Good day, everyone, and thank you for standing by. My name is Perla, and I will be your conference operator today. At this time, I would like to welcome everyone to the Xenon Pharmaceuticals 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. If you would like to withdraw your question, please press star one again. Thank you. I would now like to turn the call over to Colleen Alabiso, Senior Vice President of Corporate Affairs at Xenon. Please go ahead. Thank you. Good afternoon. Thank you for joining us on our call and webcast to discuss the azetukalner NDA submission and psychiatry program update. Joining me today are Ian Mortimer, President and Chief Executive Officer, Dr. Chris Kenney, Chief Medical Officer, Darren Cline, Chief Commercial Officer, and Tucker Kelly, Chief Financial Officer. After completing our prepared remarks today, we will open the call up for your questions. Please be advised that during this call, we will make a number of statements that are forward-looking within the meaning of applicable laws and regulations, including statements regarding the timing of and potential results from clinical studies, the potential efficacy, safety profile, future development plans and current and anticipated indications, addressable market, regulatory success, and commercial potential of our and our partners' product candidates. The efficacy of our clinical study designs, our ability to achieve milestones in our clinical development programs, including the completion of trial enrollment and the timing of top-line data readout from any studies, the timing and results of regulatory filings and our interactions with regulators, and our ability to successfully obtain regulatory approvals. Today's press release summarizing Xenon's azetukalner business update will be made available under the investors section of our website at xenon-pharma.com. I'll now turn the call over to Ian. Thanks, Colleen, and good afternoon to everyone joining us today. We'll start with brief remarks on the status of our new drug application in epilepsy, and then we'll move on to more detail on the psychiatry program updates. First, we're excited to share that we have submitted the new drug application, or NDA, for azetukalner to the U.S. FDA for the treatment of focal seizures, which is a big step forward to fulfill our goal of becoming a fully integrated neuroscience company. The NDA submission is based on positive clinical data from two pivotal randomized double-blind placebo-controlled trials for azetukalner in focal seizures, including the phase IIb X-TOLE study and the phase III X-TOLE2 study. Across both studies, treatment with all four doses of azetukalner, or AZK, demonstrated a statistically significant reduction from baseline in monthly seizure frequency compared with placebo. X-TOLE II outperformed X-TOLE with a 42.7% placebo-adjusted median percent change, or MPC, which to our knowledge is the highest placebo-adjusted MPC ever seen in a pivotal focal seizure study. azetukalner was generally well-tolerated, with a consistent safety profile observed in both studies, as well as the long-term safety observed in open label extension or OLE studies, such that across the entire epilepsy program, we now have more than 1,500 patient years of safety and exposure data. Our NDA submission is a significant milestone for Xenon as we continue to work toward the potential approval and launch of our first product. We also continue to broaden the potential geographic and therapeutic reach of azetukalner in epilepsy as we continue enrollment in our phase III X-TOLE3 and X-ACKT studies of azetukalner in focal seizures and primary generalized tonic-clonic seizures, respectively. In parallel, we continue to raise awareness and educate HCPs on our X-TOLE II data across the epilepsy community. For example, our team recently returned from the European Epilepsy Congress meeting in Athens, Greece, where they interacted with hundreds of HCPs and KOLs throughout the meeting. In addition, we had six presentations over the course of the congress. It was incredibly gratifying to hear unsolicited comments during our X-TOLE II podium data presentation, where two KOLs shared stories about how their patients' lives were significantly impacted with AZK. Beyond these congresses, our MSLs have been out in the community responding to HCP requests to learn more about our data. Epileptologists and general neurologists consistently provide us with positive feedback and excitement for both the X-TOLE II results and AZK's differentiated profile, including a novel mechanism of action, rapid onset of effect, durable reductions in seizure frequency, a generally well-tolerated safety profile, as well as once-daily dosing without titration, and no need for dose adjustments for other anti-seizure medicines. We feel increasingly confident in AZK's potential to become a preferred add-on therapy for the significant number of patients who do not achieve seizure control with initial treatment. Now, with our NDA submission complete, we continue to focus on building awareness of Xenon as an emerging leader and committed partner to the epilepsy community. Beyond epilepsy, we have been exploring the potential of AZK in psychiatry, where we believe KV7 modulation may provide a new treatment option for patients with depression, offering a different mechanism of action from the therapeutic options that are available today to help address significant unmet medical needs. We initiated our phase III program in psychiatry based on the results of our phase II X-NOVA proof of concept study, showing clinically meaningful improvements in depression and anhedonia with early onset to efficacy and a favorable safety profile. We are currently running two phase III studies in MDD, X-NOVA2 and X-NOVA3, as well as a phase III clinical trial in bipolar depression, the X-CEED study. These three studies are evaluating 20 mg of azetukalner compared to placebo. As announced today, we have voluntarily initiated a temporary pause in enrollment for new patients in our studies in Major Depressive Disorder and bipolar depression following a recent analysis of neuropsychiatric adverse events in these studies. We initiated this enrollment pause as a precautionary measure in consultation with the Data Safety Monitoring Board, or DSMB, and we expect it to be temporary. All patients currently enrolled in the randomized controlled psychiatry studies and associated OLE studies will continue on study. It is important to note that this voluntary action does not impact our ongoing epilepsy studies, where we continue to enroll new patients, and we remain highly confident in the approval and commercial potential for azetukalner based on its strong efficacy and safety profile in epilepsy. The pause is based on a review of adverse events across the ongoing studies in psychiatry. Specifically, we observed some neuropsychiatric adverse events which were mostly mild or moderate in nature. The number and severity of the events are consistent with the known profile of azetukalner and what we have seen across over 1,500 patient years in epilepsy. Although these are well-understood adverse events for this mechanism and for azetukalner, they were not observed in our phase II X-NOVA proof of concept study in MDD, where azetukalner was very well tolerated. Therefore, we have made the decision to temporarily pause new patient enrollments in the MDD and BPD studies to make adjustments to the dosing, which we believe will improve tolerability in psychiatry. We expect to make these adjustments to the studies over the coming months. Given this pause, we have also decided to complete X-NOVA2 enrollment based on the approximately 360 patients enrolled to date, which provides for a well-powered study that will enable us to evaluate the efficacy and safety of azetukalner in MDD in the context of a phase III program. We now expect top-line results for X-NOVA2 in the first quarter of 2027. I am now going to pass the call over to Chris, who can provide some additional perspective. Okay, thanks a lot. First, I want to echo Ian's statements about how excited we are to have achieved a major milestone of submitting the azetukalner NDA in focal onset seizures. Today is an important day as we move closer to bringing this meaningful medication to people living with epilepsy. Now, moving to the psychiatry program, it is important to review the scientific hypothesis and support for this clinical development program. Our hypothesis for azetukalner in depression is based on scientific evidence that Kv7 modulation could offer a novel mechanism to help treat MDD and BPD, where innovative treatments are urgently needed, especially those that may also impact anhedonia and that have the potential to offer differentiated tolerability profiles. Evidence includes our own phase II proof of concept X-NOVA study, which showed promising signals of antidepressive effects for the Kv7 mechanism, as well as genetic links in BPD with Kv7, including evidence of Kv7 downregulation. As you have heard from me before, the safety profile was benign in our phase II proof of concept X-NOVA study, which had lower incidence of adverse events compared to what we saw in epilepsy. In the X-NOVA study, mild to moderate adverse events were low and no serious adverse events were observed in the active treatment arms. As we have treated more depression patients in the phase III studies, both the blinded randomized studies and in OLE, we have seen certain neuropsychiatric adverse events. Those adverse events were mostly mild or moderate in nature and not new safety signals. Based on what we know, the rate and severity of those events are consistent with the mechanism of action and the extensive data we have for approximately 1,500 patient years of exposure in epilepsy. Therefore, what we are seeing in psychiatry, which is consistent with epilepsy, is a small percentage of patients with confusion, aphasia, ataxia, and a very small number of patients we have seen an adverse event captured under the broad preferred term of psychosis. For example, in the epilepsy randomized studies, there was one patient in X-TOLE and one patient in X-TOLE2 with psychosis. It is important to note that the neuropsychiatric events seen in epilepsy or psychiatry are short in duration and reversible without any long-term sequelae. Therefore, we are pausing recruitment to institute changes to improve tolerability within these patient populations, MDD and BPD. For example, based on work across the AZK program and consistent with other CNS drugs broadly, dose escalation can often have an impact on improving tolerability, and we are evaluating this as an option in our psychiatry program. We will be in a position to share our plans in the coming months. Given this pause in enrolling new patients in psychiatry for the X-NOVA2 study, we have decided to close enrollment with the approximately 360 patients who have already been enrolled, and we now anticipate top-line data readout in the first quarter of 2027. Completion of X-NOVA2 will give us a good look at the overall clinical benefit in an MDD patient population and a fuller understanding of the adverse event profile. Based on our initial target enrollment of 450 patients, X-NOVA2 was powered at 90% to show a 2-point difference from placebo on the primary endpoint of the HAM-D17. With current enrollment at approximately 360, as well as an analysis of the standard deviation, we believe the study is sufficiently powered at 90% to demonstrate a 2.5-point placebo-corrected difference, which is clinically meaningful. As a reminder, in the phase II proof of concept X-NOVA study, we saw a 3.1-point separation from placebo with 21 mg using the HAM-D17 at week six. Finally, before I conclude my remarks, I want to emphasize that this is a very exciting time for Xenon with the completion of the NDA for azetukalner. I want to congratulate the team for this accomplishment. With more than 1,500 patient years of safety and exposure data, we are confident that azetukalner's profile is consistent with other well-tolerated anti-seizure medications and is indicative of a drug that is potent and active in the central nervous system. Azetukalner has the potential to deliver much-needed innovation to treat focal seizures in epilepsy with strong efficacy, a differentiated mechanism to add-on, once-daily dosing with no dose adjustments for other ASMs, and a generally well-tolerated safety profile. Ongoing scientific exchange opportunities have affirmed our belief that if approved, azetukalner will provide an important therapeutic option with appeal to epilepsy specialists, general neurologists, and advanced practice providers alike. With that, I'll turn it back to Ian for closing remarks. Thanks. Great. Thanks very much, Chris. We remain focused on our mission of delivering innovative medicines to provide a brighter future for people living with neurological and psychiatric disorders. We are making great progress toward the potential launch of azetukalner as an important new treatment option for patients living with focal seizures, and we're working to make the necessary adjustments in our psychiatry program that we believe will have a positive impact on the adverse event profile in the best interest of patients and the program. With that, operator, we can now open the call up for questions. Thank you. We'll now begin the question- and- answer session. If you would like to ask a question, please press star one on your telephone keypad, and if you would like to withdraw your question, please press star one again. As a reminder, please limit yourself to one question only. If you have additional questions, please rejoin the queue. Your first question comes from the line of Paul Matteis with Stifel. Please go ahead. Hey, thanks a lot guys for taking my questions. I appreciate it. I think when looking back at some of the data, I remember you guys seeing confusional AEs in phase I healthy studies like we see with a lot of anti-epileptic drugs. But, can you just expound upon the psychiat or I guess the psychosis AEs and like how I guess just in the grand scheme of things, how problematic is this to the risk-benefit overall in MDD if the drug works? Do you actually think you have a registerable and commercially viable profile on this based on what you've seen to date? Is there any plan here to engage the agency or any need to engage the agency, or do you feel comfortable that just in terms of studying the drug, the risk-benefit here is still overwhelmingly favorable and there is no regulatory issue? Thank you. Thanks, Paul. I will take your second one and then maybe make a couple of comments, and then Chris can go into a little bit more detail on what is really a rare event of psychosis that, as we said in the prepared remarks, we have seen a couple of patients in the epilepsy program. Overall, this was, just to be clear, and I think we were in the prepared remarks, this was a decision that we made as a company to pause the psychiatry program for new enrollment. Patients that are on study will continue on study, both in the double-blind randomized portions as well as in the open label. In terms of FDA, we have given notice to FDA on what we are doing, and we have given notice obviously to our clinical sites. We believe that we will continue to move forward in terms of making the necessary adjustments, making those adjustments to the protocol and moving forward. Overall, on the adverse event profile, as we said, the profile in epilepsy is obviously incredibly well understood with all of the exposures, and we see, as you know, dose-dependent adverse events, things like dizziness and somnolence. Then to a lesser extent, we see some of these events like confusion or aphasia or ataxia. Then, as we said, in a very small number of patients, we have seen something under this broad preferred term of psychosis. As we mentioned, we saw one patient in X-TOLE and one patient in X-TOLE2, just to give you a little bit of that background, because I think it is important to note that what we are seeing in psychiatry is consistent with what we are seeing in epilepsy. Chris can give you a little bit more detail. Yeah, thanks a lot, Ian. So just as a reminder, Paul, when we relayed the X-TOLE data, the phase IIb study, there was one patient within that study that had psychosis, and then there was a similar pattern in X-TOLE2, where there, again, we relate one patient in that study that had psychosis as well. You can do the numbers. It's hovering around 1% or under. The important point about these is that they're reversible, that they're relatively short-lived, and that none of these patients have had any long-term negative effects from these events. I think those are the critical points. If you look at other drugs that are used for depression, they do cause serious adverse events sometimes in keeping with this, along the lines of psychosis, sometimes other issues. We don't think that this is something that prevents this drug moving forward. We view this pause as temporary. We're going to make some adjustments and then go forward. Maybe, Paul, I'll just have Darren's here with us as well. Maybe Darren can just provide his comments on Chris talked about the overall profile and comfort moving forward. Obviously, we need to unblind our phase III program and determine the efficacy in Major Depressive Disorder the commercial profile as well. Darren. Yeah. Paul, clearly, I think we believe this mechanism is important in this MDD patient population, and any signs of efficacy provides still a tremendous opportunity because of the unique mechanism and some of the characteristics that azetukalner will provide for patients. I do think to Ian's point, when we unblind X-NOVA2, it'll be important for us to think about moving forward. We really remain very optimistic about the commercial opportunity. Thank you. Your next question comes from the line of Tessa Romero with JP Morgan. Please go ahead. Hey, guys. Thanks so much for taking our question. Just to kind of follow up here, what specifically leads you to think that maybe a dose regimen change might help you alleviate this, though it seems like it's quite rare? Can you talk a little bit about any kind of dosing modifications that you might want to look at here? Final question from us is just to be clear, do you see any read-through to the known profile that you have here in epilepsy based on the over 1,500 patient years of safety and exposure data that you have? Thanks. Thanks, Tessa. Maybe, yeah, let's start with your epilepsy question because I think that's critically important. Today was a big step forward for us. This is the first new drug application that we've filed as an organization and really starts the clock in getting us closer to being a fully integrated company and commercializing AZK in epilepsy. We have done an incredible amount of drug development on AZK. I think we understand the profile incredibly well, and we know it incredibly well in epilepsy. As we shared for the first time today, we have over 1,500 patient years of exposure in epilepsy. So we understand both in a double-blind randomization, the randomized period in X-TOLE and X-TOLE2. As you know, we now have patients that have been on the drug for more than five years. So we have a really good understanding of the profile. Over the last number of months, we've had a chance of writing an NDA. So putting together an ISS, really putting together our arguments on benefit risk, and we're highly confident, obviously, in the application, the approval, and how important this medicine is going to be in treating patients with focal seizures. So absolutely nothing has changed there. As we move to psychiatry, today's pause is really about can we make some adjustments to improve the tolerability profile. As Chris mentioned in his remarks, this is very common in CNS drug development, and we gave an example of dose escalation to manage around tolerability, and we believe we can make some adjustments that has the potential to have that positive impact on the tolerability profile. So we felt it was the right time to make those adjustments. We're going to have X-NOVA2 at 20 mg, and those data are going to be available quicker than we had expected. Those are going to be available in Q1 of next year. That'll give us a really good understanding of the benefit-risk, efficacy, and safety. Then in X-NOVA3, we'll have the opportunity to make this adjustment where we can see is the adjustment in dosing that we're still working through, but we have some really good ideas, and we gave the example of dose escalation. What impact will that have? Then we can compare that to the overall profile without the changes in dosing. I feel like we're in a good spot right now. We can make these adjustments. No read-through to epilepsy. We're going to learn a lot about this drug in psychiatry over the coming quarters. Yeah. Just maybe I'll build on that. We've shared the phase II and the phase III epilepsy studies. There's a bunch of work that has to be done with NDA enabling studies to enable the submission, which we've done. In the context of doing that, some of those studies, the details of which have not been shared publicly, have allowed us to use gradual increases in doses. We do have some data on that front. Then also within the epilepsy program, as patients go from whatever they were randomized to, say placebo or lower dose or higher dose, then they go to the open label study, you can get an idea of whether someone tolerates the drug better if they were started on a lower dose and then transitioned to a higher dose or not. It's sort of triangulating all that data is leading us down a path where we think that dose escalation is at least one of the options we should seriously consider to improve tolerability. Thank you. Your next question comes from the line of Andrew Tsai with Jefferies. Please go ahead. Hey, good afternoon. This is Matt Barcus calling in for Andrew Tsai. I just wanted to ask, as you saw these safety signals emerge, did you notice that they came as, was it earlier on treatment, or was it with longer drug exposure? With your NDA submission for epilepsy, do you see anything changing with your overall launch strategy there? Do you think that with the new safety signals in psychiatry, any impact on general neurologists' comfort levels with prescribing AZK? Thanks. Thanks, Matt. I am happy to take your first question, then I will pass it to Darren, because Darren has been ramping up aggressively and getting ready for launch. He can comment there. Overall, I would say, this is a general statement, and we are not going to get into specifics here, but as a general statement, most of the adverse events that you see with azetukalner, which is consistent with other drugs that are very active in the CNS, generally show up early. Patients tolerate them over time. That is a general rule that we see as well. Obviously, that is not for every single patient. Like I had mentioned earlier, I think we have a really good understanding of the profile of this medicine. As a general rule of thumb, to answer your question, patients that do show adverse events across the board, generally those are on either changes in dose or initiation of dose. I think your second question is a really good one. I will pass it to Darren just to talk about our launch plans. Yeah. With today's NDA submission, as we said, we are one step closer to becoming a fully integrated biopharma company. Nothing changes on our launch plans for AZK in focal onset seizure. Post the X-TOLE2 data, we have been able now to actually do market research, advisory boards, and we referenced the most recently last week in Athens with a lot of physicians in the profile of AZK with patients with focal, whether it is with epileptologists or general neurologists. They couldn't be more excited about the efficacy that we show. The safety profile, as we point out, are generally well-tolerated and really no surprises for them as they treat these patients with focal seizures with other anti-seizure medications. Obviously, we have talked a lot about and really rings through, which will make us a differentiator in the market as our ease-of-use attributes. I think as we think about the read-through of this with epilepsy, I do not see any at all. We are super excited and continue to be emboldened every day as we prepare for the launch of AZK in focal seizure. Matt, just one quick thing. Going back to your question about the early part. We do see rapidity of onset with this drug, whether you are talking about the depression study or you are talking about the focal onset seizure studies. From an efficacy standpoint, we see efficacy quickly. Many of these adverse events, particularly the ones that we are talking about right now, tend to happen earlier rather than later. It is a really important point. I am glad that you asked it, and it is one of the reasons that ties into why we think that going up more gradually in the dose will improve tolerability in the context of the psychiatry program. Thank you. Your next question comes from the line of Brian Skorney with Baird. Please go ahead. Brian, you might be on mute. Apologies. This is Luke on for Brian. Thanks for the question. From your analysis of the epilepsy and neuropsych trials, are there underlying familial or other risk factors for psychosis that the patients may have demonstrated? Does it seem largely stochastic in nature? With regard to monitoring, do the AEs seem correlated with other AEs, such as confusion or others? Thanks. Yeah, sure. Thanks, Brian. Thanks for the question. Yeah. We're looking really closely at what sort of predictors could there be for these adverse events. The biggest challenge is that they don't happen that often, so it makes it really tricky to be able to figure that out. So far there isn't anything that's leaping out from the data that gives us an obvious answer to that question. Although, we're going to continue to look. Yeah, I think Luke, that was your question, right? Was there something you had before that I- Yeah, just I guess the risk factors and then the correlation with other AEs. Oh, yeah. That was it. Most patients, I would say we're seeing these as isolated, although there are some where there's a clustering of some of these adverse events, depending from one patient to another. Generally, they're isolated. Okay, your next question comes from the line of Joseph Thome with TD Cowen. Please go ahead. Hi there. Good afternoon, and thank you for taking my question. Maybe can you provide a little bit more detail about what triggered the analysis? Was this sort of a pre-planned DSMB meeting, or is there something specific that kind of triggered it, like discontinuations or anything? Then second, why do you think you didn't see these AEs maybe in X-TOLE? Do you think there's anything different about the baseline populations that you enrolled, or is it just a symptom of enrolling a couple of hundred more patients in these trials? Thank you very much. Thanks, Joe. I'm happy to take it. I think in your question you said X-TOLE, but I think you were probably referring to the X-NOVA, right? The phase II psychiatry study. I think you probably were, so I'll carry on with that. Obviously we always track blinded data in all of our studies, so we have a bit of an indication. Obviously now in the phase III psychiatry program broadly, we've enrolled hundreds and hundreds of patients, so we're getting a better idea of that. Then in consultation with our DSMB, we had a review like we do with our DSMB across all of our programs, had a review of the data. That discussion between us and the DSMB resulted in the pause of the psychiatry program. I think really a discussion between us and the committee about making some of the adjustments that we've talked about. I think Chris in the last couple of questions has provided really good answers on kind of why we have confidence in making the adjustments that we're going to make going forward. Then I think the second question you had was really, we didn't see these adverse events in the phase II proof-of-concept study, which was the X-NOVA study, which Chris' prepared remarks used the term that it was reasonably benign, and it really was. As we got into a larger patient population, there is nothing that we see in the data that it is a different patient population, but rather it was a small proof of concept study, as we went to a larger study, we are seeing these events that as we have characterized them, nothing new, well understood, and really consistent with the profile that we have been seeing for a number of years across studies in epilepsy. Thank you. Your next question comes from the line of Brian Abrahams with RBC Capital Markets. Please go ahead. Hi, everyone. This is Nevin on for Brian. Brian is tuning in, but it is just in a little bit of a noisy environment, so just taking the question for him. We were just wondering if you had seen any particular imbalances in these AEs coming from either the bipolar trial or the MDD trial. Anything about the kind of nature of the patients that might have resulted in these AEs that you are seeing. Just given that we saw a recent similar kind of clinical pause from a competitor of yours with the same class, although we do not have any additional kind of color on that, just wondering if there might be potential for class effects here, or if this is something that regulators might want to see, how you think that might impact potential label in epilepsy, whether there could be a black box, any other considerations that we should take into account. Thanks, Nevin. You had a bunch there, so if we miss some of them, just jump back in and we can come back to them. I'll start on some of these, and then Chris, if you can give your perspective. Obviously, we know a lot more in the MDD program just given the advanced stage of X-TOLE2, or sorry, of X-NOVA2 and X-NOVA3. Obviously, we know a lot more. My comment, Nevin, and Chris can provide his perspective, is we know a lot more about the MDD profile than we do about the bipolar profile, just on kind of where those studies are and how many patients we've enrolled across those two therapeutic indications. Look, your question on, well, we've read what you've read in the public domain on a partial clinical hold from another Kv7 drug, and we don't have any more information than that. There's nothing that we would believe in what we've read publicly there, that there's any connection to the adverse event profile of azetukalner that's incredibly well understood. Obviously, we've done a huge amount of drug development with azetukalner over the last almost decade. Not only the large randomized studies that we've talked about, but as Chris had mentioned earlier, we've done a huge amount of work on clinical pharmacology. So we have a really good understanding of this profile, which is very consistent with this mechanism and a very active drug in the CNS and the data that we're seeing. I don't expect that this is anything that's broader than what the two Kv drugs are specifically just working through. But Chris, maybe you can just talk about, Nevin had a question about the imbalances. I think it's really too early to tell until we get a little bit more advanced, and obviously we haven't unblinded any of these phase III studies. You asked about the nature as well. The nature is similar between all the populations. Then since they're ongoing studies, I can't answer your question about what the imbalance is. In Q1, we'll have an answer to that question when we unblind X-NOVA2. Thanks, Nevin. Your next question comes from the line of Myles Minter with William Blair. Please go ahead. Hey, team, this is John on for Myles. Thanks so much for taking our question. Wondering if in the latest OLE data cut out to seven years in X-TOLE, if any of these neuropsych issues were observed, and if so, at what doses? Are these events really just limited to early dosing? Second, wondering if you could just talk to the magnitude of any potential dosing changes you could take to move forward here, especially with the knowledge that you've gained from the X-NOVA phase II, which was dose ranging. Thanks, John. I'll take the second part, and then Chris can take the first part. In terms of, obviously, we have a huge amount, as you mentioned, open label data, especially you had referenced the X-TOLE program where we have patients that are more than five years now. Just as a reminder, when patients go from a double blind to an open label, some of those patients are on placebo, so they're still getting exposure to the drug for the first time in open label. As Chris had mentioned, some of them are changing dose if they were going from a lower dose to a higher dose. In terms of what we learned from the X-NOVA program. As a reminder, the X-NOVA program, we had two active doses in placebo, 10 and 20 mg. Reasonably small study, just over 50 subjects per arm. We saw a clear dose response. 10 mg as we think about the key clinical endpoints of depression like HAM-D17 or MADRS or the endpoint of anhedonia measured by SHAPS. We saw a clear separation between 10 mg in placebo and 20 mg outperformed 10. This is really consistent about this drug and this mechanism across all of the indications that we've tried it in, right? There's a clear dose response both in terms of efficacy. In epilepsy, we've tested 10, 15, 20, and 25, and in depression we've tested 10 and 20. As you go up in dose, you see a greater effect on the efficacy measure, and you see increased adverse events as well. So it's a really well-behaved drug and well understood from a pharmacology point of view. I don't think that's any different. Obviously any different whether we're thinking about psychiatry or epilepsy. That and then taking into consideration the potential for dose escalation, I think is really how we're thinking about the plan moving forward. I think we have a plan where we can help mitigate some of these adverse events in psychiatry. Chris, do you want to go through the OLE data? Yeah. First of all, we're going to be sharing the data in detail again at the American Epilepsy Society at the end of the year. Also kind of getting into some of the pool data that's being submitted to the NDA for FDA today. Ian sort of already answered your question. So depending on which study you look at, there's more patients in active than placebo. There's a minority of the patients are going into the open label from the double blind studies, but some of them haven't been exposed to azetukalner. These events are happening. It's even less rare because most of the patients have already been exposed to drug and only a fraction of them are now being exposed to placebo. But it's in keeping with what we've seen in a double blind, but to a lesser extent because of the less newer exposures. Just one other thing. You said what is the magnitude of the dosing changes? We need to work this out, but we know our data really well. In answer to Tessa Romero's question, I talked about some of the clinical pharmacology studies that we've done. We are heading down. I think the dose escalation path makes a lot of sense, and if that's the path that we choose, we just need to mobilize drug supply, and this would be a temporary pause. Thank you. Your next question comes from the line of Cory Kasimov with Evercore. Please go ahead. Hi, this is Addy on for Corey. Can you please again explain why is there no epilepsy implication if the events are mechanism consistent given epilepsy uses 25 mg versus 20 mg in psychiatry? Thank you. Yeah. Just to be clear, we are seeing a pattern. What we are seeing within the depression population has been seen in epilepsy. It's been shared with the outside world. We talked about one case in the X-TOLE study. We talked about one case in X-TOLE2. What the difference here isn't that these events have gone up in epilepsy. What's gone up here is that we have more exposures in the depression population. As a result of that, we are starting to see similar patterns in the MDD population. The reason why we say that there's no implication in epilepsy is because we have 1,500 patient years of exposure in epilepsy. We know that data really well. We've shared all that relevant data with the outside world, and nothing has changed on that front. The big question is why did we not see any of this in phase II and now it's emerging at relatively slow rates in phase III? There's some speculation around that. One thing that's obvious is that we have substantially more patients on AZK in that population, and therefore you're better able to detect a relatively rare event. All right. Thank you. That concludes your question- and- answer session. I would like to hand it back to Ian Mortimer for closing remarks. Great. Thanks everyone for joining us today. If we didn't get a chance to get to your question during the allotted time, please reach out to us directly and we'll be available to connect. We look forward to providing additional updates as we move forward, as we advance our programs and deliver on important milestones. Operator, we can now end the call. Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you all for joining. You may now disconnect.