Q4 2024 Xenon Pharmaceuticals Inc Earnings Call
Hello, Thank you for standing by at this time I would like to welcome you to the Q4 'twenty 'twenty four she didn't Pharmaceuticals, Inc earnings Conference call.
All lines have been placed on mute to prevent any background noise.
After the Speakers' remarks, there will be a question and answer session. If you would like to ask a question. During this time simply press star followed by the number one on your telephone keypad.
Speaker Change: She was that we're drawing a question press star one again.
Chad TGF: I would now like to turn the conference over to Chad TGF. Please go ahead.
Speaker Change: Yeah.
Speaker Change: Good afternoon. Thank you for joining us on our call and webcast to discuss <unk> fourth quarter and full year 2024 financial and operating results.
Ian Mortimer: Joining me are Ian Mortimer, <unk>, President and Chief Executive Officer, Dr. Chris Kenny.
Ian Mortimer: As Chief Medical Officer, and surety, Alan <unk>, Chief Financial Officer. After completing their prepared remarks today, we will open the call up for your questions.
Ian Mortimer: Please be advised that during this call we will make a number of statements that are forward looking including statements regarding the timing and potential results from clinical trials.
Ian Mortimer: Cancel efficacy safety profile future development plan, and current and anticipated indications addressable market regulatory success and commercial potential of our and our partners' product candidate.
Ian Mortimer: The efficacy of our clinical trial designs, our ability to successfully develop and achieve milestones in our clinical development programs, including the anticipated filing of buying these 98.
Timing and results of our interactions with regulators our ability to successfully obtain regulatory approvals.
Ian Mortimer: Just be the timing of top line data readout for our clinical trials or is that your counter and our expectation that we will have sufficient cash to fund operations into 2027.
Ian Mortimer: Today's press release, summarizing we announce fourth quarter and full year 2024 financial results and the accompanying report on Form 10-Q will be made available under the investors section of our website at xenon Dash, one dot com and filed with the SEC and on SEDAR.
Ian Mortimer: I would like to turn the call over to Ian.
Ian Mortimer: Okay.
Ian Mortimer: Thank you Chad and good afternoon, everyone. Thanks for joining our call today I'll begin with a brief review of our accomplishments in 2024, and then look ahead to what promises to be an exciting year in 2025 highlighted by our first phase III epilepsy readout and the continued progress of our growing neuroscience focused pipeline after.
Ian Mortimer: For that I'll turn the call over to Chris who will share more details on our clinical development programs and then later Sherry will comment on the potential or is that your calendar and the bipolar depression treatment landscape and close with a summary of our financial results.
Ian Mortimer: Looking back at this past year I am proud of the numerous advancements across our pipeline, including the advancement of is that your calendar and our broad phase III epilepsy program. The launch of our phase III <unk> program considerable planning around further indication expansion or is that your calendar in bipolar depression and significant progress on our <unk>.
Ian Mortimer: February portfolio with several molecules across multiple targets poised to enter the clinic this year.
Ian Mortimer: 2024, it was a year of execution for xenon and the progress made across our business has positioned us well to deliver on our three key strategic priorities.
Ian Mortimer: One driving towards phase III data NDA submission and commercializing the use or is that your calendar and focal onset seizures in the U S number two broadening that to counter opportunity across additional epilepsy, and neuropsychiatric indications and number three expanding our product portfolio.
Ian Mortimer: Through advancement of our promising early stage ion channel programs.
We believe <unk> leadership in the <unk> seven landscape is unmatched and.
Ian Mortimer: And our lead asset is that your calendar is the only <unk> seven opener in development backed by long term efficacy and safety data from clinical studies of patients living with epilepsy.
Ian Mortimer: We now have amassed over 700 patient years of exposure in focal epilepsy patients.
Ian Mortimer: There remains a substantial need for new efficacious, and well tolerated epilepsy therapies, especially for those patients who continued to experience the debilitating impacts of focal seizures.
Ian Mortimer: Even while taking multiple anti seizure medications.
Ian Mortimer: Based on the significant body of compelling clinical evidence that we have generated to date.
Ian Mortimer: Long with us at your calendars other important attributes such as once daily dosing without the need for titration, a rapid onset of effect novel mechanism of action and potential move benefit we believe that as that two calendar represents a potentially best in class anti seizure medication that could be paradigm shifting in the <unk>.
Ian Mortimer: Future treatment of epilepsy.
Ian Mortimer: As we near the completion of our first phase III epilepsy, readout, which will enable the completion of an anticipated NDA filing we are excited about the potential for xenon as first commercial launch.
Ian Mortimer: Over the last 12 months they have culminated in a strong presence at the American epilepsy Society meeting or Aes, which took place in December. This is mark key medical Congress in epilepsy that hosted over 6000 attendees and we were able to present, new long term is that to calendar data from our ongoing <unk>.
Ian Mortimer: <unk> open label extension study showing a sustained monthly reduction in seizure frequency impressive seizure freedom rates in patients with epilepsy and improved quality of life measures.
Ian Mortimer: <unk> has led some of the latest surveys and research to understand in more detail the high burden of illness within the epilepsy community and Aes provided us with an opportunity to highlight some of these findings around the mental health burden and comorbidities of epilepsy.
Ian Mortimer: We believe that in an enhanced understanding of the burdens of focal onset seizures and the association between these comorbidities, particularly mental health Comorbidities like depression may enable better treatment options and help in improving patient outcomes, Chris will provide more detail about our aes data presentations.
Ian Mortimer: And activities in his prepared remarks.
Ian Mortimer: Within our phase III <unk> program, we are pleased to be enrolling patients in our <unk> study and we expect that the second of three planned studies <unk> three will initiate around mid year.
Ian Mortimer: Further we are in an incredibly fortunate position in that is that your calendars attributes may enable significant utility beyond epilepsy, and we believe that as that two calendar has broad potential and neuropsychiatric indications.
Ian Mortimer: Supported by strong scientific rationale today, we announced our plans to initiate a registrational program studying the use of the venture calendar in bipolar depression.
Speaker Change: Both Chris and Sherry will provide further details on the current unmet patient needs and market research that supported our decision to pursue this new neuropsychiatric program.
Speaker Change: This is an exciting opportunity for us at your calendar with the launch of this new program is that true or is that too calendar will be in registrational trials across four distinct epilepsy, and neuropsychiatric indications truly a pipeline in a product opportunity.
Speaker Change: We also continue to expand our pipeline by leveraging our extensive discovery knowledge and expertise in developing and potassium and sodium channel therapeutics. This past year, we made significant progress within our early stage portfolio progressing multiple drug candidates targeting <unk>, seven and NAV, one seven into India.
Speaker Change: <unk> studies.
Speaker Change: Recognizing the broad the potential broad applicability of the <unk> session kv seven mechanism of is that your calendar. We have identified multiple chemically diverse <unk> seven development candidates and we believe that this mechanism may have utility in a broad range of therapeutic indication.
Speaker Change: Indications, including seizure disorders pain, as well as neuropsychiatric disorders, such as <unk> in bipolar depression.
Speaker Change: Further I'm incredibly excited that we continue to make meaningful progress within our NAV one seven sodium channel program, our pioneering work around the NAV. One seven target has formed a core part of xenon as heritage given its important as the pain related target was strong human genetic validation, we believe NAV one.
Speaker Change: Seven could represent a new class of medicines without the limitations of opioids. We are now in a position where we expect multiple regulatory filings in 2025 coming out of our early stage portfolio to support the initiation of first in human trials across multiple targets.
Speaker Change: We also expect our lead candidate within our NAV. One one program will enter IND, enabling studies. This year, we presented some of our preclinical findings at Aes. This past December.
Speaker Change: Briefly these results showed that dosing with an orally available small molecule CNS penetrant highly selective NAV, one one potentiate or suppressed induced seizures and improved motor performance supporting the potential for improvements and drive a patient motor function.
Speaker Change: Further in these animal models chronic dosing in suppress spontaneous seizures protected against sudden unexpected death in epilepsy or <unk>.
Speaker Change: Increased long term potentiation of potential cellular correlate of learning and memory. These preclinical data are incredibly exciting and suggests that targeting NAV one one could potentially address the underlying cause symptoms of drive a syndrome.
Speaker Change: Later this year, we are planning to host an investor webinar to showcase various xenon early stage programs, including deeper dives into the mechanism underlying human genetics preclinical and other supporting data generated today as well as an overview of the unmet medical needs and commercial opportunity and more details to come at it.
Later dates.
Speaker Change: Finally, we're pleased to confirm that as part of our collaboration with Neurocrine Biosciences, a promising selective inhibitor of sodium channels NAV, one two and Nab won six there was discovered in xenon as labs has progressed into a phase one study and this triggered a milestone payment to us. This important achievement is a testament to our world.
Speaker Change: Discovery team and a direct result of zero on the deep expertise and pioneering work in the sodium channel space with our research work contributing to the discovery of new molecules and a further understanding of how mutations in the genes that encode for both NAV, one two and one six cause irregular neuronal activity.
Speaker Change: <unk> associated with several forms of epilepsy.
Speaker Change: Neurocrine has guided that this first in human study will evaluate the safety Tolerability pharmacokinetics and pharmacodynamics of investigational compound MDI 90, 21355 in healthy adult participants to support its development for the potential treatment of certain types of epilepsy.
Speaker Change: Looking ahead, we expect the next 12 to 24 months will represent a catalyst rich period for xenon as we continue to advance our deep and expanding pipeline of promising late and early stage programs. We anticipate a number of important milestones. Most importantly, the first phase III topline.
Speaker Change: Top line readout of is that two calendar and focal onset seizures expected in the second half of 2025, representing a major inflection point for xenon as we evolve from a clinical to commercial stage organization. This is an incredibly exciting time at <unk> and I look forward to keeping you updated on our progress. So I'll now turn the call over to.
Speaker Change: <unk> to provide some additional detail around our development programs.
Speaker Change: Yes.
Speaker Change: Okay. Thanks, a lot and I appreciate it to build on your comments it was inspiring for the team to connect with a broad range of health care providers advocacy groups and patients at Aes, where awareness of xenon is two calendar has grown since we first presented X tole data in 2021 and.
Speaker Change: In addition to our five peer reviewed presentations, we hosted a well attended scientific exhibit and expanded our presence within the exhibit hall.
Speaker Change: This year at Aes, we also focused on the mental health burdens associated with epilepsy at our mental health Oasis Booth.
Speaker Change: Where the team engaged in meaningful discussions about the under detected and Undertreated depression symptoms associated with epilepsy and.
Speaker Change: In our discussions with healthcare providers they directly witness this high burden of illness within the epilepsy community and support our goal to better understand the mental health Comorbidities of focal onset seizures like depression in order to offer more personalized treatments and improve patient outcomes. The patient reported served.
Speaker Change: Hey data that we collected further illustrates the substantial burden of illness for people living with epilepsy with reduced quality of life high seizure frequency and fatigue as well as well as other comorbidities such as anxiety and depression further underscoring the need for new treatments to help people living with epilepsy.
Speaker Change: Now the momentum from Aes has carried through into the new year and I'm pleased to report that our clinical development programs for two calendar continue to progress as planned.
Speaker Change: Our late stage epilepsy program includes our phase III, <unk> studies, and focal onset seizures or force and our exact study in primary generalized tonic clonic seizures as Ian noted we are anticipating the first fast topline data readout in the second half of this year, which combined with the existing data package.
Speaker Change: From our X tole clinical trial and additional supporting safety data, we expect will support our NDA filing for <unk>.
Speaker Change: In parallel with the considerable progress made across our phase III is that through calendar clinical development programs. Our medical affairs team continues to engage with the broader medical community to highlight the robust scientific evidence generated to date, we are in an enviable position as not only can we showcase the positive results from our completed ex.
Speaker Change: Total clinical trial, but we have our ongoing seven year open label extension study, providing further long term data from patients living with epilepsy, which we believe is a key differentiator from other molecules currently in development.
Speaker Change: The most recent interim data from the ongoing X Tole open label extension study presented at the American Epilepsy Society shows impressive sustained monthly reduction in seizure frequency approximately 85% at month 36, while importantly, maintaining a consistent safety profile that suggest.
Speaker Change: <unk> is at two calendar continues to be generally well tolerated.
Speaker Change: Additionally, approximately one in three patients on <unk> to calendar for at least 36 months achieved 100% seizure reduction where seizure freedom.
Speaker Change: For a period of one year or longer, giving both us and the epilepsy community tremendous confidence and is that two calendar has potential to address the significant need for new anti seizure medications.
These data are particularly impressive given that the literature supports the likelihood of achieving seizure control. Once a patient has failed three anti seizure medications is less than 5%.
Speaker Change: This is a meaningful metric for epilepsy colleges, who tell us that seizure freedom translates directly into improved quality of life for people living with epilepsy.
Speaker Change: Turning now to our clinical programs outside of epilepsy over the last year, we've been exploring the applicability of <unk> to calendar and additional potential neuropsychiatric disorders based on scientific rationale unmet medical needs and strategic fit for xenon.
Speaker Change: Today as Ian mentioned, we are outlining our plans for a phase III program in bipolar depression with the goal of initiating the first of two is that two calendar of clinical studies and bipolar one and bipolar depression by midyear.
Speaker Change: Briefly bipolar disorder as a psychiatric condition characterized by mania or hypomania and depressive episodes that can severely impact a person's quality of life.
As of 2019, approximately 40 million people worldwide were affected by bipolar disorder in the U S. It is estimated that bipolar disorder affects nearly 6 million adults or about two 6% of the U S population.
Speaker Change: Of note on average patients diagnosed with bipolar disorder spend three times as many days with depressive symptoms than with manic or hypomanic symptoms.
Speaker Change: The severity of depressive symptoms has been associated with functional impairment reduced quality of life and a higher prevalence of suicide effective treatments for depression and bipolar disorder are limited and many patients are not adherent due to in Tolerability and side effects polypharmacy is common in the treatment of bipolar depression.
Speaker Change: And there remains a significant unmet medical need for safe and effective therapies to treat patients with bipolar depression.
Speaker Change: Our expansion into bipolar depression is based on strong scientific rationale from preclinical data showing an anti depressant effect or is that to counter genetic links between bipolar disorder and KD seven evidence of <unk>, seven downregulation and bipolar disorder as well as clinical stuff.
Speaker Change: He has that explored the use of <unk> seven potential leaders in depression.
Speaker Change: Considering the treatment landscape.
Speaker Change: For PPD is that two calendars novel selective kv seven mechanism of action potential benefit on anhedonia rapid onset of effect and favorable tolerability profile are particularly attractive and bpd further we believe that as that two counters current safety profile could represent.
Speaker Change: <unk> over commonly used drugs used to treat bipolar depression, such as atypical anti psychotics lithium or valproate acid and lamotrigine, given our MDT study, where no study subjects experienced notable adverse effects on sexual function or weak.
Speaker Change: We look forward to providing more details around the bpd registration program. Once our first trial is initiated mid year.
Speaker Change: Sure.
Speaker Change: Later in this call sure. He is going to review some of the learnings from market research with prescribing physicians that further support our expansion into BPC.
Speaker Change: Turning now to our MDT program I wanted to highlight that ex Nova to the first of three planned phase III clinical trials evaluating is that two calendar in patients with M. D. D is currently enrolling patients in the next study <unk> three is expected to initiate mid year, we continue to engage with physicians who treat patients.
Speaker Change: With M D D to educate them about our ongoing clinical studies and the potentially differentiated profile of <unk> to calendar versus standard of care agents.
Speaker Change: Of note physicians are interested in is that two calendars novel selective kv seven mechanism of action and its potential benefit on anhedonia rapid onset of effect as well as potentially favorable tolerability profile with data supporting no notable adverse effects on sexual function or weekend.
Speaker Change: Yeah.
Speaker Change: We have the additional benefit of being able to reference not only the phase II <unk> the efficacy data, but also the long term tolerability data gathered from our ongoing X Tole open label extension study.
Speaker Change: Staying within M. D D patient enrollment is now complete in the phase two proof of concept study or is that too calendar and MDT led by the Icahn School of medicine at Mount Sinai and Baylor College of Medicine topline results from that study are anticipated in the first half of 2025.
Speaker Change: Looking ahead, we have a number of near term opportunities to highlight is at two calendar and engage in scientific exchange at upcoming medical Congresses, including the American Society for experimental narrow therapeutics ascend.
Speaker Change: And the American Academy of Neurology.
Speaker Change: Taking place in the first half of this year.
Speaker Change: Look forward to updating you on our efforts during our next call as we continue to build upon the foundation of strong is that two calendar clinical results amass a growing amount of supportive data from the ongoing open label extension fast study and drive towards a phase III readout. Later this year, we believe that as that two calendar provides the promise of a.
Speaker Change: Much needed anti seizure medication to people currently living with the burdens of epilepsy.
Speaker Change: I'd like to turn the call over to Sherry now who will begin by providing some additional detail around our bipolar disorder market research before summarizing our financial results surety.
Sherry: Thanks, So much Chris building upon strong mechanistic clinical and genetic rationale for our expansion and does that to counter into bipolar disorder depression, we have enhanced our understanding of the current unmet medical need based in part on our own primary research with U S based prescribing psychiatrists.
Sherry: Similar to our approach when assessing the potential opportunities in epilepsy and M. D. D. We believe that market research as an integral part of our planning process to better inform our clinical development and commercial plans.
Sherry: They surveyed high volume prescribing psychiatrist and key opinion leaders and then you asked to test a product profile that could counter that was reflective of our clinical findings to date.
Sherry: Similar to our epilepsy and MPD research physicians were interested in a drug profile that included attribute such as once daily dosing with no titration. In addition, many of the attributes of it that to counter that are attractive and MDT. We're also viewed as favorable and bpd, including physicians are interested in new agents with novel Matt.
Sherry: And in terms of action, especially given current unmet need at those patients who have already failed.
Sherry: Got it.
Sherry: Physicians are out there looking for new therapeutics that do not have the liabilities that commonly used agents such as sexual dysfunction and significant weight gain.
Sherry: There is also a keen interest in products that have the potential to deliver rapid relief of symptoms given the delayed therapeutic response with the current standard of care and lastly, physicians also identified the ability to address and <unk>, a common comorbidity of both Andy and bpd as another potential differentiator.
Sherry: In summary is that your calendars novel mechanism of action safety profile and potential benefit on <unk> identified a key strength and support of <unk>.
Sherry: File that compares favorably against the latest generation of antipsychotic and could support a compelling product set in the future be PD treatment landscape.
Sherry: We're incredibly excited by the potential of this actually counter and it's kv seven mechanism as we pursue multiple streams at late stage clinical development and key epilepsy and neuropsychiatric indications.
Sherry: Now I'll briefly turn at our fourth quarter and full year results for 2024.
Sherry: We had cash and cash equivalents and marketable securities of $754 4 million compared to $930 9 million as of December 31, 2023 based on our current operating plan, which included the completion of the is that to counter phase III epilepsy studies and supporting late stage clinical.
Sherry: Development is that to counter and both MDT and be PD, we anticipate having sufficient cash to fund operations into 2027.
Sherry: Given our proven track record of strong fiscal management <unk> is in a fortunate position of having a strong balance sheet to support multiple registrational programs or is that to counter and the continued maturation of our early stage pipeline I would refer you to our news release and 10-K report filed today for further details around our financials.
Sherry: Results.
Ian Mortimer: Before turning the call back over to Ian for concluding comments.
Speaker Change: I wanted to take a moment to reflect on the news in today's press release that I intend to step down as CFO later this year.
Speaker Change: This was not an easy decision it is solely for personal reasons and for the benefit of my family.
Speaker Change: Remain in place the CFO through to June 30, and I am committed to ensuring there's a smooth transition. It has been an honor to serve in this position and I am proud of what we've accomplished over my 10 plus years with the company with multiple phase III programs underway for our lead program, an exciting preclinical pipeline of assets in our balance.
<unk> that supports the continued advancement of these programs I am confident that <unk> is positioned for success.
Speaker Change: Dan.
Speaker Change: Thank you Sherry as many of you on the call know Sherri has made invaluable contributions to our organization over the last decade and was instrumental in helping build xenon as we evolved from a drug discovery organization to what is now a late stage clinical organization ready for our first potential drug approval and launch <unk>.
Speaker Change: Not only was Sherry key in our capital raises over the years, but she has been instrumental in the growth of our organization working to build out specific functions and systems for clinical development and then in the anticipation of commercialization.
Speaker Change: This is Jerry did not take this decision lightly and I'm grateful for her commitment to a smooth transition and multi month lead time as we search for her successor.
Speaker Change: Jerry on behalf of the board and our entire xenon team I want to sincerely. Thank you for all of your significant contributions I know, we will continue to successfully collaborate through this transition period and we wish you all the best as you embark on your next chapter.
Speaker Change: As we drive towards the significant first data readout from our phase III epilepsy program that is expected in the second half of this year. We are entering a truly transformational period for our company since positive results from our phase III program could enable the submission of our NDA with the goal of advancing is that you.
Speaker Change: Counter towards commercialization by the second half of this year, we plan to have two of three planned X Novo trials and MDT underway as well as a registrational study in Bpd initiated we are also anticipating top line results from the investigator sponsored phase II study in <unk> in the first half of this year.
Speaker Change: In addition, the continued maturity of our early stage pipeline could result in multiple IMD or equivalents in 2025 with the goal of initiating first in human trials across multiple targets consistent with our goal to be a premier fully integrated neuroscience focused company.
Speaker Change: To everyone, who has been with US on this journey. We appreciate your support and we hope you join in our excitement as we take these important steps forward that brings us closer to delivering is that your calendar to people living with epilepsy. So with that we can now open the call up for your questions operator over to you.
Speaker Change: Thank you.
Speaker Change: We'll now begin the question and answer session dialed in I would like to ask a question. Please press star one on your telephone keypad to raise your hand and joined the queue. If you would like to withdraw your question simply press Star one again.
Speaker Change: Okay.
Paul <unk>: Our first question comes from the line of Paul <unk> from Stifel.
Go ahead.
Paul <unk>: Hey, Thanks for taking my questions and Sherry sorry, two key xenon wishing you all the best.
Speaker Change: A couple of quick questions from me one as it relates to the first phase III in epilepsy I was wondering if you can share anything more on just how close you are in a full enrollment.
Speaker Change: Is it still realistic that data could come in <unk> or does it look more like 14, now and then on bipolar.
Speaker Change: As you guys move full steam ahead here how are you interpreting the results from other KD seven Readouts this year.
Speaker Change: Those data were negative would that impact your enthusiasm at all thank you.
Speaker Change: Thanks, Paul.
I'll take the first one and maybe make a couple.
Speaker Change: Couple of comments on <unk> seven in bipolar depression and.
Speaker Change: And then Chris definitely provide your perspective on the scientific rationale.
Speaker Change: Paul we're comfortable with the guidance that we have right now which is phase III epilepsy data in the second half of the year that Hasnt changed as we got closer we will narrow that so we're not there today, but we will we'll narrow that guidance as we get closer to the second half of the year.
Speaker Change: In terms of bipolar depression, I think youre, referring to there is a competitive company that's doing the cave seven in bipolar Mania, we think bipolar depression is the.
Speaker Change: As stronger scientific rationale mechanistic rationale some of the genetic data.
Speaker Change: Thats in the literature as well so our focus is on bipolar depression in terms of the expansion or is that to your calendar outside of epilepsy, and MTBE. So nothing's going to change kind of our confidence in going into bipolar depression and the work that we want to do there and maybe Chris you can just provide your perspective on moving into <unk>.
Speaker Change: <unk> as well.
Chris: Yeah happy to do so and thanks.
Speaker Change: Yeah, Hey, Paul So I mean, if you take a look at the attributes of this drug that are appealing for depression, they're very similar for bipolar that's the unique mechanism of action the improvement and anhedonia.
Speaker Change: The rapidity of onset and the Tolerability and if you think about the landscape of opportunities for patients for pharmacologic treatment in depression relative to bipolar theres quite a bit more there. So the competitive landscape is as anemic in bipolar relative to two.
Speaker Change: To <unk>. So I think all of that there is clearly an unmet need there as far as.
Speaker Change: You know the rationale I think that you know.
Speaker Change: The reason why <unk> made the most sense is because there was clinical data already gathered and so that's where we started if you take a look at the the genetic work. That's been done. There is there is just as strong or actually I would argue even maybe a stronger association between the genetics of Casey in Q2, and Casey in Q3, which are the genes that encode.
Speaker Change: And code for <unk>, 7.2, and $7, three which is what our drug targets and I would argue that that association appears to be even stronger in bipolar.
Speaker Change: And M. D. D. So we're pretty interested I think there's a really strong rationale across the board for going forward into bipolar when I look at the difference between mania versus depression. In these patients. There is an open label extension study that was done with another kv seven drugs, where I felt that.
Speaker Change: The results we felt that the results were pretty lukewarm in terms of its improvement of mania. So I think that the story for depression and bipolar is far more compelling than the story in mania. So suffice it to say that whatever I mean, obviously, we're quite interested in what those results will be in terms of the <unk>.
Speaker Change: <unk> study that should read out imminently with.
Speaker Change: With the other cave seven compound, but it's not going to change our plans.
Speaker Change: Thanks, so much for the thoughts.
Speaker Change: Okay.
Speaker Change: Our next question comes from the liner Tess Romero from JP Morgan.
Speaker Change: Okay.
Caroline Poacher: Hi team. This is Caroline poacher for Tessa Romero with Jpmorgan, thanks for taking our questions.
Speaker Change: Just a couple from us so just a quick housekeeping question, but can you just clarify that enrollment and ex told two is not yet complete.
Speaker Change: And then on bipolar depression can you just provide any additional insight into the design of the phase threes that you intend to initiate in terms of patient population and endpoints you might assess thank you.
Speaker Change: Sure Yeah, Caroline I can take both of those so the first one.
Speaker Change: Our guidance right now, we're just committed to talking about top line data in the second half of the year. So we haven't specifically commented on the completion of enrollment both the completion of enrollment and narrowing of the guidance, we will do as the year progresses.
Speaker Change: Specifically on bipolar depression more details to come so we're committed to this is going to be a registration.
Graham: Graham So a phase III study in bipolar depression, but the real details of trial design.
Graham: We'll be disclosing that in subsequent quarters as we move forward I mean, we've made great progress in terms of planning the study.
Graham: Interacting with regulators choosing <unk> as like a lot of the work that we need to do you expect where we would be to get the study initiated by mid year, but just hold off on some of the details in terms of trial design.
Graham: And endpoints and some of the statistics more to come on that in the coming quarters.
Graham: And can I just build I just wanted to build on one thing because I want to make sure that it's clear in the prepared remarks, we talked about the first of two studies beginning middle of the year and bipolar which is accurate and we also talk about <unk>.
Speaker Change: Containing both patients with bipolar one and bipolar too and I just want to be clear that that's a combination boat. Both studies will have a combination of bipolar one and bipolar two we're not doing one study in bipolar one and one and bipolar two I just want to make sure there wasn't anything confusing about the prepared remarks Tessa.
Tessa: Okay. Thanks, Kevin Thank you.
Speaker Change: Got it.
Speaker Change: Our next question comes from Andrew Tsai with Jefferies.
Matt: Hello. This is Matt <unk> on for Andrew first of all congrats Jerry on your time at Xenon and our team wishes you the best.
Speaker Change: For the phase III focal adult epilepsy study.
Speaker Change: Can you just talk a little bit about what the minimum ethics efficacy threshold is for us to counter that you wanted to see if we're best in class.
Speaker Change: In your view and then also for the Phase two study for about nine days and MDT, how granular of a dataset can we expect to see on.
Speaker Change: The secondary measures like Madras J D shops et cetera.
And can you.
Speaker Change: Can we expect to see efficacy kinetics, there as well.
Speaker Change: Thanks, Matt Yeah, I'm happy to go first and then Chris if you have things to add as well.
Speaker Change: The first question just on what is success luck in the phase III epilepsy program, maybe you could take a step back.
Speaker Change: No. We haven't reviewed the details of the phase III <unk> program and some time, obviously, we focused a lot on the open label extension, but when we look we often think about really is that your calendar and focal onset seizures really from a pretty broad lens, meaning we've talked about the novel mechanism.
Speaker Change: No titration, the rapidity of onset from the X Tole study in the short term it was the best placebo.
So just a placebo adjusted efficacy ever seen in our focal onset seizures study in a very severe or refractory patient population and then we've talked a little bit today in it. He asked about some of the long term efficacy and safety as well and we're feeling really comfortable about so what we know today is I think an incredible profile and that's why we've talked about this.
Speaker Change: As potentially being really paradigm shifting in terms of bringing a new therapy forward.
Patients that are still suffering suffering with seizures.
Speaker Change: In terms of the phase III program for later this year.
Speaker Change: We're looking for a successful study to be able to file an NDA.
Speaker Change: And be able to have this drug available more broadly to patients and so I would say the bar really is to show statistical significance to support our plans going forward.
As we get deeper when we unblinded the data we get deeper into the data than I think we can talk about it more broadly, but I would say given everything we know about the molecule and the mechanism and the long term data in short term data that we've generated to date, it's really about statistical significance on our path forward is the most important thing from the phase III study.
Speaker Change: In terms of the phase two ISG MDT Mount Sinai study your question there yes.
Yes, we're working closely with the <unk> from Mount Sinai and Baylor as Chris mentioned in his prepared remarks.
Speaker Change: The study is complete in terms of patient enrollment.
Speaker Change: And that study is still.
Speaker Change: And it needs to be on in terms of all the data analysis, we would expect when we're able to provide data publicly that we would have those key secondary endpoints that you've mentioned in terms of the clinical scales of depression and Antonia as measured in that study by Madras and shops, obviously the primary endpoint is a functional endpoints.
Speaker Change: A functional MRI endpoints, so that would be available as well, but we are working closely with Mount Sinai in terms of a communication strategy to provide all of the information that you've suggested in terms of providing that publicly in the first half of this year, Chris anything that I missed that you wanted to add to.
Chris: No you covered it thanks Ian.
Speaker Change: Okay. Thank you.
Speaker Change: Thanks for the question.
Speaker Change: Our next question comes from Brian Abrahams from RBC capital markets.
Speaker Change: Hi, everyone. This is nevin on for Brian Thanks for taking our questions and Sherry just wanted to extend our best.
Speaker Change: Do you on your next steps as well.
Speaker Change: So just a couple of questions from me I guess, how are you guys seeing exculpatory doing on the ground and based on its current uptake.
Speaker Change: Can you tell us a little bit about how acuity seven might fit into the treatment paradigm in and relative to your kind of the sales that youre seeing with exco price since launch and other competitors.
Speaker Change: Like <unk>.
Speaker Change: How do you kind of seed sales for is it calendar or relative to them on its potential launch.
Speaker Change: Do you see this as a potential comp for the initial launch or are.
Speaker Change: Or are there reasons to think that it could be.
Speaker Change: Even better.
Speaker Change: Okay, great. Thanks, Kevin Good question, Sharon can start just with some of the commercial dynamics and what we're seeing for Mexico brand. What we're hearing and then Chris and I can add in any perspective I think.
Speaker Change: Kind of core to your question is how do we believe is that the calendar is going to differentiate.
Speaker Change: From the branded medicines that are both currently available as well as how the branded medicines have done historically.
Speaker Change: So just a little bit about ex corporate I mean, I think you know their year end results were interesting and Q4.
Speaker Change: <unk> had strong results in 2024 sales exceeded the upper end of the guidance.
Speaker Change: I'm sure. Most of you are aware so they they ended up closing the year north of $320 million, which was a 60% growth over 2023, and really great given the profile of that drug.
Speaker Change: For 2025 guidance as strong as well.
Speaker Change: They provided a range of Ah.
Speaker Change: Sort of the mid four hundreds and so it does seem like they are on track to hit our longer term goal of reaching a billion in sales before the end of the decade.
Speaker Change: Which I think really tells us that there is an unmet medical need and in this space and there's a commercial opportunity for a drug that provides a better profile than what is currently available on the market. I mean, we do know ex co create of course has some liabilities associated with that.
Speaker Change: Drive does have to be titrated slowly over many many weeks.
Speaker Change: In order to manage a severe but rare risks of drug allergy.
Speaker Change: And for.
Speaker Change: For that reason I think has been a little bit slower at launch in combination with the fact that the drug was launched during the pandemic.
Speaker Change: And given that profile I think with a little bit challenging for physicians.
Speaker Change: In light of just some of the challenges with the pandemic our perspective as you look at the profile or is that your calendar and of course, we've talked a lot about the novel mechanism. The rapidity of onset the lack of titration, the tolerable safety profile and the potential benefit on mood as you bring that all together and we look at it.
Speaker Change: Cross every aspect of the drug we really feel that it sits above above others and as we look forward to the dynamics when is that to counter will launch we will be likely the only branded agents with ex co pay and so we feel very strongly that given the profile.
Speaker Change: We've described that to counter should really be the first branded drug of choice. So we would expect that as patients cycle through one extra generics that they would then be eligible for that to counter and that physicians would reach for us that to counter and in those situations.
Speaker Change: And maybe thanks, Jerry I think that's an excellent overview, maybe just to add and zoom out a little bit Ucb's <unk> results out. This morning, those were very strong in terms of growth as well.
Speaker Change: And then if we kind of really look back theres been some incredibly important.
Speaker Change: Seizure medicines over the years, including Capra, and Lamictal and Vimpat and as Sherry mentioned, if we kind of think about the profile or is that your calendar.
Speaker Change: The profile of all of those drugs I think we have tremendous confidence in what the commercial opportunity is for us at your calendar and epilepsy.
Chris: Chris anything to add from your perspective.
Speaker Change: Well, maybe just a couple of things.
Speaker Change: Obviously as exco pre is doing pretty well it has a really good reputation as being robustly efficacious.
Speaker Change: You take a look at the seizure freedom data that they frequently talk about it's usually at a dose 400 milligrams, a day, which isn't really use that much when when you take a look at our seizure freedom data that we're talking about in our open label extension study those patients are on 20 milligrams.
Speaker Change: So in our go to dose in phase three is 25 milligram. So it's in the range of a dose that we expect to be used down the road.
Speaker Change: Sure. He made a comment to the allergic reaction. We haven't had any cases of dress. So I think that you know we have more to learn about this drug and to get it approved based upon the data. So far I think we stack up pretty well from a seizure.
Speaker Change: Seizure freedom perspective, we don't have the titration, which Sheri mentioned, we havent had dress and then there's the potential for it to take care of the the mood issues, which I think is one of the.
Speaker Change: The advantages that is after counter really provides to the armamentarium for uplift hologic.
Speaker Change: Great. Thank you so much thanks, Chris.
Speaker Change: Youre welcome.
Speaker Change: Our next question comes from the line, Brian It's corny greener.
Brian Abrahams: Hey, good afternoon, guys. Thanks for taking my question. Charlie also let me Express my my Gratefulness for all the work you've done.
Speaker Change: Wish you the best in the future.
Speaker Change: So there's just another sodium channel modulator approved for acute pain and I always talk about the merits of NAV, one seven versus NAV, one eight but as we kind of get drawn at the end of each.
John: Hey, John.
Speaker Change: Start looking forward to.
Speaker Change: Proof of concept.
Speaker Change: Wondering.
Speaker Change: Where are you currently thinking kind of the initial indication target would be like what's the quickest way to kind of determine.
How you are now at 1.7 modulator might.
Speaker Change: Might address pain indications is in sort of like post operative pain setting has it been sort of.
Speaker Change: More more chronic setting and pain studies are generally done both against placebo and active control.
Speaker Change: With this approval would you look to actually.
Speaker Change: Use that as an active comparator in that study.
Speaker Change: Yeah.
Speaker Change: Thanks, Brian I think some some really important questions. There that we talk a lot about internally and we haven't quite.
Speaker Change: Come to final decisions on many of them, maybe I'll make a couple of comments, though.
I think later this year, we want to do an investor call.
Speaker Change: Like a webinar or many kind of R&D day, where we're going to be able to share a lot more data with you. So I think it will be nice to be able to kind of have a more holistic view of the program and why we think we really liked the NAV one seven target and why we think our chemistries have addressed some of the challenge.
Speaker Change: Historically.
Speaker Change: Early on we're thinking about obviously, a traditional phase one study and then quite traditional on the phase II proof of concept study so things like <unk>.
Speaker Change: Monday, inactivate or Domino class eight I think longer term is really where your question is theres nothing specific either in the genetics.
Speaker Change: Or any of the data that we've generated pre clinically that suggests that this should only work.
Speaker Change: And kind of post operative acute or has the opportunity to work in the chronic setting. So as we think about it today I think all of those options are on the table.
Speaker Change: And including you.
You asked a question around just how would we even design the proof of concept studies in terms of placebo or active control. We are working through all of that right now haven't made final decisions, but as we do we'll be able to communicate them publicly but are.
Speaker Change: I think many people know we've had a long experience on this target.
Speaker Change: And personally I'd really want to see as broad a development program as possible.
Speaker Change: We believe that we're seeing.
Speaker Change: Analgesia in a human and some of the early proof of concept studies, then I think there is an opportunity.
Speaker Change: To try and test the mechanism broadly.
Speaker Change: Alright, thank you.
Speaker Change: Yep.
Speaker Change: Our next question comes from the line of Jason Gere vary from Bank of America.
Speaker Change: Hey, good evening guys. Thanks for taking my questions and Sherry sorry to see you go but best of luck in future endeavors.
Speaker Change: So.
Speaker Change: I guess firstly.
Speaker Change: With the PPD program I know there's you're.
Speaker Change: You got a hold off on giving detailed I'm just curious if you plan on looking at this drug as an adjunct to lithium or valproate under the most recent.
Speaker Change: Approval in this space look at this both from a monotherapy and adjunctive basis.
Speaker Change: And then secondly, with the second Gen <unk> seven.
Speaker Change: Is the focus there gonna be novel indications or do you believe that the molecule may offer advantages over.
Speaker Change: As at the counter and that there can be opportunities for us.
Speaker Change: Follow on there.
Speaker Change: Yeah, Thanks, Jason Yeah on the first one.
Speaker Change: Details to come so in terms of.
Speaker Change: The trial design, and specifically mono versus the junk Devin just the sizing of the study and endpoints all of that will be in a position to disclose just in advance of.
Speaker Change: Of the initiation of that study around mid year.
Speaker Change: Your question on <unk> seven in terms of backup molecules, our nextgen molecules, yes, I think it's a really important one.
Speaker Change: What's really interesting about it is that your calendar when we just look at the profile does.
Speaker Change: Does that just gathering the data we've generated so far there isn't anything obvious that we're trying to solve for in the next generation of molecules. So.
Speaker Change: Although we have chemical diversity novel intellectual property all the things you would expect in a de novo kind of drug development drug discovery program and there is nothing specific that we're trying to solve for so many of these molecules. When we look at all of the attributes pretty clinically.
Speaker Change: In terms of choosing a candidate to move into toxicology studies a lot of them are going to look more like is that through calendar than not because I think we have real success, there and we want to build on that.
Speaker Change: In terms of where we would go therapeutically I think the answer is both.
Speaker Change: So we think we can fully answer the question on whether there is going to be differences between these nextgen molecules and is that your calendar until we run some human clinical developments I think some of these attributes and Differentiators Mei.
Speaker Change: May show up as we do human clinical development, we still think that we wanted to do continued work in Appalachia and Neuropsychiatry I also had mentioned in my prepared remarks.
Speaker Change: We like pain or the mechanism as well. So I think there is an opportunity to continue development of the mechanism in indications, where we have shown data with us that your calendar as well as broadening outside of us.
Got it thanks guys.
Speaker Change: Our next question comes from the line of ferrous scrap moved here.
Speaker Change: Hi, Thanks for taking my questions I, just wanted to add my thanks, and congratulations to Sherry.
Speaker Change: I have one quick clarifying question and then one additional.
Speaker Change: First understanding that the focus is on bipolar depression would you expect to see or could we see benefits on anemia as well or are you guys only looking at the question.
Speaker Change: And then secondly for the preclinical NAV one one program do you see this is a development opportunity in Dravet only or would you look to kind of position that for other types of epilepsy, and it's only in Germany. How do you see the treatment landscape evolving over the next three to four years.
Speaker Change: Okay.
Speaker Change: Thanks, Sir.
Speaker Change:
Speaker Change: I'm happy to Chris why don't I start.
Speaker Change: Start on the NAV one one question and then.
Speaker Change: And then if you want to address the bipolar depression Mania question.
Speaker Change: Yes.
Speaker Change: Our initial focus for our NAV, one one will be in drive a because the dravid children as you know our affluence assertion in the proteins. So they are 50% and have won one in word potentiate <unk>.
Speaker Change: And through the Wild type channel, we've shown I think an incredible preclinical data package that we were able to share at Aes a couple of months ago.
Speaker Change: We're in these drive animals weekend protections from spontaneous seizures, we can protect from suite app.
Speaker Change: And we can have an impact on long term potentiation. So I think we're and this is maybe a little bit to the core of your question I think where the field is going especially for a lot of these genetically identified Appalachia seasons, we need to get.
Speaker Change: Past seizure control into disease modification and I think there is an opportunity to do that both with the approach with an antisense oligonucleotide as well as our small molecule approach and so we're really excited I think to have an oral small molecule that you can do weight based dosing and titration I think it would be.
Speaker Change: Incredibly valuable for the field and for physicians and for their families. I mean, given the approach it does potentially have broader utility than just drive a syndrome.
Speaker Change: In other.
Speaker Change: In other forms of epilepsy and potentially there is some ideas even outside of epilepsy as well in the literature. So I would say our focus at least initially it will be on driving <unk> syndrome, but there may be an opportunity to broaden out as we move forward.
Speaker Change: Do you want to make a comment just on the bipolar question.
Speaker Change: Sure I'll make I'll make the comment from from two perspective. So if you you know our intention is to conduct a study in bipolar depression and in those studies the patients arent dramatic. So you can't really go into a study like that and expect to show that there's going to be any improvement in mania because.
Speaker Change: The patient shouldn't be exhibiting those symptoms at baseline you might follow Manny just to make sure that youre not exacerbating it but expecting a readout with media.
Speaker Change: With patients in that stage of the disease, which is with depressive symptoms isn't realistic and the flip side of that it is also true.
Speaker Change: For the <unk> study.
Speaker Change: That will be reading out soon with the other <unk> seven compound those patients come into the study with minimal depressive symptoms. So I think the module scores like 10 to 12, it's quite low so expecting a readout in that study with depressive symptoms I think is probably unlikely as well so it kind of coming from it from both angles, but.
Speaker Change: We're excited about them.
Speaker Change: I think that you know you look at the genetics, it's a pretty compelling story for bipolar. So we're excited about this this.
Speaker Change: This opportunity.
Speaker Change: Yeah.
Speaker Change: Great very helpful. Thank you.
Speaker Change: Our next question comes from the line of Flora Chico from Wedbush Securities. Please go ahead.
Speaker Change: And then on for Laurence Chico So for one for on is it your calendar.
Speaker Change: Launch what type of patients are most likely to be the early adopters.
Speaker Change: Be driven more by patients seeking better seizure control or coldness do more from patients who are experiencing mood disorders.
Speaker Change: Yes.
Speaker Change: Okay.
Speaker Change: I can start and then Chris. Please do you add your perspective, I mean, I think one.
Speaker Change: I think we need to see the totality of the package.
Speaker Change: They were generating in phase III to kind of better answer your question.
Speaker Change: And why I say that is obviously in the phase III.
Speaker Change: Onset seizure program, we're looking at the reduction in seizures the primary.
Speaker Change: Secondary endpoints of the study, but we also have exploratory endpoints on some of the comorbidities, including depression and anxiety.
Speaker Change: We're not powered for those and there arent entry criteria that it needs to be an impaired population coming in but we should have some indication of data in epilepsy patients with the psychiatric comorbidities. So I think that's going to be an interesting part of kind of the overall package, but we're.
Speaker Change: Definitely when we speak with Apple acknowledged in the epilepsy community and we talked about in our prepared remarks, I think we've done a lot in terms of.
Speaker Change: Survey work and really understanding the complete burden of illness for these patients not just the seizures, but a number of other things that are impacting their quality of life. So I think youre going to have patients that the patients that are still.
Speaker Change: Having breakthrough seizures.
Speaker Change: Are often looking for both.
Speaker Change: New medicines that will help on their seizure control, but also addressing some of the psychiatric comorbidities such as made.
Speaker Change: Prestige or provide your perspective as well.
Speaker Change: I mean, it's a great question I think it's challenging without without as you've said the phase III results without the final label and all of these things that we need to still work on in the coming months and so forth.
Speaker Change: The only thing I'll say is that one thing that we have learned about this field is the prescribing patterns are largely dictated by the prescribers and their perspective, rather than by the patients needs. So.
When you talked you asked about early adopters I think that would be just to make it clear that will certainly play a role, but it'll be more from a prescriber perspective.
Speaker Change: Of wanting to be an early adopter than probably the patient perspective.
Speaker Change: Thank you.
Speaker Change: Our next question comes from the line of Joseph.
Speaker Change: Hello.
Speaker Change: With TD count.
Speaker Change: Please go ahead.
Speaker Change: Hi, there good afternoon. Thank you for taking my question and adding my best wishes to tertiary maybe on the bipolar Depression study I saw that you are looking to launch two with M. D. D. Three planned phase III studies.
Speaker Change: I guess is there is there anything behind that decision is it a little bit easier to manage placebo response or anything in the bipolar depression.
Speaker Change: Population and then maybe jumping over to <unk> can you just comment a little bit of how enrollment is going there.
Speaker Change: Quite a bit of competition in the Sos, maybe not as much in PT Tcs I guess, what are you finding maybe easy or challenging winter willing that study. Thank you.
Speaker Change: Thanks, Joe.
Speaker Change: Yes, Chris why don't I am happy to take the second one and then you can provide your comments on <unk> as well and then you know.
Speaker Change: Our perspective on the bipolar versus M D D.
Speaker Change: Yes, I think when we when we've had these discussions.
Speaker Change: With with investors.
Speaker Change: We recognize that.
Speaker Change: Yes, Theres, probably more clinical studies youre right, Joe going on in focal onset seizures, but those patients are more prevalent and easier to recruit into a clinical study.
Speaker Change: And with the primary generalized tonic clonic seizure studies. These are often done post approval. So after the label in <unk>.
Speaker Change: And they can often take quite a number of years, if we use vimpat or ex co brand as an example.
We have taken multiple years to complete and there is a wide variety of I think reasons for that it's a lot less prevalent patient population, they're having fewer generally fewer seizures.
Speaker Change: But those seizures can be really significant.
Speaker Change: And have an impact.
Speaker Change: And due to that often physicians, one intervention immediately which would make.
Those patients are at least a subset of those patients not eligible for our clinical studies. So there are some challenges that are very specific to that therapeutic indication I think it's really important for the community for us to develop is that your calendar broadly we were the first company.
Speaker Change: First sponsor at least in our knowledge to commit to doing both Sos NPG Tcs preapproval and in parallel. So I think we're proud of that I think it's the right thing to do but we do know that the <unk> study will take longer and Chris.
Yes, so going back to the question about three studies and M D D and two in bipolar.
Speaker Change: <unk>.
Speaker Change: The reality so what we're hoping for is that by the time those bipolar studies rollout. We will have had two positive studies and M. D. D will be talking about an S. NDA for M. D D and so in that context, having one positive study or two positive studies in bipolar depression.
Speaker Change: Threshold to get the drug approved in that context will be.
Speaker Change: Somewhat lower particularly in the setting of the new FDA relatively new FDA guidance about the sufficiency potentially for a confirmatory study to be enough to yield and approve ability package.
Speaker Change: But for right now thank you very much human bipolar Youre welcome.
Speaker Change: Okay.
Speaker Change: Our next question comes from the line of Douglas Tsao from H C. Wainwright.
Douglas Tsao: Hi, good afternoon, thanks for taking the questions.
Speaker Change: First I just wanted to wish Gerry all the best.
Speaker Change: Joy working with us.
Douglas Tsao: You may need.
Douglas Tsao: Two things first I want to start with the point that you sort of briefly touched on in terms of the.
Douglas Tsao: Polk onset.
Douglas Tsao: Epilepsy study and the <unk>.
Douglas Tsao: Benefits for mood.
Douglas Tsao: Youre not powered for endpoints.
Douglas Tsao: For patients with mood disorders, but I'm just curious if you can provide some.
Douglas Tsao: E Mail a perspective about how.
Douglas Tsao: What endpoints there will be to help us.
Douglas Tsao: Characterized in group benefits for patients with <unk> and.
Douglas Tsao: Even though theyre not necessarily powered is there any chance.
Douglas Tsao: That perhaps some of them could end up on the label.
Douglas Tsao: And then the second sort of follow up question I did I just wanted.
Douglas Tsao: To touch on or get some perspective on just your R&D spend just given the significant acceleration in terms of your pipeline expansion, both with Azure to calendar <unk> in terms of new indications as well as additional molecules timeframe clinic. Thank you.
Douglas Tsao: Thanks, Doug IRA.
Douglas Tsao: We will split this up and.
Douglas Tsao: And just for the for the entire call. This is this will be the last question where.
Douglas Tsao: We're over time, but.
Douglas Tsao: But we'd be happy to follow up with everyone else later today and over the next few days.
Speaker Change: So yeah I'll make maybe a couple of comments, Chris and then if you can share kind of the patient reported outcomes on on the psychiatric comorbidities in the epilepsy program I think that'd be helpful. And then Sherry on.
Douglas Tsao: On the Opex side.
Speaker Change: So in terms of the label question, Doug I think it's just premature right I think we need to we need to see the data.
Douglas Tsao: It's premature to make a comment on whether this would be something.
Douglas Tsao: But we would publish oral would be something that we would have a discussion with our regulator on and just to be clear as I said that we weren't powered for these exploratory endpoints were also not stratify and so there may be some imbalances between the different groups as well and we're not exactly sure just how impaired.
Douglas Tsao: The population is and so what we will be looking at is there a sub population there that does have elevated depression or anxiety and being able to measure that and how theyre doing so that's kind of been our approach to it I think it's an important exploratory endpoint.
Douglas Tsao: But I just wanted to make sure that we're managing expectations west with the caveats and limitations that this is really driven as a registration study with seizure reduction as the critical endpoints.
Douglas Tsao: But Chris maybe you can just talk about how we're measuring.
Douglas Tsao: Those and then and then Sherry on the on the expense.
Douglas Tsao: Expense side.
Speaker Change: Sure happy to do it so within the phase III epilepsy program and every study at every visit for every patient we're evaluating both depression and anxiety.
Speaker Change: The anxiety is being assessed with the get seven skill and the depression is being assessed with the Beck depression inventory.
Speaker Change: So it will have a lot of data, but there are a number of caveats, which I think highlighted nicely shari.
Speaker Change: Yes, Doug on the Opex side. So I mean, one thing is we've we've reinforced our cash runway guidance into 2027, which is great of course, we've been thinking some time now about indication expansion and neuro psych. So that has been on our radar and factored into our model which is.
Speaker Change: Why our cash runway hasnt changed, but we are going to see a meaningful increase in particular on the R&D side and of course as you noted that it's because we are now we're going to have.
Speaker Change: Many phase III study is ongoing through 2025 and 2026 with the addition of bipolar disorder or depression.
Speaker Change: In addition to the fact that we now have our <unk> phase III program up and running with <unk> initiated at the end of last year and <unk> now got three starting mid this year. So that program is going to be in full swing in 2025, and continuing to incur expense over 2026.
Speaker Change: We are going to have our first phase III fos readout later this year, but there are going to continue to be cost across the epilepsy program because of course, we're going to have a second <unk> study ongoing as well as our exact study and the important open label work that we're doing both as part of the X Tole study as well as <unk>.
Speaker Change: Our open label for the Phase III epilepsy program. So all of that is factored within our runway.
Speaker Change: And then of course, we're making significant progress on the preclinical side and we're expecting multiple molecule to move into phase one this year and so we have factored those expenses and as well.
Speaker Change: And that'll that'll drive and an increase in 2025 and 2026.
Speaker Change: All that being said, we're comfortable with our cash runway position, we feel like we're in a really good place financially and have done a really nice job managing our capital with such a robust pipeline we will see.
Speaker Change: And an increase in G&A is while not as much as on the R&D side, and that's really driven by our continual expansion of our corporate functions to support the significant growth in the development side, but also to support prelaunch.
Speaker Change: But also to support pre commercial activities that we are embarking on in advance of what we expect to be the commercial launch or is that to counter Nf L.
Speaker Change: So I'll just wrap up the call now thank you everyone for joining us today I appreciate all the kind words about my departure.
Speaker Change: If we didn't get to your question as Ian noted, we will reach out to you directly to connect operator, you may now end the call.
Speaker Change: Yes. This concludes today's call. Thank you for joining you may now disconnect.
Speaker Change: [music].