Good day, and thank you for standing by. Welcome to the third quarter 2021 Xenon Pharmaceuticals Incorporated earnings conference call. 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, you will need to press star one on your telephone keypad. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to your first speaker for today, Ms. Sherry Aulin, the Chief Financial Officer of Xenon Pharmaceuticals. Please go ahead. Thank you. Good afternoon, everyone. Thank you for joining us on our call and webcast to discuss our third quarter 2021 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. Today, Ian will provide a corporate update on our proprietary programs and then turn the call over to Chris Kenney, who will provide a summary of the X-TOLE data and our XEN1101 plans moving forward. Chris von Seggern will then provide context regarding the adult focal epilepsy market based on market research with leading KOLs and treating physicians. Lastly, I will summarize our high-level financial results and milestones from both proprietary and partner programs for the months ahead before opening up the call to your questions. Please be advised that during this call, we will make a number of statements that are forward-looking, including statements regarding the research and clinical development plans and timelines and results of operations, the timing of and results from clinical trials and preclinical development activities of our proprietary and partner product candidates, the potential efficacy, safety profiles, future development plans, addressable market, regulatory success, and commercial potential of our proprietary and partner product candidates, the anticipated timing of IND or IND equivalent submissions, and the initiation of future clinical trials for our proprietary products and those related to our partners' candidates, the efficacy of our clinical trial designs, our ability to successfully develop our proprietary development programs, the timing and results of our and our collaborators' interactions with regulators, the timing and anticipated enrollment in our clinical trials, 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 publication or presentation 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 third quarter of 2021 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 would like to turn the call over to Ian. Thanks, Sherry, and good afternoon, and thanks for joining us today. Xenon marked an incredibly important milestone last month when we announced the positive top-line results from our phase II-B X-TOLE clinical trial. XEN1101 demonstrated impressive efficacy in difficult to treat adult patients with focal epilepsy. With its differentiated potassium channel mechanism of action, strong efficacy data, and ease of use attributes, including once a day evening dosing and no titration, we believe XEN1101 could play an important role in treating adult focal epilepsy. These data exceeded our expectations with consistent dose-dependent and statistically significant efficacy across the key primary and secondary seizure reduction endpoints. With these positive data in hand, we conducted a detailed analysis of our product pipeline, including the evaluation of additional indications for XEN1101. Moving forward, we intend to sharply focus our efforts on the finalization of clinical development plans for XEN1101 including a planned end-of-phase II meeting with FDA anticipated in Q2 2022, and the initiation of our phase III program in adult focal epilepsy anticipated in the second half of 2022. We look forward to providing more details on the final XEN1101 clinical development plan in the first half of 2022, including the final design of our phase III program and our plans to evaluate other epilepsy indications as well as supporting phase II development in major depressive disorder or MDD. In addition to XEN1101, our XEN496 EPIK phase III trial continues to enroll patients with KCNQ2 developmental and epileptic encephalopathy or KCNQ2-DEE. Further, this portfolio focus on XEN1101 and XEN496 has helped shape our decision around our XEN007 program. To date, a total of eight subjects have been enrolled in an investigator-led phase II proof of concept study examining the potential clinical efficacy, safety, and tolerability of XEN007 as a treatment in patients diagnosed with treatment-resistant absence seizures, including childhood and juvenile absence epilepsy. As disclosed previously, we believe XEN007 is demonstrating efficacy in these patients with absence seizures. However, given the focus and resources required to advance XEN1101 and XEN496 we do not intend to allocate any resources to company-sponsored XEN007 development activities in 2022. So, looking forward, you will see that our company objectives and activities are centered around our Kv7 potassium channel programs and advancing our proprietary neurology pipeline. In addition to our clinical advancements, we have also focused over the past few years on expanding our intellectual property portfolio for XEN1101, and we have made excellent progress on this front. Over the past few months, two new U.S. patents were issued to Xenon. The first contained claims related to four distinct crystalline forms of XEN1101 drug substance, including the form that we intend to use in our phase III development and for commercialization, along with methods for their preparation. The second patent relates to the methods of enhancing the bioavailability of XEN1101 by administration with food, and this is consistent with the dosing of XEN1101 in our clinical studies. Absent any extensions of patent term, these U.S. patents are expected to expire in 2039 and 2040 respectively, providing us with an extensive runway protecting XEN1101. Turning now to our other Kv potassium channel program, XEN496. New sites and jurisdictions continue to come online to support our EPIK study, which is a phase III randomized, double-blind, placebo-controlled, parallel-group, multicenter 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 its Kv7 mechanism of action, as well as published physician case studies, we believe that XEN496 has the potential to address an important unmet medical need for these patients. We anticipate that the EPIK study will be completed in the first half of 2023, and we look forward to keeping you updated on its progress. Before turning the call over to Chris Kenney, I want to remind everyone that we're planning a significant presence at AES 2021. This is the annual meeting of the American Epilepsy Society, held in December. We look forward to presenting additional X-TOLE data at this event, including sub-analyses of the responder analysis, as well as more detailed safety data in a late-breaking poster presented by Dr. Jackie French, as well as during our sponsored scientific symposium. Activities at AES 2021 include scientific posters related to XEN1101, including the late-breaking X-TOLE poster, as well as XEN496 and Xenon's other earlier stage pre-clinical work. We will be participating in a joint industry scientific exhibit relating to rare genetically defined epilepsies, and we will also be sponsoring a scientific symposium featuring a panel discussion with key opinion leaders in adult focal epilepsy space to discuss XEN1101 and the Kv7 mechanism. For those of you who are unable to join us in Chicago this year, we expect to host a conference call and webcast to discuss our presentations at AES, specifically focused on the new analyses within our X-TOLE data. We will circulate details in a news release closer to the event, and we look forward to connecting with you either in person or virtually. With those invitations extended, I'd now like to turn the call over to Chris Kenney, and Chris will touch upon some of the highlights from the X-TOLE data and our XEN1101 plans moving forward. Chris? Thanks, Ian. Today, I'm gonna hit on some of the highlights of the X-TOLE data, so I encourage listeners to also review the October 4 news release, or you can listen to our webinar from that date as we went into considerable detail around the X-TOLE top-line results. As a reminder, X-TOLE was designed as a randomized double-blind, placebo-controlled phase II-B study to evaluate the clinical efficacy, safety, and tolerability of XEN1101, administered as once-daily adjunctive treatment in adult patients with focal epilepsy. The study results include a total of 325 randomized and treated subjects in the safety population and 323 subjects in the modified intent to treat population for the efficacy analysis. Of the 285 subjects who completed the double-blind period, 96.5% entered the open label extension to evaluate the long-term safety, tolerability, and effectiveness of XEN1101. This high rollover rate provides important insight into the comfort of clinicians and their patients with the overall benefit and tolerability profile of XEN1101. The trial met its primary endpoint, with XEN1101 demonstrating a statistically significant dose-dependent reduction from baseline in monthly focal seizure frequency when compared to placebo. A monotonic dose response with a p-value of less than 0.001. Key secondary efficacy measures included a pairwise comparison of each active dose to placebo and the proportion of patients who achieved a 50% or greater reduction in monthly focal seizure frequency from baseline. Median percent reduction in monthly focal seizure frequency was 52.8% in the 25 mg group, 46.4% in the 20 mg group, and 33.2% in the 10 mg group, compared to 18.2% in the placebo group. These data suggest a clinically meaningful dose-response relationship for XEN1101 in the adjunctive treatment of focal seizures in adult patients. We believe these data are even more impressive when we take into consideration the history of these patients in terms of their exposure to previous antiseizure medications and the concomitant antiseizure medications while on study. In this context, XEN1101 demonstrated a statistically significant reduction from baseline in monthly focal seizure frequency compared to placebo for all three XEN1101 doses in pairwise comparisons between each dose and placebo, with two-sided P values of P of less than 0.001 for 25 mg versus placebo, P of less than 0.001 for 20 mg versus placebo, and a P value of 0.035 for 10 mg versus placebo. These efficacy data strongly suggest that XEN1101 is highly active in the central nervous system. XEN1101 was generally well tolerated in the study with adverse events consistent with other commonly utilized anti-seizure medications. There were no pigmentary abnormalities reported during the double-blind study or during the open label extension to date, with 70 subjects now treated more than 12 months. The most common treatment-emergent AEs across all XEN1101 dose groups were dizziness, somnolence, fatigue, and headache. The treatment-emergent adverse event rates were consistent with other anti-seizure medications and at rates that were expected. Overall, the safety and tolerability profile of XEN1101 is in line with other anti-seizure medications and what would be expected given XEN1101 appears highly active in the central nervous system. To summarize, the X-TOLE results demonstrate impressive efficacy of XEN1101 for adult patients with focal epilepsy, including those with seizures that are deemed difficult to treat when compared to other clinical trials. In addition, we believe physicians and patients could benefit from XEN1101's other important attributes, such as once-a-day dosing in the evening with no titration. Given XEN1101's unique potassium channel mechanism of action and the strength of these data, we believe XEN1101 could play a very important role in treating focal epilepsy in the future. Since announcing the top line data, we have focused on building out our phase III development plans. We anticipate having an end-of-phase II meeting with FDA in the second quarter of 2022 to support the initiation of our phase III clinical program in adult patients with focal epilepsy, anticipated in the second half of the year. In addition, the X-TOLE open-label extension, which has been extended to three years, is expected to continue to generate important long-term data for XEN1101. As Ian noted, we're also expanding the development of XEN1101 to MDD, major depressive disorder. We have a strong scientific rationale based on promising pre-clinical data as well as clinical results from both an open label study and a randomized placebo-controlled clinical trial that explored the targeting of KCNQ2 channels as a treatment for MDD using ezogabine, an earlier generation Kv7 potassium channel opener that's no longer commercially available. We're collaborating with the School of Medicine at Mount Sinai to conduct an investigator-sponsored phase II proof of concept randomized placebo-controlled clinical trial of XEN1101 for the treatment of major depressive disorder with patient screening and randomization currently underway. Approximately 60 patients with MDD will be randomized in a one-to-one fashion to XEN1101 or placebo, with subjects taking 20 mg once a day of either XEN1101 or placebo over the course of eight weeks. The primary objective is to investigate the effect of XEN1101 on brain measures of reward using functional magnetic resonance imaging. Secondary endpoints include clinical measures of depression and anhedonia. In addition, we're planning a larger company-sponsored clinical study in major depressive disorder with XEN1101, which is expected to be initiated in the first half of 2022. Now, a few months ago, I joined Xenon based in part on the promise of Xenon's maturing neurology pipeline, and I couldn't be more excited that the X-TOLE results exceeded our expectations, which allowed us to accelerate our phase III development program for XEN1101. As Ian noted, we're committed and focused on advancing XEN1101 as we believe it could benefit a large number of patients suffering with adult focal epilepsy. With that, I'd like to turn the call to Chris von Seggern, who will share some market research insights shaping our current plans for XEN1101. Chris, turn it to you. Briefly, by way of background, prior to the X-TOLE top line readout, we conducted primary market research in a blinded fashion with 50 clinicians ranging from academic epileptologists to high-volume prescribing neurologists and epileptologists across the U.S. This earlier market research underscored the enduring unmet need that remains despite the availability of numerous anti-seizure medications for the treatment of adult FOS. Physicians emphasized that high clinical unmet need exists, particularly among patients who are not well controlled despite being treated with multiple drugs in a polypharmacy approach. The results of our prior market research suggested that the potential profile of XEN1101 was compelling, given an anticipated efficacy profile that at the time was in line with current standard of care. We modeled a 35% reduction in the 25-mg treatment group, a comparable safety tolerability profile to existing ASMs, along with differentiated ease of use attributes such as QD dosing and no titration. Then, following the X-TOLE results, we surveyed 148 prescribing epileptologists and neurologists in the U.S. to understand their perspectives on the anticipated XEN1101 product profile based on the X-TOLE data. The survey sample following the X-TOLE results had prescribing behaviors consistent with the broader U.S. market, and surveyed physicians noted that the efficacy and safety are the most important factors contributing to the treatment decisions for ASMs. Overall, the profile of XEN1101 was very well regarded, and both neurologists and epileptologists viewed the efficacy and tolerability of XEN1101 as potential differentiators. In particular, differential efficacy was cited as a driver of use for XEN1101 across all lines of therapy. Beyond efficacy, QD dosing, no titration, and the novel mechanism of action reviewed favorably to highly favorable compared to current ASMs. In light of the strong efficacy, the overall product profile, physicians indicated comparable utilization of XEN1101 to Vimpat, competing for the first branded opportunity for patients with residual seizure burden. Given the substantial efficacy demonstrated in the X-TOLE results, combined with all we have learned from our market research, we believe the profile of XEN1101 has the potential to significantly improve the standard of care for patients with residual seizure burden and, if approved, would represent a meaningful advancement in the therapeutic armamentarium for this disease. I'd now like to turn the call over to Sherry, who will provide some financial highlights and a summary of our important milestones ahead. Sherry? Thanks, Chris. Today, I will focus on some highlights from this quarter's financial statements and would refer you to our news release and 10-Q report for further details. Cash and cash equivalents and marketable securities as of September 30, 2021 were $249.6 million, compared to $177 million as of December 31, 2020. Subsequent to the quarter, we raised additional net proceeds of approximately $324.3 million, net of underwriting discounts and commissions, but before offering expenses in a public offering. As Ian noted, following the X-TOLE data, we thoroughly analyzed our product portfolio and revisited our cash runway guidance, focusing on our most important programs. Based on current assumptions, which include fully supporting the planned XEN1101 clinical development program, our XEN496 EPIK phase III clinical trial, and our 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. Guided by our focus on our proprietary Kv7 potassium channel programs, we believe we are in a strong position to execute against our corporate goals. I would refer you to today's press release and our 10-Q filing for other specific details from this quarter's financial statements. I'll give you a quick update on our partnered programs before reviewing upcoming milestones from our proprietary pipeline. Our two key partners, Neurocrine and Flexion, have made important progress this year. Under our Neurocrine collaboration, there are now two ongoing phase II clinical trials with NBI-921352, including one study in adolescent patients aged 12 years and older with SCN8A developmental and epileptic encephalopathy. A second study has recently been initiated in adult patients with focal onset seizures. We are excited for these studies to test our hypotheses of selective Nav1.6 inhibition and the impact on seizures in both the genetic gain-of-function patients as well as the broader population of focal epilepsy. Turning to our partners at Flexion. Following the decision to expand the study with an additional cohort, Flexion anticipates data in the first quarter of 2022 from a phase I-B proof of concept trial evaluating the safety and tolerability of FX301 in patients undergoing bunionectomy. In addition, looking ahead, key objectives and milestone opportunities in our proprietary pipeline include our activities at AES 2021 and the release of additional phase II-B X-TOLE data within a scientific poster presentation and at a scientific symposium. We plan to conduct an end-of-phase II meeting with the FDA in the second quarter of 2022 to help guide our phase III development program for XEN1101, which will be initiated in the second half of 2022. We will continue support for the ongoing investigator-led study examining XEN1101 in MDD and initiate a larger company-sponsored MDD clinical study in the first half of 2022. We will continue evaluation of other epilepsy indications well suited for the future development of XEN1101. The ongoing advancement of our EPIK phase III clinical trial in pediatric patients with KCNQ2-DEE, with estimated completion in the first half of 2023. On behalf of the entire executive team, we are proud of the hard work that led us to this exciting point in Xenon's history. As we look ahead to 2022, we have multiple ongoing phase II and III clinical trials underway from both our partnered and proprietary programs. I'm excited to keep you updated on our progress as we continue to advance XEN1101 and the rest of our neurology-focused pipeline. I'll now ask the operator to open the line for any questions. Thank you, Sherry. As a reminder to our audio attendees, if you would like to register a question, please press star followed by the number one on your telephone. If your question has been answered and you would like to withdraw your registration, please press the pound key. Also, please limit yourselves to one question at a time, then re-enter the queue. One moment please for the first question. Our first question is from Paul Matteis from Stifel. Your line is now open. Hey, thanks for taking our question. This is Alex on for Paul. A couple on XEN1101, and then one on XEN007, if that's all right. I guess moving forward with XEN1101, you know, is your expectation that you would only run one phase III study, or are you planning on running two? How are you thinking about that? And then I'll ask a couple follow-ups if that's okay. Sounds good, Alex. I'll pass it to Chris Kenney just to talk about kinda what our proposal will be in front of FDA and the phase III program in focal epilepsy. Yeah, sure. Thanks, Ian. Yeah, we're certainly gonna be going out next year with more details about this, but we're of the opinion that simply conducting one more randomized controlled trial will probably not be sufficient to have a, you know, a large enough safety database at the time of the NDA submission to increase our chance of success. So, we're planning on doing, you know, more than that, and the details of which will be forthcoming. You can imagine, I mean. Okay. These are pretty straightforward in terms of their design. What you're seeing, you'll see a repeat of X, what was already done to a large extent, and then something beyond that to medium term. And- Alex, maybe Sorry. Yeah, I was just gonna maybe add to that before you jump in on XEN007. You know, look, we believe strongly in the strengths of the X-TOLE data, so we will be, you know, making our arguments in front of the FDA that this is one of two registration studies, which is, I think, maybe a bit of a nuance on your question. But as Chris mentioned, we expect that the phase III program overall will be broader than just one phase III trial. Yep, makes sense. One more on XEN1101 before XEN007, but I guess, is there anything gating for your own phase II MDD study out of the Mount Sinai study, or are you planning to, you know, start that before you might see any more data out of that? Chris, do you wanna just go through our thought process on our own company-sponsored MDD study? Sure. I mean, the quick answer to your question is that the MDD trial at Mount Sinai just began screening and randomization, and we're gonna be doing the same shortly. So, we're not waiting for any data to initiate. Makes sense. Quickly on XEN007, I guess, has your view of the molecule changed over the last, you know, quarter or so? I mean, any more color that you can give on sort of the prioritization of XEN1101 and XEN496 next year? Thanks. No, not at all. It's really about prioritization. As you can imagine, you know, a lot of the focus on the XEN1101 program, we talk about what the phase III trials will look like, but we're gearing to moving as quickly as we can to get this drug filed and approved. And so, there's a massive amount of work, both in tox as well as clin pharm, other clinical trials we'll need to run and all of the CMC work. It's those are the competing resources to put those resources on other programs. And so, to us, you know, four nine six is ongoing and the broad XEN1101 development program is the most important objective that we're focused on. So, it's really a focus on prioritization and effort there rather than anything specific around XEN007. We believe the drug's active. We've seen that. We've talked about that publicly. Obviously the investigator-led study has gone slowly, and I think a lot of that was due to COVID impacts that we've seen across clinical development. We absolutely believe that we're seeing drug activity for XEN007. Right now, we just need to focus our efforts on XEN1101 and XEN496. Makes sense. Thanks so much. Reminder again to limit yourselves to one question and one follow-up only. Thank you. Next, we have Andrew Tsai from Jefferies. Your line is open. Okay, great. Thanks for taking my questions. Good afternoon. My first one is on AES when you present the full data set. You know, you did mention responder analysis, more safety. I mean, I guess my question is could you share more? And if so, I guess, what would you encourage us to focus on, as it relates to kind of understanding XEN1101's competitive profile? And I also wanna ask, you know, could we see seizure freedom data, for instance, or even kinetics around efficacy? Just maybe talk a little bit more about that. That would be helpful. I have a follow-up. Thanks. Sure. Maybe Chris, maybe I'll give a couple comments on AES, and then you jump in, as you're close to the details. You know, I know you suggested, Andrew, kind of the full data set. The full data set would come in a publication later. There's definitely gonna be more information at AES than in our top line press release. We're still receiving, you know, additional data in terms of PK and other things from the study. I had mentioned in my prepared remarks that we'll break down the responder analysis. To answer your question very specifically, yes, you'll see seizure freedom data and also kind of those bins of those that responded more than 50%, more than 75% and other bins as well. There's some additional subgroup efficacy analysis that we're interested in that we're running right now also. You'll probably see some more efficacy data in subgroups, as well as more detailed AE tables and overall safety. You know, I think my overall comment, and then I'll pass it to Chris to add, is that nothing changes our view here. You know, I think it's always great to do additional analyses and have additional information presented in scientific forums and at medical meetings. Nothing's changed in terms of our overall view. The top line efficacy, you know, in terms of the dose dependency and the efficacy, and what we would expect to see on the safety side, nothing's changed in our views as we get deeper into the data. Chris, anything to add? Oh, okay. Sorry, I just got a note that Chris Kenney just lost connection. We'll carry on. Andrew, do you wanna go on your second question? Hey, thanks. No. Yeah, thank you for the details. My second one is actually, I would love to hear your latest thinking and your, kind of your appetite around partnerships for XEN1101. I'm curious if you're keen on licensing out U.S. rights or is it, ex-U.S. you're interested in? A corollary to that is just as I think about EU development, and tying that with your upcoming FDA meeting, I don't know. I mean, could there be a scenario where you run one phase III U.S., one phase III global, and then together that's how you can file both an NDA and a MAA down the road at the same time, I guess. Maybe talk about those two dynamics. Thanks. Yeah, I mean, there's a fair bit there. I'll give a couple of comments, and maybe Chris von Seggern, you can talk a little bit about some of our thinking on the commercial side also. Andrew, we don't give guidance on partnering and when we may be in partnering discussions or not. In terms of our strategic objectives, our goal is to launch 1101, just like to launch 496 in the U.S. market ourselves. We have focused our comments today on an end-of-phase II meeting and getting feedback from FDA, but we will be doing the same thing with European regulators. We will be going through the process to receive scientific advice. I think as we get through those meetings, we can answer one of your questions more directly, which is what are gonna be the requirements for the NDA and the filing in the U.S. versus the requirements in Europe. And so, we'll be able to get into more of those details in 2022. That's our overall thinking and overall strategy. Chris von Seggern, maybe you can comment a little bit as we think about U.S. commercialization and our forward integration. Yeah, Ian, happy to. When we think about the FOS opportunity on a global basis, the U.S. represents the lion's share of the commercial opportunity, predominantly driven by the differential pricing that one can achieve in the U.S. market. It's our belief that we have the capacity to bring this product to the market in the U.S., built on the backbone of the commercial infrastructure that we'll first have with XEN496. And it's our intention to be able to build and execute within the U.S. market. The European market is a much more challenging one, but also a very meaningful commercial opportunity in its own right, for FOS products. That's an area where we still have work to do to think through the best commercialization strategy to optimize the opportunity in that market as well. Thanks for all the color. Congrats on all the progress. Thanks, Andrew. All right. Before we proceed, I'd like to ask the speakers first, how is your audio? Is everything fine? Can you hear the questions perfectly? The audio is good on our side. We did drop one of our speakers who got disconnected, Chris Kenney. If you can reconnect him, I think he was trying to dial back in. We can continue on with the Q&A. Thank you for confirming, Chris. Sorry, Ian. Our next question is from Marc Goodman, SVB Leerink. Your line is open. Marc, are you there? Oh, Mark, withdraw the question. Next is Brian Abrahams from RBC Capital Markets. Your line is open. Hey, guys. Thanks so much for taking my questions. On XEN1101, I'm sort of curious if you've done any additional PK/PD and safety analyses since the top line X-TOLE data and maybe where that's steering you with respect to potential phase III dosing, as well as dosing for the MDD study. I had a quick follow-up. Sure. Brian, I'll take that because I think. Oh, actually, Chris Kenney, are you back online now? I am. Okay. Did you hear the question? Maybe you can. If you heard the question, maybe you can address kind of the PK/PD. I know a lot of that stuff's still coming in. Then your thinking around dose selection for phase III and MDD. Yeah, sure. Obviously, you know, the information that we already have is suggestive of which doses we could bring into phase III. We're in a very fortunate situation where I think you could make an argument that you could bring any or all of those three doses forward, and we're just trying to figure out which dose or doses would be best. PK/PD is certainly a part of that. We're in the process of having that information come in right now. Regarding the safety, we are also spending a lot of time evaluating all the safety data, and much of that will be presented at AES in a more granular format than what you saw in the press release. We're bringing in all the information, and next year we're gonna be more forthcoming about exactly which dose or doses we're bringing into phase III. Got it. Maybe just a quick follow-up, if I could. You maybe alluded to broadening out the XEN1101 program, epilepsy program, given the strength of the data. Just curious if you could expand a little bit on some of the possible other epilepsy indications you might consider, and might this also include going down in age to a pediatric population? Thanks. Yeah, Brian, good questions. I'll start, and then Chris Kenney, if you wanna join as well. You know, we did a webinar on XEN1101 in the summer where one of our KOLs talked a lot about the preclinical data. I think what's fascinating about the Kv mechanism and XEN1101 is just its broad spectrum activity. And so that gives us a lot of confidence, combined with the X-TOLE data, to go into other epilepsy indications in addition to adult focal. We're doing that evaluation right now. There are other large epilepsy markets, to give you a bit of an idea. Specifically around pediatrics, that's another part of our planning. Again, I think many of you will know kind of what the extrapolation guidance is from FDA in terms of expanding the label into younger patients with focal epilepsy, and that's something we're working through right now, and we'll be submitting definitely our formal pediatric plans to both FDA and European regulators. Chris Kenney, anything to add kind of on your thought on expansion? Yeah, I mean, it's a similar answer to what I said about doses. I mean, we have the luxury of broad spectrum activity in preclinical models in conjunction with really robust clinical data in focal onset seizures. So we're looking at all potential avenues. You can be sure. We'll be, you know, sort of specifying what our plans are, again next year. Great. Thanks, Chris. Thanks, Ian, for your help. Next, we have Laura Chico from Wedbush Securities. Your line is now open. Hi, this is Sam on for Laura Chico. Thanks for taking the question. I'm wondering if you can tell me what the communication around the XEN1101 open-label extension study. So, just curious about how you're thinking about additional updates from that study? Thanks, Sam. That's a good question. As we had mentioned in our remarks, you know, it's very common to have 12-month OLEs, but we did extend for X-TOLE our open label extension to three years to generate some of that longer term safety data. We're not gonna have any cuts of the OLE data at AES, so maybe I can just be clear on kind of the near term. I expect that we will have some updates from the OLE in 2022. We haven't quite mapped out exactly where that is, but we will be wanting to share some of that data with FDA at the end of phase II meeting. But exactly where that fits in in the medical meeting schedule, we haven't mapped out yet, but I would expect that we'll see. We'll be disclosing some additional open-label extension data during 2022. Makes sense. Thank you. Yeah. Next, we have Marc Goodman from SVB Leerink. Your line is open. Sorry about that. Not sure what happened, but can you just talk a little bit about the upcoming meeting with FDA that you're planning on having? And what are your goals? What are kind of the key questions that you feel like you need to get answered there? Thanks. Chris, do you wanna address that? Sure. I mean, one of them, Ian already alluded to. As you take a look at the X-TOLE data, it's really quite robust, right? And if you take a look at the size of that study and the convincing nature of the efficacy data, we think that, you know, there's a reasonable chance that we're considering it as a pivotal trial. We just don't know if FDA agrees with that position or not. That'll be an important topic. Then the rest of it is, you know, sort of the typical stuff that you would expect. We're planning on doing, you know, at least we're gonna do at least one more randomized controlled trial in focal onset seizure. We wanna run the study design by them for that, although it's pretty basic from study to study, so not expecting any sort of surprises there. We've already talked about, you know, considering other areas of epilepsy besides focal onset seizures. We're gonna wanna go through, you know, all the implications of that in terms of making sure that they're on board with the study design and what implications there would be from a label perspective. Of course, there's toxicology, making sure that you're gonna be coming to the NDA with everything that they're gonna need to be able to support the clinical program from the tox perspective. Of course, the clinical pharmacology. So, we have a clinical pharmacology plan with several NDA-enabling studies, and we wanna make sure that they think that what we're doing is sufficient. Just so I'm clear, your plan is to do probably two studies, but that's not necessarily because you feel like you need two studies. You really think, I mean, obviously they'll confirm it, but you feel X-TOLE is a pivotal. You only need one more pivotal. The reason you do two studies is not for efficacy, it's really more for just enough safety data. Is that correct? The primary driver there is that, you know, if you take a look at the other antiseizure medications in terms of what they brought to the table at the time of approval, you know, they're fairly robust safety databases. So, we don't think that just doing another randomized controlled trial in epilepsy. We think that there would be, you know, a certain amount of regulatory risk there, that it would be a very thin NDA. So, we're planning on doing more, and what we're trying to figure out is, you know, what exactly that means. And so does that, you know, what other areas in epilepsy would we consider, et cetera. Thanks. All right. Next we have Yatin Suneja from Guggenheim. Your line is now open. Thanks. This is Eddie on for Yatin. Appreciate you guys taking the question. Thanks for the IP update. Can you remind us when the composition of matter patent and polymorph patents expire? And do you have any additional patents pending that could extend protection beyond 2040? And then when do you think we could see some MDD data from either the investigator or company-generated studies? Are there any post-hoc analyses from the X-TOLE study to support the MDD indication? Thanks. Thanks, Eddie. I mean, thanks for the question on IP. I think we've done an excellent job, you know, really identifying other ways to extend exclusivity. Obviously some of the work we've done over the last couple of years is now coming to fruition with some of these patents being issued. I think many people on the call know the base composition of matter when we acquired the drug, under Hatch-Waxman took us into the 2030s, but we wanted to extend that, and obviously we've had a strategy that's so far has been successful focus on the food effect as well as on polymorph. And the polymorph is, you know, polymorphs are compositions, in terms of the polymorph patent that's now being issued, that gets us out to, you know, 2039, 2040, absent any patent term extension there. There we do have other ideas that we are working on, but nothing yet that would take us past that timeframe. We're really focusing on that timeframe. In terms of your MDD question, we haven't guided on this. We believe although the Mount Sinai study's up and running, meaning that they are screening and they've randomized patients, so that's a really nice progress in the last quarter. Our study will start later, but we expect our study would probably go more quickly 'cause it'll be at multiple centers rather than just two. And when we've looked at other companies that have run kind of these phase II proof of concept studies, they've often had data in a reasonable period of time. So if we can get the study up and running, which is our expectation in the first half of next year, I think we could see MDD data in 2023. Appreciate it. Thanks for the color. Yeah, there was also a question there about whether X-TOLE data is needed to inform those studies. I mean, the major driver for the MDD trials is the preclinical data with XEN1101 and then the clinical data with ezogabine. So we don't necessarily need X-TOLE data to inform what we wanna do. All right. Next, we have Tim Lugo from William Blair. Your line is now open. Hey, guys. This is Lachlan for Tim. Thanks for taking the questions. On the topic of the MDD trials, you know, I realize it's early in the investigator-initiated study generally enrolled pretty slowly, but is there anything you can say about the enrollment progress or trends there that you're seeing in that study? On the company-sponsored one, have you made progress on the design for that in terms of, you know, I know dosing has been mentioned earlier, are you gonna allow concomitant therapies, any sort of high level criteria like that that you've decided on? Sure, Lachlan. I'll give a couple comments and then Chris can add as well. You know, we don't give guidance on any of our studies in terms of where we are with enrollment. But I will give the caveat that the investigator study is just up and running now, so it's very early days for that, but they have randomized, which is great. And in terms of our study, you know, we've given a little bit of color previously. I think one of the things that we have kind of paused on, although we're making good progress, is just trying to now incorporate our thinking with the X-TOLE data. So, that's really around kind of the final dose selection for our company-sponsored study. In terms of the endpoints, we will not have a functional MRI endpoint, which is the primary endpoint in the IST with Mount Sinai. We'll be focused on the clinical endpoints of depression and anhedonia, and it's currently being designed as a monotherapy study. Chris, any additional color in your thinking? I think you covered it. Nothing to add. Okay, great. Next, we have David Huang from SMBC. Your line is now open. It looks like David withdrew the question. Our last question is from Serge Belanger from Needham & Company. Your line is now open. Hi. Thanks for squeezing me in. A couple questions. First one on XEN007. Do you still plan to report results from the ongoing investigator study? Is that a program you could eventually partner? Secondly, regarding the Flexion collaboration, just curious if there's any changes in the economics of that collaboration with the expected change in control of that company? Thank you. Thanks, Serge. I'll answer the second one first. No changes to any of the economics as Flexion is going through their transactions. The new company would just step into their shoes in terms of the economics to the Xenon. So, no change there. In terms of XEN007, so the IST is continuing and will really be driven by the investigator in terms of her plan to publish data or present data at medical meetings. So, I do expect at some point we will see more data from that XEN007 study. And as I had answered in one of the questions earlier, we believe that the drug is active based on what we've seen. This is an open label study. And so, in terms of what our strategic optionality for that asset, I still think we have some really today's decision and communication in what we've been focused on internally in our planning is the work that that is coming for XEN1101 and XEN496 and the focus on that. But we absolutely feel that XEN007 is an active drug and we'll continue to support the investigator as she finishes off her study. And there are no further questions and that concludes the Q&A session. I will now turn the call back to Sherry Aulin for closing remark. I just wanted to say thank you everyone for joining us today and operator we will now end the call. And this concludes today's conference call. Thank you all for your participation. Enjoy the rest of your day. Keep safe and you may not disconnect.