Q1 2025 Mineralys Therapeutics Inc Earnings Call
David: Show!</p><p begin="00.2 Holmes 3.2.1.2. Impact XD wand and bls. and and and didn't do.</p><p begin="00.2.1.2.0.1. insertXD gdXEHow to ended="002.01.0 Officially turtles have had their rumoured shash")</p><point
Speaker Change: If any time during this call. If you require immediate assistance. Please press star zero for the operator.
Speaker Change: This fall is being recorded on Monday may 12 of 2025.
Dan Ferry: I would now like to turn the conference over to Dan Ferry. Please go ahead.
Dan Ferry: Thank you Robert.
Speaker Change: We'd like to welcome everyone joining us today for our first quarter 2025 conference call.
Speaker Change: Earlier. This afternoon, we issued a press release, providing our first quarter 2025 financial results and business updates.
Speaker Change: A replay of today's call will be available on the investors section of our website.
Speaker Change: Approximately one hour after its completion.
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 will 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 company's business.
Speaker Change: These forward looking statements are qualified by the cautionary statements contained in today's press release interest SEC filings.
Speaker Change: Our annual report on Form 10-K.
Speaker Change: And subsequent filings.
Speaker Change: Please note that these forward looking statements reflect our opinions only as of today may.
Speaker Change: May 12 2025.
Speaker Change: And as except as required by law, we specifically disclaim any obligation to update or revise these forward looking statements in light of new information or future events.
Speaker Change: I would now like to turn the call over to John call Litton, Chief Executive Officer of minerals Therapeutics.
John Litton: Thank you Dan and good afternoon, good afternoon, everyone and welcome to our first quarter 2025 financial results and corporate update conference call.
John Litton: I'm joined today by Adam <unk>, our Chief Financial Officer, and Dr. David Rodman, our Chief Medical Officer.
John Litton: I'll begin with an overview of the business and Dave will discuss our clinical programs and recent milestones followed by Adam to review, our first quarter financial results before we open up the call for your questions.
John Litton: This has been an exciting past few months for med analysis our team.
Speaker Change: I've heard on several clinical milestones to make significant progress across our entire development pipeline.
Speaker Change: Most highly anticipated the visa accomplishments was the simultaneous announcement of positive topline data from the pivotal trials launch H Chan and advanced H D N, which evaluated will render center in uncontrolled and resistant hypertension subjects.
Speaker Change: We were pleased to announce in March that both trials successfully achieved statistical significance and clinically meaningful in their primary efficacy endpoints and demonstrated a favorable safety and tolerability profile.
Speaker Change: Detailed results from the advance <unk> trial were also published in the New England Journal of Medicine and presented at a late breaking presentation at the American College of Cardiology as ACC 'twenty five meeting.
Speaker Change: The launch H T. N data has been accepted for a late breaking presentation at the European Society of hypertension meeting on May 24, with a planned future publication.
Speaker Change: Each of these exciting outcomes helps to underscore the strength of these clinical data and the potentially transformative nature of law render stat to help people achieve their blood pressure goal and potentially reduce their cardiovascular risk.
Speaker Change: Positive efficacy safety and Tolerability data from these two pivotal trials along with the data from our target 18 phase III trial level of runners that are key elements of our planned new drug application to the FDA.
Speaker Change: We continue to believe the dis regulated aldosterone is not adequately addressed with the currently available Ras directed therapeutics, including mineralocorticoid receptor antagonist.
Speaker Change: These results, we have seen with where understand reinforced the need for a new aldosterone directed therapeutic approach.
Speaker Change: The transform H T and open label extension trial is evaluating the safety and efficacy able or understand long term use which will be an important aspect of Laura I understand its profile and a critical component of our new drug application.
Speaker Change: We anticipate discussing the results from the advance launch target and transform H TN trials as well as they explore CK D trial with the FDA at a pre NDA meeting in the fourth quarter of 2025.
Speaker Change: And which we expect to define the path forward for an NDA submission and potential approval level or understand.
Speaker Change: We look forward to providing updates on this program throughout the remainder of 2025.
Speaker Change: We're very optimistic about the interest of physicians, having to understand the overall clinical profile based on the pivotal data, especially given the double digit absolute reduction in systolic blood pressure.
Speaker Change: Supporting our excitement around the market opportunity for them to render set or the data we collected in our surmount survey fielded in March which evaluated the data from the launch <unk> and advance HG and trials with cardiologists and primary care physicians.
Speaker Change: The revolt results from that survey showed airflow renders that is approved 95% of the physicians are likely to prescribe will render stat broadly for hypertension, and specifically in the third and fourth line position.
Speaker Change: This intent to prescribe is based on the health care professionals interpretation of the efficacy data relative to what they currently have available for uncontrolled and resistant hypertension as well as Lorenzo <unk> safety and Tolerability profile.
Speaker Change: The overall results speak to the desire for innovative solutions that physicians want and their treatment armamentarium to address uncontrolled and resistant hypertension.
Speaker Change: Our two ongoing proof of concept trials address advanced chronic kidney disease, specifically, those with uncontrolled hypertension as well as the obstructive sleep apnea with nocturnal hypertension.
Speaker Change: These trials are designed to enhance and extend those were understaffed profile and hypertension subjects with comorbid conditions, largely driven by inadequately controlled blood pressure in this regulated aldosterone.
Speaker Change: We've made steady progress with both trials since the beginning of 2025 and anticipate announcing top line data from explore CK D trial later this quarter.
Speaker Change: We're also pleased to announce the appointment of Eric Warren as Chief Commercial Officer.
Speaker Change: Eric brings approximately 30 years of experience in the pharmaceutical industry during which he has developed a breadth of commercial and partnering expertise.
Focusing primarily on cardio metabolic in acute care medicine.
Speaker Change: He started his career as a pharmacist and then joined Merck and company, where he went on to hold commercial positions of increasing responsibility for almost two decades.
Eric Warren: In addition, Eric has held commercial leadership roles at Santa Fe, and Abreva and was most recently the chief commercial officer at <unk> Therapeutics.
Eric Warren: As the Chief commercial officer, and men or Alice he'll lead our commercial strategy as we prepare for the potential FDA approval level or understand and support our partnering ambitions in the U S and ex U S markets.
Eric Warren: In March we completed a public equity financing that raised gross proceeds of approximately $201 2 million before deducting fees and expenses.
Eric Warren: This financing contributed meaningfully to the strength of our balance sheet.
Eric Warren: Now to provide more color on our clinical pipeline and recent milestones I'll turn the call over to Dave.
Dave: Thank you John and good afternoon, everyone.
As John mentioned, our team has been had an exciting few months with the advancement of our clinical programs I'll start by summarizing the topline results of the pivotal phase III launch HTS trial, which randomized 1083 subjects in North America, and Europe, who have failed to achieve the U S guidelines specific specified.
Dave: Blood pressure targets.
Dave: Despite having been prescribed a multi drug antihypertensive regimen.
Dave: Trial, which tested the Rajasthan in a real world clinical context met its primary and secondary endpoints with highly statistically significant and clinically meaningful placebo adjusted reduction in systolic blood pressure as well as in the observed change in blood pressure that is conventionally used by prescribing physicians.
Dave: <unk> to assess response to antihypertensive therapy.
Dave: At week six the primary endpoint the 50 milligram once daily were understaffed arm demonstrate nine one millimeters of Mercury placebo adjusted reduction in systolic blood pressure and a $16 nine millimeter of Mercury reduction in observed systolic blood pressure at week 12 the reduction.
Dave: Systolic BP was maintained with the point estimate being greater than that observed at week six.
Dave: 11, seven millimeters of Mercury and 19 mill with Merck meters and Mercury for placebo adjusted.
Dave: There are changes respectively.
Dave: Reductions in blood pressure of this magnitude are relate to significant reduction in <unk>.
Dave: Overall, cardiovascular risk and the incidence of major adverse cardiovascular events.
Dave: I wanted to HTM trial, confirming expected modest on targeted increase in serum potassium.
Dave: Companies the therapeutic benefit in individuals with inadequately controlled hypertension, as well as an overall safe and well tolerated profile.
Dave: The incidents of any potassium measurement over six millimole per liter in the launch HTS trial in the 50 milligram arm was one 1% in placebo.
Dave: Active and zero, 7% in placebo the pre specified rate, excluding falsely elevated where fac tissues hyperkalemia was comparable to placebo with the demonstrated incidences, 0.6% <unk>, 0.4% respectively.
Dave: Well quantitative comparisons between different clinical trials are difficult the incidence of moderate or severe hyperkalemia as approximately one half of 1% compares quite favorably with most prior reports of men or Alex <unk> receptor antagonist tested in a similar clinical context.
Dave: But once HTM global pivotal trial is the largest aldosterone synthes synthase inhibitor trial reported to date and the benefit risk profile compares quite favorably with previously reported smaller trials three other add to Australia synthase inhibitors that have been tested in hypertension.
Dave: Individuals.
Dave: Now turning to the advance <unk> trial here, we tested the effect of <unk> in the clinical context of hypertension tenths of individuals who are the most refractory to current standard of care and often referred to hypertension specialists.
Dave: The trial used highly rigorous criteria for enrolling at randomize.
Dave: Does that randomization designed to mirror best practice care provided in the most advanced hypertension referral centers.
Dave: <unk> of conventional best practice, two and three drug treatment regimens, along with active monitoring of compliance where you used to document and confirm the existence of uncontrolled or resistant hypertension.
Dave: The results from the trial in the 50 milligram once daily or understand arm were highly statistically significant the seven nine millimetre of Mercury reduction in placebo adjusted systolic blood pressure and 15 four millimeters of Mercury reduction in observed systolic blood pressure measured.
By 24 hour ambulatory blood pressure were observed at the pre specified 12 week visit the Rogers that demonstrated a favorable safety and tolerability profile with modest on target changes in serum potassium sodium and egfr in a low discontinuation rate.
Speaker Change: This trial was designed and conducted in partnership with the comprehensive hypertension Senate Center at the Cleveland Clinic and <unk> Research team results were presented by the co director of the Cleveland Clinic Hypertension clinic, Dr. Luke laughing in a late breaking session at the American College of Carty.
Dave: Allergies ACC 'twenty five meeting and published in the New England Journal of Medicine on May eight.
Dave: As was reported in the New England Journal of Medicine paper, the advance HTM trial per protocol confirmed incidents of hyperkalemia over six millimole per liter in the 50 milligram arm was two 1%.
Dave: Hi, Joseph almost certain a potent long acting or which also elevated serum potassium we feel that this incidence of serum potassium greater than six millimole per liter has an acceptable benefit risk profile appropriate for the use in these patients.
Dave: Okay now turning to our other programs explore CK D and explore OSA USA phase II proof of concept trials. Both of these trials are designed to provide data that augments. The antetype Pretensive protocol of their understand by profiling, the safety and efficacy of <unk> in these two special.
Dave: Populations hypertensive individuals.
Dave: During the first quarter, we announced the completion of enrollment in the explorer <unk> phase two trial. This trial evaluates the safety and efficacy of the run through staff for treatment of hypertension in subjects with an Egfr from 30 to 90 and at least 200 milligrams of UAE C. R. Despite receiving.
Dave: Stable treatment with an ace inhibitor or an art as well as an <unk> two inhibitor hypertension and associated hypertensive nephropathy is a leading cause of kidney damage alone and in combination with other obesity associated Comorbidities. This is another area with great.
Dave: Unmet medical need where aldosterone synthesis inhibition with where understand has the potential for transformation for transformative benefit to patients.
Dave: In this trial the primary outcome measure is change in systolic blood pressure during a four week treatment period.
Dave: Relative to that seen in a four week placebo treatment period in the same individuals.
Dave: The key mechanism of kidney damage in hypertensive nephropathy.
Dave: It's elevated blood pressure induced.
Dave: Hello burial or hyper perfusion scarring and reduction of the number of <unk> available to filter the blood change improvement area is being assessed in this trial as well in contrast to CTD due to diabetes and metabolic syndrome, where prudent area. It's a useful surrogate endpoint.
Dave: Individuals with predominant hypertensive nephropathy tend to have modest levels of proteinuria change in blood pressure, along with the physiological reduction in egfr rather than change improvement area, maybe a more useful outcome measure.
Dave: Trial in this population.
Speaker Change: In the first quarter of 2025, we announced initiation of the explorer OSA phase II trial to evaluate the effect of lower understand the treatment of moderate to severe obstructive sleep apnea.
Speaker Change: Pressure increases significantly as arterial oxygenation falls during upper airway obstruction at night.
Speaker Change: Dosing will understand at Bedtime, we believe we will suppress the majority of aldosterone produced during sleep well, maintaining 24 hour blood pressure control episodes of nocturnal hypertension are under diagnosed and lack of demonstrated highly effective treatment.
Speaker Change: The current treatment armamentarium as limited to weight loss and the use of positive airway pressure. We believe that neither is sufficiently effective at minimizing the impact of OSA on major adverse clinical outcomes.
Speaker Change: In summary, we have now demonstrated a clinically meaningful benefit risk profile of the run just add an individual's without doster. One mediated hypertension. We are focused both on moving the rudders that towards an NDA submission as well as exploring it to use in prevalent co morbidities such as always.
Speaker Change: Say in hypertensive nephropathy, or which normalizing aldosterone production may result in meaningful clinical benefit.
Speaker Change: I'll now turn the call over to Adam to review, our financial results for the first quarter of 2025.
Adam: Thank you Dave Good afternoon, everyone today, I will discuss select portions of our first quarter 2025 financial results. Additional details can be found in our Form 10-Q, which will be filed with the SEC today may 12.
Adam: We ended the quarter with cash cash equivalents and investments of $343 million as of March 31, 2025, compared to $198 $2 million as of December 31, 2024, we believe that our current cash cash equivalents and investments will be so.
Adam: Fisher to fund our planned clinical trials and regulatory activities as well as support corporate operations into 2027.
Adam: R&D expenses for the quarter ended March 31, 2025 were $37 $9 million compared to $38 million for the quarter ended March 31, 2008 for <unk>.
Adam: Increase in R&D expenses was primarily due to increases of $4 $8 million in preclinical and clinical costs and $2 $8 million in compensation expense, resulting from additions to head count increases in salaries and accrued bonuses and increased stock based compensation, partially offset by.
Adam: Zero point $5 million, and lower clinical supply manufacturing and regulatory costs.
Adam: G&A expenses were $6 6 million for the quarter ended March 31, 2025, compared to $4 $6 million for the quarter ended March 31, 2024, the increase in G&A expenses was primarily due to $1 $2 million and higher compensation expense, resulting from additions.
Adam: To head count increases in salaries, and accrued bonuses and increased stock based compensation and <unk> $7 million and higher professional fees.
Adam: Total other income net was $2 $2 million for the quarter ended March 31, 2025, compared to $3 9 million for the quarter ended March 31, 2024. The decrease was primarily attributable to decreased interest earned on our investments in money market funds and U S treasuries.
Adam: Net loss was $42 2 million for the quarter ended March 31, 2025, compared to $31 $5 million for the quarter ended March 31 2020 for the.
Adam: The increase was primarily attributable to the factors impacting the company's expenses described above with that I'll ask the operator to open the call for questions operator.
Speaker Change: Thank you ladies.
Speaker Change: Ladies and gentlemen, we will now begin the question and answer session.
Speaker Change: So do you have a question. Please press star one on your Touchtone phone.
Speaker Change: You'll hear a prompt that your hand is being raised.
Speaker Change: Should you wish to decline from the polling process. Please press star two.
Speaker Change: If you are using a speaker phone please lift the handset before pressing the keys.
Speaker Change: One moment. Please for your first question.
Speaker Change: Your first question comes from Michael <unk> of Evercore. Your line is already open.
Michael Evercore: Hey, guys. Thanks for taking my question and congrats on all the progress just two from me.
Michael Evercore: With regards to the <unk> trial in the past you said that these patients are so sick that physicians will readily accept some level of hyperkalemia. If it means that that will improve their blood pressure.
Michael Evercore: I guess my question is what will be the Max level of great two hyperkalemia that would be acceptable.
Michael Evercore: Yes.
Michael Evercore: Laura understand where to yield a high single digit placebo adjusted SPP reduction and then I have a follow up.
Mike: Yeah, Mike just.
Mike: Quick response, and I don't know that we've categorized what would be an acceptable level I think what what's key and critical as we talk to specialists and our advisers, who are treating these patients with hypertension and more advanced kidney disease, they're really looking at providing a benefit to the BP.
Mike: As well as relieving or improving the kidney function overall, I think these specials, which tend to be predominantly nephrologist.
Mike: Are more comfortable with a higher level.
Mike: Potassium meetings within these patients they have a means to manage that they've got tools to use that there are also more likely to modulate other background treatments in other words, if theyre getting the BP reduction with Miranda has that they may reduce the dose of ace or arb. So I think the key takeaway for us is.
Mike: As with and explore CK do you get a clear sense of the safety characterized the efficacy with this drug.
Mike: And knowing full well they'd providing a benefit on both BP as well as kidney function in these subjects is what.
Mike: You know the specialists who are treating these patients predominantly are looking for.
Mike: Got it that's helpful and.
Mike: My final question is like despite like address that shorter half life and lesser selectivity for aldosterone synthesis inhibition relative to I understand.
Mike: Yeah.
Mike: It's still showed a high single digit percent.
Mike: S. B P reduction over 14 weeks in the in their phase III <unk> trial. So I guess should we expect similar efficacy and safety with well I understand.
Mike: Yeah.
Mike: Yeah, Mike I think it's too hard to hard to hedge what we expect to see I think we would anticipate seeing a clinically meaningful reduction in BP.
Mike: The profile for Laura understand has been well characterized now with three successful studies from target H D in advance and launch.
Mike: But it's too early to hedge, but we do anticipate seeing but I would anticipate certainly a clinically meaningful reduction.
Mike: And then we'll see how the data unfolds as far as for those other human genomic characteristics.
Mike: I see thank you.
Mike: Yeah.
Speaker Change: Your next question comes from Richard Law of Goldman Sachs.
Speaker Change: Line is already open.
Richard Law: Okay, great. Thank you so much and congrats on the progress with me as well.
Speaker Change: So a couple of questions for me can you discuss how the overall like the explorer study.
Richard Law: The strategy.
Richard Law: But I'm, sorry, something I shouldn't but launch in advance.
Richard Law: My understanding is that this study is employing to provide clinical support for patient below Egfr 45.
Speaker Change: And it will be great to hear your latest thinking on that and if that has evolved and I have a follow up.
Speaker Change: Yeah rich. Thanks for the question. We're certainly excited about the benefit risk profile. That's emerged now with lenders that with the successful completion of the advanced study and the launch studies seen double digit reduction in BP.
Speaker Change: With.
Speaker Change: A really acceptable safety tolerability profile.
Speaker Change: The submission of the writers that NDA will be inclusive of all three of those studies as I noted as well as the transform open label extension and explore <unk> there'll be a component of that.
Speaker Change: Really the biggest driver of explore CK D was relate to inform the blood pressure response in subjects with an egfr down to 30.
Speaker Change: As well as going in with a lower dose of 25 milligrams QD and so it will be a component I think it's going to be part of the totality of evidence of Laura understand that will go into the NDA.
Speaker Change: If I could open at this point as far as the specific language that will be included in the label from explore but it's certainly a part of the the total package will be having the dialogue with the agency on.
Speaker Change: Great Fantastic and then.
Speaker Change: So we saw in the new England Journal publication that the patients who have the potassium levels create them have a much lower average egfr compared to the rest of the population.
Speaker Change: I mean in your view like what is the typical egfr delta between like such a study published in exports. The KD study and dosing the general hypertension study like the one in your pivotal study program I guess B I E.
Speaker Change: Study is that a good benchmark in terms of patient population or is it or is it flat.
Speaker Change: Population from that.
Richard Law: Richard and I'm, sorry to do this can you rephrase. Your question I just want to make sure im answering what you're looking for.
Speaker Change: Yeah. So in your new England Journal publication, the patients who have the higher protective levels, great that'll fix multimodal. They all have like lower than average egfr compared to the rest of the population.
Speaker Change: Question here is that how do we think about sort of the differences between the Egfr in your sports TKD study compared to be advanced and launched.
Speaker Change: And it's like what would be a good benchmark in terms of the type of patient.
Speaker Change: That you know in terms of the Egfr Egfr level.
For your security study.
Speaker Change: Alright, Thanks, Rich I appreciate that yeah. It takes.
Speaker Change: It's why we're doing the explore CTD study, we know the Egfr mean Egfr in March was higher than that in law in advance advance was obviously a more high risk population truly uncontrolled truly confirmed resistant hypertension. They had a lower egfr I think youre alluding to what Luc shared at.
Speaker Change: The ACC about the subjects above six had a mean of about 58.
Speaker Change: As far as how tight is the correlation between Egfr and risk of Hyperkalemia, I think we need more data and more evidence, but it's part of why we're doing the explore CTD trial.
Speaker Change: Looking at subjects going down to an Egfr 30, we know they have the risk of potential more challenges in managing electrolyte is why we're testing the 25 milligram QD that we believe is an effective dose seller under stat.
Speaker Change: But as far as the correlation I think that's something that we'll continue to unfold, Dave if you've got some additional thoughts. Please hey, rich good question and how are you doing.
Speaker Change: Sure.
Rich: When you talk about studies like this the outliers are in some ways more important than the means right. So.
Rich: The mean was above 60 saved for the people who.
Rich: Didn't have any.
Rich: Incidence it was a little bit lower than they had it in this trial, what we're really looking for those individuals who are in that 30 to 45 range.
Maybe on the lower side and seeing what happens to them no.
Rich: None of this is the issue other than giving guidance to clinicians.
Rich: We need to keep an eye on and probably who to give a potassium binder if needed or as John said back off on the Arb and see if you can maintain the same blood pressure. So it's a guidance. It's what we call a special population profiling study and we anticipate looking just as much it out where we do without.
Rich: Means in that trial.
Speaker Change: Got it very helpful. And then just one last question so I'm going to take <unk> do you expect to include data from the explore OSA in your filing package.
Richard Law: I think rich it's a fair question I think it's too early to opine on that we haven't guided on topline data. We're excited about that study too.
Richard Law: Address a significant unmet need within that.
Richard Law: Hypertension OSA population.
Richard Law: But it's too early to comment what or would that not be included in the discussions with the FDA.
Richard Law: Great. Thank you.
Rich: Thanks Rich.
Speaker Change: Your next question comes from CMS Fernandez of Guggenheim. Your line is already open.
Rich: Great.
Speaker Change: Thank you for the questions guys. So.
Rich: No John I think on the last.
Rich: Discussion call you mentioned that as many as 47000 physicians could actually be appropriate.
Rich: Or.
Rich: Promotion.
Rich: And the uncontrolled and resistant hypertension.
Rich: <unk> and then you also at ACC.
Rich: And besides that the opportunity may set a little bit more initially and the sort of.
Rich: Fourth line hypertension opportunity.
Speaker Change: Can you just help us understand.
Speaker Change: How does the sort of intersection of that broad physician base intersect with your view of the needs of a partner.
Speaker Change: In that context, and what are you really looking for in the context of either a partner or something perhaps more strategic or you know.
Speaker Change: An opportunity that actually started dancing the opportunity to promote on your own. Thanks.
Speaker Change: The 47000 rich for those that maybe hadn't heard before so we did a significant project about a year ago with that caveat with about $1 6 billion.
Speaker Change: Prescription claims within that and when you basically narrow down where does 50% of the prescribing come from for third line or later prescribing. There's about 47 47000 doctors that account for about half of that prescribing and a significant portion of the influence on the other 50%.
Speaker Change: And so from our standpoint, there is a very efficient commercial model, particularly with the kind of clinical profile, but we're under stat has now demonstrated two go out and target those 47000, prescribers and generate significant value, but as we've talked about in the past partnering for us.
Speaker Change: Is inclusive of U S. But certainly global you know looking for partners that they could help maximize the opportunity of Laura understand ex U S. Because we have no intentions of creating.
Speaker Change: Minneapolis commercial entities standalone outside of the United States. So finding partners that could help maximize that opportunity ex U S. But then really fully tap in to the opportunity in the United States as well and that would basically mean.
Speaker Change: You know some level of overlap maybe what the targeted physicians that we've talked about but certainly coverage of those outside of those 47000 that we target.
Speaker Change: And in fact that target, maybe a little bit smaller as we think about you know an initial launch of law render set fourth line is probably going to be the ideal place to go that's where there's.
Speaker Change: Minimal benefit with existing treatments beyond aldosterone directed therapeutics, we know sprung lactone is thought to be valuable there, but its greatly under utilized I think our clinical program to date, where we've targeted those subjects failing to get to go on tour more med shows the value of it at the Astro direct.
Speaker Change: Treatment that physicians are going to want to work with the patients are going to want to take and persist with.
Speaker Change: So we think theres significant opportunity there, we think we could tap into a significant portion of those prescribers, but having apart partner clearly is going to help us Max.
Speaker Change: Maximize the value of the asset in the United States.
Speaker Change: Okay.
Speaker Change: Great and maybe just one follow up can you just remind us what.
Speaker Change: What the gating factors are to sort of.
Speaker Change: Finalizing and filing the NDA specifically thanks.
Speaker Change: Yeah happy to do that.
Speaker Change: First and foremost, we're obviously very pleased with the benefit risk profile that we continue to see with this molecule now with the two active portions of the pivotal program completed.
Speaker Change: As we've stated before the open label extension is a critical aspect of that if you think about when the last subjects enrolled in launch in advance that was at.
Speaker Change: At the end of October last year, we would anticipate all subject to completing the 52 week open label by Q1 of next year now we don't need to have all of those subjects to enable a filing but we need the certainly a majority of those subjects through 52 weeks before we'd be comfortable with the NDA, but that's part of what will have a dialogue.
Speaker Change: With the FDA in Q4, as we've discussed in the pre NDA meeting and so it'll be both the pivotal programs for advance and launch it will be part of the target data. They explore CK D data and then a portion of that open label extension will be informative for that pre NDA meeting that.
Speaker Change: That will then have better guidance for timing of an NDA submission.
Speaker Change: Alright, great Thanks, guys and congrats.
Seamus: Thanks Seamus.
Speaker Change: Okay.
Speaker Change: Your next question comes from Tim Anderson of Bank of America. Your line is already open.
Speaker Change: Hi, This is Alex on for Tom. Thank you for taking our questions and I just wanted to check can you hear me okay.
Speaker Change: Yes, we can okay perfect.
Speaker Change: Just following on from Seamus this questions on partnering.
Speaker Change: Could you talk about any early discussions you may have had so far and what are the limiting factors that a partner may be looking for so we're going to have the full data from launch and the top line from a study by <unk>, but do you potential partners need to wait for the outcome of the pre NDA meeting for example, as well as the Astrazeneca Baxter.
Speaker Change: Full data.
Speaker Change: And then I have a follow up.
Speaker Change: Sure. So today, we haven't given updates on our partnering discussions but.
Speaker Change: We do continue to believe that.
Speaker Change: Partner or multiple partners will be a part of our story and we will.
Speaker Change: Keep you updated as appropriate.
Speaker Change: Okay.
Speaker Change: Okay. Thank you.
Speaker Change: And then Astrazeneca, commonly referenced says a 5 billion dollar peak sales for Baxter to start.
Speaker Change: Curious how are you thinking that you can best leverage our partner in order to realize this potential with her into Scott.
Speaker Change: For example, it does it involve developing fixed.
Speaker Change: <unk> fixed dose combination so you know.
Speaker Change: Other indications and things like that thank you.
Speaker Change: Yeah, Thanks, Alex Theres Theres clearly.
Speaker Change: A great deal of unmet need in this space.
Speaker Change: We're focused exquisitely right now in the hypertension, but we know there's utility.
Speaker Change: For an ideal all doctor directed treatment beyond that it's why we're looking at the Adjacencies because theres such an overlap in all of these cordero renal metabolic syndromes that have either or hypertension or diabetes kind of at the central point and so for US. We think there is significant unmet need there is significant value too.
Speaker Change: To provide to patients to help reduce their BP, which is the leading modifiable risk factor for cardiovascular risk.
Speaker Change: But moving from hypertension into Adjacencies, such as obstructive sleep apnea hypertensive nephropathy as you heard David speak about we think.
Speaker Change: Basically generate significant value for us as we are partnering dialogues as I've spoken about in the past part of that is pardon.
Speaker Change: Pardon me from a commercial perspective, but for those that have a shared vision. It also could be development partnerships as well looking at some of these adjacent areas such as heart failure or <unk> again, we know that now the Astra and plays a role across the spectrum and having what we believe to be a leading ASI gives us significant.
Speaker Change: It would be to tap into that value.
Speaker Change: Okay.
Speaker Change: Thank you very much.
Speaker Change: Thank you.
Speaker Change: Your next question comes from Annabel <unk>.
Speaker Change: <unk> of Stifel.
Your line is already open.
Diana: Hey, guys occur Diana on for Annabel, Thanks for taking our questions I.
Speaker Change: I have two questions first.
Speaker Change: At what point do you think guidelines for hypertension guidelines would start including launch an AD that's HCM data.
Speaker Change: Any possibility that.
Speaker Change: It could be updated before you guys would theoretically launch.
Speaker Change: Yeah I appreciate the question.
Speaker Change: I don't know that we can opine on when the timing will be specifically I think we can only look at.
Speaker Change: Historical precedents in I think the various guideline committees when faced with new valued innovations have been responsive to try to guide their constituents on how they should think about and integrate these new innovations into their treatment paradigm.
Speaker Change: So it's too early to opine, but it's it's a fair question. That's why we went to therefore, we did in advance HTS because I think it's fundamentally addresses the kind of questions. These guideline committees wish to have and that is not only in.
Speaker Change: Maybe an existing background treatment, but when you get to truly high risk patients like we tested in advance what is the profile physicians could expect and how we'd guideline committees inform their communication to their constituents.
Speaker Change: Got it. Thank you for that my other question is related to <unk>.
Speaker Change: What.
Speaker Change: What do you think there is the primary on the telecom right now Youre looking for safety in this population.
Speaker Change: Concomitant drugs like <unk> and <unk>.
Speaker Change: Inhibitors that are in.
Speaker Change: And do you expect.
Speaker Change: And then L. A b and a line of what you saw in marketing back or are there some nuances with that patient population.
We should know.
Speaker Change: Yeah, I'll, just reiterate what Dave had said with a profiling study like the safety is a key element of the.
Speaker Change: The analysis and what we expect from a.
Speaker Change: Clinical benefit standpoint would be clinically meaningful reduction in blood pressure I think that's been well characterized in the three studies to date, that's what we would anticipate to see in this population and then providing additional information about the 25 milligram QD dose.
Speaker Change: Alright, Thanks, guys, that's all I have.
Speaker Change: Thank you.
Speaker Change: Okay.
Speaker Change: Your next question comes from Mohit Bansal of Wells Fargo.
Speaker Change: Line is already open.
Speaker Change: This is Bobby aren't mine on for Mohit, Thanks for taking the questions and congrats on all the recent progress.
Speaker Change: So on the hypertension Readouts you previously mentioned plans for subgroup analyses.
Speaker Change: Can you elaborate on those plans for which subgroups you're focused on and the timeline for presentation of that data.
Speaker Change: And then can you talk about how it could potentially help physicians select patients for randstad.
Speaker Change: And is it could also influence placement.
Well I understand into treatment guidelines.
Speaker Change: Yes, I did thank you for the question as you know.
Speaker Change: The.
Speaker Change: That effort is to pre specify analysis of populations that may be unique responders till the runners that.
Speaker Change: You saw some of that data within the advanced H T N ACC as well as Nathan.
Speaker Change: Presentation and publications, respectively, I would anticipate seeing something similar with launch H T. N. I think to date, what we've seen and it's frankly beneficial for our prescribers, whether failing to achieve goal on two meds or three meds, so uncontrolled or resistant hypertension, youre seeing a pretty profound reduction in BP regardless of gender.
Speaker Change: Age raised number of background medications and so it creates a predictable.
Speaker Change: Predictable response.
Speaker Change: Physicians can anticipate when using <unk>.
Speaker Change: We're going to continue to investigate and dive into the data I mean, what we've shared to date has been very informative about the value from a clinical reduction and safety standpoint, but theres a great deal of data, we're going to continue to dig into with then launch in advance and eventually explore seek a D C.
Speaker Change: <unk> continued to further inform all right what is the ideal population to respond to this drug but to date, we've seen great responses across multitude.
Speaker Change: Subsets of patients.
Speaker Change: Great. Thanks, and then on the OSA trial.
Speaker Change: How are you thinking about this four week endpoint, how it aligns with expected timelines for improvements in.
Speaker Change: The Appia hypoxia and nights and nocturnal blood pressure.
Speaker Change: And what magnitude of them.
Speaker Change: <unk> reduction would you consider to be clinically meaningful.
Speaker Change: And also a competitor.
Speaker Change: In the context of B C.
Speaker Change: Data reported with Great plans for example.
Speaker Change: Really good questions, let me try to take those one at a time.
Speaker Change: The first question was four weeks, what we see.
Speaker Change: As far as apnea Hypopnea index, the primary mechanism through which our drug will work is the diuretic effects and reducing the amount of salt and water overload because when you laid down at night.
Speaker Change: Excess salt water with fluid shifts up it's called roster coddle redistribution into your upper body and NEC.
Speaker Change: That benefit has accrued within a few weeks and so by four weeks, we would expect to see the benefit on apnea Hypopnea index.
Speaker Change: As you know.
Speaker Change: Around a 50% reduction has been seen with b.
Speaker Change: <unk> study are similar with the <unk> study of <unk>.
Speaker Change: A different mechanism where power down to about 30%.
Speaker Change: And these are small trials so.
Speaker Change: We would ultimately be.
Speaker Change: B.
Speaker Change: Serving where we are in that range. So.
Speaker Change: So let me just say something <unk>.
Speaker Change: Trading at the FDA Hypopnea index is important.
Speaker Change: The main risk for adverse outcomes is this.
Speaker Change: Extreme bursts of hypertension. These spikes that you see at night, when those things happen and we're going to be doing the first trial using sub one second measurements beat to be blood.
Speaker Change: Blood pressure over the course of an entire night. So we will be able to look at how well does this drug actually reduce the risk for adverse clinical.
Speaker Change: Outcomes in many ways, that's a more important endpoint, however, apnea hypopnea index and.
Speaker Change: Patient reported performance metrics are the current guidance from the agency for approval. So we're going down both of those paths.
Speaker Change: This is an antihypertensive drug and it's a sodium depleter, we expect to see benefits on both but both are going to be meaningful. So I can't tell you for sure if apnea high power proxy indexes 30, but we see a terrific impact on nighttime blood pressure, maybe restoration nighttime dipping.
Speaker Change: We'll be the only ones with those data at that point, and we will be reporting them and I think that will be real.
Speaker Change: An important milestone in studying this disease.
Speaker Change: Great appreciate the context. Thank you.
Ed: Thanks, Ed.
Speaker Change: Yes.
Speaker Change: Your next question comes from Ramey.
Speaker Change: Of Lifesize capital.
Speaker Change: Your line is already open.
Speaker Change: Hey, guys. Thanks for taking our questions as well I guess I just wanted to confirm a statement that Dr. Robin made that patients with hypertension property may have more modest levels of proteinuria I guess is the patient population and explore cqb similar to that of the bow ringer steady or are there other key differences.
Speaker Change: And enrollment criteria and I guess is that 37% placebo adjusted you ATR reduction related monotherapy. The catch is that a fair bar here.
Speaker Change: Okay. Those are good questions.
Speaker Change: If we think about this and this has happened in other diseases chronic kidney disease is a syndrome.
Speaker Change: It can be autoimmune and you want to use an anti iga.
Speaker Change: Which has been very effective.
Speaker Change: If you if it's in the context of obesity and diabetes is for metabolic syndrome and that is the one that's associated with a fair amount of.
Speaker Change: Protein area, even nephrotic syndrome, which is an extreme is that.
We're looking at some of these patients may have high levels of protein area, but we.
Speaker Change: We anticipate that that will not be the majority in this trial. So it will be a different subset and it's actually a different subset of CK D. These people have.
Speaker Change: Scarring of the external part of their cortex of their kidney lots of these <unk> from this water hammer effect.
Speaker Change: The pounding of blood pressure for these people getting their blood pressure down to $125 130 <unk>.
Speaker Change: Not all they need they need lower blood pressure and nose to truly protects the globe that are left and so we're going to be looking at that and continuing to explore the possibility of differentiating on that basis as we get into this quote climate.
Speaker Change: Adney disease space.
Speaker Change: Our primary objective per se because we are going after hypertension broadly we're now since we've proven that it's a highly safe and effective drug for uncontrolled and resistant hypertension now we're starting to go to the very high unmet need subpopulations.
Speaker Change: Which right now is we consider to be hypertensive form.
Speaker Change: Property and OSA.
Rami: And Rami just to add to that.
Speaker Change: The distinctions between the studies I think the baseline systolic BP in that study was below what is our inclusion criteria. So to Dave's point, we really are recruiting those subjects with low egfr in hypertension, and I think that does create distinct population between the two studies.
Speaker Change: Got it that makes a lot of sense. Thank you.
Speaker Change: Mhm.
Speaker Change: Okay.
Speaker Change: There are no further questions at this time I would.
Speaker Change: I hand over the call to Jon Congleton for closing remarks. Please go ahead.
Jon Congleton: Yeah. Thank you operator.
Jon Congleton: <unk> therapeutics, we're committed to improving the lives of patients with cardio renal metabolic diseases uncontrolled and resistant hypertension are significant unmet medical needs impacted more than 20 million patients in the U S alone.
Jon Congleton: Our launch in advanced studies reinforce the differentiated clinical profile of <unk> versus agents that are typically used in the third and fourth line treatment in positions and the quantitative research that we've done supports the commercial potential we're excited for key upcoming milestones and look forward to sharing updates with you in the coming quarters. Thank you.
Jon Congleton: You all thank you for joining for joining us today and with that we'll close the call and have a good day everyone.
Jon Congleton: Okay.
Jon Congleton: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation and you may now disconnect.