Good day, and thank you for standing by. Welcome to today's conference call. Xenon Pharmaceuticals provides corporate update. At this time, all participant lines are in listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you'll need to press Star, then one on your telephone keypad. Please be advised today's conference may be recorded. If you require operator assistance during the call, please press Star, then zero. I'd now like to hand the conference over to Sherry Aulin, Chief Financial Officer of Xenon Pharmaceuticals. Please go ahead. Good morning. Thank you for joining us on our call and webcast to discuss our XEN 1101 program, including phase IIb X-TOLE clinical data that will be presented in a poster session at a Xenon-sponsored scientific symposium at the 2021 annual meeting of the American Epilepsy Society, or AES. Joining me today 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. Ian will provide some opening remarks. Chris Kenney will provide a summary of the top-line X-TOLE data which was previously announced on October 4th, as well as the additional completed sub-analyses to be presented at AES. Chris Von Seggern will provide some commercial context for the X-TOLE data. Finally, Ian will provide a summary of our XEN 1101 plans moving forward 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 potential efficacy, safety profile, future development plans, addressable market, regulatory success, and commercial potential of XEN 1101, the anticipated initiation of future clinical trials for XEN 1101, the timing and results of our planned interactions with regulators regarding XEN 1101, and our ability to successfully develop and obtain regulatory approval of XEN 1101. 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. A news release summarizing our X-TOLE-related presentation at AES was distributed this morning, along with a separate news release outlining our other scientific posters and activities at AES. To support our call this morning, a slide deck summarizing all of the X-TOLE data presented at AES has been uploaded to the investor section of our website. Concurrent with our various AES activities, we will post additional materials, including the symposium slide deck and each of our scientific posters on the publications page under the medical affairs section of our website. Now, I would like to turn the call over to Ian. Thanks, Sherry, and good morning, everyone, and thanks for joining us today. We are incredibly excited to be in Chicago with a significant presence at AES, built around our positive phase IIb X-TOLE top-line clinical data announced in early October. Our late-breaking abstract with lead author Dr. Jacqueline French was accepted by AES and will be presented in a session tomorrow afternoon. We are also hosting a scientific symposium this evening highlighting the role of potassium channel openers in the treatment of epilepsy and depression. At both of these sessions, we will outline the X-TOLE top-line data and share additional sub-analyses that have been completed since the release of top-line data in October. These new analyses continue to support our high degree of confidence in XEN 1101 and our belief that XEN 1101 could play an important role in treating adult focal epilepsy, with potential in other indications as well. In addition to these events, we are participating in a joint industry scientific exhibit related to rare genetically defined epilepsies, with a particular focus on our other Kv7 program, XEN 496. As Sherry mentioned, I encourage you to read today's news releases, download the slides accompanying this call, and review our other posters at AES once they're posted on the website. I'll now turn the call over to Chris Kenney, who will comment on the X-TOLE data as presented at AES. Chris. Thanks, Ian. We're excited to present detailed clinical data from our XEN 1101 X-TOLE phase IIb clinical trial at the AES meeting. Importantly, data from additional analyses of subgroups in the X-TOLE study are consistent with the top-line data set, which demonstrated strong evidence supporting the efficacy, safety, and tolerability of XEN 1101. 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. Beginning first with the efficacy results. The trial met its primary efficacy endpoint, showing a monotonic dose response relationship between the XEN 1101 active dose groups compared to placebo, which was statistically significant. In other words, a P value less than 0.001. XEN 1101 also demonstrated a statistically significant reduction from baseline in monthly focal seizure frequency in pairwise comparisons to placebo from all three XEN 1101 doses with two-sided P values of less than 0.001 for both high doses, 20 mg and 25 mg doses. A pre-specified secondary endpoint of the study was a responder analysis, which compared the proportion of study subjects treated with XEN 1101 who achieved a greater than 50% reduction in monthly focal seizures versus placebo. The percentage of subjects who achieved a greater than 50% reduction in monthly focal seizures was 54.5% in the XEN 1101 25 mg group, 43.1% in the XEN 1101 20 mg group and 28.3% in the XEN 1101 10 mg group, compared to 14.9% in the placebo group. Statistical significance was achieved for all dose groups compared to placebo with two-sided P values of less than 0.001 for both the 20 mg and 25 mg doses. Additional sub-analysis of these top-line data have been completed and are being presented at AES, including an analysis of the proportion of patients with at least a 75% reduction in monthly focal seizure frequency from baseline, along with the proportion of patients who achieved 100% reduction in monthly seizure frequency from baseline. Some of these sub-analyses were performed in subgroups of patients with varying baseline characteristics, given that X-TOLE included a difficult to treat patient population, as defined by the number of prior failed anti-seizure medications, concomitant anti-seizure medications while on study, and baseline seizure burden. Upon review of the scientific literature, we believe that the X-TOLE demographics represent one of the most severe patient populations studied in an adult focal epilepsy clinical trial to date. Even in the context of this very difficult to treat population, XEN 1101 demonstrated impressive efficacy. More than half of the patients in the 25 milligram group experienced at least a 50% reduction in monthly focal seizure frequency from baseline, and further, the majority of these patients actually experienced a 75% or greater reduction in monthly focal seizure frequency from baseline. Seizure freedom was attained in a subset of patients consistent with other anti-seizure medications, despite the higher level of disease severity in the X-TOLE population compared to other focal onset seizure studies completed to date. At 20 mg and 25 mg, the seizure freedom rates were 7.8% and 6.3%, respectively. Importantly, in those patients with less severe seizure burden at baseline, less than 8.5 seizures per month, we saw seizure freedom rates of 17.6% and 13.8% in the 20 mg and 25 mg dose groups, respectively. These data suggest that seizure freedom rates might be higher in a population of patients with less disease severity. Building on these analyses of the less severe patients, we analyzed the median reductions from baseline in monthly focal seizures at 25 mg based on the number of previous anti-seizure medications failed, the number of concomitant anti-seizure medications, and the baseline seizure burden. Across the board, we see increases in seizure reduction in patients with less disease severity. For example, the median reduction of seizure frequency was 58% in patients who had failed less than a median of 6 anti-seizure medications prior to study initiation and 64.5% in patients who are on 1 or 2 concomitant anti-seizure medications. In patients who had less than 8.5 monthly seizures at baseline, the data was even more dramatic, with a median reduction of seizure frequency of 70.6%. Another interesting sub-analysis looked at seizure reduction across seizure subtypes, including Type 4 seizures, defined as focal seizures that lead to the more severe generalized tonic-clonic seizures. These data showed a median percent reduction in monthly focal seizure frequency of 86.9% in Type 4 seizures in the 25 mg dose group. Overall, we believe these data continue to support our confidence in the significant efficacy of XEN 1101 in the potential clinical use population. Turning now to XEN 1101 the safety profile. XEN 1101 was generally well tolerated in this study, with adverse events consistent with other commonly utilized anti-seizure medications. The complete adverse event table will be presented at AES. In summary, the most common treatment-emergent adverse events, or TEAEs, were dizziness, somnolence, fatigue, and headache, and these were seen in a dose-dependent manner. Dizziness was the most common adverse event seen in 31.6% of patients in the high-dose 25 mg group. As a reminder, the vast majority of these AEs are mild or moderate, and with additional analysis now complete, we know that the majority of these occur in the early treatment period. In addition, we do observe other adverse events consistent with an active CNS drug. These are generally seen in a dose-dependent manner, were expected, and consistent with a highly active anti-seizure medicine. As discussed in October with our top-line results, the incidence of treatment-emergent serious adverse events was balanced across the four arms of the study. AEs that led to treatment discontinuations was also presented in October and was seen in a dose-dependent manner, with 3.5% of subjects in the placebo group, 2.2% of subjects in the XEN 1101 10-mg group, 13.7% of subjects in the XEN 1101 20-mg group, and 15.8% of subjects in the XEN 1101 25-mg group that had an adverse event leading to treatment discontinuation. A few additional comments on safety and tolerability. As we disclosed previously, there were two transient adverse events of urinary retention that were reported in the active treatment groups, one of which required a dose reduction, and both subjects remained on drug with no other changes or interventions required. We now have additional data from the American Urological Association Symptom Index, completed by all patients, which show no evidence of urinary retention based upon mean differences across treatment groups in either the total or individual items. There was no cardiovascular signal of concern based on vital signs, including orthostatic tests. There were no safety signals of concern from physical or neurological exams, and there was no signal of concern from ECG safety labs or urinalysis. Weight changes were modest, with an increase noted in all treatment groups. The mean increase of 0.2 kg was noted in placebo, 0.6 kg in the 10-mg group, 1.6 kg in the 20-mg group, and 1.9 kg in the 25-mg group. There have been no treatment-emergent adverse events of pigmentary abnormalities reported during the double-blind phase of the study or in preliminary analyses during the ongoing open-label extension to date, with approximately 80 subjects now treated more than 12 months. Overall, now that we've spent a significantly more time with the safety data and completed additional analyses, we're very comfortable with the AE profile of XEN 1101, given the impressive efficacy and that AE seen to date are predictable, dose dependent, the majority are mild or moderate and occur early in treatment. This adverse event profile is in line with other anti-seizure medications and as expected, given XEN 1101's high degree of activity in the central nervous system. Based on the totality of these X-TOLE results and given XEN 1101's ease of use attributes and unique potassium channel mechanism of action, we believe XEN 1101 could play a very important role in treating focal epilepsy in the future. Which is a good segue to turn the call over to Chris Von Seggern, who will share some insights from our primary market research. Chris. Thanks, Chris. We continue to share our XEN1101 data with epileptologists and neurologists to gather feedback and shape our thinking going forward. As a reminder, following the X-TOLE results, we surveyed 148 prescribing epileptologists and neurologists in the U.S. to understand their perspectives on the XEN1101's anticipated product profile. To build upon the learnings we gained from earlier primary market research with 50 clinicians across the U.S. Overall, the profile of XEN1101 was very well regarded. 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. As Ian and Chris noted, XEN1101 showed a dose dependent, highly statistically significant and clinically meaningful seizure reduction in a patient population that could be characterized as very difficult to treat. For context, this heavily pretreated patient population failed a median of 6 ASMs, and 50.8% were on 3 background ASMs. Further, in the patients with less severe disease at baseline, XEN1101 demonstrated improved efficacy, suggesting a very strong profile in the patient population that we believe is most likely to receive XEN1101 if approved. In light of the strong efficacy in the overall product profile, physicians indicated comparable utilization of XEN1101 to Vimpat, which, if approved, would position XEN1101 to compete for the first branded opportunity for patients with residual seizure burden. Given the substantial efficacy demonstrated in the X-TOLE results, combined with all that 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 a therapeutic armamentarium for this disease. I'd now like to turn the call back to Ian for an outline of our future development plans with XEN1101 and closing remarks. Ian? Thanks, Chris. Since announcing the top line data, we've focused on building out our phase III development plans for XEN1101. We believe the X-TOLE data package provides compelling evidence of XEN1101's activity in the CNS, and our team is focused on finalizing the clinical development plans for XEN1101, including a phase III program in adult focal epilepsy and likely other epilepsy indications. We expect to conduct a planned end of phase II meeting with the FDA in the second quarter of 2022, followed by the initiation of our phase III adult focal epilepsy program anticipated in the second half of 2022. In addition, the X-TOLE open-label extension, which has been expanded to three years, is expected to generate important long-term data for XEN1101. We are also advancing the clinical development of XEN 1101 in major depressive disorder through an investigator-led phase II proof of concept study with collaborators at Mount Sinai, and we intend to initiate a company-sponsored MDD clinical trial in the first half of 2022. In addition to these clinical advancements, we also continue to expand the intellectual property portfolio covering XEN 1101. We've made excellent progress on this front with two new U.S. patents issued to Xenon this year that we believe provides long exclusivity for XEN 1101. We are excited to have the opportunity at AES to further educate and inform leading epilepsy clinicians and physicians about XEN 1101. 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 XEN 1101 could play an important role in treating adult focal epilepsy. For those of you who are attending AES, we look forward to connecting with you in person. As always, you can set up virtual meetings to discuss the progress and plans for XEN1101 and the other innovative neurology-focused therapeutics in our pipeline. I'll now ask the operator to open the line for any questions. Liz? Our first question comes from Brian Abrahams with RBC Capital Markets. Hey, good morning. Thanks guys for taking my questions and congratulations on the continued promising data and appreciate all the details in the slides. Just a couple of questions for me. I guess first off on dosing and how you're thinking about dosing going forward. I mean, if you take a look at the response rate analyses, 75% and 100% responders, 20 milligrams seems to be tracking about as good as 25 milligrams, a nd it also seemed to show a large drop in monthly seizures, even though even if the medians were maybe a little bit less robust on the change versus the 25 milligrams. Just given what you're seeing there on efficacy with these, with some of these new sub-analyses, as well as some of the lesser AEs in terms of dizziness and weight gain, how do you think about 20 milligrams as a potential go forward dose? What's your latest view on what you might be taking into phase III based on what you're seeing emerge here, as well as maybe some of the other PK that you're looking at as well? I had a follow-up. Okay. Thanks, Brian. I'll start and Chris will add as well. We haven't. I mean, great question, and probably what we're spending the most of the time internally is figuring out the final phase III program, including the dosing. You know, I think we're comfortable that we'll take two doses into the phase III program. We haven't yet finalized the two doses, but obviously in the range in which we've presented data so far, between the 10 and 25 mg. I mean, your comments, I think, are good ones on starting to tease apart the differential between 20 and 25 mg. We're just not there yet in terms of the final dose selection. We do feel when we have the product eventually, commercially marketed, that there will be, you know, more than one dose, available, as obviously, we're seeing increased efficacy at the higher doses. We need other doses for patients to go to if there are tolerability concerns or any AEs that are. Chris, more detail? Yeah, sure. I mean, I think, as I said, when we presented the top line data, I think we're in a luxury position where we have three doses, all of which or any of which could go forward into phase III. To your point, you know, comparing and contrasting 20 and 25, I think both doses behaved really well, both exceeded ezogabine as an example., b ut, you know, when I look at the totality of the data, 25 milligrams, at least in my mind, outperforms 20 milligrams across the board. So as you look at, you know, the mean percent change in seizure frequency, as you look at the responder rates at 50%, as you look at Clinical Global Impression of Change, Patient Global Impression of Change. Across the board, all these sub-analyses that we shared today, 25 always outperforms 20 from an efficacy standpoint. Then, you know, on the safety side, there is a small cost for that increase in dose in terms of dropouts and common AEs like dizziness. At least in my mind, as a clinician, I think that the benefits outweigh the downsides by a substantial margin. That said, I think they're both good doses, and as Ian said, we're working through trying to figure out which doses should go forward in the coming months. Got it. That's really helpful. Just maybe one more quick follow-up on the safety side. It looks like there was a little bit of blurred vision that seemed to be highest at the 25-milligram dose. Just wanted to clarify, I guess whether this was more related to kind of the spectrum of dizziness, somnolence, and CNS AEs, or whether you had done any particular ophthalmologic exams on those patients, just given the pigmentation history with ezogabine. I'll hop back in the queue. Thanks. In terms of the safety, I mean, this was a large trial, over 300 patients. Y ou think in the scheme of things in terms of figuring out what sort of safety signal is real or not, it really is on the lower side. I think that, something like blurred vision, I would wanna sort of pool a larger number of patients before I was convinced that anything was going on. I think what's behind that question, and tell me if I'm wrong, could this be an indicator of something more ominous from an ophthalmologic standpoint? A s many of you know, ezogabine can dimerize because of its chemical structure, not because of its mechanism of action. Our chemical structure differs from ezogabine in an important manner that makes us think that this drug cannot dimerize. That said, we're putting an enormous amount of effort in checking ophthalmologic examinations for all patients prospectively. We haven't seen any pigmented changes in the retina in any of these patients from the ophthalmologic standpoint, with like more than 80 patients treated for over a year. We're pretty confident based upon the data set, at least where it is right now, that we're not having any ophthalmologic toxicity. You know, yeah. Does that answer your question? That does. Thanks again. Just a reminder that is star then one, if you'd like to ask a question. In the interest of time, we ask that you limit yourself to one question, then rejoin the queue for any follow-ups. Our next question comes from Andrew Tsai with Jefferies. Okay, great. Thanks. Good morning. Thanks for sharing all this data sets. I think the breakdown by efficacy, by line of therapy, I mean, is interesting and might be underappreciated. A s I think about your phase III studies, and the design, would you guys consider enrolling a slightly less severe patient population or would you try to keep the aspect all the same? Maybe talk about that dynamic. Thank you. Thanks, Andrew. Yeah, I think, you know, maybe just some high-level comments. You know, going into the X-TOLE study, I'm not sure we expected the type of patients in terms of kind of this difficult to treat, the heavy pretreatment and failed ASMs and the high proportion of con-meds and the high amount of seizure burden at baseline. That, you know, going in, I don't think we expected that. Once we saw the data and over the last month or two that we've had opportunity to kind of dig in and also review the literature, I mean, our comments that we believe this is probably one of the most difficult, if not the most difficult to treat patient population. Then you start to tease apart some of the efficacy by you know, by that disease severity. As you see, the efficacy continues to improve, which I think is logical. Those with less failures and less con-meds and less baseline disease, we see those seizure reductions go even higher. I think we're really pleased to see that. It really continues to add to our confidence that we're seeing remarkable consistency in the data set. As we think about the phase III program, we haven't finalized the design, so I think it's a good question. I would say overall probably unlikely that we're gonna make material changes. We had a very, very successful study, and so kind of our baseline going in is that the next study, the phase III study, will look very similar to the phase II X-TOLE study, but maybe some adjustments kind of on the edges. For the most part it'll probably look very similar. A s Chris Von Seggern has mentioned, we believe that the profile and some of these sub-analyses give us confidence in where the drug will be used eventually from a commercial perspective. Can I add on that? Thanks. Yeah. This is Chris. I would like to add on that a little bit, just kind of go higher level. I mean, the critical path for this drug to approval is to get through the phase III program. We wanna get there as quickly as we can. Any sort of restrictions that are made along those lines could slow us down. That's one thing. I think more importantly, we're looking at X-TOLE as we're positioning X-TOLE as the first pivotal trial in focal onset seizures. We have yet to know whether FDA agrees with that position, but we'll find out soon. The more we deviate from that study design that was used in X-TOLE, the more it puts that approach at risk. I Y ou always wanna kind of fine-tune things. There are some things that we can do, but we wanna kinda keep that to a minimum 'cause we're coming off a success, so don't fix it if it's not broken kind of thing. Very good color. Thank you, guys. Our next question comes from Paul Matteis with Stifel. Hey. Thanks for taking our question. This is Alex on for Paul. Just wondering if you could provide a little bit more context on, you know, the dose-dependent weight gain you saw here. Curious how that compares to, you know, other anti-seizure medications, how you're thinking about it, and whether, you know, I guess in the high-dose group you saw any association with cardiovascular signals. Thanks. Yeah, sure. Yeah, this is Chris. As I said, you know, on from the mean perspective, there was a modest increase. If you wanna compare the high dose of 25 milligrams to placebo, it was 1.9 kilograms versus 0.2. You have a difference of 1.7. Something on the order of 3 or 4 pounds in the high dose versus placebo. You know, to add a little bit of color to that, we have looked at that data in the open-label, and that increase doesn't. It tops out there. It doesn't continue to trend upwards. It's you know, to put it in the context of other anti-seizure medications, this is nothing along the lines of what has been seen with valproic acid, that's for sure. We're characterizing it as a modest increase in weight gain since it's sort of capping out on a mean level around less than two kilograms. I don't think that this is any—this isn't anything that we're concerned about. If you're I think the question about cardiovascular perhaps is tying it into are there any more ominous issues ongoing. If you were causing excessive weight gain, could you end up with glucose intolerance? Could you end up with an exacerbation of obstructive sleep apnea or cardiovascular events? We're not certainly seeing anything along those lines. If those two questions were tied together. If the question about cardiovascular risk was just sort of a question on its own, we're not seeing anything in terms of, you know, imbalances on any of the in-interval changes on ECG, vital sign changes at rest or orthostatic, anything like that. The cardiovascular signal as of yet is completely clean. Modest increases in weight, nothing that we think will slow down the development of this drug. Yep. That answered my question. Thanks so much. Our next question comes from Laura Chico with Wedbush Securities. Hey. Good morning, guys. Thanks very much. I think the responder analyses look pretty impressive. I just have one follow-up on the weight changes. I know you were just talking about this, Chris, but it sounded like this was also a bit variable in terms of gain and loss. APA reported earlier this year that 61% of adults experienced undesired weight changes during the pandemic. Among those, the median weight changes were ±12-15 pounds. I guess my question would be is what you're observing in these weight changes in X-TOLE, are these solely related to 1101, or could this also be an effect of the pandemic? Thanks. Yeah, I do think that. There's a lot of different ways of looking at weight gain, right? We're talking about mean changes in the population. You can also look at outlier analyses, and we're presenting some of that at AES. Typically in epilepsy, there's a sort of somewhat of an arbitrary cutoff of 7%, used to define that. We are seeing more patients in the high-dose group compared to placebo who had a greater than 7% change in weight. Most of those, almost all of them were an increase, not a decrease. We did, to your point about the pandemic, half of those patients actually gained weight between screening and baseline. It sort of you know artificially elevated that number that's being presented at AES. That said, I think that some of this can be contributed, you know, attributed to the pandemic or whatever weight gain in general. There is an imbalance in the treatment arm, so I don't think that you can completely chalk this up to COVID. As you look at patients who were in placebo and then went into the open-label, there is a similar pattern that we're seeing sort of a 1-2 kg increase in weight. We think that there is a real signal outside of COVID where there's, 1 or 2 kg increase over time that plateaus after exposure to XEN 1101. Laura, just to add to Chris's point, just so it's not lost, is just the way in our statistical analysis plan that weight gain was done is you average. Patients go through a screening, and then as you know, this 2-month baseline period. The weight was averaged over visits over those 2 to 3 months into the study before randomization, and then through the double-blind portion. Some of the weight gain may have happened before someone was actually randomized and on drug. A s Chris mentioned, I think the other. Just to be clear on how the analysis is done. As Chris mentioned, when we look at the kind of broader data set including open label, we believe we're seeing a modest amount of weight gain with the drug. That's helpful. Thank you, guys. Just to build on that, because of COVID, you know, the baseline, we had to be flexible in terms of the duration of that baseline prior to randomization. It was, you know, in some patients, substantially longer than what was planned. More time for that weight gain to occur. Our next question comes from Yatin Suneja with Guggenheim Partners. Hey, guys. Thank you for taking my question. Just a couple for me. Can you just put in perspective the seizure-free rate that you are seeing with XEN1101 versus, you know, current standard of care? For patient with less than 8.5, you gave us the number for 20- and 25-mg arm. Can you maybe tell us what the number is for placebo? Maybe one final question. Can you just talk about, you know, is there a mechanistic reason why we see a little bit different response depending on the motor seizure type you have? I f you look at the data that you presented, I think type 3 you are seeing a lower response, but very high in type 4. Just talk about what the mechanistic reason there is. I actually don't have that placebo number at hand right now. I have the difference between active and placebo, so I simply can't provide it to you even though I would like to. Yeah. Although the, I mean, the overall seizure freedom rate in placebo is 1.8%. Even if we looked at those with less seizure burden, it's still gonna be a very low number 'cause it's starting from a low number. We don't have that cut in front of us, Yatin, but I think it's, we really didn't see a lot of seizure freedom obviously in the placebo group. When we've looked at the literature, very, you know, obviously it varies and our analysis suggests that it varies based on those characteristics of the patients. When you look at other clinical trials, often you see kind of low to mid single digits in terms of seizure freedom. But these aren't perfect comparisons 'cause they're cross trial comparisons. As we showed that our seizure freedom rate, you know, is into the teens if you look at patients with less severe seizure burden at baseline, which is probably more consistent in the range of what other studies had. Again, I think, for us, given the patient population, I think the data are very competitive, and impressive overall. Chris, I don't know if you have anything on seizure freedom, but we should just talk about maybe the types of different seizures that we measured in the study and the type three versus type four. Yeah. I mean, what I would say about the seizure freedom, I mean, if you think about the chance that somebody's gonna respond to an anti-seizure medication after they've failed one, there's a pretty big drop and then an even further drop. Once you get to 3 failures, I mean, you're sort of down into single digits in terms of the response rate for anti-seizure medication. When you think about that and you think about the fact that this population had a median failure of ASMs of 6, it's really quite amazing that there was anybody who was seizure-free, frankly. I think that this is, you know, on par with other ASMs and perhaps better even if you take into consideration the population. With regard to the seizure types, I would just be cautious, you know, having looked at a lot of clinical trials and slicing, data in multiple different ways, you know. You have to be careful when numbers get small. We saw a substantial improvement in type 4 seizures, the secondary generalization. That was definitely a real signal, we believe, in the 25 mg and 10 mg for that matter. I would be cautious about saying it's less effective in type 3 just because of the numbers of patients. I mean, even if it is, I mean, if I had the choice, I would certainly wanna decrease generalized seizures given the risk with SUDEP and so forth. Got it. Thanks. Our next question comes from David Wong with SMBC Securities. Hey, thanks for taking the questions, and thanks for providing this really great update. I just had, you know, I had a question here. If you can bear with me. I'm just trying to eyeball some of the data from the cenobamate studies. Again, you know, I recognize there's a caveat of cross-trial comparisons. If I look at the cenobamate data, you know, the seizure freedom rate, I think they're reporting like mid-20, you know, 20%, maybe like 25-28%, something like that. The placebo rate is also, I guess, relatively high. You have about 9% of patients reporting seizure freedom. you know, can we kind of just, again, is that probably mostly stemming from maybe the baseline population enrolled in the trial where, you know, maybe you have a more severe population? Is that sort of perhaps the right way to think or contextualize this data? Yeah. Yeah, I'll make some comments and then Chris can jump in as well. Yeah, I mean, we get a lot of questions on trying to compare this to cenobamate and maybe a couple of comments. You know, when we look at the prescribing information for cenobamate, they had 11% seizure freedom in their 200 mg dose, and I think it was in the low 20s. I think it was like 20 or 21% in the 400 mg dose. I mean, when you talk to clinicians and KOLs, and we did an ad board yesterday where we spent a good part of the day, really it's 100 or 200 mg is the dose that's being used in the real world. I think that's the comparison that we should be thinking about. If we looked at their two studies, their median baseline seizure was 8.5, and that's why we've done this 8.5 cut. If you look at the 8.5 cut, you know, we have for the 20 and 25 mg, we have a seizure freedom rate in the teens. Again, with all the caveats of doing cross-trial comparisons that we just talked about, we're very comfortable in terms of kind of the competitive rate of seizure freedom that we're seeing with 1101. Chris. Yeah, just, you know, a few things come to mind in terms of the comparison with cenobamate. I mean, first of all, you think about the mechanism. We believe based upon preclinical data and the mechanism that we could have, you know, benefits beyond focal-onset seizures, and so we're considering other options within the development plan. You know, based upon the mechanism, we see more flexibility there. Two, you know, to date, we don't have any sort of idiosyncratic safety issue, which, you know, of concern that that could emerge in the future, but it has not done yet. You know, we don't have to worry about DRESS. We don't, you know, we did not titrate this drug. We went right to the effective dose and saw benefits in the 25-milligram group within one week. The extent of the benefit that you're seeing at the end of the study was also 100% prevalent or present at one week. The other thing I would say in terms of the comparison to cenobamate is if you look at, like, let's say, median% change in frequency, median% change in seizure frequency at the high dose, it's on par, but our placebo effect was actually less. If you look at the delta between the two, and I agree with you, it's difficult to compare clinical trials, although we do it all the time. You know, the delta there is on par or perhaps even bigger. Got it. Thanks for the context. If I could just sneak in one quick follow-up. Just the comments on the American Urological Association Symptom Index. If you know, if I'm reading that correctly, is this to say that those you know, those urinary retention events that were reported may not sort of be you know, so-called, I guess, real events if you go by I guess the AUA classification? Is that you know, sort of where that is coming from? This is sort of an analogous situation to the waking, right? There's like a lot of different ways to look at safety, and I think you can look at a population, and then you can also look at, you know, sort of an outlier analysis. The scale that you're referencing, you know, I would put it, a little bit more on the crude side in terms of being able to, you know, detect a signal. It's good that we're not seeing any changes, but I do want to, you know, I don't want that to diminish the fact that we did see urinary retention in two patients, one of whom had to decrease the dose, the other didn't. I mean, those patients didn't have to stop study drug. They didn't require any intervention. They were a long ways from being catheterized. Still, I don't want to minimize the fact that there were two patients with urinary retention. You know, this could change in time, but I think that you know, that there may be a signal in terms of urinary retention in you know, 1% of patients. I don't think it's anything that will slow down the development of the drug, but it's certainly something that we want physicians and investigators to be aware of so that you know, there's no delay in a reaction should it be more substantial in some patients. Okay. Understood. Thanks very much. Our next question comes from Tim Lugo with William Blair. Hey, guys. This is Lachlan on for Tim. Thanks for taking the questions. I was, you know, obviously looking at all the various subgroup analyses you've got there and was wondering from your perspective, both, as a clinician, but also from the market research, are there any there that kind of stand out as particularly meaningful or differentiated from that perspective? Um. Yeah. I guess in terms of the differentiators specifically that stand out, clearly the efficacy is what's been pointed to beyond the thing that's gonna drive utilization. We've heard that time and time again, even in recent ad boards, as Chris and Ian had mentioned, just really compelling interest in that efficacy data, particularly as you move to earlier lines of therapy where the data just get increasingly impressive. When you think about true clinical use in the future, patients on one or two ASMs showed a markedly improved seizure reduction. We imagine that that's the primary audience that would receive XEN 1101 in the future, rather than the more difficult to treat clinical trial population that has to, by nature, pass through many more therapies ultimately to get on a clinical product. In light of that efficacy, the other thing that clinicians point to is, and Chris mentioned this earlier, we see efficacy very quickly. You have to put yourself in the frame of the patient and the frame of the clinician the time that they're writing the product. This patient is likely seeking an additional therapy because they've recently had a breakthrough seizure. That's why you change drug. Our product works remarkably quickly given the lack of titration. We're talking 1 or 2 weeks, you see therapeutic benefit, and that's simply unseen with other products where you can have to wait weeks, sometimes months, potentially still seeing seizures while you're going through that titration period. The combination of really significant efficacy combined with rapid onset of action and other candid ease of use attributes make clinicians really excited. Again, it's because of what they're looking at. This patient is seeking alternatives because they're having breakthrough seizures, and we have that ability to address that need very quickly. The last component, and we don't spend a lot of time talking about this, but it's important. It's often considered in this marketplace, one of the reasons for breakthrough seizures is missed doses. In fact, there are several products that the clinicians will point to that if you miss one of your doses, four hours later you're likely to have a seizure. We don't have that issue. We have protection for missed doses, and it provides another level of comfort for the most concerning features in this marketplace of having a seizure. We have an attribute that potentially offers us a little bit of coverage and benefit in the event that a patient unfortunately misses a dose. I think all of this is coming from the mechanism, right? I mean, this is an entirely different mechanism than any of the other drugs are using. That's why we're seeing the benefits in these patients who are heavily treated at baseline. Got it. Thanks. That's very helpful. Our next question comes from Serge Belanger with Needham & Company. Hi, good morning. A couple questions for me. First one on the survey work that you've recently done with epileptologists. Chris mentioned that from that survey work, XEN 1101 was viewed as potentially playing a role on par or similar to Vimpat. Just curious if that is in line with your expectations and how it could guide your future phase III trial design plans. Well, I can answer the survey aspect of it. We saw coming out of the survey, comparable utilization or expectations, based on the 1101 profile, without actually some of the more sophisticated analyses we've done over the last, several weeks. You know, apples to apples comparison from a profile, clinicians were pointing to utilization that it's in line with Vimpat, which as you know, is the commercial market leader today. That does guide our thinking in terms of both expectations as well as where we're likely to play in a clinical use population. Vimpat is widely used as an add-on therapy after patients pass through one or two, generic medications, and still has residual seizure burden. Okay. This is the other Chris. The only thing I would add is that, you know, we think we're differentiated in terms of the more novel mechanism of action. You know, again, there are always caveats with comparing clinical trials, but we're seeing what on the surface looks like more robust efficacy in a population of patients who has more severe disease severity at baseline. A follow-up regarding the open-label extension trial. I think Ian mentioned that 80 patients have now been in that trial for 12 months. Curious when you expect to start reporting data from that trial. The trial's ongoing. As we mentioned, we, based on feedback and asks from clinicians, had extended that to three years. I'd mentioned on our Q3 quarterly call that we will be doing a more formal cut of that data as we prepare for our end of phase II meeting with the agency. I'd expect that you'll see some more of the open-label data in 2022. Great. All right. Thank you. That concludes today's question and answer session. I'd like to turn the call back to Sherry Aulin for closing remarks. Great. Thanks everyone for joining us on our call today. Operator will now end the call. This concludes today's conference call. Thank you for participating. You may now disconnect.