

Speaker #3: Our selectivity is about four times more selective for aldosterone than cortisol. The half-life of 10 to 12 hours we believe is kind of ideal.

Speaker #3: Mirroring the diurnal nature of elevated aldosterone, theirs is 25 to 30 hours. It'll be interesting, and I think that's one of the things that we're interested to see: just how does that all translate into their clinical profile.

Speaker #3: But it's hard to opine ahead of actually seeing the data.

Speaker #8: Got it. Thanks. And then regarding the open label extension trial, do you plan to release more data from or any data from that trial later this year?

Speaker 6: Got it. Thanks. And then regarding the open-label extension trial, do you plan to release more data from, or any data from that trial later this year? And can you talk about the potassium monitoring that you're doing in that trial and what additional data from hyperkalemia we can see?

Speaker #8: And can you talk about the potassium monitoring that you're doing in that trial and what additional data from hyperkalemia we can see?

Speaker #3: Yeah, to broadly answer your question, we're excited about the data we're capturing within transformH10, which is the name of the open label extension. That study will provide not only a longer-term view of efficacy and safety, but within that, we also have our randomized treatment withdrawal study.

Jon Congleton: Yeah, to broadly answer your question, we're excited about the data we're capturing within Transform HTN, which is the name of the open-label extension. That study will provide not only a longer-term view of efficacy and safety, but within that, we also have our randomized treatment withdrawal study, which is part of the NDA submission as well. We do plan on continuing to publish data out of both of those trials. I can't really give you a timeframe for that because that could be dependent upon conference schedule as well as publication. But we certainly do plan on getting that data out into the public in due course.

Speaker #3: Which is part of the NDA submission as well. We do plan on continuing to publish data out of that both of those trials. I can't really give you a timeframe for that.

Speaker #3: Because that could be dependent upon the conference schedule as well as publication. But we certainly do plan on getting that data out into the public in due course.

Speaker #8: Great. Thank you.

Speaker 6: Great. Thank you.

Speaker #1: Thank you. Our next question comes from the line of Matthew Caulfield with HC Wainwright. Please proceed with your question.

Operator: Thank you. Our next question comes from the line of Matthew Caulfield with HC Wainwright. Please proceed with your question.

Speaker #10: Hi, thank you, guys. And great to see the success. So I think KOL takeaways for lower understanding safety have been that the serum potassium is to be expected.

Speaker 5: Hi, thank you guys, and great to see the success. So I think KOL takeaways for Lorandrstat safety have been that the serum potassium is to be expected. It can be managed, and it's not expected to add to occurring levels over time. Could you foresee any reasons the agency could be more scrutinizing of the serum potassium safety assessment as we head into the pre-NDA meeting in fourth quarter? Thanks.

Speaker #10: It can be managed and it's not expected to add to a creatinine levels over time. Could you foresee any reasons the agency could be more scrutinizing of the serum potassium safety assessment as we head into the pre-NDA meeting in fourth quarter?

Speaker #10: Thanks.

Speaker #3: No, Matt, thanks for the call. The, you know, again, I think it's why it was important that we built the program the way we did, the way that Dave designed it was to really give us a sense for lower understanding's profile across the spectrum of patients.

Jon Congleton: No, Matt, thanks for the call. And B, you know, again, I think it's why it was important that we built the program the way we did, the way that Dave designed it, was to really give us a sense for Lorandrstat's profile across the spectrum of patients. And so I think that's something the FDA actually will value and appreciate that we characterize not only the clinical benefit, but also the safety profile in an existing kind of real-world population and an optimized treated population and in a population with CKD and proteinuria. And so we're very confident with the package that we have right now to go to the FDA to characterize Lorandrstat's profile in some of these distinct populations.

Speaker #3: And so I think that's something the FDA actually will value and appreciate that we've characterized not only the clinical benefit, but also the safety profile in an existing kind of real-world population and an optimized treated population, in a population with CKD and proteinuria.

Speaker #3: And so we're very confident with the package that we have right now to go to the FDA. To characterize lower understanding's profile in some of these distinct populations.

Speaker #10: Understood. Very helpful, guys. Thank you.

Speaker 5: Understood. Very helpful, guys. Thank you.

Speaker #3: Thanks, Matt.

Jon Congleton: Thanks, Matt.

Speaker #1: Thank you. Our next question comes from the line of Dennis Ding with Jefferies. Please proceed with your question.

Operator: Thank you. Our next question comes from the line of Dennis Ding with Jeffries. Please proceed with your question.

Speaker #11: Hi, thanks for taking my question. I have two real quick ones. Number one, as you're thinking about commercializing either on your own or with a partner, what do you think are the critical factors, generally speaking, for cardiology?

Speaker 5: Hi, thanks for taking my question. I have two real quick. Number one, as you're thinking about commercializing either on your own or with a partner, what do you think are the critical factors, you know, generally speaking for cardiology that you will build out or are looking for in a partner to help with uptake, assuming the data does look similar between both ASIs, which I think is generally a consensus field? Is it size of the salesforce, duration of relationships with doctors? Is it magnitude of rebating? Like, I guess what specific factors will you be hyper-focused on to mitigate the commercial delta between you and AstraZeneca? And then my second question is just around R&D synergy for an ASI.

Speaker #11: That you will build out or are looking for in a partner to help with uptake, assuming the data does look similar between both ASIs, which I think is generally a consensus view?

Speaker #11: Is it size of the sales force, duration of relationships with doctors? Is it magnitude of rebating? Like I guess what specific factors will you be hyper-focused on to mitigate the commercial delta between you and AstraZeneca?

Speaker #11: And then my second question is just around R&D synergy for an ASI. I mean, I guess CKD and heart failure are obvious, but what other indications do you think an ASI could add incremental value to on top of standard of care?

Speaker 5: I mean, I guess CKD and heart failure are obvious, but what other indications do you think an ASI could add incremental value to on top of standard of care? And you know, I presume that's something that pharma could potentially be weighing as they think about the NPV and specifically the tail value of Lorandrstat. Thank you.

Speaker #11: And you know I presume that's something that pharma could potentially be weighing as they think about the NPV and specifically the tail value of lower understanding.

Speaker #11: Thank you.

Speaker #3: Yeah, Dennis, thanks for the question. To the first one, you know I think what we're looking broadly at within a partner is how we can maximize reach to both prescribers and patients.

Jon Congleton: Yeah. Dennis, thanks for the question. To the first one, you know, I think what we're looking broadly at within a partner is how we can maximize reach to both prescribers and patients. You know, if we look at how we've developed this molecule to date, it's been with a pretty keen eye towards the commercial marketplace, realizing that it's highly genericized, knowing that going first line would probably have significant barriers. But as you heard Eric opine later or earlier on, in that third line position with proper pricing and rebate strategy, we believe that access is very manageable. And the reason for that is the significant unmet need there. Now that prescribing is driven, you know, to a fairly large degree, and we note this in our corporate deck, by about 47 to 50,000 doctors in those top five deciles of third line or later prescribing.

Speaker #3: You know, if we look at how we've developed this molecule today, it's been with a pretty keen eye towards the commercial marketplace realizing that it's highly genericized.

Speaker #3: Knowing that going first line would probably have significant barriers, but as you heard Eric opine later or earlier on, in that third line position, with proper pricing and rebate strategy, we believe that access is very manageable.

Speaker #3: And the reason for that is the significant unmet need there. Now that prescribing is driven, you know, to a fairly large degree, and we note this in our corporate deck, by about 47,000 to 50,000 doctors.

Speaker #3: In those top five deciles, a third line or later prescribing. And that's a mix of cardiologists and primary care. So as we think about partnering we factor that into that consideration.

Jon Congleton: And that's a mix of cardiologists and primary care. So as we think about partnering, we factor that into that consideration. And you know, all those elements that you described as far as current coverage, relationships, those are all, you know, informative to how we think about partner. To your second question, as far as the increment of an ASI in other categories, you know, I don't know that I could share with you all of the different areas that we've thought about. You highlighted certainly two, CKD and heart failure. You know, from our standpoint, hypertension is a massive overlap with all of those. And that's why we've framed our program the way we have. That's why we think the EXPLORE CKD program is so interesting and exciting because it allows us to operate within those patients that have an overlap.

Speaker #3: And you know all those elements that you described as far as current coverage, relationships, those are all you know informative to how we think about a partner.

Speaker #3: To your second question regarding the increment of an ASI and other categories, I don’t know that I could share with you all of the different areas that we thought about.

Speaker #3: You highlighted certainly two. CKD and heart failure, you know from our standpoint, hypertension is a massive overlap with all of those. And that's why we've framed our program the way we have.

Speaker #3: That's why we think the Explorer CKD program is so interesting and exciting because it allows us to operate within those patients that have an overlap.

Speaker #3: And you know the ability to actively promote lower understanding for patients who have hypertension as well as comorbid CKD. And we know that there could be a dual benefit of reduction of UACR, which is a known surrogate for renal protection.

Jon Congleton: And you know, the ability to actively promote Lorandrstat for patients who have hypertension, as well as comorbid CKD. And we know that there could be a dual benefit on a reduction of UACR, which is a known surrogate for renal protection. But it's also why we're so excited about OSA. As I said in the prepared remarks, there's significant overlap between not only resistant but uncontrolled hypertension and OSA. And there's good evidence that shows targeting aldosterone will not only be a benefit for the blood pressure, but also for the symptoms of OSA. At this stage, I think we're very comfortable in the profile of this drug as far as what it does to aldosterone, what it does to hypertension, how it does so safely, but also beginning to get indications of the benefits it can have on hypertension-related comorbidities.

Speaker #3: But it's also why we're so excited about OSA. As I said in the prepared remarks, there's significant overlap. Between not only resistant, but uncontrolled hypertension and OSA.

Speaker #3: And there's good evidence that shows targeting aldosterone will not only be a benefit to the blood pressure, but also for the symptoms of OSA.

Speaker #3: At this stage, I think we're very comfortable in the profile of this drug. As far as what it does to aldosterone, what it does to hypertension, how it does so safely.

Speaker #3: But also beginning to get indications of the benefits it can have on hypertension-related comorbidities. And so that's something we'll continue to evaluate as we think about further development of lower understanding.

Jon Congleton: And so that's something we'll continue to evaluate as we think about further development of Lorandrstat.

Speaker #11: Got it. Thank you. And I had a quick follow-up. I think your competitor AstraZeneca is running a new trial a new trial in primary aldosteronism.

Speaker 5: Got it. Thank you. And I had a quick follow-up. I think your competitor AstraZeneca is running a new trial in primary aldosteronism. I feel like that could be an area where higher doses will be used and where your better selectivity could eventually come out positive. So are you considering going after that indication and you know why or why not? Thank you.

Speaker #11: I feel like that could be an area where higher doses will be used and where you're better selectivity could eventually come out positive. So are you considering going after that indication and you know why or why not?

Speaker #11: Thank you.

Speaker #3: Yeah, thanks, Dennis. I think I would put PA into some of the other categories that certainly is something we're contemplating. Clearly, that's probably the extreme edge of hypertension with aldosterone as a driver for that.

Jon Congleton: Yeah, thanks, Dennis. I think I would put PA into some of the other categories. It's certainly something we're contemplating. Clearly, that's probably the extreme edge of hypertension with aldosterone as a driver for that. As it relates to dose, I think it's too early to opine on that, but it's certainly an area of consideration as we look at all the different options that are out there.

Speaker #3: As it relates to dose, I think it's too early to opine on that, but it's certainly an area of consideration as we look at all the different options that are out there.

Speaker #11: Excellent.

Speaker 5: Thanks a lot.

Speaker #3: Thank you.

Jon Congleton: Thank you.

Speaker #1: Thank you. We have reached the end of the question and answer session. I would like to turn the floor back over to CEO Jon Congleton for closing remarks.

Operator: Thank you. And we have reached the end of the question and answer session. I would like to turn the floor back over to CEO John Conkleton for closing remarks.

Speaker #3: Thank you, operator. I appreciate everybody's attention today. We believe the strength of the clinical results for lower understanding shows the potential benefit from controlled and resistant hypertension in those related comorbidities, such as CKD and OSA.

Jon Congleton: Thank you, operator. Appreciate everybody's attention today. We believe the strength of the clinical results for Lorandrstat showed the potential benefit for uncontrolled and resistant hypertension and those related comorbidities such as CKD and OSA we've discussed today. We do look forward to our upcoming pre-NDA meeting with the FDA later this year. This is an exciting time for our team. The hypertension patients who may benefit from treatment with Lorandrstat, the physicians and the researchers that have worked so hard in support of bringing Lorandrstat through our pivotal program, and most certainly our shareholders. We're excited for key upcoming milestones and look forward to sharing updates with you in the upcoming quarters. With that said, I'll say thank you, operator, and thank you to everyone for joining us today. With that, we'll close the call.

Speaker #3: We've discussed today. We do look forward to our upcoming pre-NDA meeting with the FDA later this year. This is an exciting time for our team.

Speaker #3: A hypertension patient who may benefit from treatment with lower understanding. The physicians and researchers that have worked so hard in support of bringing lower understanding through our pivotal program and, most certainly, our shareholders.

Speaker #3: We're excited for key upcoming milestones and look forward to sharing updates with you in the upcoming quarters. With that said, I'll say thank you.

Speaker #3: Operator, and thank you to everyone for joining us today. With that, we'll close the call.

Operator: Thank you. And ladies and gentlemen, this does conclude today's conference, and you may disconnect your lines at this time. Thank you for your participation.