Q1 2025 Lexicon Pharmaceuticals Inc Earnings Call
Speaker Change: Michael Exton, Jeffrey Wade, Scott Coiante, Jeffrey Wade, Scott Coiante, Jeffrey Wade,
Speaker Change: Welcome to the Lexicon Pharmaceuticals first quarter 2025 financial results conference call. At this time, all participants are in a listen-only mode. Following management's prepared remarks, we will hold a brief questioning and answer session. As a reminder, this call is being recorded today, May 13, 2025. I will now turn the call over to Lisa DeFrancesco, SVP, Investor Relations and Corporate Communications for Lexicon. Please go ahead, Lisa.
Speaker Change: Starting with our most recent announcement at the end of March we announced an exclusive license agreement never noticed Alex 9851, a first in class oral morning, Cretin candidate for obesity and other metabolic conditions now this agreement grants <unk> exclusive worldwide license to develop manufacture and commercialize nor a knife fight.
Speaker Change: One in all indications.
Speaker Change: Under the 10 flex com was eligible to receive upfront and near term milestone payments of up to $75 million of which 45 million was received in April.
Speaker Change: Up to 1 billion in aggregate upfront and development regulatory and sales milestone payments as well as T O tiered royalties on future net sales of 90 851.
Speaker Change: I'd like to come and be responsible for completing agreed upon investigational new drug application, enabling activities for <unk>, five one and providing clinical supply to Nova Nordisk at an agreed upon transfer price for a limited time period.
Speaker Change: Nobody will be responsible for filing the IMD and conducting all further development manufacturing and commercialization.
Speaker Change: 905, one now.
Speaker Change: Now we couldn't be more pleased with this collaboration never noticed experience and global capabilities and are basically make them an ideal partner to maximize the value of <unk> 905. One this truly is a validation of the science and the potential of this novel asset.
Speaker Change: Gratified that we have continued to make great progress on our partnering strategy to find the highest quality partners that augment our capabilities and realize the full value about assets.
Speaker Change: Now the other major development in the first quarter was the top line readout of our progress phase two based study of til evaporated.
Speaker Change: As our oral non opioid drug candidate for D. P. M P.
Speaker Change: We're pleased to wherever that abide a well tolerated dose that has repeatedly shown clear evidence of effect take forward in phase III studies.
Speaker Change: Once we have the full data package lighter in Q2, and we look forward to engaging the FDA on the phase III design using 10 milligrams a pill it back.
Speaker Change: And finally, we completely revised our cost structure to reflect our pivot to an R&D focused company by reducing our operating costs and utilizing the upfront payment from the Nova Nordisk agreement to reduce our debt.
Speaker Change: While ensuring we have the cash runway to meet our objectives and support continued development of our R&D programs.
Speaker Change: So all in all we ended the first quarter and a very strong position.
Speaker Change: Our fourth pillar happening, Dave BNP, having cleared the hurdle of identifying the appropriate dose for phase III, we improved our balance sheet and a strong financial footing for the milestones ahead.
Speaker Change: So I'd like to dive a little bit deeper now into our DPM paid programming, primarily reiterate two key points.
Speaker Change: Okay.
Speaker Change: First and importantly across both the relief in progress studies, we've now demonstrated three times a.
Speaker Change: Of the 10 milligram dose shows early and sustained separation versus placebo.
Speaker Change: And second.
Speaker Change: Absence of a day, one loading dose improved the tolerability of bulk til evaporative arms in progress.
Speaker Change: At 10 milligram dosing schedule was particularly well tolerated showing placebo like completion rates.
Speaker Change: Collectively in our view these data de risk advancement into phase III with the 10 milligram dose and gives us great confidence in the potential of <unk> to be the first novel oral non IPO D. P M P medication and more than two decades.
Speaker Change: Current emphasize enough the opportunity for innovation in this market as I talk with patients caregivers and payers, it's absolutely clear that there's a tremendous need for new non opioid treatment options for neuropathic pain.
Speaker Change: TPN phase a relatively common complication of diabetes impacting one in every all people with diabetes.
Speaker Change: Today, there are approximately 9 million people in the U S with D. P. M P.
Speaker Change: That number is expected to grow to $13 million by 2035.
Speaker Change: This is a chronic and progressive pain disorder that severely impairs people's quality of life.
Speaker Change: Not only is a painful but it is unrelenting and burdensome to patients in late two other complications like a loss of sensation.
Speaker Change: All practices.
Speaker Change: Limb amputation.
Speaker Change: And so the message from all stakeholders is lapping the community needs new embedded medications to managed APLP.
Speaker Change: The 70% of people with deep BNP currently available treatment options provide adequate relief.
Speaker Change: 60% of tried multiple therapies, either by switching or by adding on to their treatment regimen.
Speaker Change: People with deep BNP, often feel like they're stuck in a cycle of trial and failure with different treatments.
Speaker Change: The need for new non opioid treatments for pain is also I wanted to score by recent proposed legislation such as the alternative pilot that's being proposed supporting greater access to non opioid therapies.
Speaker Change: We're committed to advancing our <unk> development program as quickly as possible with the aim of providing a novel oral treatment that can improve the lives of people with J P. M P.
Speaker Change: So we look forward to providing further updates as the year progresses, including full data from the progress study at an upcoming medical meeting we're targeting a phase III study initiation could fill evaporative DPM paid later this.
Speaker Change: Following our end of Phase II review meeting with the FDA.
Speaker Change: Okay.
Speaker Change: Moving on now to a cyclical plays and we remain on track with enrollment in a global pivotal <unk> study started with players in hypertrophic cardiomyopathy or HCM.
Speaker Change: HCM represents an area of significant opportunity and need where we feel sorry that has the potential to offer a differentiated treatment option.
Speaker Change: Now in the U S. They were just over 1 million people with HCM.
Speaker Change: All of that is approximately a third have non obstructive HCM, which the heart muscle was thinking but doesn't.
Speaker Change: Hello, whereas two thirds of diagnosed with obstructive HCM, which the thickening of the heart muscle wall blocks or reduces blood flow from the heart.
Speaker Change: An important characteristic of <unk> that might not be fully appreciated is that is a chronic progressive disease <unk> can deteriorate over time.
Speaker Change: Leading to other complications including heart failure.
Speaker Change: In the 43% of people with HCM also have progressive heart failure.
Speaker Change: Now we have great confidence in site or as an option for HCM as Youre. All aware there have been a number of innovations that target the sarcomere being developed for this disease, one of which is approved for the treatment of obstructive HCM.
Speaker Change: Nevertheless, despite significant investment in increasing awareness and H C. M is not licensed <unk> penetrated about 1% of the market.
Speaker Change: So we believe the potential approval of Scioto would significantly expand the population traded with novel agents.
Speaker Change: Covenants derives from a number of exciting features first of all besides its approval in the U S for heart failure. They are important data that gives us confidence that cider will be effective in both obstructive and non obstructive HCM.
Speaker Change: Namely we have observed significant benefit of side of the plays in heart failure in mice in patients with left ventricular hypertrophy with normal blood pressure.
Speaker Change: Furthermore, mechanistically cider appears to reduce cardiac work and improved cardiac metabolism.
Speaker Change: Importantly, we would expect no rems for cider and <unk> consistent with our heart failure label, which would provide access to a broad prescriber base.
Speaker Change: And finally, we can have confidence that tonight in clinical trials and post marketing experience soda has not been associated with an increased risk of atrial fibrillation.
Speaker Change: Therefore, we expect soda has the potential to become a disruptor in this space and become widely used in the market across the spectrum of disease.
Speaker Change: The next slide provides an overview of our global Phase III Sonata study of soda in H C M.
Speaker Change: <unk> is enrolling at full speed with EU, and Latam sites, either already online or imminent.
Speaker Change: Now, we expect that all of the phase III sites will be up and running by the third quarter of this year. So we're pleased with that progress.
Speaker Change: So neither is the only ongoing study evaluating a treatment in both obstructive and non obstructive HCM.
Speaker Change: We feel that there is potential for this study to support an NDA with a broad label.
Speaker Change: Once the Sonata study is complete and we have that data in hand, we will also have an opportunity to revisit the totality of the side of the flows in potential opportunity across the indications in the U S.
Speaker Change: We continue to build differentiating effort that the mechanism of dual inhibition of <unk>, one and two does have different outcomes in mace events, including MRI and stroke as most recently published in the lancet.
Speaker Change: Now touching briefly on business development.
Speaker Change: As I mentioned at the top of our core we're very pleased with our recently announced collaboration with Novo Nordisk for <unk> 501, which by strengthens our financial position and provides Alex 905, one the best possible chance of success by benefiting from the expertise of resources and capability of Novo Nordisk and established later.
Speaker Change: In the obesity market.
Speaker Change: As the basically treatment landscape continues to grow and evolve we expect to see an opportunity for nexgen treatments to build on the success of the earlier <unk> based therapies.
Speaker Change: Based on <unk> 500 one's unique mechanism oral administration preclinical findings to date and possibility for both monotherapy and combination applications. We feel <unk> has the opportunity to occupy a unique space in the treatment landscape for obesity and metabolic conditions.
Speaker Change: We look forward to working with <unk> to maximize the potential of this innovative medicine.
Speaker Change: Okay.
Speaker Change: Presuming out to look at business development more broadly.
Speaker Change: Innovative and flexible partnership approach is unlocking long term value for lexicon.
Speaker Change: Okay.
Speaker Change: The interest has been a committed and collaborative partner for soda outside of the U S and Europe and is extending the geographical rates for soda across cardio metabolic and other indications.
Speaker Change: This agreement included a $25 million upfront payment and potential milestone payments of up to almost $200 million.
Speaker Change: This collaboration Leverages basis, as global scales and capabilities.
Speaker Change: Wowing us to reach more patients worldwide.
Speaker Change: <unk> recently announced its been preparing regulatory approval applications for <unk> and a number of ex U S markets.
Speaker Change: Filings.
Speaker Change: And Saudi Arabia have been submitted in the filing in Canada is expected to be submitted shortly.
Speaker Change: But as you can see we've been working closely with Beatrix and making significant progress together.
Speaker Change: Now as I just noted our partnership with Novo has the potential to generate significant value for <unk> 905, one and are basically in <unk> as a partner.
Speaker Change: And as.
Speaker Change: As we look to our future partnerships, we're heavily focused on <unk>.
Speaker Change: I am as to unlock value globally across multiple indications with a partner that is complementary capabilities therapeutic area expertise and a global commercial footprint to help fully realized spill of evidence pipeline in a pill potential.
Speaker Change: With our significant clinical expertise in the space, we have flexibility in the types of partners that would be great fit to this asset we've been having a significant amount of interest and dialogue with these potential partners.
Speaker Change: With that I'd like to now turn it over to Scott to walk you through our financial results for the quarter ended March 31 2025.
Scott: Thank you Mike for the first quarter of 2025.
Scott: From sales of <unk> compared to $1 1 million for the first quarter of 2024.
Scott: Research and development expenses for the first quarter of 2025 increased to $15 3 million from $14 4 million for the same period in 2024, and primarily reflect expenses associated with our late stage development programs, including the Sonata Phase III study for HCM and our progress phase <unk>.
Scott: Study of <unk> and DP.
Scott: Selling general and administrative expenses for the first quarter of 2025 decreased to 11 6 million compared to $32 1 million for the first quarter of 2024, primarily due to the efforts of our strategic repositioning in late 2024, and the reduced marketing efforts for <unk>.
Scott: Net loss for the first quarter of 2025 was $25 3 million or <unk> <unk> per share as compared to a net loss of $48 4 million or <unk> 20 per share for the same period in 2024.
Scott: We ended the first quarter with $194 8 million in cash and short term investments as compared to $238 million of cash and short term investments as of December 31 2024.
Scott: I'd like to take a minute to note a few items.
Scott: First quarter is typically the quarter with the greatest use of cash and included in the cash used for Q1 2025 was approximately $7 5 million in severance payments related to our restructuring which were accrued in Q4 2024.
We expect the use of cash to be less in the subsequent quarters of this year.
Scott: Revenue associated with the $45 million upfront payment from Novo has been deferred and will be recognized over the estimated completion period of our obligations under the exclusive licensing agreement.
Scott: We anticipate stable U S. <unk> revenues this year despite limited promotional activity.
Scott: And we are also reiterating our previously provided operating expense guidance and expect total operating expenses to be between $135 and $145 million.
Scott: For 2025, with R&D expected between $100 million and $105 million.
And SG&A expected between $35 million and $40 million.
Scott: We also expect lower interest expense for the remainder of the year as a result of our partial debt repayment in April.
Scott: We are confident that we are capitalized to meet our objectives to support our phase III readiness for DPM P. Our ongoing phase III trial in HCM, and all IND, enabling activities related to 95 one.
Speaker Change: I'd now like to turn it back to Mike for closing remarks, yes, Thanks, a lot Scott.
Summary.
Speaker Change: Significant amount of progress we've made so far this year, we're incredibly well positioned with a number of pipeline in a pill assets that we can continue to explore ways to leverage and add value for lexicon with potential for new indications new partnerships and late stage regulatory developments. Our goal is to advance these additional <unk>.
Speaker Change: Graham's on iron ore in the case of <unk> in partnership with the committed collaborate.
Speaker Change: Yeah.
Speaker Change: With therapeutic expertise and global scale.
Speaker Change: We have demonstrated our ability to find the right high quality partners for our assets where appropriate.
Speaker Change: Earlier in the year, we introduced late to succeed.
Speaker Change: It's important that we continue to discuss this as an important pillar of our strategy as we think about the opportunities that we have in our pipeline.
Speaker Change: In particular I feel it's important that we focus on areas, where we believe we have the greatest chance of success, where we can be first or only.
Speaker Change: In large markets with significant unmet need and where we have the internal clinical and medical experience necessary to be successful.
Speaker Change: We will continue to apply this lens to our future opportunities as we develop our path forward.
Speaker Change: Now importantly, we've got a number of very important and impactful catalysts as we look towards the remainder of this year.
Speaker Change: For <unk> and VPN, Pete we anticipate sharing full progress either in Q3, along with an end of phase two meeting.
Speaker Change: We're also preparing to present data at upcoming medical meetings and partnership discussions are ongoing.
Speaker Change: <unk>, one and obesity and weight management will collaborate with novo nordisk on IMD, enabling activities and nobody will be responsible for the R&D submission.
Speaker Change: For <unk>, we're actively enrolling out sonata HCM study with all phase III study sites expected to be operational by Q3.
<unk> continues to advance regulatory submissions decided to floating and hardcore you outside of the U S and Europe with.
Speaker Change: With the UAE and Saudi Arabia complete.
Speaker Change: Canada anticipated shortly.
Speaker Change: As we discussed last quarter, we see opportunities to differentiate <unk> as a mechanism and believe that the recent mace data potentially supports expanding the use of this medicine into adjacent indications.
Speaker Change: We plan to engage in a regulatory process regarding this data later this year.
Speaker Change: Finally regarding the <unk> for type one diabetes with <unk>, while we're not currently actively investing in this program. It's important that we continue to move forward with the NDA review process in support of the significant number of patients that continue to actively and strongly advocate for approval of this drug.
Speaker Change: Underscoring the need in <unk>.
Speaker Change: To that end, we held an end of review meeting with the FDA in Q2, and we expect to continue discussions with the FDA.
Speaker Change: We remain enthusiastic as we look to the potential updates in the remainder of this year and we look forward to keeping you all informed of progress across all of these programs in the coming months.
Speaker Change: With that Greg you can join us and we will have time to take everyones questions over to you operator.
Speaker Change: Thank you to ask a question. Please press star one one of your telephone and wait for your name to be announced to withdraw. Your question. Please press star one again please.
Speaker Change: Please standby, while we compile the Q&A roster.
Speaker Change: Our first question comes from the line of Andrew Tsai of Jefferies. Your line is now open.
Andrew Tsai: Hi, Thanks for the update I appreciate you taking my questions.
Andrew Tsai: First is on the pain program I know the base case is going to be running two pivotal phase III studies can you talk about the intended trial designs, whether they are identical and could it actually makes sense to do three studies instead with a third one serving as a backup.
Craig: Andrew It's Craig granted it's thank you for your question.
Craig: Our plan is still as we've previously communicated to run two parallel trials with very similar design, one would most likely be U S. Only and the other would be a worldwide trial, including U S and non U S sites.
Craig: There's been nothing since our last update that would change our plans in that regard.
Craig: As a reminder, the sites would be.
Craig: Roughly about 300 or 350 patients per arm.
Craig: Two armed trials of a 10 milligram dose flat from the outset versus placebo and run in parallel in patients with moderate to severe pain with a subset of that group stratified for an underlying D Pnp medication.
Craig: With respect to the third trial, we don't believe as Mike mentioned during the prepared remarks, we believe that we have a robust clinical sin.
Craig: Signal in these trials that is observable and reproducible and rapidly separating from placebo in each case with the 10 milligram dose arm.
Craig: And also as a reminder, the reduction of pain score from patient baseline is approaching one five to two point drop from baseline, which is what the patients would experience.
Craig: So with all of that and a drug that we feel confident that once daily as placebo like completion rates and no identified yet drug drug interactions or other safety concerns of significance, we feel quite confident in this program.
Craig: Depending upon what we hear from the FDA that would obviously be subject to change.
Craig: Certainly our intention going into the end of phase two meeting.
Craig: Alright, and assuming the phase two does go well and you start the phase threes and let's just say Q4 win with the pain datasets B and then.
Craig: As those phase Iis are studying what.
Craig: Other peripheral studies do you think you need to accomplish our finish to ensure you can file.
Craig: Right after the phase III data. Thank you.
Yeah, great questions Andrew.
Craig: I think as we're all drugs that are centrally acting in this category, we need to look at.
Craig: Addiction liability, we believe and hope that those would be animal model studies only because we have no indications we've seen no rebound or other unusual liking behavior with the use of <unk> that would be a critical study. There are some additional metabolism studies that we're looking at as a reminder, this drug is <unk>.
Craig: Generally cleared.
Craig: And were looking to validate that the clearance and.
Craig: The level of renal impairment that we can include in the trials. Those those studies, we think will be important.
And then obviously there are long term karch studies and a few other preclinical trials.
Craig: We feel quite confident that we have a robust manufacturing process that we're ready to go right into phase III in pre commercial scale manufacturing with a process that is robust and I don't think will be cost prohibitive in that regard. So I think there's always more things to do I am sure that FDA might have some.
Craig: Suggestions for US in addition, based on our interactions with the FDA. We believe that those are going to be the major components of things we need to look at.
Craig: Thank you.
Craig: Thank you.
Speaker Change: Our next question comes from the line of rollout of release with Leerink Partners. Your line is now open.
Speaker Change: Hey, good afternoon, everyone.
Speaker Change: A couple from me I'll start with 90 851.
Speaker Change: The R&D, enabling studies progressing and could you talk a bit about any remaining gating factors for at this stage of development and da Vinci entering the clinic.
Speaker Change: And I was also curious how closely involved as novo with your work and development here for this asset at this stage.
Ronny: Yeah. Thanks for the question Ronny.
Speaker Change: Actually the <unk>.
Ronny: And the enabling studies are going splendidly.
Ronny: The roll on track for finishing this year end.
Ronny: The relationship with Novo was very strong they're very engaged in the data and we are.
Ronny: We're actually giving them direct line to the outputs of that data so they vary.
Ronny: Collaborative and engaged as we go through this process and.
Ronny: I'm very pleased with the progress so far.
Ronny: And so as we have.
Have outlined we expect that that will all conclude this year and then.
Ronny: The information will be over to novo to submit the R&D.
Ronny: Got it thanks, and one more follow up for me I noticed we had a couple of updates in the HCM space from other companies, including the sale of the Odyssey trial for Bev Kimpton, then non obstructive HCM I was curious if that updates or refine some of your thinking around so does potential.
Ronny: Going after non obstructive HCM would you actually consider upsizing, the sonata trial or making any modifications based on what youre seeing in the field.
Ronny: Yeah look it's really been an amazing quarter for HCM and there's been a lot of information a lot of updates and a lot of interest in.
Ronny: I think what.
A number of the outputs that we've seen for modesty and others just reinforces our belief in soda.
Ronny: As we outlined in the prepared remarks, there's a number of pieces of evidence that we.
Ronny: Collected both pre clinically and in clinical and preclinical studies that give us confidence in.
Ronny: The efficacy of <unk> in non obstructive HCM.
Ronny: And.
Greg: We're actually powered to see an effect in both non obstructive and obstructive as it is so we don't think that it's necessary to increase to any degree the sample sizes that we seen sonata and confidently moving forward with that so Greg do you have any thoughts there yes.
Speaker Change: Yes, well said, Mike Brian I think the other important.
Speaker Change: Development really is the opportunity now to rapidly enroll the trial.
Speaker Change: So as.
As BMS mentioned.
Speaker Change: There is no further work that they're doing on Odyssey.
Speaker Change: The long term extension trial is my understanding not not taking place and as a.
Speaker Change: Cytogenetics mentioned they have now fully enrolled in Acacia.
Speaker Change: So there are no other large trials that are running currently right now actively enrolling patients and I think between the ease of.
Speaker Change: Our protocol for sites to complete and as a reminder, we allow the use of <unk> or not <unk>, we have an ejection fraction down to 50%.
Speaker Change: We include both obstructive and non obstructive patients the burden on the sites is relatively limited in terms of the number of echo's, which as a rate limiting step I think for some other companies just in terms of the capacity to do all of those echos.
Speaker Change: The lack of the need for giving the peak <unk> measurements.
Speaker Change: <unk> to our other difficult too.
Speaker Change: Execute physiologic tests the feedback we've had from really all sites, whether we've talked to sites in Europe. The U S or Latin America is that this is a trial that people are excited to participate in both patients.
Speaker Change: And the study sites themselves.
Speaker Change: Got it thanks again.
Speaker Change: Thank you. Our next question comes from the line of Yasmin Rahimi with Piper Sandler Your line is now open.
Yasmin Rahimi: Good afternoon team. Thank you so much for all the updates I guess the first question.
Speaker Change: Sure obviously as you guys have been engaging with the agency on <unk> and <unk> meetings and in preparation for <unk>.
Yasmin Rahimi: Do you see getting the minutes and the line and.
Yasmin Rahimi: On the phase III that a gating factor for the strategic discussions youre having in parallel.
Yasmin Rahimi: Or is it just.
Yasmin Rahimi: Both are kind of concurrently ongoing one is not.
Yasmin Rahimi: Take care.
Yasmin Rahimi: Hum.
Speaker Change: Thanks, Yes, it doesn't seem to be guiding factor at the moment, that's not the conversations that we're having.
Speaker Change: As we sort of a white the full dataset.
Speaker Change: All of the full analyses.
Speaker Change: We'll continue to have those discussions with the strategics.
Speaker Change: And that will be the sort of natural course of.
Speaker Change: The engagement going forward. So now we don't see at this stage.
Speaker Change: The FDA end of phase II meeting being a gating factor.
Speaker Change: Thank you and maybe the second question is obviously top line data.
Very helpful.
Speaker Change: Paul but I think there is upside we will.
Speaker Change: Will and I think even in the press release today, you are planning to share more data at medical meetings.
Speaker Change: Can you help us understand the type of data that we could see what are some of the key additional analyses that you hope to present and maybe the significance of that.
Speaker Change: Third last question.
Craig: Yes, yes, it's Craig Thanks for your question.
What we intend to show later on in the year will be additional detail on the secondary analysis.
Craig: B, the qualitative aspects related to the quality and types of pain and functionality.
Craig: Which were series.
Craig: Series of secondary endpoints I also think we might be able to place into better context, the 20 milligram dose arm.
Craig: With exposure in some other.
Craig: Pharmacokinetic and other data to place that in in additional context of why that arm performed the way that it performed so I think this data will be very helpful for both the medical community and the Investor community to provide additional context.
Craig: Our confidence in the trial and the results that we've seen.
Craig: Thank you and then last question on the economic study sort of consistent with her question that she asked around non obstructive study of recently Odyssey failing I think it was clear that the commentary at least personally have been just saying non obstructive is a very distinct population different from them.
Craig: Obstructive.
Craig: So I think it has raised sort of the bar for a lot of investors.
Speaker Change: Thinking about how do company.
Speaker Change: Great a homogeneous population, obviously you haven't seen the data, but could you maybe talk about as you guys designs on auto in terms of inclusion exclusion what what was built in to create maybe.
Speaker Change: A more homogeneous population with a non obstructive specific claims.
Speaker Change: To the extent you.
Speaker Change: He can comment on that would be helpful and I'll jump back in the queue.
Speaker Change: Yes, Thanks again, yes, great great question.
Speaker Change: The major criteria, we have for the trial is symptomatic disease.
Speaker Change: And I think that is really reflective of the diastolic dysfunction.
Speaker Change: And that is our center core non of HCM and it's funny I think we've had this conversation or other calls previously about people feeling more confident that at least from the investor community of the activity sort of are posted in the non obstructive group as opposed to the obstructive.
Speaker Change: We believe that non obstructive is really is a great surrogate and as a subset of <unk>.
Speaker Change: And we feel very confident in our health Tech results and that the high degree of efficacy that we see both in heart failure reduction and mace reduction.
Speaker Change: And those with half path.
Speaker Change: I think that on top of the data.
Speaker Change: That we've.
Speaker Change: <unk> demonstrated in terms of that left ventricular hypertrophy group with normal blood pressure, which is a real surrogate for HCM and again that 50% reduction in both mace and heart failure is really encouraging to us and as a reminder, one of the reasons why we've tried to highlight the mace data.
Speaker Change: That was recently published in lancet is that patients with HCM remain at significantly elevated risk of MRI and stroke. So I think having that additional benefit and a group of heart failure patients is all continue to be supportive, particularly in the non obstructive group.
Speaker Change: And it's important for us yes.
Speaker Change: We think across the breadth of the HCM market.
Speaker Change: The non obstructive HCM is we know it's about a third of all HCM patients.
Speaker Change: Which at the moment as you know it doesn't have an indicated.
Speaker Change: The same is having.
Speaker Change: I haven't shown robust efficacy there and so it's all.
Speaker Change: Aligning with our approach of broad.
Speaker Change: <unk> potential application for a broad prescriber base and broad applicability across the patient population as well. So we actually have a lot of data now that gives us great confidence in non obstructive HCM.
Speaker Change: And.
Speaker Change: So not a trial was built to capitalize on both opportunities.
Speaker Change: Thank you so much.
Speaker Change: Thank you. Our next question comes from the line of Yigal <unk> with Citigroup. Your line is now open.
Speaker Change: Hi, guys. Thank you for taking my questions a few more on the design of sonata.
Speaker Change: You'd mentioned Craig.
Speaker Change: Powered for both obstructive and non obstructive.
Speaker Change: Curious are those co primary endpoints what is the exact detail around how that.
Speaker Change: Measurement is structured in the protocol.
Speaker Change: And then with regard to the relative proportions of obstructive and non obstructive and you just mentioned there was a third two thirds how is that playing out in terms of the enrollment is as balanced adhering to those those ratios are you trying to go from over $50 15. Thank you.
Speaker Change: Yes, Greg quite quick questions Yigal similar to what we did in the <unk>.
Speaker Change: Scored trial and soloist trial.
Speaker Change: Study is powered for the overall endpoint.
Speaker Change: And that in the case of.
The preserved ejection fraction and reduced ejection fraction. It really is the issue of consistency across the results. So FDA has not asked for in a sense to independently powered arms and if I gave that a misimpression one of my answers I apologize for any misunderstanding on that so the study is powered on the base of 500 patients.
Speaker Change: With the difference in <unk> compared to placebo and really what FDA would be looking for similar to what we showed in scored and soloist that there'll be consistency, but not necessarily formally powered for each one of the two subgroups.
Speaker Change: So I think that really is the critical design element there.
Speaker Change: The trial is designed as a.
Stratified with a one to one enrollment of obstructive and non obstructive and right now we don't really have enough patients in the study for me to say, whether we're going to have more or less difficulty enrolling one or other of those two groups and as Mike had mentioned there are a vast majority of the patients right.
Speaker Change: Now are not being treated and again, we're looking for just patients with symptomatic disease.
Speaker Change: Whether or not they're on a on a CMI. So we think that there are certainly adequate patient number and again we are.
Speaker Change: The study includes patients with it.
Speaker Change: Injection fraction down, 50%, which is one that the currently approved agent is.
Speaker Change: As <unk> indicated to treat so we think we have a number of opportunities to enroll patients, especially with no competing trials right now and the drug really not being available outside the United States.
Speaker Change: Okay got it. Thank you and then on the choice of the endpoints, specifically Casey CQ CSS I am just wondering you mentioned <unk> has got is cumbersome complicated endpoint was that the reason we picked Casey Q or was it also because since youre doing HCM and non obstructive that it's just the easier and.
Speaker Change: To deal with given the broader population as opposed to what we saw this morning with Maple HCM, where they did the <unk>, but that was only obstructive.
Speaker Change: Yes, great Great question as always Yugo.
Speaker Change: The advantage with soda because we have outcomes.
Speaker Change: So we have heart failure outcomes in 12000 patients and we have an FDA approval for outcomes and we've demonstrated reductions in mace as well as heart failure events I think one of the issues with.
Speaker Change: Newer class of agents as they don't have the experience to have anything with outcome. So what they're really looking for is a surrogate for outcome. Besides.
Speaker Change: Functionality is that Theyre looking for some sort of metabolic parameter.
Speaker Change: And I think that it's going to be really one of the long term questions as are they.
Speaker Change: Modifying the disease in any any way we know we modify the disease, we prevent heart failure events and cardiovascular event cardiovascular death, and we reduced stroke in MRI.
Speaker Change: In overlapping and similar groups of patients so far.
Speaker Change: From that standpoint, the FDA didn't ask for any additional.
Speaker Change: Endpoints and we really wanted to run a pragmatic study we wanted to have it as open and inclusive it's possible to give us the broadest possible label just like what we did with scored and soloist is we have a very broad label.
Speaker Change: That provides the maximum opportunity for labeling and for patient inclusion criteria and we took that same mindset and approach to how we structured scenario with a lot of input from the medical community and agreement from the FDA.
Speaker Change: And just to pile on on top of that really coming from a patient perspective.
Speaker Change: Patients with HCM, not too dissimilar from a patient with heart failure quite frankly, the primary issue or the primary want the primary needs that they have is the symptomatic benefit.
Speaker Change: Primary thing that a patient with HCM wants to be able to do is to have the energy to walk outside walk to the letter box.
Speaker Change: To feel better.
Speaker Change: And that's frankly, what the semis do as well, yes. They are.
Speaker Change: <unk> for symptomatic and functional benefit, but the primary reason to believe is that <unk>.
Speaker Change: The patients feel better at least in obstructive HCM.
Speaker Change: And so you combine the pragmatism in the trial with developing something on what patients actually need and in fact, we've seen the benefit in <unk>.
Speaker Change: Already in diastolic dysfunction.
Speaker Change: It not only gives us confidence in the outcome that we're going to produce but confidence in that should the trial be positive, but something that patients really really want.
Speaker Change: Yes.
Speaker Change: To make it really pragmatic yigal I mean, what having the primary as cases in Q and a secondary as New York Heart at the end of the day as Mike said people want functionality I think it's very hard to explain to a patient.
Speaker Change: You can achieve 15 meters more than a six minute walk test.
Speaker Change: That's pretty hard to try to wrap your head around as a patient and a provider but to say, it's very likely that youll be able to do your activities of daily living.
Speaker Change: With an improvement for patients again were focused on symptomatic patients that I think is meaningful and that's really why the CMI as had been approved is for symptom benefit.
Speaker Change: Got it thank you very much.
Speaker Change: Thank you. Our final question comes from the line of Joe Pat Guinness with H C. Wainwright. Your line is now open.
Speaker Change: Hello, everyone. This is landon on for Joe Thanks for taking our questions. So just to follow up with the pain program and regarding additional progress data anticipated. Soon do you expect pillar <unk> to have a differential effect in the stratification analysis based on background therapy, and if so would this observation.
Speaker Change: <unk> changed the design of the upcoming Registrational Phase III studies. Thank you.
Speaker Change: So I think what we can say and I think we've already communicated is we see a benefit whether or not the patient is on an underlying <unk> medication.
Speaker Change: Again, the sample sizes and I think we've had some of these conversations so I apologize if I'm being redundant but.
Speaker Change: There were only 30% or 50% of 100 patients in each one of the trials. So I wouldn't want to over interpret the data, whether it's better with or without a underlying <unk> medication and as a reminder, about 90% of the patients were on gabapentin. So that is the most widely used agent I think what we have.
Speaker Change: <unk> already published on and we presented previously on progress as well as relief is that we're seeing a benefit regardless of whether they are on an underlying <unk> medication, which is not surprising because they have a different mechanisms of action and its not surprising youll get additive benefit whether we're.
Speaker Change: Not there on a <unk> medications.
Speaker Change: Perfect. Thanks, a lot.
Mike: Thank you I would now like to turn the call back over to Mike <unk> for closing remarks.
Speaker Change: Well, thanks, very much and thanks for the question guys always very engaging.
Speaker Change: So that wraps up our Q1 earnings call.
Speaker Change: Busy and productive quarter for us and a lot more to do in quarter, two and throughout the year. We've got a lot of important catalysts coming up for the rest of the year.
Speaker Change: And look forward to updating you as the year progresses. So thanks very much for your time and we'll speak to you soon.
Speaker Change: This concludes today's conference call. Thank you for your participation you may now disconnect.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Okay.
Speaker Change: Yes.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Yes.
Speaker Change: [music].
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: Sure.
Speaker Change: [music].
Speaker Change: Yes.
Speaker Change: Sure.
Speaker Change: [music].
Speaker Change: Yes.
Speaker Change: Yes.
Speaker Change: [music].