Hi, good afternoon, and welcome to Needham's 23rd Annual Healthcare Conference. We're happy to have for our next session the Xenon Pharmaceuticals team. Xenon is clinical-stage biopharma in addressing neurological disorders, and I think they're on track to be in two late-stage programs by the end of the year. So with us this afternoon, we have the company's president and CEO, Ian Mortimer, as well as the company's CFO, Sherry Aulin. So I guess I'll hand it over to you guys to give us a quick overview of the company for the few people that may not be familiar with Xenon. But maybe before we do that, I just want to remind the audience that you do have the option to submit questions via the portal you're watching the presentation on. You can also send them to me to my email. So with that said, I'll hand it over to the Xenon team. Perfect. Thanks, Serge. Appreciate you hosting us today. Always nice to connect with you and with shareholders. So I'll provide a bit of an overview. I think as you mentioned, many people know the Xenon story quite well, and then Sherry will walk through some upcoming milestones, cash runway, balance sheet. But you set it up nicely. We're really well into one late-stage clinical program with XEN1101, and then we have another one that we expect to be up and running by the end of this year. And so if we think about Xenon today, you know, kinda, we really talk about three kinda key messages overall: XEN1101 in epilepsy, which I'll give a few comments on, XEN1101, the expansion into major depressive disorder. And then what you're hearing a little bit more from us recently that we'd like to spend some time on as well, is just the maturity of our discovery portfolio. We've made some really nice progress over the last couple of years. We've been more quiet on it, but you're going to hear more from us on a couple of targets that we're excited about, that we've made good progress on, so we'll touch upon that at the end. Obviously, we're well known for our work on ion channels in the CNS, and XEN1101, a potassium channel modulator, as we mentioned, is in a late-stage clinical program. For epilepsy, we have three phase III clinical trials in epilepsy ongoing, two in focal epilepsy called X-TOLE2 and X-TOLE3, and then a third phase III clinical trial called the X-ACKT study, which is in primary generalized tonic-clonic seizure. Obviously, this builds off a fair amount of data that we have on the molecule in epilepsy, starting with our phase IIb X-TOLE study, which was a really positive outcome at the end of 2021. And then, what investors have heard from us over the last couple of years is maturing data in open label extension. We now have patients dosed more than four years, and that, the maturity of that data is really nice in terms of seeing the overall population have significant reduction in their seizure burden and longer periods of seizure freedom for a subgroup of those patients. So in epilepsy, we think XEN1101 stacks up really well. Obviously, it's a novel mechanism, so if we have, you know, the opportunity for this drug to be approved commercially post the phase III program, it'll be an only in class mechanism drug, which we would combine in a polypharmacy environment with other medicines to treat epilepsy. We have, on a placebo-adjusted basis, the best efficacy ever seen in a study in focal onset seizures in the population that we believe was the most severe ever trialed, and we've shown some of our subgroup analysis to support that statement. We have rapidity of onset, so we're statistically significant at week 1, and now I mentioned we have a huge amount of data in open-label extension. So we think there's clear differentiators with XEN1101 as an epilepsy drug. Maybe a good segue to depression, we also think actually a differentiation on mood is important in epilepsy because depression is such an important comorbidity for epilepsy patients. We're also excited about doing our own late-stage clinical development in major depressive disorder. So we had really interesting clinical data at the end of last year, which I know we'll talk about. We've got an upcoming end of phase II meeting with the agency in April, this month, and then we expect to enter into a broad phase III program in major depressive disorder starting later this year. So maybe I'll pause there, 'cause I know we're gonna go deeper in all of the comments I've made, but I will pass it on to Sherry, just to provide a little bit more guidance in terms of milestones and cash. Great. Thanks, Ian. So I think importantly, 2024 is gonna be a big execution year for us at Xenon. You know, as Ian was laying out our phase III program in epilepsy, we've got multiple studies now ongoing in that program. And importantly, there, we expect to complete patient enrollment in X-TOLE2, which is really the study that is gating or critical for us to get to NDA for the epilepsy program, in late 2024 or early 2025. So we're excited to continue to make progress across those epilepsy studies and look forward to completing patient enrollment soon. And then, as Ian alluded to, yeah, we'll talk more, Serge, I'm sure about MDD program and how we're thinking about the phase III study design. We've said our end of phase II meeting is this month with FDA, so we'll be in a position, hopefully, shortly thereafter that meeting, to provide more details to the market on how that phase II meeting, end of phase II meeting went. And then we'll initiate our first of three studies later this year, and I'm sure we'll touch on that a bit more. We're continuing to evaluate other potential opportunities for indications for XEN1101, so that work's ongoing internally, and we hope to be in a position to say more publicly in the near future. Yeah, excited about the progress we've made over the last couple of years in our preclinical pipeline, and it's really the first time this year where we've started to talk more about just the breadth of work that we're doing in-house and leveraging our capabilities around ion channel drug discovery, and the huge capabilities that we've developed on the development side of the organization that we hope to be able to leverage to progress, you know, additional molecules into clinical development over the next number of years. So hopefully we're poised to have a number of these preclinical molecules entering IND-enabling studies this year and into next year. And then lastly, on the cash runway, we're in a, I think, a great position from a cash perspective. We ended last year with north of $930 million in cash, which fully funds our phase III epilepsy program, as well as the phase III MDD program that we have planned, and gives us cash into 2027. So I think a great position for us to be able to execute on our robust pipeline. Great. Well, nice overview. We like the setup of a high-quality asset with good data and well-financed, obviously. I'll start with, I guess, the more advanced program, epilepsy. Ian, like you said, you reported really highly efficacious phase IIb data. This is a mechanism of action that's mostly been de-risked at this point through your program and ezogabine. So maybe you can just remind us the differences between the phase IIb X-TOLE trial and the design of the phase III X-TOLE2 and X-TOLE3 studies. Yeah, and maybe before I get into that, Serge, I mean, just to reiterate, you know, the point that you made on the data that we've generated to date, I mean, I think really impressive, as we said, the best placebo-adjusted efficacy of any drug in the FOS patient population, where we saw close to 53% reduction in seizures in the high-dose group. We've also generated a ton of data through our open label extension. We presented the 30-month cut of those data at the American Epilepsy Society meeting just this past December, and there we saw this improved, continued response, where patients who have stayed on drug are actually getting over 90% reduction in their seizures at 30 months. And that's really impressive, again, as you think back to the severity of these patients, where they were experiencing, on average, you know, 13.5 seizures at baseline entering into the X-TOLE study. And then, as well on the seizure freedom side, we've seen really, again, really, really great data there, where patients who've been in the open label extension for at least two years, a quarter of them have actually achieved at least 12 months of consecutive seizure freedom. Again, when you compare that to their seizure burden at baseline, and you think about the ability for, you know, many of these patients now to have, life-changing ability to, you know, drive again and potentially have, a job and really be able to engage more, you know, more in their lives than they were previously. And then a ton on the safety and tolerability side, obviously now with, you know, patients out on drug more than four years in the open-label extension, we have over 600 patient years of exposure data. So just a lot known about, you know, the molecule overall. And so that does translate for us into a high degree of confidence in our phase III program, both on the efficacy side, but as well as, again, the totality of information we have on the tolerability. So when we think about phase III studies in epilepsy, I mean, generally speaking, this is a therapeutic area where there's really good translatability from phase II to phase III, but we also have really designed around our X-TOLE study, in hopes that we can really try to replicate the results in X-TOLE. We've kept our X-TOLE2 and X-TOLE3 studies, you know, very true to our the design elements of X-TOLE. So the same endpoint, the same inclusion/exclusion criteria, and we've said many times that we're also leveraging many of our X-TOLE sites into X-TOLE2, and staying consistent from a jurisdictional perspective in really trying to, you know, manage our outcome here and our placebo rate. So we're very confident as we look forward to the phase III program. One other point to mention is, X-TOLE2, or the phase III FOS studies are looking at a 12-week endpoint versus 8, which is what we measured in phase IIb. However, we did continue to track patients through that 8- to 12-week period in our X-TOLE open-label extension, and there we actually saw continued reduction in seizures from weeks eight to 12. So again, we're confident in the design, and hopefully the success of our phase III studies. Great. I guess on the tolerability side, since this is a molecule that's similar to ezogabine, and ezogabine had some, say, tolerability issues, over time, just curious, given all the data we've seen now, if these concerns have been put to bed now that we have so much data? Yeah. I mean, we're feeling really comfortable. You know, we could think about some of the more significant adverse events or the adverse event profile of ezogabine, and we compare it to XEN1101, same mechanism, but obviously different chemistries and different molecules. You know, many of these drugs are really all anti-seizure medicines as you're pushing the dose or having some Cmax-related CNS adverse events, right? And we see that with ezogabine, and we see that with XEN1101. We really think about those, at least for something like dizziness, which is the most common adverse event that was seen with both molecules. It's actually on target, right? As you push the dose higher and you're dampening hyperexcitability in the brain, you are seeing some of those CNS-related adverse events. Those normally show up early in dosing, and are transient or mild in nature. I think what you're referring to, I mean, the significant adverse event that I think was very unusual with ezogabine was the pigmentation or the tissue discoloration, which was very unique to that chemistry. And now that we have, as Sherry mentioned, patients out more than four years of dosing, we haven't seen that, and if we were going to see it, at least based on the ezogabine history, it should have shown up by now. So we don't think we should see it just from a chemistry point of view, and we don't have the chemistry that gives rise to the chemical structure that has that color associated with it. But we can also should, you know, be very comfortable with the clinical data that we've generated to date as well. So, you know, the benefit of having a significant open label extension program is not only the efficacy data that we continue to generate, gives us an opportunity every year to have another year of mature data that we can talk to epileptologists and have a nice presence at the American Epilepsy Society meeting. But again, now, from a safety perspective, we have a huge amount of knowledge around the molecule that we're feeling very comfortable. So I think there are clear differentiators between XEN1101 and ezogabine. Okay. And I think you've mentioned in the past that X-TOLE2 is kind of the, on the critical path, so the main focus, I guess, of, of the two studies. I think last quarterly update, you mentioned that you expect enrollment to be complete around later this year or early 2025. That's right. I assume there's been no change to that target? That's correct. Yeah, we're. We've been really clear. You know, I think the X-TOLE data was very robust, and at our end of phase II meeting in epilepsy with the neurology division, we discussed that we would file after X-TOLE2, and that's why we talk about X-TOLE2 being on the critical path to filing an NDA and having the drug commercially available in the U.S. And so there's been a significant emphasis and focus on X-TOLE2, and as you mentioned, and we've discussed as well, the current guidance is that we expect patient enrollment to be complete late this year or early in 2025. Got it. So let's talk about the other phase III trial in primary generalized tonic-clonic seizures, or we'll just use the acronym. Maybe what got you interested in running that study concurrently with the X-TOLE studies? Yeah, so we talked a little bit about this. This is called the X-ACKT study. It's ongoing. We do have agreement with FDA, which we reached at the end of phase II meeting, that we're running a single phase III study in this patient population. It's a smaller study than our FOS studies, so we're targeting 160 patients total. Yeah, PGTCS is an important, you know, part of the overall epilepsy market, so it's about 30%, as you look at kind of the overall 3 million adults in the U.S. that have epilepsy. It's a different phenotype, though, so there are less frequent seizures, but the seizures are much more severe. Patients will experience stiffening of muscles and convulsions. This is also. They're also known as grand mal seizures. So, there is a risk of death. These can be life-threatening. People can experience, you know, falls and injure themselves, and there is a higher risk of SUDEP, which is an epilepsy-related sudden death. If you look across, you know, other ASMs, we know that many of the drugs that are approved for focal onset seizure are also approved for PGTCS. But the typical sort of cadence is that anti-seizure medications are first developed and approved in FOS with PGTCS data, and then label expansion coming later in their product life cycle. We've seen this with, again, other ASMs. If you look at, you know, Vimpat, for example, or even Xcopri, which is just completing their PGTCS study. You know, we have interesting data on XEN1101 that really helps support our conviction that it should work in PGTCS. You know, we had about 20% of our patients in the X-TOLE study who had the primary diagnosis of FOS, but some of their seizures started as a focal that progressed to a bilateral. And those patients, actually, in that subtype of seizures, we saw more than an 85% reduction in seizure frequency, and that made up about 20% of the seizures that we saw, or patients experienced, in the X-TOLE study. And then, as well, XEN1101, you know, in all of the preclinical animal models of epilepsy, which we know have really good translatability into the clinic, XEN1101 works across all of those preclinical animal models, which is unique to the molecule. That's not the case with all other anti-seizure medications. So for those reasons, we're confident that it should work. I will say, given the lower prevalence of PGTCS, again, less common than FOS. We do know that these studies can take a little bit longer to recruit. So our thought process was really to start the study in parallel with FOS, in hopes that we could add, you know, to the label sooner in the product life cycle, and therefore enable physicians to more broadly prescribe XEN1101 once it's on the market. Remind me again, should we expect efficacy to be similar in PGTCS as it was in FOS, for the focal onset seizures? So we generally see about the same delta between the active and placebo. Generally, that's in the 30% range, but given again that the seizures are less frequent, you'll see kind of higher rates, both on the placebo side as well as on the active drug side. So, you know, generally, you'll see, or, we've designed our study to show, you know, expecting about a 40% reduction in the placebo arm, and then a 70% in the active arm. So a 30% delta. But those numbers are higher, given that your denominator of total seizure count is lower. Got it. Okay. So let's assume all three of these phase IIIs come in, report positive results. What does that set you up in terms of the potential label and the commercial opportunity that you could address? Yeah, let's, let's take those in order. So let's talk about focal epilepsy, and then we can talk about generalized. So on the focal epilepsy side, we can talk about, just the prevalence of the indication. So what's the need and, and the patient population, if you really think about what would be a model that you would build? And then let's talk about some of the commercial successes and other drugs that have been successful in the space. And that'll bridge nicely to, to generalized epilepsy as well. So we know that overall, there's 3 million adults that have epilepsy in the U.S. 60% of them have focal seizures, and it's about up to half of them, so that's 1.8 million, the 60% of the 3 million, and then it's about up to half of them that are not getting good seizure control, that we believe there's a need for new medicines and new branded medicines to help these patients. And so when we look at that patient population, and then of the remaining non-focal patients, the vast majority of those have generalized epilepsy, and the vast majority of the generalized patients have primary generalized tonic-clonic seizures. When we add the total population together, for focal and generalized, which we think is the opportunity for XEN1101, and then you also get into some of the adolescents or pediatric patients, well over 1 million patients that we think could benefit from a therapy like XEN1101. Then we look at the pricing, we think that the commercial opportunity is significant. Then, when we look at some of the drugs that have been successful commercially, so if we go back quite a number of years, we had branded drugs like Keppra and Lamictal that both have done very well. Most recently, the branded drug that just lost exclusivity was Vimpat, which the last year of sales before loss of exclusivity was $1.8 billion. You know, that wasn't a drug that had a novel mechanism, and, and so I think there are clear differentiating factors between XEN1101 and Vimpat, but Vimpat did very well commercially. Generally, these drugs are often used both in focal epilepsy as well as generalized. Obviously, the most recent branded drug that has been launched in epilepsy that currently just has the focal label, but they are completing their primary generalized study, is Xcopri or cenobamate. And that drug was launched a few years ago, actually during the pandemic, and I think the uptake of that drug has been quite, quite strong as well. So overall, you know, if we look at it, either from the medical need and the patient population or the commercial success of other branded medicines, we think there's a significant opportunity here. We're still a few years out from when we should expect a launch, but how many other branded products do you expect could be out there by that time? So likely, yeah, it's, you know, we can't completely predict exactly when things are necessarily gonna go off patent, but there are a number, a handful of branded medicines right now. Our best estimate when we would launch XEN1101 commercially in the U.S., that it would only be Xcopri or cenobamate that would be the branded medicine. So I think often we get questions from investors just on the compare and contrast between, cenobamate and XEN1101, and, as we've said, on a placebo-adjusted basis, you know, our efficacy is stronger in a, a more severe patient population in which we were trialed, for the data we have so far, which is the phase IIb X-TOLE study. Obviously, we have, we have a novel mechanism. Cenobamate has mixed pharmacology, but it is a sodium channel inhibitor, which, we know there's lots of drugs of that mechanism available. And then one of the other benefits of XEN1101, I think that we actually haven't touched upon today, but we've definitely spoken about previously, is that we don't have to titrate the drug, and so you're on your therapeutic dose on day 1. And so we do see statistical significance in terms of efficacy at week 1. And remember, these patients are having breakthrough seizure, and so the benefit of them getting, early seizure control is important, whereas cenobamate is a 12- to 16-week slow titration, because they did see some drug allergy when the titration wasn't slow early in their clinical development. So a significant difference on when you are on a therapeutic dose when we compare XEN1101 to cenobamate. Then the last point, which I think is an important one, which obviously may be a good segue into major depressive disorder as well, is we do know that depression is an important comorbidity in epilepsy. And obviously, XEN1101, we've now seen some really interesting data on the antidepressant effects of the mechanism as well. Okay, maybe just one more before we jump to depression. On your commercial plans, I imagine you're, at this point, you're planning to build your own infrastructure for a launch in the U.S. What are plans for ex-U.S. commercialization? Yeah, so why don't we talk about both? So we've been really clear on our strategic objectives, which is to forward integrate and have commercial infrastructure in the U.S. That would start with epilepsy, and then it would grow from there into depression. Obviously, this would be a staged approach, with epilepsy being the first launch. We think it's completely doable for a company our size. We've already started. We hired our Chief Commercial Officer a few years ago, and he's starting to build out his team. It's small right now, but we have a roadmap on what we need to do to forward integrate to commercialization. To give a bit of an idea, it's about 100-125 sales reps would cover the epileptologists and the key neurologists that are prescribing a branded anti-seizure medicine. So again, we think that's really, you know, very doable from a company our size, and so we're looking forward to going through those steps as we move forward. Obviously, with the commitment to build infrastructure in the U.S., we've also been very clear that the strategic objective is not to build that infrastructure outside of the U.S., and so at some point, we will be accessing a partner for ex-U.S. commercial for commercialization. Obviously, when we think about partnering, we think about, you know, potentially access to capital or access to capabilities or access to the commercial market. We feel very comfortable, as we mentioned, both on the ability to execute in late-stage clinical development, as well as having the capital required to do it. So there's no need to rush into a partnering arrangement ex-U.S. That will come at some point in the future. Great. So on the MDD program, you reported your proof of concept data back in November. I'm impressed. We're already talking about a pretty extensive phase III program. So maybe just talk about your thinking there. I guess the proof of concept data and how that supported your plans for phase III development. Yeah, we're really excited about the data that we were able to show at the end of last year, and I think our team has made really quick progress to get us where we are today. And both to be in front of the agency with an end-of-phase II meeting this month. And then also, we've really planned out the full late-stage clinical development program. So let's touch upon a few of these. Let's go back to the data to start. So this was a proof-of-concept study. We were looking at two active doses versus placebo. Proof-of-concept study, meaning it was about 50 subjects, just over 50 subjects per arm. We looked at the 10 mg, the 20 mg doses of XEN1101 versus placebo, and we're really excited about the totality of the data. We saw a clear dose response, so regardless of the endpoint we were looking at, either on clinical scales of depression or anhedonia, we did see a clear dose response between the 10 mg and 20 mg. We saw a consistent separation between active and placebo, so that was about a three-point separation on the clinical scale of depression using MADRS, and about a three-point separation on HAM-D17. MADRS was the primary endpoint, HAM-D17 was a key secondary endpoint. Based on some of the variability in the data, we narrowly missed statistical significance on MADRS. We were statistically significant on Hamilton. We were also statistically significant on MADRS at week one. So again, we're really seeing this consistency of data in terms of separation, clear dose response, rapidity of onset. We're seeing that consistency between epilepsy and major depressive disorder as well. Based on some of the mechanism data, we also think that this has an opportunity to have an impact on anhedonia, and that's a clear medical need in in MDD, and we were statistically significant on a clinical scale of anhedonia, called the SHAPS scale. So overall, I think for a proof of concept data, we're really excited by the data and supported by shareholders as we move forward into late-stage clinical development. In terms of, w e have shared some of the broad overview of the phase III program. Sherry touched upon some of these points earlier, but I will reiterate, our current objective is to run three phase III clinical trials, single dose in each of those studies, so we've chosen the 20 mg dose versus placebo. We know when you go from two active arms to one active arm, that enables a better management of the placebo, right? We are gonna look to use HAM-D17 as the primary endpoint. The studies will obviously be bigger than a phase II proof of concept study. We haven't yet disclosed sample size, but that'll come in the future. And we'll likely increase the baseline criteria for entry into the study a little bit higher, and that'll bias the study to more moderate to severe MDD patients in the phase III program. So we've got all of that information in a protocol synopsis, which is part of the end of phase II briefing package, to discuss with the psychiatry division at FDA in preparation for starting the first phase III clinical trial later this year. Great. So would all three phase III more or less be identical? Is that kind of the thought right now? Yeah, they're gonna be designed the same, and Ian went through some of those key design elements, Serge. I think one probably distinction between the studies is gonna be to actually be able to successfully enroll across three studies. We're probably gonna have to go to sites outside of the U.S. a nd we've seen that consistently with other study sponsors. So there will just be a differentiator between the studies on, you know, what jurisdictions we're going to. But otherwise, as we think about the randomization, the study design elements that Ian covered, those are all gonna be consistent across the three studies. From the end of phase II meeting later this month, I guess just looking for confirmation from the FDA on, on those plans, or is there anything else that you're looking for in terms of feedback? Yeah, exactly. I mean, we submit to the FDA with our briefing package or protocol synopsis, and FDA has a chance to review that and provide any comments. But look, ultimately, you know, depression, there have been many drugs, you know, developed in this area. And so we're not expecting any surprises here, as it pertains to kind of our key design elements. We do plan to just review the overall, you know, package from, you know, an sNDA perspective, and ensure that some of the other elements outside of the studies are aligned with FDA's expectations as we think about the broader clin pharm and tox packages. But again, we've had those discussions previously with the neurology division as it pertains to our epilepsy program, and we expect that we'll be able to leverage a lot of that work. So, you know, I think this is good, for good measure, we're going through an end-of-phase II meeting, but really, we don't expect any significant aha moments coming out of the interaction. Okay. And I know it's early, and you'll probably need the phase III data, and to really nail this down, but how are you thinking about the commercial opportunity in major depressive disorder right now? Yeah, I mean, I don't think there's any doubt, you know, around the fact that this is a significant commercial opportunity. You know, there's tens of millions of Americans that have depression, and millions are treated, you know, annually, for depression with antidepressants. And so it is a huge opportunity, just given the patient numbers. You know, I think people know the mainstay treatment, you know, are SSRIs and SNRIs, and those do have significant liabilities associated with them, like weight gain and sexual dysfunction. So really, you know, we're thinking about how XEN1101 can differentiate from what else is out there. One of the significant pieces is really the novel mechanism. We know depression is heterogeneous, and there's still a significant unmet medical need, despite the range of treatment options. And that is supported by our market research. And when we look at just the totality of the profile in XEN1101 that is emerging, we are thinking about, you know, how we can differentiate. And as we talked about earlier, you know, we saw really good safety and tolerability of XEN1101 in X-NOVA. Actually, somewhat to our surprise, the drug is really well tolerated within this patient population. Really kind of a benign, you know, to safety profile and benign AEs that we saw. And importantly, again, as I mentioned earlier about the standard of care, we don't see sexual dysfunction or significant weight gain with XEN1101, which is common of other antidepressants. The kinetics of onset, so the rapidity of onset, something that we're looking at in phase III, and that's an important differentiator, given, you know, again, the standard of care can take weeks to get to efficacy. And then lastly, the anhedonia piece, which we are again looking at in phase III, and what we've heard time and time again from physicians is that when patients are put on standard of care, they do have their depressed, you know, their, their depression can resolve. However, they continue to have symptoms of anhedonia, even after treatment, and so this could really be a commercial differentiator for, for XEN1101. So we're looking at all of those elements again in phase III, and obviously, once we have more data, we'll have a better sense of how the profile, the clinical profile will be supported in the commercial market. But big opportunity, I think, you know, we're moving in the right direction here. Yeah. So I think we only have a few minutes left. I wanted to talk about the pipeline. I think you started this closing, again, last quarterly update, talked about the next generation potassium channel modulator candidates, as well as Nav1.7 and Nav1.8. And I may be wrong here, and correct me if I am, I believe Xenon was working on these molecules as far back as the IPO over a decade ago. I'm probably aging myself here, but I think you guys started working on these way before they were in the hands of Vertex and other companies. Am I correct? Yeah, it goes back actually even further than that. So Xenon started years and years ago as a genetics company. So we were the first to clone the 1.7 gene, which is called SCN9A. And then we did a lot of early biology and chemistry with some proprietary assays on the biology side. Yeah, if you go back 10 years, we had a large agreement with Genentech. We were working on the target with Teva on different chemistries as well. And so we've learned a huge amount over that timeframe. I think we're uniquely, you know, uniquely suited to have another go at this. And, you know, the genetics has always been really strong, right? These homozygous loss of function patients that don't feel pain, regardless of noxious stimuli, if they're a complete loss of function in Nav1.7. And it's just really been trying to get the right chemistries with the right properties, with the right receptor occupancy to prosecute. And so, I think we've made tremendous progress. We've now got a bunch of proprietary chemistries, and what we've said for both the Nav1.7 program as well as the Kv7 program. I think Kv7, we truly believe, there's an opportunity for a pipeline and a mechanism here. And then on Nav1.1, which is an important target in seizure control in seizure reduction and seizure control. So those are kind of the three main discovery projects that we're working on. For all of them, we haven't given very specific guidance, but for all of them, we're really at candidate selection, so multiple molecules that are being nominated to go into GLP toxicology studies. So what you'll see later this year and next year, as we progress these molecules through tox is INDs starting to be filed and these molecules maturing and transitioning into human clinical development. So obviously, a huge amount of focus and execution on the XEN1101 program. But, you know, we do really want to communicate to folks that there's a lot more going on at Xenon, and that portfolio is going to mature nicely over the coming years. Okay. Well, I think we're up on time here, so I think we'll have to end our chat. I wanna thank you both for spending time with us this afternoon. That's a great overview, and the company is at, t hey've got a great place with some great programs and some nice catalysts ahead of you. So thank you.