Good day. Thank you for standing by, and welcome to today's Xenon Pharmaceuticals Reports First Quarter Results Call 2022. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during that session, you will need to press star one on your telephone keypad. If you require any further assistance, please press star zero. Thank you. I would now like to hand the conference over to your speaker today, Ms. Sherry Aulin, Chief Financial Officer of Xenon Pharmaceuticals. The floor is yours. Thank you. Good afternoon, everyone. Thank you for joining us on our call and webcast to discuss Xenon's first quarter 2022 financial and operating results. Joining me are Ian Mortimer, Xenon's President and Chief Executive Officer, Dr. Chris Kenney, Xenon's Chief Medical Officer, and Dr. Chris von Seggern, Xenon's Chief Commercial Officer. Please be advised that during this call we will make a number of statements that are forward-looking, including statements regarding our and our collaborators' development plans, anticipated regulatory interactions and submissions, anticipated results and release timelines, the potential efficacy, safety profile, addressable market, and commercial potential of our proprietary and partnered product candidates, the efficacy of our clinical trial designs and anticipated enrollment, the potential receipt of milestone payments and royalties from our collaborators, our expectation of having sufficient cash to fund operations into at least 2024, and the timing of potential release of future clinical data. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected on today's call. We undertake no obligation to publicly update any forward-looking statement. Today's press release summarizing Xenon's first quarter of 2022 financial results and the accompanying quarterly report on Form 10-Q will be made available under the investor section of our website at www.xenon-pharma.com and filed with the SEC and on SEDAR. Now I'd like to turn the call over to Ian. Thanks, Sherry. Good afternoon, everyone. Thanks for joining our call. Today, I will provide a high-level update on our proprietary pipeline programs, and then I'll turn the call over to Chris Kenney, who will provide additional color around the new developments and next steps within our XEN1101 program, including the newly initiated XEN1101 phase II clinical trial in major depressive disorder or MDD. Sherry will conclude our call by providing an update on our partnered programs and briefly summarizing our financial results and anticipated key milestone events ahead. Chris von Seggern is also on the call to provide his perspective during the Q&A session. Within our own proprietary pipeline, we continue to support our ongoing XEN496 phase III EPIC pediatric clinical trial, which is a randomized, double-blind, placebo-controlled parallel group clinical trial evaluating the efficacy, safety, and tolerability of XEN496 in approximately 40 pediatric patients aged 1 month to less than 6 years with KCNQ2-DEE. Based on published physician case studies with ezogabine and its Kv7 mechanism of action, we believe that XEN496 has the potential to address an important unmet medical need. We continue to receive encouraging feedback from clinicians, caregivers, and patient advocates on our XEN496 program, including most recently at the Pediatric Academic Societies conference in Denver. There is significant interest in the opportunity to provide a precision medicine which has the potential to positively impact the lives of these young patients. We continue to build momentum with new sites and jurisdictions coming on board, and we expect to complete the XEN496 EPIC phase III clinical trial in 2023. Turning now to our XEN1101 program. We have made significant progress advancing XEN1101 into a broad clinical development program in both epilepsy and depression. Building on our top-line phase IIb X-TOLE results in adult focal epilepsy from last fall, we continue to accrue compelling evidence from various subgroup analyses of the X-TOLE data and interim safety and efficacy data from the ongoing X-TOLE open-label extension study or OLE. Most recently at ASCENT 2022, the annual meeting hosted by the American Society for Experimental Neurotherapeutics, we presented additional data showing that XEN1101 has demonstrated substantial efficacy in a difficult to treat patient population with even more impressive efficacy in subgroup analyses of patients with less severe disease. Later this year, we expect to be in a position to share additional XEN1101 X-TOLE data, both from additional subgroup analyses, including a time course to efficacy analysis, as well as data from the ongoing X-TOLE OLE. As we analyze additional XEN1101 data, our confidence continues to grow based on robust, compelling, and consistent data across seizure reduction endpoints and subgroups and in the OLE, indicating that XEN1101 could play a key role in treating adult patients with focal epilepsy. We are excited to be able to share additional data augmenting the already impressive profile of XEN1101. In addition to its robust efficacy, the tolerability profile of XEN1101 is consistent with an active CNS drug, and its AE profile is in line with other anti-seizure medications. XEN1101 also presents other differentiating attributes, including its only-in-class potassium channel mechanism and a dosing regimen of one pill once a day with no titration required. Our team is excited to continue to advance this program and has made considerable progress over the last quarter. We have finalized the proposed trial designs for our two phase III clinical trials, along with completing CRO vendor selection. Our end of phase II meeting with the US FDA taking place this quarter also marks an important milestone. We look forward to providing an update from this important regulatory interaction after we receive written FDA minutes. In addition, we anticipate providing further details around the potential expansion into another epilepsy-related indication in the coming months. We have also made great progress in our work examining indications outside of epilepsy. We are excited that our Xenon-sponsored phase II clinical trial, which we are calling X-NOVA, is now underway to assess if XEN1101 improves depressive symptoms in patients with MDD and anhedonia. In addition, the investigator-led phase II MDD study with our collaborators at Mount Sinai continues to progress. In summary, this is an incredibly exciting time at Xenon with a number of mid- and late-stage clinical trials ongoing and more on the horizon. On behalf of the entire team, we look forward to keeping you posted on our progress. I'll pause here and ask Chris Kenney to provide some more details on X-NOVA and other developments within our clinical programs. Chris. Thanks a lot, Ian. We've made a lot of progress driving forward multiple ongoing clinical trials and planning for XEN1101 phase III initiation. Let me start by providing further details about the Xenon-led XEN1101 MDD trial. As background, we've built a strong scientific rationale to support our exploration of XEN1101 as a treatment for symptoms of depression and anhedonia. Published preclinical studies suggest that increased activity of KCNQ type potassium channels reverses depressive phenotypes following chronic social defeat stress. We conducted our own preclinical work with XEN1101, including data published at the 2021 ASCENT Conference that demonstrated a potential benefit of XEN1101 in mood disorders. Further, the efficacious doses in plasma concentrations from the rodent depression, anhedonia, and epilepsy-related MES studies overlap, suggesting that the exposure concentrations of XEN1101 in epilepsy patients may also provide appropriate drug exposure to have a beneficial impact on mood. In addition, a paper published in the American Journal of Psychiatry outlines statistically significant clinical results generated from a randomized placebo-controlled clinical trial that explored the targeting of KCNQ channels as a treatment for MDD and anhedonia using ezogabine. The results from our own X-TOLE phase IIb epilepsy clinical trial showed an efficacy signal in focal onset seizures with all doses, including the low dose of 10 mg, which had an excellent tolerability profile. You will see within our MDD trial design, we intend to further study the 10-mg dose alongside the 20-mg dose. X-NOVA will enroll approximately 150 subjects who will be randomized on a one-to-one-to-one basis into three treatment arms, 10 milligrams, 20 milligrams, and placebo. The primary objective is to assess the efficacy of 10 milligrams and 20 milligram doses of XEN1101 compared to placebo on improvement of depressive symptoms in subjects diagnosed with moderate to severe MDD using the Montgomery–Åsberg Depression Rating Scale or MADRS change through week six. Secondary endpoints include improvement of anhedonia as assessed by the Snaith-Hamilton Pleasure Scale or SHAPS through week six, as well as improvement of anxiety using the Beck Anxiety Inventory scale. We anticipate top-line results from the X-NOVA study in 2023. In parallel, our collaborators at the Icahn School of Medicine at Mount Sinai are conducting an investigator-led clinical trial examining XEN1101 in approximately 60 subjects with MDD. Their primary objective is to look at the effect of XEN1101 on the brain reward circuit as measured by the change in bilateral ventral striatum activity using functional MRI. Secondary measures will look at the effect of XEN1101 compared to placebo on depression and anhedonia using the MADRS and SHAPS scales, respectively. We believe there's a strong medical need for new therapies and modalities to treat depression, and importantly, depression commonly exists as a comorbidity in epilepsy patients. Our belief is bolstered by the market research we conducted to better understand the treatment landscape and unmet medical need in MDD. Physicians indicated the need for new treatments with alternative mechanisms of action for patients inadequately managed with SSRIs and SNRIs. We believe the Kv7 mechanism may offer a compelling clinical alternative for these patients in the future. I'm looking forward to keeping you up to date on our progress as we further explore the use of XEN1101 as a treatment for MDD. In summary, and as Ian noted, in addition to MDD, we're excited to move forward with our phase III plans for XEN1101 in focal onset seizures. Our end- of- phase II meeting with FDA allows us to obtain agreement on our phase III program and the overall data package needed for NDA filing. After incorporating this feedback, we intend to engage European regulators through scientific advice to obtain agreement on the XEN1101 phase III program. Our indication expansion efforts also continue, and I look forward to updating these plans in the coming months as well. I would like to now turn it over to Sherry to summarize our partnered programs, financial position, and briefly recap upcoming milestones. Sherry? Thanks, Chris. Before I make a few comments on our Q1 financials, I'm pleased to report progress from our partnered programs with Neurocrine Biosciences and Pacira BioSciences. Of note, we received a milestone payment from Neurocrine Biosciences in connection with successfully reaching a collaborative milestone within the quarter. Both collaborators have clinical studies underway. Pacira is conducting a phase Ib proof- of- concept trial that's evaluating the safety and tolerability of PCRX-301 administered as a single dose in patients undergoing bunionectomy. Neurocrine now has two separate phase II clinical trials underway evaluating NBI-921352 in adult patients with focal-onset seizures and pediatric patients with SCN8A-related epilepsy. Neurocrine has guided that they expect to have data from the focal epilepsy study in 2023. We look forward to keeping you updated as these partners' programs reach important milestones. Next, I'll briefly touch on the highlights from this quarter's financial statements. Please refer to our news release and 10-Q report filed today for more detailed information from Xenon's financial statements. Cash and cash equivalents and marketable securities as of March 31, 2022 were $537.9 million, compared to $551.8 million as of December 31, 2021. Based on current assumptions, which include fully supporting the planned XEN1101 clinical development program, XEN496, and preclinical and discovery programs, we anticipate having sufficient cash to fund operations into at least 2024, excluding any revenue generated from existing partnerships or potential new partnering arrangements. Looking ahead, there are a number of key objectives and milestone opportunities within the Xenon pipeline. Following our end- of- phase II meeting in the second quarter and receipt of final FDA minutes, we anticipate being in a position to share our final phase III plans for XEN1101. In parallel, we'll continue to evaluate and plan for an XEN1101 program in another epilepsy indication and expect to be in a position to outline our plans in the coming months. We'll provide continued support for both X-NOVA and the ongoing investigator-led study examining XEN1101 in MDD. With the ongoing advancement of our EPIC phase III clinical trial in pediatric patients with KCNQ2-DEE, our team is striving towards study completion in 2023. In summary, we intend to continue to build on the positive momentum and excitement generated since the release of our top-line phase IIb X-TOLE results last fall. We're grateful for the ongoing support of our shareholders, and Ian and I have had the pleasure of conducting in-person meetings at recent conferences with some of you on the call. With a strong balance sheet and prudent management of capital, we believe Xenon is well- positioned to support our business objectives across our proprietary programs, and we look forward to reporting our progress in the coming quarters. I'll now ask the operator to open the line for any questions. As a reminder, to ask a question, you will need to press star one on your telephone keypad. Again, that is star one on your telephone keypad. To withdraw your question, please press the pound key. Also, we'll limit participants to one question and one follow-up only. Your first question comes from the line of Andrew Tsai from Jefferies. Your line is now open. Okay, very good. Thanks, and good afternoon. Thank you for taking my questions. My first one is on 1101. You know, clearly the base case for you guys for your phase III program is to do two studies regardless, although you will see if the FDA is willing to consider X-TOLE as a pivotal study. My question is, are there precedents out there where the FDA kind of explicitly told the sponsor, "Yeah, we'll consider your phase II as a pivotal study." You know, in other words, can we expect that level of detailed confirmation from the FDA? Thanks. Thanks, Andrew, for the question. Happy to address it. You know, we've been really consistent with our messaging and communication with investors. We believe the X-TOLE data were very robust, and we're going to ask the FDA as part of the end-of-phase II meeting on whether X-TOLE can be one of the two registration studies. Regardless, we've been clear that we're going to run two phase III clinical trials regardless of the outcome. You asked about. We are going to try to get clarity and obviously, you know, what we can receive in terms of clarity from the FDA once we're in the receipt of minutes, then we'll be in a position to communicate that publicly. In terms of precedent, obviously, we don't have the opportunity to read regulatory minutes from other companies, but we have seen other companies and disclosure that is consistent with being able to communicate on whether their phase II study has been a registration or has been seen as a registration study from an efficacy point of view. Obviously, when we think about the broader clinical development of any program in the NDA, it's a much broader package than just looking at efficacy results. Makes sense. Thank you. My follow-up is on the MDD program that you started up. Can you kind of talk about the powering assumptions, whether both doses need to work for the study to succeed, and how have you tailored your MDD study to succeed in terms of the trial design? Any differences here for the X-NOVA study versus ezogabine's prior placebo-controlled study, for instance? Thank you guys again. Sure. Chris Kenney, do you want to walk through both kind of our company sponsored design and some of the things that we're doing a little bit differently as well as the powering question? Yeah, sure. Happy to do so, Ian. I mean, I think the first thing, you know, to just kind of take a step back. I mean, you have with ezogabine, you have a drug, you know, that demonstrated improvement in focal onset seizures. Now we've done the same with a similar mechanism using XEN1101. When we think about the differences in the potencies, we think about the, you know, there's a significant difference there. We think that there's overlap in terms of the doses that we use and the doses that they use that was effective in FOS. Same thing with MDD, that we're currently using doses, you know, that were quite similar when you take into account differences in potency with what ezogabine used in the small proof- of- concept study that was positive in MDD that was alluded to earlier. The difference there is that they were able to demonstrate statistical significance in a study with about half the number of patients, you know, per treatment arm. In the context of that, you know, we think that there's a reasonable chance that if XEN1101 is effective in MDD that we'll see it. You know, I mean, Ian, do you want me to go further in terms of that, or do you want me to leave it there and then go back to the study design? Let's go through a little bit of the study design and obviously there's always questions around trying to manage the placebo rate, so we can talk a little bit about that, and then we can get more specific on the powering calculations. I'm happy to walk through those as well. Okay. You know, in terms of, like, planning for success with this study, say a few different things. I mean, first of all, you're very careful to keep the number of sites, you know, limited and then to make sure that the quality of the sites is as good as it can possibly be. Can sometimes see differences in terms of placebo effect in different regions. What we can tell you is that the sites that have been chosen are all U.S.-based. Obviously you need to pick a good CRO, and so we went through a rigorous process to choose that. You know, we're working with CTNI to complete eligibility review of patients so that once a site determines that a particular patient is eligible for the study, that patient is then reviewed remotely for eligibility based upon everything that the site has provided and an independent assessment. Well, confirmation of the diagnosis of MDD and then also an assessment of the extent of the MDD. That group, which is composed of psychiatrists and psychologists from Mass General, will also be involved with training the raters and then keeping an eye on them with surveillance over a period of time. There's a lot of different things that we're doing in hopes of planning for success with that trial. You know, obviously having the number of patients per arm twofold higher than the POC that was positive with ezogabine should help with that as well. Thanks, Chris. Let's go. Operator, if we can go to the next question. Your next question comes from the line of Paul Matteis from Stifel. Your line is now open. Hey, thanks so much for taking my questions. I had a couple, if you don't mind. On XEN1101 in epilepsy, as it relates to FDA and EMA feedback, is your expectation that the EMA will prefer responder analysis as the registrational endpoint, whereas FDA may or may prefer median seizure reduction and any other discrepancies that you may anticipate? On the additional seizure indication, I was just curious, you know, again, I don't want to speculate on what you might pursue, but if you're going to do generalized seizures or something like that, you know, can you just sort of point to, you know, what other seizure populations out there that would materially change the way this drug is used in the real world? I guess asked another way, if you have a label for focal seizures, do you need a broader indication to really kind of broaden the prescribing within the refractory population? Just lastly in MDD, I was just curious how you're handling concomitant antidepressant use or prior antidepressant use in treatment-refractory MDD. Thanks so much. Okay. Great. Thanks, Paul. Why don't I tackle the first one, and then Chris Von Seggern, why don't you talk a little bit about the market opportunity and other seizure disorders outside of focal and how we think about, you know, kind of the market there. And then Chris Kenney, we can get to the con med question on MDD. Your first question, Paul, was just around regulators in the U.S. versus Europe. Yes, I think you described it well that EMA or U.S. regulators, FDA, we expect will focus on MPC. That was the primary endpoint in the X-TOLE study and would be the primary endpoint in the phase III program. European regulators will focus on the responder analysis or the RR50, and that's the key. That was the first secondary endpoint in X-TOLE. We can do that analysis and look at that under the statistical analysis plan. Obviously, given the robustness of the data with XEN1101, you just see massive consistency between those two endpoints, regardless of which one you do. We see very strong statistical significance, which is to be expected with a very active drug, based on those two statistical analyses. Chris Von Seggern, the kind of expanding the market opportunity outside of focal. Yeah, absolutely. As we said previously, focal onset is the biggest component of the epilepsy opportunity, representing approximately 60% of the patients who are treated and managed. That leaves a fairly sizable segment of the marketplace that has either what we would generally consider a generalized form of epilepsy or a mixed etiology within that bucket. That side of the equation is much more fragmented with different conditions contributing to the different manifestations that would fall into a broader generalized bucket. They are broadly treated similarly, although not the same. There are products that have indications that sit on either side of the FOS versus the primary generalized marketplace. As a result, we do think expansion of the clinical label is important for two reasons. First, having clinical data in unique patient populations will be important given that not all products are broad-spectrum, and we want to be able to be in a position where we can have data specifically supporting use in adjacent patient population. As well as that we do believe this is a promotionally sensitive market, and being able to communicate that data through commercial and medical means will be important in order to establish positioning for a product, even in light of having a potential broad-spectrum outcome. Both of those reasons necessitate exploration of at least generating data and pursuing labeling should the data be positive is something we feel quite strongly about. Thanks, Chris. And then- Chris Kenney on the MDD CONMED question. Yeah. Hey, Paul. With regard to the medication, patients entering the study will not be allowed to be taking an antidepressant. In terms of eligibility, it's okay to have failed one antidepressant in the current depressive episode, but no more than one. Then any failure of greater than three antidepressants at any point in time will be exclusionary as well. All right. Thank you all very much. Thanks, Paul. Your next question comes from the line of Brian Abrahams from RBC Capital Markets. Please go ahead. Hi, good afternoon. Thanks for taking my questions. It sounds like you mentioned your confidence is continuing to grow on XEN1101 as the data continue to evolve. I'm actually curious if you could talk maybe a little bit more about the emerging data. I know the specifics around the open label extension update are going to be presented later this year, but maybe if you could just remind us how far along patients are at this point on dosing and maybe qualitatively what you're seeing out of that that helps shape your confidence. And then secondarily, you did mention we were going to see updated cuts from X-TOLE later this year. I'm just curious if you could maybe talk broadly about how some of those analyses, such as the time to efficacy, could further help differentiate 1101's profile. Thanks. Thanks, Brian. Chris, I'll make a few comments, and then I'll pass it over to you on maybe some a little bit of color on the open label extension. Chris, I don't know if you know off the top of your head, just kind of I know we have patients that are out quite some exposure now, but maybe we can just give a little bit of information if you have it at your fingertips on how many patients we're seeing kind of out 12-24 months. Yeah, Brian, I think, you know, one of the things that's really strong about the dataset overall is regardless of how we cut the data, it's remarkably consistent and very intuitive. You know, a lot of these subgroup analyses in patients with less severe disease, the data looks even more impressive, which is what you would expect, but it's nice to see that consistency. We're interested in this time course to efficacy because of the no titration. Although this is a novel mechanism and we would say, you know, likely best in category efficacy that we've seen so far, you know, continuing to look at other ways where we could differentiate against what are a number of other anti-seizure medicines that are available. What we've been doing is we've been looking at cuts of the data on efficacy at, you know, this was an 8-week study, so on a weekly basis, and we can start to look at where efficacy shows up. Again, without the drug being titrated, the hypothesis is there's an opportunity to see that earlier than you may see it with some of the other drugs. That's something that we're interested in among other things. I'll pass it to Chris maybe just to give a bit of color on OLE 'cause we're just starting to dig into some of that data. We had focused on the OLE safety data initially, as part of preparation for our end-of-phase II meeting. Now we're starting to think about the efficacy cuts that we would like to share later this year as well. Chris? Yeah, sure. Yeah, I mean, I think that's. The main point is that as we look into the data, you know, the double-blind data, regardless of how we cut it, the signal persists. So that's part of the story in terms of being reassured. The other part, you know, will be messaged clearly in the second half of this year regarding interrogating the open label data, and we're just getting our hands around it. You know, it's a moving target, right? Because it's an ongoing study, and every day patients have one more day of exposure. The other thing is that, you know, the number. Not all patients have finished up the first year because they wrapped up in the summer last year. The last patients who enrolled wrapped up in the summer. Roughly speaking, we're closing in on having 200 patients up to a year and then about 50 or 2 years. It's a fairly robust data set, and we're taking a look at that data and obviously having it vetted by key opinion leaders who are respected and then being sure that we go out with a, you know, a balanced story about what we're seeing. Great. Thanks, Chris. Again, if you would like to ask a question, please press star one on your telephone keypad. Your next question comes from the line of Marc Goodman from SVB Securities. Your line is now open. Hey, thanks for taking my question. It's Rudy on the line for Marc. Just a quick follow-up question for the X-NOVA study for XEN1101. Can you provide more color on the powering the study? Like, what are your expectations for the magnitude of effect in measures for both placebo and XEN1101? And secondly, given the enrollment criteria, it seems like we are targeting monotherapy instead of adjunctive use. Maybe you can provide more color here on the clinical setting for XEN1101. Thanks. Yeah. Do you want me to do the powering, or do you want to do the powering and the monotherapy? I'm happy to make it, you know, start it off, and then maybe you can add color to it afterwards. Perfect. I sort of alluded to the fact that, you know, we're going to have about twice the number of patients that were in the ezogabine proof- of- concept study. From, like, a Cohen's d perspective, you're shooting for an effect size around 0.5. But in terms of the separation between active and placebo, where the powering assumptions assume that there would be about a five-point separation between active and placebo, and that would give us an 80% power to detect a change for each one of the doses compared to placebo. That's the powering. Then, in terms of the monotherapy, you're... Yeah, I mean, you have it right. These patients will not be on an additional antidepressant, and so we're looking for a signal in patients who are not being treated with another antidepressant at the same time. Got it. That's very helpful. Thank you. Again, that is star one to ask a question. Your next question comes from the line of Yatin Suneja from Guggenheim. Please go ahead. Hey, guys. Just a couple questions from me on the MDD side. Can you just talk about the dose selection there, using a 10-milligram dose there? Just curious, how did you come up with the lower dose? Then did you mention the effect size that you are looking is 0.5? Can you just talk about, I mean, how did you arrive at that 0.5 Cohen's d effect size and five-point delta in your powering assumption? Yeah. Ian, do you want me to go? Yeah. Why don't you start, and I'm happy to add in. Yeah. The 10-milligram dose in the focal onset seizure study demonstrated efficacy and tolerability and a safety signal that was made it difficult to extinguish the 10-milligram group from placebo. Really good tolerability and evidence of efficacy. We want to take that forward into MDD and see if the same would be true within MDD. As far as the powering, I think it's probably better to just focus on, you know, this is an MDD study. We're expecting a fairly pronounced placebo effect, as has been the case historically, despite, you know, efforts to keep it minimized. The separation between active and placebo, we're assuming is 5 points and a standard deviation that's about twofold higher than that. That's, you know, a little bit less than what was seen with the ezogabine proof- of- concept study completed in two sites. We're going to be going to more sites so that signal may become less robust, as we do that. That's the powering background. Got it. Do we have any clarity on when we might see the data from investigator-initiated MDD study? Yeah, I mean, still early days. The Mount Sinai study started in Q4 of last year. We're not giving specific guidance on it. I will mention just because it's publicly available on ClinicalTrials.gov, they say that it's going to be early 2024 when that study completes. Our expectation has always been that our company-sponsored study, although has started after the IST, will read out before the IST 'cause we expect data from our study in 2023. Got it. Thank you. Next question is from the line of David Hoang from SMBC. Please go ahead. Hi. Thanks for taking the questions. I had one and then a follow-up. First in terms of 1101 in MDD, if we think about how it might be positioned and adopted in the real-world setting, you know, do you think about the low-hanging fruit as epilepsy patients with comorbid MDD, or is this really more of something for the broad, you know, all-comer MDD population that could be conceivably used in anyone who had maybe failed an SSRI? Chris, one second. Do you want to talk about the opportunity? Yeah. No, absolutely. First let's start with MDD. That indication, while it does have numerous available agents, as you've mentioned, an overwhelming number of patients will be treated with an SSRI or SNRI. Many of those patients will fail first or second-line therapy, and just like in the FOS space, there's A sizable percentage of patients that require an alternative mechanism, in this situation, predominantly monotherapy, to address their depression symptoms. We do believe that there is an opportunity for an agent with a novel mechanism of action that has a good safety tolerability profile to fit in nicely despite the competitive dynamic that sits in that space. Your second question, though, relates to the fact that within the FOS patient population, there is a sizable percentage of patients that have comorbid depression. It's one of the most common comorbidities within the epilepsy space. There certainly is the opportunity to differentiate with appropriate data in that segment of the patient population where you can imagine that you can be a go-to agent with compelling antidepressant effect as well as best-in-class efficacy, as we've seen with XEN1101. That's helpful. Thanks. Just quickly, if I may. In terms of the IST study, which we'll read out after your company-sponsored study, are there any, you know, key learnings that you expect to glean from that study, that may not be apparent in the company-sponsored study? I don't think so. I mean, Chris mentioned in his prepared remarks, and if you look at the ezogabine publication from a year ago from the study. It's the same group out of Mount Sinai and Baylor that ran the ezogabine study that was published last year, and then they're the same ones running our IST or the IST with eleven oh one. They're interested in a functional endpoint, functional MRI at primary 'cause they're interested based on some of the preclinical data and where the expression is, the increased expression of Kv7.3 in the brain. That's going to be an endpoint that we're not replicating, so that'll be new information from their study. When they get into their secondary endpoints in terms of the clinical scales of depression and anhedonia, that will be consistent with our study. I'm not sure that we learn a lot, David, from their study that would be a read-through in terms of our future development. Okay. Thanks a lot. Appreciate it. Again, to ask a question, please press star one on your telephone keypad. You have your next question coming from the line of Laura Chico from Wedbush. Please go ahead. Hey, good afternoon, and thank you for taking the questions. I just have two. One, we saw a recent report looking at correlation of seizure frequency and quality of life in DEE patients. Interestingly, there's better correlation between quality of life and days of uninterrupted due to seizures. When you're looking at the recent XEN1101 data, I'm wondering if there's a similar type of relationship that exists in the focal epilepsy setting, so not necessarily seizure freedom days, but days that were uninterrupted due to seizures. Secondarily, I guess with respect to the study in MDD, the X-NOVA trial, could you just elaborate a little bit more fully in terms of how you're going to be assessing patients remotely, kind of what steps you're taking to kind of control placebo response? Thank you. Dr. Chris Kenney, both of those, can you address? Well, I don't know if I can address the placebo response any better than I already did. I'll just go through it again, quickly. Basically, it had to do with choosing good sites, U.S.-focused, making sure that the sites were trained properly by CTNI, ensuring that we choose a good CRO, assessing the eligibility criteria for entrance into this study using a different scale that's being used to assess the primary endpoints, so specifically HAM-D versus MADRS. Using this group of CTNI, who are Mass General attendings in psychology or psychiatry, performing this remote assessment of patient eligibility, ensuring that the HAM-D score is appropriate for recruitment into the study. Keeping... Using those same folks to train the sites and to surveil them over a period of time to ensure that there isn't anything aberrant going on with the data. Don't think I can add anything more to that. What was the other one? I apologize. No, sorry. It was just a question. Oh, go ahead, Laura. I remember. Yeah. It was the seizure-free. Yeah, we've taken a look at seizure freedom. Some of that has been released previously in press releases. We've also looked at seizure-free days. That data hasn't been released, although it sort of shows what you might expect it would show. We haven't tried to correlate that seizure freedom or seizure-free days with quality of life. Okay. If I could maybe sneak in a quick one. I'm sorry if I missed this on XEN1101 and the MDD study. Have you disclosed kind of expectations around a screening failure rate? Thanks very much. Just to answer that last question, operator. No, Laura, we haven't given any guidance on where we expect the screen failure rate may be. That's something that I think we can track over time and then give more information on. Okay. Thank you. That ends our question and answer session. I'll turn the call back over to Sherry Aulin for closing remarks. Thank you, everyone, for joining our call and webcast to discuss our first quarter 2022 results. Operator, you may now end the call. Ladies and gentlemen, that concludes this conference call. Thank you all for participating. You may now disconnect.