Q4 2023 Mineralys Therapeutics Inc Earnings Call

Welcome to the minerals for a few ticks fourth quarter and full year 2020 Free conference call. At this time all lines are in listen only mode. Following the presentation, we will conduct a question and answer session.

Operator: Welcome to the Mineralys Therapeutics fourth quarter and full year 2023 conference call. At this time, all lines are in listen only.

Operator: Following the presentation, we will conduct a question and answer session. If at any time during this call you require immediate assistance, please press star zero for operator assistance. This call is being recorded on Thursday, March 1st, 2020. It is now my pleasure to introduce your host, Dan Ferry of Licefire Advisors. Please go ahead.

During the school year require immediate assistance. Please press star zero for operator assistance.

This call is being recorded on Thursday March 12 2024 it.

Speaker Change: It is now my pleasure to introduce your highest I'm sorry of life Science voices. Please go ahead Sir.

Daniel Ferry: Thank you, operator. Good morning, everyone. Welcome to our fourth quarter and full year 2023 conference call. Earlier this morning, we issued a press release providing our fourth quarter and full year 2023 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 it's completed.

Speaker Change: Thank you operator, good morning, everyone and welcome to our fourth quarter and full year 2023 conference call.

Speaker Change: Earlier. This morning, we issued a press release, providing our fourth quarter and full year 2023 financial results and business updates.

Speaker Change: A replay of today's call will be available on the investors section of our website approximately one hour after its completion.

Daniel Ferry: 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 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 Change: After our prepared remarks, we will open the call for Q&A.

Speaker Change: Before we begin I would like to remind everyone that this conference call and webcast contain forward looking statements about the company.

Speaker Change: Actual results could differ materially from those stated or implied by these forward looking statements due to risks and uncertainties associated with the Companys business.

Daniel Ferry: These forward-looking statements are qualified by the cautionary statements contained in today's press release and in our SEC filings, including our annual report on Form 10-K and subsequent files. Please note that these forward-looking statements reflect our opinions only as of today, March 25th. We specifically disclaim any obligation to update or revise these forward-looking statements in light of new information or future events. I would now like to turn the call over to Jon Congleton, Chief Executive Officer of Mineralys Therapeutics. Jon?

Speaker Change: 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.

Speaker Change: Please note that these forward looking statements reflect our opinions only as of today March 'twenty one.

Speaker Change: 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 Change: I would now like to turn the call over to John <unk>, Chief Executive Officer of mineral Therapeutics John.

John: Thank you Dan Good morning, everyone and welcome to our fourth quarter and full year 2023 financial results and corporate update conference call I'm joined today by Adam <unk>, Our Chief Financial Officer, and Dr. David Rodman, Our Chief Medical Officer.

Jon Congleton: Thank you, Dan. Good morning, everyone. And welcome to our fourth quarter and full year 2023 financial results in our Corporate Update Conference. I'm joined today by Adam Levy, our Chief Financial Officer, and Dr. David Rodman, our Chief Medical Officer. I'll begin with a brief overview of the business and recent milestones, followed by David, who will discuss our clinical programs, and then Adam will review our fourth quarter and full year financial results before we open up the call for your questions. Looking back over the past year, we have so much to be proud of at Mineralys.

David Rodman: I'll begin with a brief overview of the business and recent milestones followed by David <unk>, who will discuss our clinical programs and then Adam will review, our fourth quarter and full year financial results.

David Rodman: Before we open up the call for your questions.

David Rodman: Looking back over the past year, we've had so much to be proud of at Minera Alice our entire team worked together to achieve several key milestones on both the clinical and corporate level.

Jon Congleton: Our entire team worked together to achieve several key milestones on both the clinical and corporate levels. I believe this success speaks to the dedication the team has to our exciting programs that target diseases driven by abnormally elevated aldosterone. In 2024, we're working towards achieving several clinical events that are expected to expand the data package of LaRunderstaff. We believe excess aldosterone is common and is a significant contributor in approximately 25% of all hypertension patients and is tightly linked to obesity.

I believe this success speaks to the dedication of the team has to our exciting programs that target diseases, driven by abnormally elevated aldosterone.

David Rodman: In 2024, we're working towards achieving several clinical events, which are expected to expand the data package of more understand.

David Rodman: We believe excess aldosterone as common and is a significant contributor and approximately 25% of all hypertension patients and is tightly linked to obesity.

Jon Congleton: Aldosterone is also a significant driver of cardiorenal metabolic syndrome, and thus, our pursuit of an aldosterone-targeted treatment approach that has the potential to benefit millions of patients who are impacted by hypertension, kidney disease, and heart disease. I'm pleased by the significant progress our clinical team continues to make in implementing our development strategy for Lorandostat. Most importantly, we remain on track with our pivotal program for hypertension, which includes the two pivotal clinical trials, ADVANCE H10 and LAUNCH H10. ADVANCE H10 is the only study of an aldosterone-directed therapy that we know of that is utilizing the standardized background treatment approach and we believe will be highly informative to LaRunderSats' profile.

David Rodman: Australia is also a significant driver of cardio renal metabolic syndrome, and thus our pursuit of an aldosterone targeted treatment approach that has the potential to benefit millions of patients who are impacted by hypertension kidney disease and heart disease.

David Rodman: I am pleased by the significant progress our clinical team continues to make in implementing our development strategy for <unk> I understand.

David Rodman: Most importantly, we remain on track with our pivotal program for hypertension, which includes the two pivotal clinical trials advance H Chan and launch <unk>.

David Rodman: Advanced age 10 is the only study of an aldosterone directed therapy that we know of that is utilizing the standardized background treatment approach and we believe will be highly informative total are under <unk> profile.

Jon Congleton: Since initiating the trial in April of 2023, we have found that the rigorous nature of the trial's design has impacted the pace of enrollment. As we discussed on our earnings call in November, we made some meaningful modifications to the advanced HTM protocol and execution plan while maintaining our focus on delivering the highest quality data set. Based on our modeling, we have narrowed our guidance for top-line data delivery to the fourth quarter of this year.

David Rodman: Since initiating the trial in April of 2023, we have found the rigorous nature of the trials design has impacted the pace of enrollment.

David Rodman: As we discussed on our earnings call in November we made some meaningful modifications to the advanced HDI and protocol and execution plan, while maintaining our focus on delivering the highest quality dataset.

Just on our modeling we have narrowed our guidance for top line data to delivery to the fourth quarter of this year.

David Rodman: The trial is designed to allow us to demonstrate the value of Lora understaffed when added to standardized optimized a J guideline background treatment in patients with uncontrolled or resistant hypertension as confirmed by 24 hour ambulatory BP measurement.

Jon Congleton: The trial is designed to allow us to demonstrate the value of loranderstat when added to standardized, optimized AHA guideline background treatment in patients with uncontrolled or resistant hypertension as confirmed by 24-hour ambulatory BP measurement. We believe this trial has the potential to generate the highest level of evidence that will be important for potential inclusion in hypertension guidelines, for treating physicians, and for creating favorable access via the payer. We then initiated the Launch HTN Phase III trial in the fourth quarter of 2023, which is expected to have top-line results in the second half of 2025. The objective of this trial is to model the real-world setting of larunderstat when added to existing treatment for uncontrolled or resistant hypertension in the primary care setting.

David Rodman: We believe this trial has the potential to generate the highest level of evidence that will be important for potential inclusion in hypertension guidelines for treating physicians and for creating favorable access via the payers.

David Rodman: We then initiated the launch HCN phase III trial in the fourth quarter of 2023, which is expected to have topline results in the second half of 2025, we.

David Rodman: The objective of this trial is to model the real world setting of Laura understand when added to existing treatment Frank control no resistant hypertension in the primary care setting.

Jon Congleton: This trial is expected to enroll up to approximately 1,000 adult subjects. Throughout the past year, we've published or presented follow-up data and analysis from the completed TARGET-HTN trial, which was our Phase II trial of lorondersat in hypertension. These additional data have further supported our strategy for developing lorandastat as a targeted approach to treat uncontrolled or resistant hypertension, as well as our design of the PIVLT program. The latest example of this came in the fourth quarter when we presented the data at the American Hypertension Association Scientific Sessions meeting in 2023. This new analysis shows that increased BMI is correlated with both increased leptin and increased aldosterone production.

David Rodman: This trial is expected to enroll up to approximately 1000 adult subjects.

David Rodman: Throughout the past year, we've published or presented follow up data and analysis from the completed target Ht and trial, which was our phase II trial of <unk> and hypertension.

David Rodman: These additional data have further supported our strategy for developing or understand as a targeted approach to treat uncontrolled or resistant hypertension as well as our design of the pivotal program.

David Rodman: The latest example of US came in the fourth quarter. When we presented the data at the American Hypertension Association scientific sessions meeting in 2023.

David Rodman: This new analysis showed that increased BMI was correlated with both increase leptin and increased aldosterone production.

Jon Congleton: These data expand our understanding of mechanisms that may link the increasing prevalence of obesity to a parallel increase in uncontrolled and resistant hypertension. Our EXPLORE-CKD Phase 2 trial for lorandosatin in patients with hypertension and Stage 2-3b chronic kidney disease was initiated in late 2023. The intent of this proof-of-concept trial is to demonstrate the benefit of loranderstat in reducing blood pressure and provide supportive evidence for the potential benefit in chronic kidney disease. The initial design was to compare the efficacy of lorandazet alone and in combination with an SGLT2 inhibitor in patients naive to SGLT2 inhibitor treatment.

David Rodman: These data to expand our understanding of mechanisms that may link the increasing prevalence of obesity to a parallel increase in uncontrolled and resistant hypertension.

David Rodman: Our explorer <unk> phase III trial for <unk> in patients with hypertension and stage two to three be chronic kidney disease was initiated in late 2023.

David Rodman: The intent of this proof of concept trial is to demonstrate the benefit of lower under stat, and reducing blood pressure and provide supportive evidence for the potential benefit on chronic kidney disease. The initial.

David Rodman: Design was to compare the efficacy of renters that alone and in combination with an <unk> inhibitor in patients naive to ask <unk> two inhibitor treatment.

David Rodman: The evolving treatment paradigm in <unk> resulted in the proportion of <unk> patients being treated with <unk> two inhibitors rapidly increasing over the past year to the point, where identification of S. G. L. T too naive subjects has proven to be greater than anticipated.

Jon Congleton: The evolving treatment paradigm in CKD has resulted in the proportion of CKD patients being treated with SGLT2 inhibitors rapidly increasing over the past year, to the point where identification of SGLT2 nave subjects has proven to be a greater than anticipated impediment to trial enrollment. Therefore, we will be modifying this trial designed to enroll patients who are either on SGLT2 inhibitors or naive to SG Additionally, all trial participants will remain on an SGLT2 inhibitor throughout the conduct of the trial. Dave will provide more detail on the trial design changes, but these changes ensure that all trial participants have access to SGLT2 inhibitor treatment while allowing us to achieve our objective of evaluating the benefit of lorandastat on BP reduction in kidney disease. We continue to anticipate top-line data from this trial within the prior stated guidance of Q4 2024 to Q1 2025. As I mentioned earlier, our team has been growing over the past year as we ramp up our clinical activity. We recently appointed Dr. Minji Kim as our new Chief Business Officer.

David Rodman: Greater than anticipated impediment to trial enrollment there.

David Rodman: And therefore, we will be modifying this trial designed to enroll patients who are either on <unk>, two inhibitors or naive to <unk> inhibitor treatment.

David Rodman: Additionally, all trial participants will remain on an <unk> two inhibitor throughout the conduct of the trial.

David Rodman: Dave will provide more detail on the trial design changes, but these changes is ensure that all trial participants have access to <unk> two inhibitor treatment, while allowing us to achieve our objective of evaluating the benefit of lower under stat on BP reduction in kidney disease. We continue to anticipate top line data from this trial.

David Rodman: Within the prior stated guidance of Q4 2024 to Q1 of 2025.

David Rodman: As I mentioned earlier, our team has been growing over the past year as we ramped up our clinical activities. We recently appointed Dr. <unk> as our new Chief business Officer she.

David Rodman: She brings a solid track record of generating value for multiple companies and brings more than two decades of experience in business development, strategic leadership, and scientific research. During her career, she has worked with biotech companies in the U.S. and overseas across broad therapeutic and technical areas. As you can see, we've built up a lot of momentum in our clinical program over the past year and are well positioned to continue executing on our clinical strategy. I will now turn the call over to Dr. David Rodman, Chief Medical Officer of Mineralys Therapeutics, who will provide additional details on our clinical program for laryngostasis. Dave

David Rodman: She brings a solid track record of generating value for multiple companies and brings more than two decades of experience in business development strategic leadership and scientific research.

David Rodman: During her career she has worked with biotech companies in the U S and overseas across broad therapeutic and technical areas.

David Rodman: As you can see we've built up a lot of momentum in our clinical program over the past year and are well positioned to continue executing on our clinical strategy.

Speaker Change: Let me now turn the call over to Dr. David Rodman, Chief Medical Officer of <unk> Therapeutics, who will provide additional details on our clinical program for all of them understand Dave.

David Rodman: Dave Thank you John and good morning, everybody today I'll provide an update on the pivotal clinical program for <unk> and then I'll give a summary update on a revised phase III explorer CK D trial as Theyre under staffed for hypertension and CTV.

David Rodman: Thank you, Jon, and good morning, everybody. Today I'll provide an update on the Pivotal Clinical Program for laryngostat, and then I'll give a summary update on the revised Phase 2 Explore CKD trial of laryngostat for hypertension and CKD. We were very pleased to announce at the end of the fourth quarter that we had dosed the first subject in our pivotal LAUNCH-HTN trial. As Jon mentioned earlier, this is the second part of our pivotal clinical program for laryngostat for the treatment of hypertension. Total enrollment is expected to be approximately 1,000 students.

David Rodman: We're very pleased we were very pleased to announce at the end of the fourth quarter that we have dosed. The first subject in our pivotal launch HCN trial as John mentioned earlier. This is the second part of our pivotal clinical program for <unk> for treatment of hypertension total enrollment is expected to be approximately 1000 subs.

David Rodman: <unk> launch HCN is a randomized double blind placebo controlled three arm trial design is similar to the target HTM proof of concept trial enrolling subjects, who will remain on their previously prescribed background regimen of two to five antihypertensive subjects will be randomized one to two two.

David Rodman: LAUNCH-HTN is a randomized, double-blind, placebo-controlled, three-arm trial. The design is similar to the Target-HTN proof-of-concept trial, enrolling subjects who will remain on their previously prescribed background regimen of 2 to 5 antihypertensives. Subjects will be randomized 1 to 2 to 1 to either placebo, once daily 50 milligrams of lorandristat, or once daily 50 milligrams of lorandristat, but with the option to titrate up to 100 milligrams once daily as needed after week six.

David Rodman: One to either placebo once daily 50 milligrams that will or under stat or once daily 50 milligrams of <unk>, but with the option to titrate up to 100 milligrams once daily as needed after week six the primary endpoint for this trial will be the change in systolic blood.

David Rodman: The primary endpoint for this trial will be the change in systolic blood pressure as measured by automated office blood pressure, which was the same primary endpoint we used in Target HTN. We believe this endpoint reflects a real-world measurement that will be relevant to the primary care provider this trial targets. In addition, subjects from this trial will be offered the opportunity to roll over into an ongoing open-label extension trial. Now turning to the Pivotal ADVANCE HTN trial, we're progressing on track after implementation of the protocol changes and operational enhancements we discussed in our Q3 2023 earnings. As Jon noted in his comments, ADVANCE-HTN is a state-of-the-art, extremely rigorous hypertension trial designed and executed in collaboration with the very experienced cardiovascular research team at the Cleveland Clinic.

David Rodman: Pressure as measured by automated office blood pressure, which was the same primary endpoint we used in target H T. M. We believe this endpoint reflects a real world measurement that will be relevant to the primary care provider. This trial targets. In addition subjects from this trial will be offered the opportunity to rollover.

David Rodman: Her into an ongoing open label extension.

David Rodman: <unk> trial.

David Rodman: Now turning to the pivotal advance HTM trial, we're progressing on track after implementation of the protocol changes and operational enhancements, we discussed in our Q3 2023 earnings call.

David Rodman: As John noted in his comments advance HCN is a state of the art extremely rigorous hypertension trial designed and executed in collaboration with the very experienced cardiovascular research team at the Cleveland Clinic.

David Rodman: We placed all trial participants on a standardized.

David Rodman: We placed all trial participants on a standardized AHA guidelines-directed treatment regimen at maximum tolerated doses. In addition, we're using real-time monitoring of adherence and blood pressure assessment utilizing the gold standard 24-hour ambulatory BP measurement. In this way, we exclude any subjects whose poor blood pressure control is due to noncompliance, inadequate doses, or choice of background medications or white coat hypertension.

David Rodman: Guidelines directed treatment regimen at maximum tolerated doses. In addition, we used real time.

David Rodman: Using real time monitoring of adherence and blood pressure assessment utilizing the gold standard 24 hour ambulatory BP measurement in this way, we exclude any subjects, whose poor blood pressure control is due to noncompliance inadequate doses or choice of background.

David Rodman: <unk> or white coat hypertension.

David Rodman: This ensures that an extremely high proportion of trial participants truly have uncontrolled wear resistant hypertension. We also believe given the broad targeting it's other standard mechanisms of hypertension. The randomized trial population will be enriched with aldosterone dependent hypertensive subjects more likely to do.

David Rodman: This ensures that an extremely high proportion of trial participants truly have uncontrolled or resistant hypertension. We also believe, given the broad targeting of other standard mechanisms of hypertension, the randomized trial population will be enriched with aldosterone-dependent hypertensive subjects more likely to derive benefit from laryngoscopy. We believe that the overlap between obesity-associated hypertension and Aldosterone-Mediated Mechanisms is fundamental.

David Rodman: Arrived benefit from <unk>.

David Rodman: We believe that the overlap between obesity associated hypertension, and aldosterone mediated mechanisms is fundamental in our pre specified analysis of the target HTM data presented in our Jama paper last year supports that hypothesis. The planned analysis at the advanced <unk>.

David Rodman: And our pre-specified analysis of the target HTN data presented in our JAMA paper last year supports that hypothesis. The planned analysis of the ADVANCE-HTN trial includes a well-powered confirmatory test of the predictive value of obesity on the efficacy of lorandristat. We believe that in the clinical setting, inability of an optimized two or three-drug standard antihypertensive regimen to reduce blood pressure sufficiently to a goal in the setting of obesity will be a straightforward approach to identifying candidates for treatment with laryngostats.

David Rodman: <unk> trial includes a well powered confirmatory test of the predictive value of obesity on the efficacy of <unk>, we believe that in the clinical setting.

David Rodman: And the ability of an optimized two or three drugs standard antihypertensive regimen to reduce blood pressure sufficiently to go in the setting of obesity will be a straightforward approach to identifying candidates for treatment with <unk>.

David Rodman: In addition, we plan to continue to explore other positive and negative predictive tools using an unbiased artificial intelligence model to expand the repertoire of useful tools for targeting laryngostats to individuals most likely to derive long-term clinical benefit. We expect to announce top-line data from the ADVANCE-HTN trial in the fourth quarter of 2024 and top-line data from LAUNCH-HTN in the second half of 2025. Moving on to our hypertension and CKD program, as Jon mentioned earlier, we're making some modifications to our Phase 2 Explore CKD trial, ensuring all trial participants have access to an SGLT2 inhibitor. We believe this amendment better reflects the current treatment approach for subjects who have CKD.

David Rodman: In addition, we plan to continue to explore other positive and negative predictive tools using an unbiased artificial intelligence model to expand the repertoire of useful tools for targeting we were understaffed to individuals' most likely to derive long term clinical benefit.

David Rodman: We expect to announce topline data from the advanced HTS trial in the fourth quarter of 2024 and topline data from launch HTM in the second half of 2025.

Moving onto our hypertension and CK deep program as John mentioned earlier were making some modifications to our phase II explore CK D trial, ensuring all trial participants have access to an <unk> inhibitor. We believe this amendment better reflects the current treatment approach for subjects, who have CK D.

David Rodman: We will be reducing the lower limit of baseline egfr from 45% to 30 ml per minute per one 703 meters squared, which will allow us to eliminate the original part b profiling portion of this trial lastly, the treatment periods will be reduced from eight weeks to four weeks.

David Rodman: We'll be reducing the lower limit of baseline EGFR from 45 to 30 ml per minute per 1.73 meters squared, which will allow us to eliminate the original Part B profiling portion of this trial. Lastly, the treatment periods will be reduced from eight weeks to four weeks, which we believe will still provide ample time to demonstrate clinical benefit on blood pressure, as well as insights into kidney benefit assessed by albuminuria. The primary objective remains reduction in elevated systolic blood pressure, which we believe is an important contributor to progression of CKD, particularly in individuals with obesity and cardiovascular renal metabolic syndrome. In terms of how we'll be treating subjects enrolled to date, they will be separately analyzed and offered participation in the open-label extension trial, contributing to the characterization of long-term safety. We maintain our expectation to announce top-line data in the fourth quarter of this year or the first quarter of 2025. We look forward to keeping you apprised of the status of the La Runderstadt Development Program. I will now turn the call over to Adam, who will provide a financial review for the fourth quarter and full year 2023. Adam?

David Rodman: Which we believe will still provide ample time to demonstrate clinical benefit on blood pressure as well as insights into kidney benefit SaaS by albumin area.

David Rodman: The primary objective remains reduction in elevated systolic blood pressure, which we believe is an important contributor to progression of CK D, particularly in individuals with obesity and cardiovascular renal metabolic syndrome.

David Rodman: In terms of how we'll be treating subject enrolled to date, they will be separately analyzed and offered participation in the open label extension trial contributing to the characterization of long term safety.

David Rodman: We maintain our expectation to announce top line data in the fourth quarter of this year or the first quarter of 2025.

David Rodman: We look forward to keeping you apprised of the status of the <unk> development program I will now turn the call over to Adam who will provide a financial review for the fourth quarter and full year 2023, Adam.

Adam Scott Levy: Thank you, Dave. Good morning, everyone. Today I will discuss select portions of our fourth quarter and full year 2023 financial results. Additional details can be found in our Form 10-K, which was filed with the SEC earlier today. We ended the year with cash equivalents and investments of $239 million compared to $110.1 million as of December 31, 2022.

Adam: Dave Good morning, everyone today, I will discuss select portions of our fourth quarter and full year 2023 financial results. Additional details can be found in our Form 10-K, which was filed with the SEC earlier today, we ended the year with cash cash equivalents and investments of 239.

Adam: Million compared to $110 1 million as of December 31, 2022.

Adam Scott Levy: In February 2024, we completed a private placement financing for gross proceeds of approximately $120 million before deducting fees and expenses. We believe that our cash, cash equivalents, and investments will be sufficient to allow us to fund our planned clinical trials, as well as support corporate operations into 2026. R&D expenses were $70.4 million for the year ending December 31st, 2023, compared to $26.3 million for the prior year. R&D expenses for the quarter ending December 31st, 2023 were $23.7 million, compared to $7.8 million for the same quarter of 2022.

Adam: In February 2024, we completed a private placement financing for gross proceeds of approximately $120 million before deducting fees and expenses, we believe that our cash cash equivalents and investments will be sufficient to allow us to fund our planned clinical trials as well as support corporate operations into 2002.

Adam: <unk> six <unk>.

Adam: R&D expenses were $74 million for the year ended December 31, 2023, compared to $26 3 million for the prior year.

Adam: R&D expenses for the quarter ended December 31, 2023 were $23 $7 million compared to $7 8 million for the same quarter of 2022. The annual increase in R&D expenses was primarily due to increases of $21 $4 million in frequency.

Adam Scott Levy: The annual increase in R&D expenses was primarily due to increases of $21.4 million in free clinical and clinical costs driven by the initiation of the Lorendra Stat Pivotal Program beginning in the second quarter of 2023. $9 million in license fees upon achieving the development milestones of Loranderstadt in 2023, $7.8 million in clinical supply manufacturing and regulatory, $5.6 million in higher compensation expenses resulting from additions to headcount and stock-based compensation, and $0.3 million in other research and development expenses. G&A expenses were $14.3 million for the year ending December 31, 2023, compared to $5.2 million for the prior year. G&A expenses were $4 million for the quarter ended December 31, 2023, compared to $2.2 million for the same quarter of the prior year. The annual increase in G&A expenses was primarily due to $3.8 million in higher professional fees associated with operating as a public company.

Adam: Call in clinical costs.

Adam: Driven by the initiation of the <unk> pivotal program beginning in the second quarter of 2023.

Adam: $9 million in license fees upon achieving development milestones of our understaffed in 2023, $7 8 million and clinical supply manufacturing and regulatory costs $5 $6 million and higher compensation expenses, resulting from additions to head count and stock based compensation and.

Zero point $3 million and other research and development expenses.

Adam: G&A expenses were $14 3 million for the year ended December 31, 2023, compared to $5 2 million for the prior year.

Adam: G&A expenses were $4 million for the quarter ended December 31, 2023, compared to $2 2 million for the same quarter of the prior year.

Adam: The increase in G&A expenses was primarily due to $3 $8 million and higher professional fees associated with operating as a public company.

Adam: $3 4 million and higher compensation expenses, resulting from additions to head count and stock based compensation $1 $1 million of higher insurance expenses, primarily associated with new director and officer insurance policies and zero point $8 million in higher other administrative expenses.

Adam Scott Levy: $3.4 million in higher compensation expenses resulting from additions to headcount and stock-based compensation, $1.1 million of higher insurance expenses primarily associated with new director and officer insurance policies, and $0.8 million in higher other administrative expenses. Total other income was $12.8 million for the year ended December 31, 2023, compared to $1.7 million for the prior year. Total other income was $3.3 million for the quarter ended December 31, 2023, compared to $0.9 million for the same quarter of 2022. The annual increase was primarily attributable to increased interest earned on our investments in money market funds and U.S. Treasury securities. The net loss was $71.9 billion for the year ended December 31, 2023, compared to $29.8 million for the prior year. The net loss was $24.4 million for the quarter ending on December 31st, 2023, compared to $9.1 million for the same quarter of 2022.

Adam: Total other income was $12 $8 million for the year ended December 31, 2023, compared to $1 7 million for the prior year.

Adam: Total other income was $3 $3 million for the quarter ended December 31, 2023, compared to zero point $9 million for the same quarter of 2022.

Adam: The annual increase was primarily attributable to increased interest earned on our investments in money market funds and U S. Treasuries net loss was $71 $9 billion for the year ended December 31, 2023, compared to $29 8 million for the prior year net.

Adam: Net loss was $24 $4 million for the quarter ended December 31, 2023, compared to $9 1 million for the same quarter of 2022.

Speaker Change: The increase was primarily attributable to the factors I described earlier with that I'll ask the operator to open the call for questions operator.

Adam: Yes.

Speaker Change: Operator, we're ready for questions.

Speaker Change: Thank you if you wish to ask.

Adam Scott Levy: The annual increase was primarily attributable to the factors I described earlier. With that, I'll ask the operator to open the call for questions. Operator?

Speaker Change: Question. Please style star one on your telephone keypad smelter entered the queue. Once your name has been announced you can ask you. A question. If you found your question is I'll answer it before it so it sounds like you can down start seems to cancel.

Operator: Operator, we're ready for questions. Thank you. If you wish to ask a question, please dial star 1 on your telephone keypad now to enter the queue. Once your name has been announced, you can ask your question. If you find your question is answered before it's your turn to speak, you can dial star 2 to cancel. Our first question comes from the line of Michael DiFiore of Evercore ISI. Please go ahead; your line is open.

Speaker Change: Our first question comes from the line of Michael D. Fury of Evercore ISI. Please go ahead. Your line is open.

Speaker Change: Hi, guys. Thanks, so much for taking my question and congrats on all the progress a few for me number one regarding the advanced HTS trial any color on what we could expect in terms of placebo effect here just given the standard background regimen.

Michael Gennaro DiFiore: Hi guys, thanks so much for taking my question and congrats on all the..., a few for me. Number one, regarding the ADVANCE HDN trial, any color on what we could expect in terms of placebo given the standard background?

David Rodman: If we assume that equal amounts of patient... on 2 vs. 3. I think that the literature suggests around 6 milliliters of mercury for non-resistant. We just want to get you started. Thank you. Thank you, and Abbe Qufalds. So just so we're both on the same page, there's a run-in period on the background regimen during which we'll establish a new baseline due to those medicines. And then after that is when they'll enter a placebo-controlled period compared to laryngostat. So we really don't expect that full placebo effect you were talking about to be manifest. Most of that will be in the run-in period.

Speaker Change: If we assume that equal amounts of patients will be on two versus three background drugs. I mean, I think that the literature suggests around six millimeters of mercury for non resistant hypertension versus nine millimeters in resistant patients, but just wanted to get your view on that.

Speaker Change: And I have two follow up questions.

Speaker Change: So just so I'm sure. We're both on the same page there is a run in period on the background regimen.

During which we will establish a new baseline due to those medicines and then after that is when they'll enter placebo controlled period comparing to <unk>. So we really don't expect.

Speaker Change: That full placebo effect, you were talking about to be manifest most of that will be in the run in period.

Speaker Change: B.

Jon Congleton: The run-in period is three weeks, and so it could be that there'd be a little residual effect, but I don't think it'll change much from what we saw and in the target HTN study using A, B, and ABPM, our placebo effect was under two millimeters of mercury, so I think it'll be in that under five millimeter mercury range for most likely, not the larger numbers that you quoted. A question too, earlier this week a competitor antihypertensive drug recently got approved, with its label having a black box warning, a REMS program, and other notable... Despite all of this, and only having a roughly four-point treatment effect, the drug was approved for a seemingly broad population. Just want to get your views on the KLL appetite for this drug, given its benefit-risk profile and how this approval builds for laryngitis. Yeah, Mike, this is Jon.

Speaker Change: We're running period is three weeks and so it could be that there'll be a little residual effect, but I don't think it will.

Speaker Change: Change much from what we saw and in the target HTM steady using a beep.

Speaker Change: A BPM or placebo effect was under two millimeters of Mercury. So I think it'll be in that under five millimeter Mercury range, most likely not the larger numbers that you've quoted.

Speaker Change: Very helpful.

Speaker Change: Another question to it earlier.

Speaker Change: Earlier this week a competitor anti hypertensive drug recently got approved.

Speaker Change: With its label, having a black box warning a rems program and other notable safety warnings.

Speaker Change: All of this.

Speaker Change: It will be having a four point roughly for treatment effect, the drug was approved and seemingly broad population.

Speaker Change: To get your views on the kalo appetite for this drug given its benefit risk profile and how how this approval bodes for lower interest rates.

Speaker Change: Yes, Mike This is John.

Jon Congleton: You know, I think the introduction of any kind of new modalities is not a bad thing. We've seen an absence of innovation for well over 20 years in this space. We know the unmet need, with roughly 50 percent of the treated population getting the goal, means that we need new approaches. You know, as far as the KOL appetite for it, I think it's more broadly we haven't really dug into the details around the label. The label was interesting, and that creates a bit of a challenge, but again, I think the unmet need being met with new innovation, I think that's going to Certainly, probably not in a first-line category, but for us, our focus has always been on how do we bring a targeted approach, how do we bring that toolkit forward for prescribers so they can really identify those subjects that will have an enhanced response to lorandristat. We're very confident in what we've seen to date as it relates to the safety and tolerability profile of lorandristat.

John: I think the the introduction of any kind of new modalities.

John: Not a bad thing we've seen in absence of innovation for well over 20 years in this space, we know the unmet need.

John: With roughly 50% of the treated population not getting to goal.

John: Means that we need to have new approaches.

John: As far as the Kols appetite for it I think it's more broadly we haven't really dug into the details around interest and effort and 10 Tan.

John: The label was interesting and that creates a bit of a challenge, but again I think the unmet need being met with new innovation.

John: I think that's going to be valued by Kols.

John: Certainly probably not in first line category, but for US our focus has always been on how do we bring a targeted approach how do we bring that toolkit forward for prescribers. So they can really identify those subjects that will have an enhanced response to or understand.

We're very <unk>.

John: Confident in what we've seen to date as it relates to the safety and Tolerability profile of where under stat.

Adam Scott Levy: That's why we're doing the broader pivotal program that we're doing to fully characterize that. But again, I think we're on the cusp of a lot of innovation that's needed, given where the unmet need exists in this space right now. And one final question, any color you could provide on OPEX guidance this year? Mike, I'm sorry. OPEX guidance? Yeah, Mike, this is Adam.

John: That's why we're doing the broader pivotal program that we're doing to fully characterize that.

But again I think we're on the cusp of a lot of innovation.

John: That's needed given where the unmet need exists in this space right now.

Speaker Change: Got it and one final question.

Speaker Change: Any color you can provide that provide on opex guidance this year.

Speaker Change: Mike I'm, sorry, Opex guidance.

Speaker Change: Yes, Mike this is Adam you're providing it.

Speaker Change: Yes.

We haven't provided any.

Adam: Guidance going forward on expenses, what we have said is that our cash runway brings us into 2026, we'll be running several clinical trials this year or so.

Adam Scott Levy: What we have said is that our cash runway brings us into 2026. We'll be running several clinical trials this year, so burn is expected to continue to ramp up. Thanks, bye. Bye

Adam: Burn is expected to continue to ramp up.

Mike: Thanks, so much.

Speaker Change: Thanks, Mike.

Speaker Change: Thank you Alan that question comes from the line of Greg Harrison at Bank of America. Please go ahead. Your line is open.

Operator: Thank you. Our next question comes from the line of Greg Harrison at Bank of America. Please go ahead, your line is open. Hi, good morning. This is Mary Caton on behalf of Gregg Harrison.

Speaker Change: Hi, Good morning. This is Mary Kate on for Greg. Thanks for taking our question looking at the top line data expected later this year what are your expectations for the advanced topline readout and maybe what would be a success for you here.

Mary Kate Davis: Thanks for taking our question. Looking at the top-line data expected later this year, what are your expectations for the advanced top-line readout and maybe what would be a success for you here? Yeah, Mary Kate, this is Jon.

Speaker Change: Yes, Mary Kate this is John.

Jon Congleton: You know, it's hard to forecast forward. I think if we look back at target HTN, we saw about an eight to 10 millimeter placebo-adjusted reduction in systolic BP across the whole population; we saw an enhanced response for those on a diuretic and, obviously, those with increased BMI. I think the way that we have framed the boat pedal programs to mitigate the risk is likely guiding to a similar response, that 8 to 10 millimeter mercury reduction. Bear in mind that both Advance HTN and Launch HTN have diuretic as part of a background, and we know that we saw an enhanced response with diuretic and loranderstat, so I think that's a positive read-through. The market research that we've done, we've done a pretty exhaustive amount of that with primary care as well as specialists. If you're in that 8-10 mm mercury improvement on an uncontrolled or resistant population, that's extremely meaningful. That's something they currently don't have access to when you're looking at a third or fourth line agent being added.

John: It's hard to forecast forward I think the if we look back at target HTM, we saw about an eight to 10 millimeter placebo adjusted reduction in systolic BP.

John: Across the whole population, we saw an enhanced response for those on a diuretic and obviously those with increased BMI.

John: I think the way that we have framed.

John: Both peddled programs.

John: To mitigate the risk.

John: Is it is likely guiding to a similar response that eight to 10 millimeter Mercury reduction.

John: Bear in mind that both advanced H C. N N launch H T N have diuretic required as part of a background and we know that we saw an enhanced response with diabetic and <unk>. So I think thats a positive read through.

John: The market research that we've done and we've done a pretty exhaustive amount of that with primary care as well as specialists.

John: You are in that eight to 10 millimeter Mercury improvement.

John: On a uncontrolled or resistant population.

John: It's extremely meaningful.

John: That's something that they currently don't have access to when Youre looking into third or fourth line agent being added typically with what's currently available when you add a third or fourth agent you get about a five to six millimeters of Mercury production based on <unk>.

Jon Congleton: Typically, with what's currently available, when you add a third or fourth agent, you get about a 5-6 mm mercury reduction based on extensive meta-analysis. And so that's why that 8-10 mm mercury resonances with prescribers, and particularly if we can bring forward the toolkit again to identify those subjects like an obese hypertensive subject that's going to have an enhanced response. And we saw a 12-16 mm mercury improvement in target HTN. We'll see if that's replicated within this study. I make a point that it's why we're doing advanced HTN in a more rigorous way than launch HTN with that standardized background, because we truly are identifying subjects that are on the right drug, at the right dose, compliant, and yet still uncontrolled and resistant. And I think applying LaRunderstat to that rigorous kind of study really gives us a chance to replicate and possibly improve upon the data that we saw in target HTN, but Great, thank you.

John: Extensive meta analysis and so that's why that eight to 10 millimeter Mercury resonates with prescribers and particularly if we can bring forward the tool kit again to identify those subjects like an obese hypertensive subject.

John: It's going to have an enhanced response and we saw a 12% to 16 millimeter mercury improvement in target HCN.

John: We'll see if that's replicated within this study I'll make a point that and it's why we're doing advance H T N and a more rigorous conduct and launch HCN where that standardized background is we truly are identifying subjects that are on the right drug at the right dose compliant and yet still on <unk>.

John: <unk> and resistant and I make apply and Lamar understand to that rigorous kind of steady really gives us a chance to replicate and possibly improve upon the data that we saw in target HCN, but in a data set or a population, particularly for specialists.

John: Yes.

John: Clearly uncontrolled and resistant without any questions around proper dose proper compliance or whitecoat hypertension.

Speaker Change: Great. Thank you.

Speaker Change: Thank you. Our next question comes from the line of Seamus Fernandez at Guggenheim Securities. Please go ahead. Your line is open.

Operator: Thank you. Our next question comes from the line of Seamus Fernandes at Guggenheim Securities. Please go ahead, your line is open.

Seamus Fernandez: Great. Thanks for the question so.

Seamus Fernandes: Great, thanks for the question. So, and congrats on all the progress. Just one of the questions that we're getting from investors is, you know, the importance and impact of GLP-1s, specifically on two things. Number one, the flow trial is going to be presented at ACC. And, you know, I think there's some enthusiasm within the, I guess, cardiology and endocrinology community for those results and its impact of one milligram of semiglutide on outcomes in patients with limitations in disease there. Just wanted to know what your thoughts are on the impact of GLP-1s on both weight loss and in a CKD patient population.

Seamus Fernandez: And congrats on all the progress just one of the questions that we're getting from investors is the.

Seamus Fernandez: The importance and impact of GOP ones.

Seamus Fernandez: Specifically on the.

Seamus Fernandez: Two things number one.

Seamus Fernandez: The flow trial is going to be presented at ACC.

Seamus Fernandez: And I think there are some enthusiasm within the I guess.

Seamus Fernandez: Cardiology and endocrinology community for those results and its impact of one milligram.

Seamus Fernandez: Seven glue tied on the outcomes in patients with.

Seamus Fernandez: With with limitations in disease, there just wanted to know what your.

Seamus Fernandez: Thoughts are on the impact of <unk> on.

Both weight loss and NSE.

Seamus Fernandez: <unk> patient population and then second question.

Jon Congleton: And then the second question is really about, you know, the baseline patient characteristics in advanced HTN. You know, I assume that you've got a pretty good feel for what the baseline patient characteristics are kind of shaping up to. But I'm just hoping that you'll reveal the baseline patient characteristics prior to publication, and maybe you could just share with us what you think are the most important measures that you'll be looking at in exploratory analyses. Thanks. Yeah, Seamus, thanks for the question.

Seamus Fernandez: It's really on the baseline patient characteristics.

Seamus Fernandez: In advanced HTM.

Speaker Change: I assume that you've got a pretty good feel for what the baseline patient characteristics are kind of shaping up too, but just hoping that you will reveal the baseline patient characteristics prior to.

Speaker Change: The publication and maybe you could just share with US what you think are the most important.

Speaker Change: Measures that youll be looking at an exploratory.

Speaker Change: <unk>. Thanks.

Speaker Change: Yes.

Speaker Change: <unk> thanks for the question.

David Rodman: The GLP-1s and the GLP-1 GIP, and the GGGs are all obviously presenting really interesting data as it relates to weight loss and then as it relates to the corollary benefits to comorbidities. We, like others, are interested to see the full data set. I don't think it's overly surprising that if you see weight loss reduction, you see improvement in overall cardio-renal metabolic health. I think that's been known for a long time through diet, exercise, and everything else. I think the, and I'll maybe have Dave add a point to this, From what we've seen of some of the data presented, I think it was with terzapatide and some of the prior data over the last three to six months. There still remains significant residual risk that needs to be addressed.

G L P ones and the G. L. P. One G IP in the Triple Gs are all.

Speaker Change: Obviously presenting.

Speaker Change: Really interesting data as it relates to weight loss and then as it relates to the corollary benefits to co morbidities.

Speaker Change: We like others are interested to see the full dataset.

Speaker Change: I don't think its overly surprising that if you see weight loss reduction you see improvement in overall cardio renal metabolic health.

Speaker Change: I think that's been known for a long time through diet exercise and everything else I think the and maybe have Dave add at a point to this.

Dave: From what we've seen of some of the data presented.

Dave: I think it was with <unk>.

Dave: And some of the prior data over the last three to six months.

Dave: There still remains significant residual risk.

Dave: That needs to be addressed.

David Rodman: We think that addressing that broader cardiovascular and renal risk is going to be multifactorial. We know from, frankly, decades of research that aldosterone is a significant driver of hypertension, of CKD, of heart failure, and heart disease, and that's where we think an ASI like lorandostat becomes a really interesting component of that broader treatment to get as much of the residual risk reduced as possible. But Dave, do you have any additional thoughts you want to add to that?

Dave: Think that addressing that broader cardiovascular and renal risk is going to be multifactorial.

Dave: We know from frankly decades of research that aldosterone as a significant driver of hypertension of CK D of heart failure and heart disease.

Dave: And that's where we think in ASI like Laura understand.

Dave: It becomes a really interesting component of that broader treatment to get as much of the residual risk reduce as possible, but Dave do you have any additional thoughts you want to add to that.

David Rodman: Well, thanks, Jon. I'm going to add a little bit to that, and then I'll answer your second part of your question following that. So we get this question a lot. It's a really interesting question, right?

Dave: Well, thanks, John I'm going to add a little bit to that and then I'll answer your second part of your question following that so.

Dave: We get this question a lot it's a really interesting question rate debt.

Dave: Weight loss is going to be important in reducing risk, but with John referred to as the as the trial that he spoke about reported a 20% reduction in cardiovascular events major cardiovascular events, but that really translated going from 8% incidents to six 5%. So.

David Rodman: That weight loss is going to be important in reducing risk. But what Jon referred to was this, the trial that he spoke about reported a 20% reduction in cardiovascular events, major cardiovascular events, but that really translated going from 8% incidence to 6.5%. So 8% per 100 versus 6.5% per 100, that's 20%, but in the real world, it's 1.5%. And there's still more than 6% event rate to improve upon.

Dave: <unk> hundred versus six and a half per hundred that's 20%, but in the real world. It's one 5% and there is still more than 6% event rate to improve upon.

David Rodman: Weight loss is only part of it. Jon mentioned a healthy lifestyle and exercise. All of these things, avoiding tobacco and alcohol, these things all add together, and just having a drug that allows you to lose weight is not by itself a replacement for that. And so, what we'll see over time is that people will look at this as a multi-factorial treatment. The idea would be these lifestyle changes, but in reality, there's room for other medications to be combined. And that's what we're seeing with everything in cardiovascular and renal metabolism, three and four drugs together making the difference. We believe our drug's gonna be an important component of that. We will, regardless of weight loss, have the potential to lower all cardiovascular risk. There is a reason why aldosterone-targeted therapies are useful in things like heart failure.

Dave: Net loss is only part of it John mentioned healthy lifestyle exercise.

Dave: All of these things avoiding tobacco alcohol. These things all add together and just having a drug that allows you to lose weight is not by itself a replacement for that and so what we'll see over time is that people look at this as a multi factorial treatment.

Dave: The ideal would be these lifestyle changes, but in reality there is a room for other medications to be combined and Thats what were seeing in everything in cardiovascular renal metabolic three and four drugs together, making the difference we believe our drug is going to be an important component of that we will regardless of weight loss.

Dave: Have the potential to lower all cause cardiovascular risks. There's a reason why <unk> targeted therapies are useful in things like heart failure, our drug as a next generation approach to that so I hope that just gives you some color for where we think it's not an either or and we're going to be obviously very interested in.

David Rodman: Our drug is a next-generation approach, so I hope that just gives you some color for where we think it's not an either/or choice, and we're going to be, obviously, very interested in discussing this with companies that are focused on GLP-1s going forward. Now, your second question was characteristic. I'm not going to go into that in depth, but what I'll tell you is this: we had a really nice demographic profile in the target HTN tribe. 40% African American, about 50-50 male-female.

Dave: This with companies that are focused on <unk> going forward now your second question was characteristics.

Dave: What I can't I'm, not going to go into that and deeply but what I'll tell you is this that we.

Dave: Had a really nice demographic profile in the target HCN trial, 40% African American about 50 50 male female.

Dave: We had about 50% on two drags up 50% on three drugs. So our aspiration is to be in that range and so far we've seen no reason to think we won't be in that range using the inclusion exclusion criteria we have.

David Rodman: We had about 50% on two drugs and 50% on three drugs. So our aspiration is to be in that range, and so far, we've seen no reason to think we won't be in that range using the inclusion-exclusion criteria we have. Great. And if I could ask one question,

Speaker Change: Great and then if I could ask.

One.

Speaker Change: Follow up.

Speaker Change: <unk>.

Speaker Change: The reduction.

David Rodman: Follow-up, the reduction in the baseline EGFR from 45 down to 30, can you maybe just talk a little bit more about the importance of that inclusion criteria? Sure, I can. So from a practical standpoint, the trial sites where we go to for trials like this, or referral sites, that have primary care doctors referring patients to more specialized centers with chronic kidney disease, and so they tend to see enrichment in people with GFRs below 45, so stage 3D. And so it'll be much more efficient to include those in one arm instead of two different arms of the trial. Now, one might ask the question, though, Since Part B also had a dose range discussion, is it important for us to be looking at dose ranges? One of the advantages of making sure everybody's on an SGLT2 is that SGLT2s lower your potassium.

In the baseline Egfr from 45 down to 30.

Speaker Change: Can you, maybe just talk a little bit more about the importance of that.

Speaker Change: That inclusion criteria.

Speaker Change: Sure I can so from a practical standpoint.

Speaker Change: <unk>.

Trial sites, where we go to first trials like this our referral sites that have primary care doctors, referring the patients to more specialized centers with chronic kidney disease.

Speaker Change: So they tend to see enrichment with people with GFR is below 45, so stage three D and so it'll be a much more efficient to include those in one arm instead of a two different arms of the trial now one might ask the question though.

Speaker Change: Since part B also had a dose range discussion are we is it important for us to be looking at dose ranging one of the advantages that making sure everybody is on in <unk> is <unk> lower your potassium.

David Rodman: And that's why there are two competitors in this space, let's say AstraZeneca and Beringer-Ingelheim, who are both committed to CKD trials now, are looking at the combination. And so we'll be doing the same thing. So it's just a practical thing.

Speaker Change: And that's why in that our two competitors in this space, let's say Astrazeneca and Beringer Ingelheim, who are both committed to CTD trials now are you looking at the combination and so we will be doing the same thing. So it's just a practical thing those two practical changes everybody on <unk>.

David Rodman: Those two practical changes, everybody on an SGLT2 inhibitor in the trial and allowing the EGFRs down to 30, are going to be a much broader population, a much more efficient way to recruit the trial, and will give us the same information we were looking for in terms of safety and efficacy of the combination. Great, thanks so much. Appreciate it, guys. Thanks, Sam.

Speaker Change: <unk> two inhibitor in the trial and allowing the Egfr is down to 30 is going to be a much broader population a much more efficient way to recruit the trial and will give us. The same information we were looking for in terms of safety efficacy of the combination.

Speaker Change: Great. Thanks, so much I appreciate it guys.

Speaker Change: Thanks Seamus.

Speaker Change: Thank you and our next question comes from the line of Mohit Bansal of Wells Fargo. Please go ahead. Your line is open.

Operator: Thank you. And our next question comes from the line of Mohit Bansal of Wells Fargo. Please go ahead, your line is open. Hey, this is Adam on behalf of Mohit.

Speaker Change: Hey, this is Adam on for Mohit. Thanks for taking my question. My question, sorry for David with regard to the OLED study.

Mohit Bansal: Thanks for taking our question. My questions are for David with regard to the OLE study. So trying to understand, you know, firstly, instead of running a single-arm OLE, you're pursuing one that includes a treatment withdrawal sub-study. So I want to understand what you could ultimately drop from that approach there. And then secondly, does the inclusion of CKD patients in the OLE give importance to hyperkalemia risk? Or was this pursued for another reason?

Speaker Change: Im trying to understand firstly in February a single arm.

Adam: Youre pursuing one that includes a treatment withdrawal sub study so wanted to understand what you could ultimately drop from that approach. There and then secondly does the inclusion of <unk> patients in the OLED give important throughout hyperkalemia risk or was this pursuit for another recent.

Speaker Change: Okay, well, thanks for the questions and so just to break it down into its component parts. The first question was about the randomized treatment withdrawal. So.

David Rodman: Okay. Well, thanks for the questions. And so just to break it down into its component parts, the first question was about the randomized treatment withdrawal. The FDA requires that we do a randomized treatment withdrawal. And what that means is anybody who is in the open label extension on active, and obviously, so they're informative, would then be randomized to either stay on the drug or go on placebo. They don't tell you how many, but it'll be in the hundreds of subjects that go through that. The purpose of it is just to see what you would refer to as an on-off-on approach. In other words, they come in on a certain amount of drug, they go off it, then they go back on it. How reversible are these things?

Speaker Change: <unk> requires that we do a randomized treatment withdrawal and what that means is anybody who is in the open label extension on active.

Speaker Change: And obviously they are on active drug who has a benefit on blood pressure.

Speaker Change: So they are informative.

Speaker Change: And then have be randomized to either stay on drug or go on placebo. They don't tell you how many but it'll be in the hundreds of subjects that go through that the purpose of it is just to see what you would refer to as an on off on.

Speaker Change: Approach in other words, they come in on a certain amount of drug. They go off. It then they go back on it how reversible or these things.

David Rodman: What time course, et cetera? We know our drug has a major advantage in that it's only got about a 10- to 12-hour half-life, meaning that things like hyperkalemia can be turned off and on very quickly, but we also can restore normal circadian rhythm, so aldo goes up and down the way it's supposed to. And so that's what that's for. So we expect to learn a lot about those details, but primarily, it's because it's a requirement as well. So let me just stop there for a second. Did that answer your question, that part? Yes.

Speaker Change: What time course et cetera.

Speaker Change: We know our drug has a major advantage in that it's only got about it of 10 to 12 hour half life meeting that things like hyperkalemia, we can turn off and on very quickly but.

Speaker Change: But we also can restore normal circadian rhythms, so Aldo goes up and down the way, it's supposed to and so thats what thats four so we expect to learn a lot about those details, but primarily it's because it's a requirement as well. So let me just stop there for a second did that answer your question that part.

Speaker Change: Sure.

Yes. Thanks.

Speaker Change: Okay.

David Rodman: Okay, so... Another part of your question was about putting CKD patients in. What we're doing from a logistics standpoint is having one omnibus open-label extension. We have to have an integrated safety database of every single patient who got even one dose of the drug.

Speaker Change: So.

Speaker Change: Another part of your question was.

Speaker Change: About putting CK D patients in what we're doing from a logistics standpoint is having one omnibus.

Speaker Change: Open label extension, but we don't we all we have to have an integrated safety database of every single patient who got even one dose of drug and they're included in that but beyond that they're going to be a separate cohort that's analyzed within the trial.

David Rodman: And that will be included in that. But beyond that, there's going to be a separate cohort that's analyzed within the trial. And so we'll be able to say, for instance, in subjects whose EGFR started at 30 to 45, what was their relative risk of a change in potassium? And that's very important, because when we talk to experts at the referral center sites I mentioned, they're not in the least bit worried about it. They deal with it all the time, they use the new potassium binders, and they just want that blood pressure to go up. So we'll be able to provide those data in that subset, and then for primary care doctors who may see somebody with an EGFR of 60. They really don't want that patient's potassium to go up over, you know, a certain threshold because they're in a different space in terms of management.

Speaker Change: And so we will be able to say for instance in subjects, whose egfr started at <unk>.

Speaker Change: 30 to 45, what was their relative risk of a change in potassium and thats very important because when we talk to experts at these referral center sites I mentioned, they're not in the least bit worried about potassium they deal with it all the time they use the new potassium binders and they just want that blood pressure to go down.

Speaker Change: So we will be able to provide those data in that subset and then for primary care Docs, who may see somebody with an Egfr 60.

Speaker Change: They really don't want that patients' potassium to go up over <unk>.

Speaker Change: Certain threshold because they're in a different space in terms of management and so we're going to have very very good control over saying in this subset here's the safety profile in this other subset here's the safety profile. So I don't think we have concerns about suddenly getting a warning that you might get a hyper task.

David Rodman: And so we're going to have very, very good control over saying, in this subset, here's the safety profile, in this other subset, here's the safety profile. So I don't think we have concerns about suddenly getting a warning that you might get high potassium. In fact, just the opposite.

Speaker Change: Jim.

Speaker Change: In fact, just the opposite we're going to have a very informative set of data to go into the label.

David Rodman: We're going to have a very informative set of data to go into the lab. I appreciate the detail. Thank you, and there are no further questions in the queue at this time, so this concludes the question and answer session, and I'd like to turn the call back to Jon Congleton for the closing. Thank you, operator, and thank you, everyone, for joining us today. We're very excited about the progress we've made over the past year and the advances in our clinical programs and remain enthusiastic about the upcoming milestones for the rest of the year and into 2024. We look forward to updating you as our pivotal program for La Runderstad continues to advance. With that, we'll close the call. Thank you. This now concludes the conference. Thank you all very much for attending. You may now disconnect.

Speaker Change: I appreciate the detail.

Speaker Change: Thank you and there are no further questions in the queue. At this time. So this concludes the question answer session and I'd like to turn the call back to John Congress for the closing remarks.

Jon Congleton: Thank you operator, and thank you everyone for joining US today, we're very excited about the progress we've made over the past year in advancing our clinical programs and remain enthusiastic about the upcoming milestones for the rest of the year and into 2024.

Jon Congleton: We look forward to updating you as our pivotal program for Laura understand continues to advance with that we'll close the call.

Speaker Change: Thank you. This now concludes the conference. Thank you very much for attending you may now disconnect your lines.