Q3 2024 Lexicon Pharmaceuticals Inc Earnings Call
Speaker Change: Good day and welcome to the Lexicon Pharmaceuticals third quarter 2024 results conference call. All participants will be in a listen-only mode. Should you need assistance please signal a conference specialist by pressing the star key followed by zero.
Speaker Change: After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then 1 on a touch-tone phone. To withdraw your question, please press star and then 2.
Speaker Change: Please note this event is being recorded. I would now like to turn the conference over to Lisa.
Lisa DeFrancesco: DeFrancesco, Head of Investor Relations and Corporate Communications. Please go ahead.
Lisa DeFrancesco: Thank you, Dave. Good afternoon and welcome to the Lexicon Pharmaceuticals third quarter 2024 financial results conference call.
Lisa DeFrancesco: Joining me today are Dr. Mike Exton, Lexicon's Chief Executive Officer and Director, Tom Garner, Senior Vice President and Chief Commercial Officer, Dr. Craig Granowitz, Senior Vice President and Chief Medical Officer, and Dr. Alan Main, Executive Vice President, Innovation and Chemical Sciences.
Lisa DeFrancesco: Earlier this afternoon, Lexicon issued a press release announcing our financial results for the third quarter of 2024, which is available on our website at www.lexpharma.com and through our SEC filing. A webcast of this call along with a slide presentation is also available on our website.
Lisa DeFrancesco: During this call, we will review the information provided in the release, provide a corporate update, and then use the remainder of our time to answer your questions.
Lisa DeFrancesco: Before we begin, let me remind you that we will be making forward-looking statements, including statements related to the safety, efficacy, clinical development, regulatory
Lisa DeFrancesco: and therapeutic and commercial potential of Empepa, Zinquista, LX9211, LX9851 and our other drug programs, as well as our business generally.
Lisa DeFrancesco: These statements may also include characterizations and projections relating to our commercial launch of MPEFA and heart failure, as well as the clinical development, regulatory status, and market opportunity for all of our drug programs.
Lisa DeFrancesco: This call may also contain forward-looking statements relating to our growth and future operating results, discovering development of our drug candidates, strategic alliances, and intellectual property, as well as other matters that are not historical facts or information.
Lisa DeFrancesco: Various risks may cause our actual results to differ materially from those expressed or implied in such forward-looking statements. We refer you to our most recent annual report on Form 10-K and other SEC filings for detailed information describing such risks.
Mike Exton: I would now like to turn the call over to Mike Exton.
Mike Exton: Thanks Lisa and G'day everyone. Thanks for joining us on the call. Before we begin our discussion on Lexicon's results and business update for the third quarter of 2024, I'd like to discuss the progress we've made throughout this year, specifically over the last quarter, where there have been a considerable number of important achievements.
and Michael Eaton. Thank you. Thank you.
Mike Exton: Summarising just the last few months we've completed the resubmission of our NDA for the inquest of a glycemic control in people with type 1 diabetes and chronic kidney disease.
Mike Exton: The FDA held an advisory committee meeting for our NDA on October 31st, and we are continuing to work toward the PDUFA goal date of December 20th of this year.
Mike Exton: We're planning for multiple outcome scenarios as we approach the PDUFA date in a few weeks.
Mike Exton: We also completed a strategic repositioning and continued focus promotion of mPEPR to targeted high prescribers.
Mike Exton: Furthermore we have two major assets undergoing late-stage clinical development and we're making excellent progress in the development of both.
Mike Exton: A phase 3 study for sotagluplosin in hypertrophic cardiomyopathy, or HCM, is underway and the study is making good progress in sites open and enrolling patients.
Mike Exton: Our Phase 2B study for LX9211 in Diabetic Peripheral Neuropathic Pain, or DPNP, has crossed a big milestone by completing enrolment screening earlier than anticipated.
Mike Exton: Now, we anticipate top-line data in the first quarter of 2025.
Mike Exton: From our earlier clinical pipeline we've made progress with our exciting novel drug candidate LX9851, an oral therapy with IND enabling studies underway for obesity and associated cardiometabolic disorders.
Mike Exton: Last week, we were able to share important data on this asset at Obesity Week.
And we believe LX9851 has the potential
and we also know booming and yet evolving market.
Mike Exton: And lastly, but importantly, we've taken steps to reinvigorate our business development efforts with a substantial near-term focus on partnering.
Mike Exton: One result of these efforts was the recent exclusive licensing agreement we completed for SodaGluflozin outside of the US and Europe with Viatris.
Mike Exton: a company with strong cardiometabolic expertise and a successful track record of commercializing medicines.
Mike Exton: So I'm going to begin our business overview today by sharing an update on Zinquistr following our recent adcom.
Speaker Change: The committee voted 11-3 that the benefits of Zinquista do not outweigh the risks in adults with T1D and CKD, as defined by Lexicon as the T1D-CKD population in the primary vote in question.
Now importantly...
Speaker Change: Following the vote of the initial population, there were additional robust discussions surrounding the benefit risks for Zinquist in the 60-90 population, which was predefined and discussed at length during both the lexicon and FDA presentations.
Speaker Change: As a part of the discussion, additional committee members expressed support for sodium glufosin in this subpopulation, where they believe the benefits potentially outweigh the risks.
Speaker Change: Indeed, we saw an overwhelming outpouring of support, reflective of the unmet need that exists in this population.
Speaker Change: The meeting was widely attended by patient communities, advocates and healthcare professionals and included 23 presentations shared during the public hearing and a total of 148 submissions to the MDAC docket.
Speaker Change: Though there have been few advancements in insulin and CGM technology, the vast majority of people with T1D struggle to maintain glycemic control.
Speaker Change: Glycemic control is especially critical in the higher risk population of people with both T1D and CKD to slow the progression of kidney disease, heart failure and death.
Speaker Change: So the Lexicon team remains hard at work towards our PDUPA date of December 20th.
Speaker Change: And while we work towards the PDUFA date and remain committed to launch readiness in order to bring Zinquista to patients if approved.
Speaker Change: We're vigilant about our cash position and spending. Accordingly, we're preparing for all PDUFA outcome scenarios, with each plan mindful of both cash and focusing resources on the opportunities provided by our strong pipeline.
Speaker Change: Presently, we've paused any new spending related to launch preparation until we have more clarity on the path forward.
Speaker Change: However, in the event that we do have a successful outcome at PDUFA, our goal is to make Zinquista available to the appropriate patients as quickly as possible, and as early as the first quarter of 2025.
We've done a significant amount of planning and preparation for this launch and there are a number of key title wins, including an established supply chain and manufacturing capabilities ready to scale given our prior launch of sorry to get flows them as in pipe off of heart failure.
Speaker Change: We've done a significant amount of planning and preparation to this launch and have a number of key tailwinds including an established supply chain and manufacturing capabilities ready to scale given our prior launch of Sodegaflozen, as in pepper, for heart failure.
Speaker Change: proven commercial leadership expertise and a highly experienced team with significant launch experience.
Speaker Change: Proven commercial leadership expertise and a highly experienced team with significant launch experience.
Speaker Change: and operating in a highly concentrated market know that 80% of people with T1D and CKD are treated by a concentrated group of approximately 4,000 endocrinologists.
Speaker Change: And operating in a highly concentrated market.
Speaker Change: No the 90% of people with tier one day in CCI D. I traded by a concentrated group of approximately 4000 endocrinologists.
Speaker Change: which will allow us the opportunity to have a significant impact with our existing field team.
Speaker Change: Which will allow us the opportunity to have a significant impact without existing field team.
And most importantly, using christa has the potential to be the first and only adjunct therapy to insulin for lifetime at control.
Speaker Change: And most importantly, Zinquista has the potential to be the first and only adjunct therapy to insulin for glycemic control.
Speaker Change: There's been a dearth of innovation for this patient population despite the significant need and we believe Zinquista could satisfy a strong pent-up demand if and when we align with the FDA on the right patient population to benefit from this therapy.
Speaker Change: There's been adopter of innovation for this patient population despite the significant need.
Speaker Change: He believes in Quebec would satisfy a strong pent up demand if and when we align with the FDA on the right patient population to benefit from this therapy.
Speaker Change: So moving on that now next to briefly discuss in Peppa for heart failure.
Speaker Change: So moving on now next to briefly discuss in PEPFAR for heart failure.
Speaker Change: Net sales for the third quarter of 2024, with $1 $7 million, which represents 8% quarter on quarter growth, yielding four and a half million dollars via Tonight, but 'twenty 'twenty four.
Speaker Change: Net sales for the third quarter of 2024 were $1.7 million, which represents 8% quarter-on-quarter growth, yielding $4.5 million year-to-date for 2024.
Speaker Change: Through Q3, we saw improvements in field T Rx volumes across both commercially insured and Medicare patients with gross unit volume, increasing by 26% driven predominantly by increased depth of prescribing among the growing base and repaid in Peppa prescribers.
Speaker Change: Through Q3, we saw improvements in field TRX volumes across both commercially insured and Medicare patients, with gross unit volume increasing by 26%, driven predominantly by increased depth of prescribing among the growing base and repeat in PEPFAR prescribers.
Speaker Change: This progress continues to be driven by the focused efforts of our sales team.
Speaker Change: This progress continues to be driven by the focused efforts of our sales team, even with the strategic repositioning that included a 50% reduction in field force, which was effective in September.
Speaker Change: Even with the strategic repositioning that.
Speaker Change: That included a 50% reduction in field force, which was effective in September.
[laughter].
Thank you. Thank you.
Speaker Change: Continuing with the discussion of sotagliflozin, which remains a pipeline and appeal opportunity for Lexicon, we have made significant progress in our clinical development strategy for patients with symptomatic HCM.
Speaker Change: Continuing with the discussion have started the flows and which remains a pipeline in a pill opportunity for lexicon. We have made significant progress in our clinical development strategy for patients with symptomatic HCM.
Speaker Change: Enrollment is now under the wife is not a H C. M. A pivotal phase III placebo controlled study with a targeted enrollment of 500 patients with obstructive.
Speaker Change: Non obstructive HCM.
Speaker Change: [laughter].
Speaker Change: The primary endpoint of the study is change from baseline in case, they say Q school.
Speaker Change: And then point that has been accepted by the FDA as the primary endpoint in this and other label, enabling Hydro dam trials.
Speaker Change: And with which we've previously achieved success in house all of his top priority trial.
Speaker Change: Importantly, so not a H C. M is studying a broader patient population than that studying other ongoing trials and how you see them as we allow patients to be on cardiac myosin inhibitors as well as allowing the use of beta blockers and calcium channel blockers.
Speaker Change: If approved this clinical approach would potentially enable broad adoption and ease of use.
Speaker Change: Would be no need necessarily to change the current treatment regimen.
Speaker Change: We have obtained feedback from the FDA and the success in the single study could support a broad label for Saratoga players and in H C M.
Speaker Change: Once again.
Speaker Change: This fits they'll lead to succeed strategy is an important area of growing unmet need where we have the potential to be the only indicated S. G. L T inhibitor.
Speaker Change: Current estimates suggest that approximately 1 million patients in the U S. Today, you have H C M.
Speaker Change: Many are not diagnosed in part given the nonspecific Nitro HCM symptoms.
Speaker Change: Diagnostic rights have been rising rapidly a trend which is expected to continue over the next decade with increasing increased awareness and understanding of this disease.
Speaker Change: Okay.
Speaker Change: Looking further into our pipeline and I really want to spend some time today on <unk> nine to one one.
Speaker Change: As we near the finish line of our Phase II study.
Alex: Alex nine two on one is another pipeline in a pill opportunity for lexicon with what we believe to be a multi blockbuster potential across numerous possible therapeutic applications in important areas of need.
Alex: These include diabetic peripheral neuropathic pain, which is currently under a valuation but also in other forms of neuropathic pain, such as post herpetic neuralgia and potential in forms of spasticity.
Alex: <unk> nine to one one offers the opportunity to potentially redefine the standard of care in D. P. M P.
Alex: Targeting the enzyme I K, one <unk> nine to one one as a non opioid medication and it has the potential to be the first new oral treatment for neuropathic pain in more than two decades.
Alex: Alex 91, one of them.
Alex: Receipts excuse me fast track designation from the FDA.
Alex: <unk> in D. P M P.
Alex: So as you can tell we're really excited about the potential for this program [noise].
Alex: And now progress face to be dose optimization study completed screening for enrollment this past quarter that.
Alex: That's significantly ahead of schedule.
Alex: We now anticipate top line data in the first quarter of 2025, So that's really right around the corner for us.
Alex: We believe this study was really well designed like our previous proof of concept study. It's a placebo controlled allows patients to remain on stable dose of standard of care therapy, rather than removing old pain medications, that's really consistent with how novel D. P. N pay drugs are likely to be used in real world practice.
Alex: There are approximately 20 million patients in the U S suffering from neuropathic pain and about $5 million of barriers at diabetic peripheral neuropathic pain. So if approved we believe that Alex 9211 could offer real benefit to patients and the clinical community, who are looking for benefit better options to improve outcomes for patients.
Alex: With various types of neuropathic pain.
Alex: So we're really looking forward to these results.
Alex: The protocol of the study was also designed to find the correct dose them to optimize the phase III program. Both in terms of length and overall study size.
Alex: But while lexicon is well positioned to continue the clinical development of D. P. M P.
Alex: Been actively discussing potential partnerships to realize the full value and potential for this asset.
Alex: Our newest drug candidate is Alex Knight five one a novel compound currently in preclinical studies for basically eating associated metabolic disorders.
Alex: We believe that Alex not at five one has the potential lockout other assets to be developed in additional indications and to be used as a potential combination therapy.
Alex: 905, one is a small molecule inhibitor of the novel target IC S. O five an enzyme that is highly expressed in intestinal mucosa.
Alex: It's unique illegal break mechanism appears to provide benefit versus nine limitations of J O P ones.
Alex: Such as lean muscle loss dice related adverse Gi side effects and white rebound post discontinuation.
Alex: We believe 9851 could be given orally for chronic weight management.
Alex: Iron ore in combination within cretin mechanisms with a target product profile that produces body fat and improves the overall metabolic profile.
Alex: On the next couple of slides here I'd like to show you. Some preclinical data, which was presented last week the basically wake.
Alex: The first slide shows the significant reduction in body weight observed with diet induced obese or Dio mice fed a high fat diet.
Alex: Notably.
Alex: The addition of Alex 995 wanted to semi Glu, Todd resulted in significantly greater weight loss than that achieved by simply tired alone.
Alex: Furthermore, we also presented data on what happens to weight loss, if semegran Todd is discontinued and then Alex not at five one treatment is initiated.
Speaker Change: He will say the blue line that shows white loss associated with administration of semi Glu Todd.
Speaker Change: Importantly, when Semigloss taught treatment is withdrawn after day 14, it quickly rebound rebounds back to baseline.
Speaker Change: If however, Alex 9851 treatment commences upon some agree Todd discontinuation.
Speaker Change: The Green line shows have weight loss is substantially maintained.
Speaker Change: Look we're really enthused about the promise of these early results and all the preclinical data we've generated demonstrating improvements in cholesterol triglycerides, and insulin sensitivity, which might get white for additional related indications and metabolic syndrome and match.
Speaker Change: As we know the obesity and weight management space is an area of tremendous interest in the industry and.
Speaker Change: And we're very excited about the potential for an oral therapy that complements and enhances current therapies alone or in combination. So we continue to advance L. I N. The enabling studies and are actively preparing for R&D filing by mid 2025.
Speaker Change: So in summary.
Speaker Change: We've made really great progress across every one of our invested pipeline assets as we explore the potential applications of our novel unique products.
Speaker Change: My focused on making progress across the board on this pipeline in 2025.
Speaker Change: Let's now touch on the financials for the quarter, and then I'll talk a little bit more in depth about our partnering strategy.
Speaker Change: So we ended the quarter with $258 $4 million.
Speaker Change: Cash and investments.
And that doesn't include the upfront payment of $25 million that we received from the licensing agreement with V interests, which was received in the fourth quarter.
Speaker Change: As indicated in our press release. This afternoon, we had $1 $8 million in revenues in third quarter of 24.
Speaker Change: Almost all of that from net sales I mean pepper.
Speaker Change: R&D expenses for the third quarter of 24 increased to $25 8 million from $17 6 million for the corresponding period of 2023.
Speaker Change: Yeah that was primarily due primarily due to investments in our late stage development programs, including the commencement of Sonata phase III study of soda good flows in an H C M.
Speaker Change: And the earlier recognition of expenses related to the progress face to be due to the enrollment acceleration.
Selling general and administrative expenses for the third quarter increased to $39 6 million from $32 2 million for the corresponding period in 2023.
Speaker Change: That reflects higher marketing costs in conjunction with the commercialized commercialization of being pepper.
Speaker Change: And launch planning for <unk> as well as severance cost, resulting from the strategic re positioning announced in August which included a 50% reduction in the field force at that time.
Speaker Change: In total net loss for the second quarter of 2024 was $64 8 million or 18 cents a share compared to a net loss of $55 million or 21 cents a share in the corresponding period of last year.
Speaker Change: For the third quarters of 24, and 23 net loss included noncash stock based compensation expense of $2 8 million and $3 9 million respectively.
Speaker Change: Now, let me just pivot and talk a little bit more about our strategy for partnering which as I mentioned earlier is going to be a key value driver for lexicon going forward.
We've really reinvigorated our business development efforts over the last quarter.
Speaker Change: Is going to be a key part of our latest succeed strategy moving forward.
Speaker Change: We have really three key priorities when it comes to evaluating partnership opportunities to create value.
Speaker Change: Augmenting our commercial capabilities advancing our pipeline in any or all potential indications and expanding access to new geographies or territories to deliver on the night value of their products.
Speaker Change: Importantly, any partnerships would be a major source of non diluted capital to invest in our future.
Speaker Change: A fantastic late example of this strategy in action, we announced this quarter an exclusive licensing arrangement with Beatrice company with strong cardio metabolic expertise a global commercial capability and successful track record of launching medicines in new territories.
Speaker Change: This deal represents an exclusive opportunity to expand the reach of side of the flows and potentially across all indications.
Speaker Change: In other markets outside of the U S and outside of the EU now as I mentioned earlier the deal included a $25 million cash upfront payment.
And close to $200 million in potential regulatory and sales milestone payments as well as two tiered royalties from the low double digit to high teens.
Speaker Change: We're excited to work with very interesting even in these early weeks I've already been an engaged and motivated partner we.
Speaker Change: We are confident that they are the right collaborate collaborate a synthetic of flows and in these territories.
Speaker Change: With a renewed emphasis on beta we've reshaped our bay de team, who are laser focused on our pipeline and potential near term partnering opportunities right.
Speaker Change: <unk> nine to one one and Alex Knight 515.
Speaker Change: Focused in disease areas with proven.
Speaker Change: Clearly articulated multi blockbuster potential for new medicines.
Speaker Change: We continue our engagement with potential partners in this space now sharing important data as they progress.
Speaker Change: Importantly, we also now have a focused lead generation program.
Speaker Change: Against additional undisclosed targets from J 95000, and preclinical validation.
Speaker Change: Within the cardio metabolic and neuroscience spices.
Speaker Change: So the 'twenty 'twenty four is being transformative for lexicon in the next 12 to 18 months promises to be just as pivotal with several important potential catalyst coming in the relatively near term.
Speaker Change: For certain whether we have the ability to launch the inquisitor in just a few short weeks.
Speaker Change: And as I stated earlier, we're ready today for multiple scenarios.
<unk> Phase III study of started flows in an H C. M is well underway and we look forward to continuing to enroll patients.
Speaker Change: We expect that our progress phase Iia study of <unk> nine to one one in D. P. M P.
We will report topline data in the early part of next year.
Speaker Change: Which is coming very very quickly.
Speaker Change: And the R&D, enabling studies of Alex Knight five one in the rapidly evolving area of a basically an associate to carry multiple metabolic disorders are underway with a nine day filing anticipated in middle of next year.
Speaker Change: But each of these opportunities have large potential in areas of significant unmet need and clearly represent large commercial opportunities.
Any one of these is successful and has the potential to redefine lexicons future and create significant value for stakeholders, including the patients that we are also committed to.
Speaker Change: Now with that said I'll turn the back the call back to the operator and I look forward to your questions.
Speaker Change: We will now begin the question and answer session to ask a question you May Press Star then one on your Touchtone phone, if you're using a speakerphone. Please pick up your handset before pressing the keys. If at any time. Your question has been addressed and you would look to Australia. Your question. Please press Star then two.
Speaker Change: First question comes from Andrew Tsai with Jefferies. Please go ahead.
Speaker Change: Hey, good afternoon. Thanks, so much for taking my questions I appreciate the updates so after the AD com what would you guys say is your confidence that you will be getting a skinnier label within that 60 to 90 CK D subgroup and is there anything you can do in the coming weeks.
Speaker Change: Maybe sharing some more data or anything else to help convince the F D a to getting an approval. Thanks.
Speaker Change: Yeah, great. Thanks, Andrew I'll, let Craig comment initially.
Craig Granowitz: Yeah. Thanks, Andrew we remain involved and engaged with the F D. A.
Craig Granowitz: After the Amdek process.
Craig Granowitz: And I think really at this point all we can say is that we've continued our engagement with them and we remain committed to.
Craig Granowitz: Two the target date of December 20th I think anything further at this point would be premature for us to comment on one way or the other.
Speaker Change: And okay recognize Andrew.
Andrew Tsai: Just to add a little bit of flavor.
Andrew Tsai: Both us and the FDA did.
Andrew Tsai: Called out 60 to 90 groups as a as a group that potentially may have improved benefit risk.
Andrew Tsai: And indeed that doesn't represent a skinny label.
Andrew Tsai: In fact compared to the indication that we submitted an outbreak and document.
Andrew Tsai: It represents a population are about with another 15% to 20% of eligible <unk> patients. So.
Andrew Tsai: That we don't think that would represent a skinny label and we're going to continue to work with the FDA on potential scenarios.
Speaker Change: Yes, thanks for the clarification and then secondly for the pain program, obviously, the data is coming faster.
Speaker Change: What we had expected.
Speaker Change: At the end of the day are you expecting a larger placebo adjusted efficacy separation.
Speaker Change: You saw in the prior phase two a M life. Thanks.
Speaker Change: Yeah, Andrew It's Craig graduates again, thank you for the question then.
Speaker Change: As we've mentioned, we always analyze our data and not from a completer analysis standpoint, but on an intent to treat basis.
I think if the data holds up and the percentage of patients that are completing the trial is greater.
Speaker Change: And the dropout rates that we saw in the two.
Speaker Change: 201 study as the pilot study.
Speaker Change: You know one might expect that the response rates might be greater and certainly that's what we're hoping for was to have a better efficacy safety profile and I think as we've shared with you before.
Speaker Change: The dizziness signal, we saw was really a Z Max effect that was very much correlated.
Speaker Change: Do that initial tenfold loading dose on day, one and I think as we've shared in prior calls.
Speaker Change: What we've seen is that a very different profile again, all blinded data, but a very different profile and the.
Speaker Change: Tolerability of treatment during during this study so why don't want to overstate. The case again analyzing that data on an intent to treat not a completer analysis the more drugs.
Speaker Change: <unk> get in.
Speaker Change: The drug is active the more likely it is that we will see an enhancement of relative efficacy.
Compared to placebo.
Speaker Change: Okay, that's very encouraging thank you.
Speaker Change: Thanks, Ed.
Speaker Change: And the next question comes from Yasmin Rahimi with Piper Sandler. Please go ahead.
Speaker Change: Okay.
Speaker Change: Hey, Deane this is going to be longer yes. Thank you for taking our questions.
Speaker Change: The pain program or could you comment on what types of data you are perfect you on a blended basis across our efficacy and safety and secondly is it reasonable to expect a dose response in the study as well.
Speaker Change: Yes, so the data we get is extraordinarily limited and again, it's all blinded data. So we don't know which patients are on drug or not on drug and it's really driven totally around safety and we continue to monitor that because patient safety is obviously, our most important priority and we continue to do that.
Speaker Change: On an ongoing basis.
Speaker Change: Regarding all the patients that are enrolled so really all we can comment is the overall results in terms of a.
Speaker Change: Dropouts and Tolerability, so I really can't say anything other than what.
Speaker Change: What I've already shared is that the profile in the blinded data.
Speaker Change: It seems to be somewhat different than what we saw in the pilot trial and I think I really can't comment more than that.
Speaker Change: On on the overall profile of the drug.
Speaker Change: Got it thank you.
Speaker Change: And the next question comes from Joseph Stringer with Needham and company. Please go ahead.
Speaker Change: Hi, Thanks for taking our questions.
Speaker Change: On the CS three HCM trial.
Speaker Change: Are you aligned with FDA on the T six EQ primary endpoint and.
Speaker Change: What would you consider a successful placebo adjusted change and the case in situ as the bar for success here.
Speaker Change: On on this endpoint the mother and the African dataset.
Craig Granowitz: Yeah, Joe it's Craig graduates again.
Speaker Change: We feel quite confident.
Speaker Change: In this end point, we did have this discussion with the FDA prior to initiating the trial.
Speaker Change: Both in terms of the endpoint the magnitude of the benefit the statistical plan and the powering of the study the inclusion of both obstructive and non obstructive in the realm.
Speaker Change: Relative numbers that are included in the trial. So all the parameters that we've shared previously on the trial design and endpoints, we feel quite confident.
Speaker Change: We've not shared.
Speaker Change: The overall expected Casey CQ Delta achieved in a trial, but as Mike mentioned in the prepared remarks. This is an endpoint that we feel quite confident we can reach based on what we've seen in the AR and the soloist trial and as a reminder, the inclusion criteria.
Speaker Change: For patients with symptomatic disease with a maximum case you see Q of 85 is the enrollment which means the median is gonna be somewhat lower than that so based on our prior experience based on the fact that FDA has allowed approval of other studies as label, enabling studies that are running.
Speaker Change: In non obstructive HCM, we feel quite confident in the endpoint.
Speaker Change: As well as the expected.
Speaker Change: Outcomes using this instrument with soda with Fosun in a group of patients with symptomatic heart failure.
Speaker Change: Great. Thank you very much.
Speaker Change: The next question comes from Joe Pant, Guinness with H C. Wainwright. Please go ahead.
Speaker Change: Good afternoon, thanks for taking the questions. So I know I know Craig mentioned that.
Speaker Change: I'm, assuming you might be a further restricted as to the comments around the AD com, but just curious.
Speaker Change:
How much like you said, obviously, the FDA and you guys brought it up very well about the role of the more targeted population, but how much that may or may not be playing into your current FDA discussions, but more importantly, I'm sure one of the scenarios you're looking at is if you do get another CR rail and the F. D. A C.
Speaker Change: Yes. Another study in that defined population are you prepared to do it yourself.
Speaker Change: Yeah, it's a.
Speaker Change: Barry are intriguing and insightful question as always Joe.
Speaker Change: Luca.
Speaker Change: At this stage, where we're going to have white the.
Speaker Change: Are the results of the <unk> to do so obviously to make any concrete decisions.
Speaker Change: We've been in this game and pursuing with the F D. A.
Speaker Change: Now over six years or so.
Speaker Change: And it will be very difficult to think about continuing certainly to do more studies. When in fact, we think we have a ton of evidence that we presented at the AD com.
Speaker Change: And.
Speaker Change: That.
Speaker Change: Would make it a difficult proposition to pursue further investments.
Speaker Change: When frankly, it makes it difficult to have confidence that that would be sufficient.
Speaker Change: So so I never say never but it would be a tough one Greg you thoughts Yeah. Joe you know I think we did have that specific discussion during the Q&A of some of the Ambac advisers asked us about that.
Speaker Change: I'll I'll, just very very briefly remind the group that we did three large independently.
Speaker Change: [laughter] trials.
Speaker Change: All of which achieved the primary and all secondary endpoints.
Speaker Change: The 60 to 90 group was actually a predefined group prior to the initiation of the study.
Speaker Change: We showed previously and again at the meeting that achieved statistical significance in all three of those trials.
Speaker Change: There was never a discussion at the Advisory Committee did we achieve the endpoint, which was a one C reduction or all of the key secondary endpoints blood pressure control weight management time and range reduction in level two hypo.
Speaker Change: So we felt at the time of the last year L and particularly in this population there's no basis to have to rerun. The efficacy trials. We think that has been definitively established as the safety profile.
Speaker Change: And the mitigation strategies that have been well adopted across the medical community of how to deal with.
Speaker Change: Diabetic ketoacidosis and again as a reminder.
Speaker Change: The diabetic ketoacidosis character in patients on an S. G O T inhibitor is no different than.
Speaker Change: And those not on an S. L. P inhibitor the initiating factors for that are the same the mitigation factors are the same the recovery is the same and as we reminded the EM back 50% of the patients.
Speaker Change: Whether they were on drug or not on drug restarted the therapy during treatment. So again, there's no basis to run a study looking at mitigation of decay a based on these international consensus guidelines that have been widely adopted so just from a medical standpoint.
Speaker Change: We just don't see any basis, nor frankly do the does the medical community to run another efficacy trial for Oh, I've seen like management Theres, just no no rationale to do so.
Speaker Change: Very fair answers I appreciate it and also the reminders.
Speaker Change: Quick question and then my second question, but so the quick question is for the HCM study with soda just curious as to any I mean, obviously, you're looking for a different profile, but any views towards patient competition with regard with approved products for HCM as well as.
Speaker Change: Developmental assets.
Speaker Change: And then the second question is for 90 211 since we're approaching data if you could remind everyone publicly said.
Speaker Change: Since this could be the first non opioid approved for D. P. N. P. You know what are some of the key benchmarks, we'd be looking at when the data come out.
Speaker Change: So I'll answer the first question on enrollment and competitive enrollment.
For the HCM trials.
Speaker Change: We've opened a number of sites in the U S.
Speaker Change: We presented data on the trial design at the a H M S. A meeting and at the H C. M. A meeting from the study pies.
Speaker Change: The sites that we're opening in the U S people like the protocol. They are interested in participating we expanded the number of study sites in the U S. As we've previously shared.
Speaker Change: And we're in the process of getting all the regulatory approvals for all of the other countries right now and in the other country approvals are on track are actually ahead of schedule of what we had anticipated at the time to get those government approvals to to initiate the trial. So we feel pretty good on the design.
Speaker Change: Just like our 91, one trial, it's a pragmatic trial design, it's really easy to follow you don't have to do all the echoes with the other trials. The duration is short the endpoint is simple you don't need to do a V O. Two testing a lot of other complicated physiologic testing. So the feedback we had at the investigator meeting.
Speaker Change: He has been very very favorable it's pretty easy study to do.
Speaker Change: So I hope that answers I'll pause answering.
Mike Exton: Very good maybe I'll turn it back over to Mike on benchmarks or or the 90 211 studying what we might be looking for like me to answer that look I think maybe the I've seen Joe you were talking about the primary endpoint and what Delta we might say in pain score is that yeah bright primary and secondary you know what.
Speaker Change: I mean, you could throw out some data there but also maybe include you know.
Speaker Change: What you're looking to surpass and also meaningfulness to patients.
Speaker Change: Great Great question, and I think when you look at our pain program you have to look at two parameters there.
Speaker Change: The first is the placebo adjusted reduction in pain score.
Speaker Change: The second is the baseline to the maximum reduction in pain score because patients don't get treated compared to placebo they get treated compared to their baseline.
Speaker Change: And as you know these patients have a significant placebo effect, regardless so the reductions in pain score of patients to their baseline is quite significant and in all of these trials.
Speaker Change: That notwithstanding we did hear from our clinical experts and the FDA that the reduction in pain score that we were achieving in the pilot study both in the D. P. N P and in the PHN study were clinically meaningful compared to placebo and that's looking in the range of 0.652 0.8 and the <unk>.
Speaker Change: City of the reduction in median pain scores, even larger than in the D. P. N P trial so.
Speaker Change: I think as evidenced by the fact that there was tremendous uptake of the trial and again, we ran that entire study in the United States and we finished it many weeks early.
Speaker Change: The interest level is high the protocol as easy to follow and you.
You can take what you will the study enrolled more quickly than expected, but I think that.
Speaker Change: People found value.
Speaker Change: <unk> sites and patients found value in participating in the trial.
Speaker Change: Allow me to sort of extrapolate into a into the real clinical world If you like and.
Speaker Change: The beauty of this trial as Craig mentioned that pregnant pragmatism in association with how its likely patients again, we trade for D. P. M P.
Speaker Change: When when and if this gets approved.
Speaker Change: That is any new pain medicine is going to be step through generic medicines and whether it would be gabapentin pregabalin et cetera.
Speaker Change: Both from the physician perspective, as well as from a managed care perspective that you can pretty much guarantee happens in any genericize marketplace.
Speaker Change: And so to then demonstrate that you have significant efficacy on top of standard of care.
Speaker Change: Allows a physician in and pay us quite frankly to then say, okay, let's start with the generic which like will do anyway, but give some confidence that the physician instead of switching at pain Meds can add Alex <unk> to one one on top.
Speaker Change: As we all know physicians prefer to do rather than particularly in pain to switching out meds from one to the other.
Speaker Change: And so what do you think that is not only scientifically most the most valid way to go because it shows.
Speaker Change: <unk> over and above the standard of care, but is likely to be welcomed by payers and physicians alike.
Speaker Change: Very very helpful. Thanks for all the answers and good luck going into next month.
Speaker Change: Thanks, Joe.
Speaker Change: And the next question comes from you guys or not to move it with Citigroup. Please go ahead.
Yeah, Hi, Thanks for taking my question.
Speaker Change: I'm, a little time talking about how you're thinking about the trajectory going forward into 2025 in terms of quarterly growth in and what the appropriate level of investments should be in that and that launch and then also just regard to which types of patients are receiving it and how many.
Speaker Change: Two of them had to gone through the you know the prior author.
Speaker Change: Is it to try them.
Speaker Change: The other <unk>.
Speaker Change: Okay.
Speaker Change: It's is homegrown.
Speaker Change: I'll take that one first and then mark or anything else that you can yes.
Speaker Change: Additionally, so as we look to Q3 and I think as Mike mentioned earlier, we did actually see some encouraging.
Speaker Change: Continued modest growth within peffer, even post.
Speaker Change: The restructure that took place during the quarter so.
Speaker Change: If you just look at our overall dispense volume that was up about 40% quarter over quarter. The number of unique prescribers grew by about 20%.
Speaker Change: Look at our new to brand share actually grew by about 20% as well I guess, the corresponding you may well have as well in which case then board that the net revenues not colored those same trends and that was because we had a significant gross to net true up at the start of the quarter, which impacts total net revenues.
Speaker Change: Just as a reminder.
Speaker Change: The dynamics within the heart failure market places. This is a patient population that tends to skew heavily part D. So a med D exposure is in excess of 60% and commercial makes up around 30, with Medicare with Medicaid and others, making up the remaining 10%.
Speaker Change: In terms of our access and coverage.
Speaker Change: It's about 50% of lives covered in the U S. Although I think it's worth noting again that most of those patients required some kind of step through utilization management as it regards to our favorite medications. So it potentially having to step through another S. J O T before being able to be able to prescribe it.
Speaker Change: Perfect for these patients.
Speaker Change: The value and access team that we have are continuing to engage very heavily involved with.
Speaker Change: Our community with regards to in peso.
Speaker Change: We have a number of outstanding bids to Medicare and commercial that we are hoping to pull through and I think we're now also beginning to see some of the dynamics clear in terms of the overhang that we saw throughout this year, which was the Ohio array because.
Speaker Change: With our major competitors, we're listed on the top 10 drug list, but I think that that snow, giving payers clarity as to what the world looks like moving forward. So.
Speaker Change: We continue to push in peso with target prescribers were continuing to grow the prescriber base and now we have the refocus sales force. Our primary focus is pushing increased deaths amongst our Reuters, so we anticipate modest growth quarter over quarter moving forwards.
Speaker Change: Obviously, we also have is in peso for HCM in the future as well and it's worth noting that this will be largely the same customer base that we'll be talking to as it relates to Asia.
Speaker Change: So they'd be able to cut I think the on the additional add here is some.
Speaker Change: You know when we did the restructure in September we were very focused and targeted in how we created the new field and commercial organization with the balance of zinc twister on in peso.
Speaker Change: We will continue to evaluate that as we said with all scenarios as we move forward towards substitute for December 'twenty.
Speaker Change: So to get to your question around what is the right.
Speaker Change: Our level of investment that will be part of that scenario planning as we as we learn more and get greater clarity.
Speaker Change: Between now and December 'twenty.
Speaker Change: Okay. Thank you very much.
Speaker Change: And the next question comes from Rowena Ruiz with Alere, Inc.
Speaker Change: <unk>. Please go ahead.
Speaker Change: Okay.
Speaker Change: Great. Thanks afternoon, everyone. So could you elaborate on what drove the recent via interest agreement first of all liquid frozen and given your comment about greater focus on partnering I was curious what is your outlook on how to prioritize future partnerships across soda or the other pipeline assets and considering different regions globally.
Speaker Change: Well.
Yeah.
Speaker Change: Not to speak with you again I think.
Speaker Change: Look for Beatrice and the global partnership.
Speaker Change: Clearly our focus as a company is the U S in terms of our commercial footprint.
At the moment.
Speaker Change: And so we were really looking for a strong global partner, who had the ability to commercialize in the.
Rest of World market, if you like and I'm really theatricism tying to the to the top of the pile when we thought about that and so.
Speaker Change: And the engagement that we had with that company and and and Tom and team led led the way from a commercial perspective. It was really a very very good negotiation back and forth and I think we got a win win out of it with Beatrice and so I would expect that to be a really fruitful partnership actually and.
Clearly as we mentioned already.
Speaker Change: They're highly engaged way highly engaged and that provides a.
Speaker Change: I think pretty significant additional value to the company that we wouldn't have pretty lives by ourselves.
Speaker Change: That is clear.
As it relates to sort of prioritizing the pipeline.
Speaker Change: I think for both nine to one one in 9851, they lend themselves.
Speaker Change: The partnering are pretty significantly and so I wouldn't necessarily.
Speaker Change: Differentiate on the two.
Speaker Change: Having said that with 91 one.
Speaker Change: Being a lifestyle to be asset that if it's successful shows strong efficacy replicating what we've seen in the original trial.
Speaker Change: So that is a strong value creator in fact.
Speaker Change: Not only are there are a number of our.
Speaker Change: Pharma companies that don't currently have a pain franchise, but clearly there are others that are showing interest that.
Have a neuroscience presence or have a and adjacent interest in pain.
That we think being the the nearest sort of laid out as a significant opportunity, but clearly given the number of deals that have been happening in the white management white loss and that basically and some engaged partners that we've been discussing with them that also was a.
Speaker Change: It's an opportunity.
Speaker Change: For partnering in both of those to truly realize the value of the assets.
Speaker Change: Lend themselves towards partnering in some way.
Speaker Change: Both to realize the commercial opportunity in the commercial footprint, you would make to commercialize those as well as the breadth of indications and the investment that you would need to make that successful and so that's where it really over the next.
Speaker Change: Three to six months, we will be doubling down in those discussions.
Speaker Change: Got it thanks, and then I was curious if ROE on it so yeah I just wanted to ask one other quick thing that about.
Speaker Change: The interest is that they have deep experience in cardiovascular medicine, both historically.
Speaker Change: And currently you know they have the old Pfizer portfolio some of their most important drugs or cardiovascular and they have a deep experience in that area and some of the more recent deals they've done have also been in the in the CD space. So in that regard we have a partner that has a lot of shared vision around.
Speaker Change: The heart and the heart failure market so.
Speaker Change: I'm excited about having them as a as a partner in that.
Speaker Change: It makes sense and that's my second question I was curious could you elaborate a bit more on your thoughts on 90 851 fitting into the treatment paradigm I know you've talked about obesity, but also I think you've alluded to cardio metabolic disorders as well as their sort of interrogate that.
Speaker Change: Product what sort of differentiate features do you hope shine through for this asset.
Yeah.
Speaker Change: Look I.
Speaker Change: I think there are a number of our critical features and as we noted this whole space is evolving rapidly and a lot of interest and a lot of different.
Companies getting involved but yes.
A couple of very unique features that are quite different to the general failed as we say it now one is a small molecule it's going to be an oral once a day medicine, which as we know a lot of patients prefer over injectables for whatever reason and that continues despite the.
Speaker Change: Use of Injectables over a decade now.
Speaker Change: Secondly, this is a not a J O pay one or or give a it's a completely different mechanism and I think this we can extrapolate from the data even though we presented today from basically wait if you wanted to fast forward into into white loss.
Speaker Change: Couple of the unique features on this preservation of lean body mass, which could potentially be important as we learn more about the current treatment paradigm.
Speaker Change: The idea that it can be used in combination therapies and certainly in diabetes and the other cardiac hypertension and other cardio metabolic diseases Hyperlipidemia and you can go on and on it's all about combination therapies.
Speaker Change: Be surprised if it basically gives them the same way.
Speaker Change: And so having completely different and complementary mechanisms is helpful for that.
Speaker Change: And then there is this interesting perspective of.
Speaker Change: The tolerability, because we know that J O pay ones now we used on average about seven months and then people go off and often times. They do get this rebounding in white that we demonstrated in the in the mouse model here.
Speaker Change: And so you could foresee an area of this being a sort of a maintenance therapy. That's used in conjunction with a significant weight loss you get initially with the J L. P. One so there's there's lots of areas, where you could predict a number of years into the future. How this could be a very valuable very valuable ad.
Speaker Change: To a company that has a a number of different types of asset in the portfolio and is able to mix and match those to really target the patient and the patient lifestyle that they see fit so.
Speaker Change: So for that reason, we say that this is a very complementary mechanism and potential asset or partners.
Speaker Change: Got it thanks.
Speaker Change: Thanks.
Speaker Change: This concludes our question and answer session I would like to turn the conference back over to Mike <unk> for any closing remarks.
Mike Exton: Yeah look firstly, thanks, a lot for the great insightful questions guys, some really great to catch up with you and.
Mike Exton: We we have a really unique time not only between now and December 'twenty, where we will get some clarity on how we move forward with the same quipster.
Mike Exton: But beyond there as we progress these three really important our pipeline opportunities with startup a pleasant and H C M.
The very.
Seem to be read out of our non tier one won't.
Mike Exton: All in the progress to be study, which is another major catalytic event for us and continuing to execute with Alan and pain to finalize the R&D, enabling studies for 9851 that are going as per plan and to have that submitted mid next year. So.
Mike Exton: While we are very much focused on this near term and saying how we move forward without without commercial efforts as enquist, Oh, we have a lot of things coming up in the very near future to look forward to when we're really.
Mike Exton: Excited about the breadth of opportunity that we have and look forward to giving further updates as we gain more clarity over the coming weeks. So appreciate everyone listening in and we will no doubt catch up with some of you are again later on so thanks very much and back to you what the write up.
Speaker Change: The conference has now concluded. Thank you for attending today's presentation you may now disconnect.
Speaker Change: Yeah.