Xenon Pharmaceuticals Inc. (XENE) Earnings Call Transcript & Summary

Okay. We'll continue with the next session. I'm Paul Choi and I cover the SMID cap biotech technology sector here at Goldman Sachs. It's my pleasure to welcome Xenon to our session here. Joining me, to my immediate left is CEO, Ian Mortimer, on far side there is Chris Von Seggern, Commercial Head. And so what we'll maybe do is let Ian kick it off maybe with some high-level remarks for those listening in on the webcast. Maybe just giving a brief background on Xenon, its core competencies and the markets you're targeting.

Yes, for sure. And thanks, Paul, for hosting us today. We really appreciate it, and it's nice to be joined with Chris Von Seggern, our Chief Commercial Officer. So I know in the Q&A, we'll weave through a number of commercial questions which we often get from investors as well and a good opportunity to do that today. Yes, in terms of Xenon for those that are less familiar with the company, we're obviously a neurology company, deep expertise of drug and ion channels in the CNS. And you see that as a theme that runs through our pipeline. I kind of think about the business kind of in the kind of 3 big parts right now, and we'll talk about all of them throughout the Q&A session. So one, we've got our lead molecule. This is a potassium channel modulator called -- we used to call it XEN1101. We're now using the generic name of azetukalner. We'll probably flip back and forth but really the opportunity for azetukalner in epilepsy. This is off the base of really strong Phase IIb data, which was our X-TOLE study where we were able to show that the drug was statistically significant at every dose on every seizure reduction endpoint. Those data, released the double-blind data couple of years ago, but we continue to follow up in open-label extension and really seeing some very impressive overall seizure reduction in the population. We now have patients that have been dosed more than 4 years and we have over 600 patient years of exposure. So we're seeing really nice data in terms of overall seizure reduction. And these patients, a subset of them are seeing seizure freedom, as well. And we're defining that as 12 months with no seizure, which is really impressive. So overall, in epilepsy, we think we have a really compelling profile. This will be an only in-class mechanism when launched in a polypharmacy environment. On a placebo-adjusted basis, this is the best efficacy ever seen in epilepsy, we're seeing rapidity of onset, we're statistically significant at week 1 in the Phase II data. And then one of the nice segues from this first kind of focus on epilepsy into depression, we're also seeing a mood benefit of the drug. And I think today, let's talk not only about the opportunity in major depressive disorder and our work there, but the importance of these data in epilepsy because comorbidity of mood is really important in the epilepsy patient population. The second thing that we're really focused on is indication expansion outside of epilepsy, for azetukalner and obviously, major depressive disorder is a big part of that. We had really interesting proof-of-concept data at the end of last year in our X-NOVA study. And we've made excellent progress over the last 6 months. We've engaged with the agency at an end of Phase II meeting. We fully planned out the late-stage clinical development plan, and we'll be in a position to initiate our first Phase III clinical trial in major depressive disorder later this year. And then the third thing that we're starting to talk a little bit more about is our discovery pipeline. And there's 3 targets that we're spending time on. One is Kv7. Obviously, we have deep expertise here with azetukalner, and we think that there's an opportunity really to think about a pipeline and a mechanism here and be able to expand even outside of epilepsy and psychiatric disorders. And so you'll hear more from us on our Kv program. And then we've got 2 sodium channels that we're targeting in 2 different programs. One is Nav1.1 where we've got potentiators. This would be an opportunity in Dravet syndrome where there is this genetic -- most -- the vast majority of Dravet children are haploinsufficient in Nav1.1. And then I would say the target that we probably spend more time with investors on preclinically is Nav1.7 which is a novel pain target. And I think the genetic validation, we believe for many, many years is exquisite in Nav1.7. The chemistries have been challenging, but I think we're really comfortable that we've made some important progress there and we'll be in a position to move some molecules into development over the next year or 2. Obviously, the company has been well funded historically, really good support from investors. $885 million at the end of Q1. We're guiding that cash runway into 2027, fully funding the Phase III epilepsy program, epilepsy clinical studies, fully funding the Phase III MDD program. We're going to run 3 Phase III clinical studies in major depressive disorder as well as the maturity of the pipeline.

Okay. Great. Maybe we can start with MDD for which, azetukalner, you had most -- your most recent clinical data with X-NOVA. So can you maybe summarize the results for us and help us understand what does this data look like in terms of context versus other mid-stage studies because we want to try and keep it like-for-like, not necessarily versus approved agents and at least how does that fit in, at least in the current MDD treatment landscape?

So I'll talk a little bit about the data and maybe I'll transition a bit also into the future development and make a couple of comments there, which we can go deeper if you'd like. And then Chris can really put those data into context in terms of the rest of what we're seeing in terms of both the development. And I think we need to think about the commercial opportunity and where a novel agent. When we think about depression, similar to epilepsy, there are lots of approved therapies, but there's also a significant unmet medical need. And so Chris can walk you through some of that. So as I mentioned earlier, we had our X-NOVA data. This was a proof-of-concept study that read out at the end of last year. This was a 3-arm study. We looked at 2 active doses versus placebo. It was a proof-of-concept study, so a little bit on the smaller side from a sample size perspective. So we looked at 10 milligrams of azetukalner, 20 milligrams versus placebo. We saw a clear dose response between the 10 and the 20 milligrams, 10 separated from placebo and 20 separated from 10. So I think that's really positive. As we've talked about, the primary end point in the study was MADRS, this is the clinical scale of depression. We had a clinically meaningful 3-point separation between active and placebo. That narrowly missed statistical significance on a couple of points. One, just on sample size, it was a smaller study. Based on our analysis, if we had an additional 20 subjects per arm, we would have hit statistical significance. And we saw some more variability in the data on the MADRS endpoint. And that's an important 1 because I'll come back to some of the changes we're making as we move into Phase III development. Importantly, we also saw rapidity of onset in major depressive disorder. So consistent with our epilepsy data, we see separation at week 1 and we were statistically significant at week 1 in MDD. We were also statistically significant on Hamilton on the HAM-D17 endpoint, which is a different scale of depression. We were also statistically significant on a scale of anhedonia, which is called the SHAPS scale. So a lot to like about the data set overall and a lot for us to learn and take forward into late-stage clinical development. As I mentioned, we've interacted with the agency, and we've now planned out the Phase III development. A couple of the changes. We're going to use HAM-D17 as the primary endpoint in the Phase III program. We are going to have one-to-one randomization. We know that will have an impact on placebo rate, at least that's what the literature shows us. We also know that HAM-D17 had less variability. We see that in the literature, and we saw that in our study as well. So that gives us some confidence as well. So HAM-D17 is the primary endpoint. It's going to be a much larger study. We'll get into sample size a little bit later once we finalize the protocol in the next number of months, but it will be one-to-one randomization, looking at the 20-milligram dose versus placebo. We're going to increase the baseline cutoffs to get in, meaning it will be a little bit more of a severe population than we saw in Phase II in the Phase III program. And some of the other things we looked at in Phase II we'll look at in Phase III as well. Namely, we'll look at that week on endpoint in terms of rapidity of onset, and we'll also look at anhedonia because as Chris is going to mention, I think anhedonia is a really nice potential differentiator in the marketplace and so we're going to be looking at scales of anhedonia as a secondary endpoint as well. But I'll pass it to Chris to give a little bit more how we put those data into context with other agents.

Yes, that would be great.

Yes. So when we think about azetukalner and the data that have been generated to date, we're really excited about the value proposition as Ian has articulated. I think when you take a step back and think about major depressive disorder, mainstay of treatment that are obviously SSRIs and SNRIs, and those products offer efficacy and benefit for a wide range of patients with side effects. And that side effect profile, I think, is the -- is where I wanted to begin because you can think about 2 major side effects that emerged from those profiles. The first is sexual dysfunction and the other is significant weight gain. And under both of those scenarios azetukalner doesn't have meaningful sexual dysfunction and we haven't seen significant weight gain in the clinic. From there, you can think about a novel mechanism of action. So again, patients often will receive multiple SSRIs or SNRIs. And therapeutically, you can benefit within that mechanistic category. But as you move to third or fourth line agents, you're really starting to think about looking for something else beyond the mainstay of therapy. We have rapidity of onset. And then importantly, what we hear in our market research is the anhedonia hook is really important. SSRIs, SNRIs are known not to address the anhedonia, which is a core component of the symptomatology of major depressive disorder. And we hear very consistently this is the hook to bring patients to azetukalner, for patients who have residual medical need. Importantly though, and it can't be forgotten as we think about epilepsy, it's also an incredible differentiator. So our patient population when we think about commercial use in the focal onset market, the majority of patients who are difficult to treat, who pass through 1 or 2 lines of therapy have depressive symptoms. And clinicians consistently point to an unmet medical need to address the comorbidity of depression. And those data alone on top of the excellent data coming out of X-TOLE are really compelling in that patient population. So really 2 ways to think about the X-NOVA data from a differentiation for azetukalner.

Okay. I want to touch briefly on something you mentioned, Ian, which is talked about some of the changes for your endpoints in terms of Phase III. One of the other things that we also have seen in the literature and I think, this is also seen in X-NOVA is you see differential responses depending on severity of disease. And so can you maybe speak to a little bit to how you're thinking about inclusion, exclusion criteria, where you want to see -- enroll more severe, more depressed population to increase your probability of technical success here?

Yes, I think you teed it up really well. I think the literature is clear is that in these studies, we do want to try to really get more of those severe patients rather than the milder patients. So the cutoff as we went into X-NOVA in the Phase II program was a HAM-D17 cutoff of 20. We're looking to increase that into 22 in the Phase III program. Interesting, when we look at the -- and we've talked about this previously, but -- when we look at the X-NOVA data, whenever you're running a proof-of-concept study in a smaller sample size, you sometimes get some minor imbalances in the groups. And we did see if we look at the 20-milligram group versus placebo that there were some milder patients in that placebo arm. And we know that, that does impact the data, and we saw that when we looked at those specific patients. And looked at that impact. And so as the sample size increases materially, we'll have a multiple of the Phase II size from a sample size perspective per arm. As that increases, any of those imbalances kind of work their way out. And then as I mentioned, we're going to increase that baseline criteria to get into the study, which I think will help manage that as well.

Okay. Great. I think 1 of the things that probably has been most interesting about the Xenon story is that when you laid out your -- historically, your preclinical literature in the animal models, the simulations of depression there, the dosing curve performances and severity has translated very well, obviously, in terms of your Phase II clinic. So the science there, I think, is really elegant. Maybe other things, you talked a little bit about sample size which has yet to be finalized, but just in terms of like maybe what you can paint for us in terms of broad strokes in terms of how you're thinking about powering. Given the recent experience of some other companies or sponsors in the MDD setting have had some issues both at clinical trial sites as well as with statistical assumptions and placebo performance. Maybe just sort of what is the state of the art, I guess, in terms of MDD trial execution and staff's plans, maybe if you could frame that for us?

Sure. I mean, a lot in those questions. I mean, first, on the sample size, even before we get to that we're going to go from a 2:1 randomization to a 1:1 randomization. And what I mean by that is we have 2 active doses in Phase II. And so you had a 67% chance to be on active and we know that the literature teaches us that can have an impact on your placebo rate as well when that's more than 50-50. And so we'll go to 1:1 randomization in the Phase III program. And as I mentioned, it will be significantly greater in terms of size. We haven't yet disclosed our sample size calculations. We'll do that but you can think about this from a powering perspective. It's going to be a well-powered Phase III study, right? And we'll be able to see in terms of the effect size, we should be very comfortable in terms of the sample size. A lot of these studies are about managing the study, managing the sites and managing the placebo rate. And we do that in a number of different ways, and we've talked about the severity of the patients coming in already. Site selection and CRO selection is critical. Analyzing data as we move through the study is important. Most of these studies now are using this third-party adjudication, which is the safer criteria that came out of MGH to, again, help with patient selection. So there's a number of things that we -- and it's not unique to Xenon that all sponsors in major depressive disorder are looking at. Because we just know that there's more subjectivity and variability in the disease, and we have to be eyes wide open about it. I think one of the reasons that we're running 3 studies, right, just from a risk mitigation point of view. So all of those things we're taking into consideration as we design the Phase III program.

Okay. Maybe to round out our discussion on MDD. Obviously, you still have to run Phase III programs, but just as you think about longer-term development here, and either combination therapies and just given a polypharmacy approach in depression, just sort of how do you think about other development aspects of MDD here and maybe looking into adjacent populations such as mixed features and things like that.

Yes. So to Ian's point earlier, these studies are monotherapy studies, and that's for a couple of reasons. One, benefit in therapeutic separation is often better in those studies than it is in an adjunctive setting, but also we hear quite commonly from physicians desire to use the product in both settings. And when we look at payer management requirements, it's rare to see anything that specifically holds the product to either a monotherapy or in adjunctive environment depending on the clinical study. So we feel comfortable that based on the profile that could emerge the physicians would choose to use it where they think it's most appropriate in that clinical environment. We hear that quite consistently from our market research. When you think more broadly though, there's clear interest in this mechanism beyond just major depressive disorder. And our work leading up to selecting MDD as a life cycle indication for azetukalner. We've looked more broadly as well. And there is clinical validation that obviously exists in epilepsy expands into the depression space. But this mechanism has applicability broader in the neuropsych environment. And there are close adjacencies to depression, bipolar depression is one, but interest in neuropsych more broadly, anxiety, PTSD. There are other areas that are really of interest for the mechanism, either for azetukalner or one of the discovery programs that's currently in development.

Okay. Great. Maybe turning to your lead program in epilepsy and FOS. You talked a little bit about enrollment updates on your last earnings and just maybe when you -- do you think you'd be able to offer more precision on whether enrollment can be completed by year-end versus early next year? Just sort of what visibility you have on the pace of enrollment and completing that?

Sure. And I'll get to the very specific question to take a little bit of a step back. Obviously, the robustness of our X-TOLE study, we discussed with the agency filing after we complete the first Phase III clinical trial, which is X-TOLE2. And so we really think about X-TOLE2 is on the critical path to filing an NDA and getting the product approved. So I think that's important to take into consideration. So we've given guidance on X-TOLE2. We said completion of enrollment or screening late this year or early next year. Yes, how we've done this historically is we've had a bit of a window and then we've narrowed the window as we've gotten closer. I do want to mention because we talked about this in other settings is that just the way the epilepsy studies are designed, once that last patient is screened, there is a baseline period. Remember, we have to -- the patient has to count seizure through the baseline period before randomization. And then you have the double-blind period, which for these studies is 12 weeks and then you've got follow-up and data analysis. So roughly from the last patient screened to top line data is about 6 to 8 months that's really common. And that really can't be shortened because there are some very specific steps that you need to go through. So you'll hear more from us as the year progresses on where we are on both the screening enrollment side and then we will get to guidance of top line data as well.

Okay. So that's a very nice data for 2025, which would look to be a very interesting year for you guys with data coming out potentially at some point, either 2Q or mid-'25, broadly speaking, potentially here. So I want to ask maybe how you're thinking about data mechanics with regard to top lining results versus balancing and saving some of the interesting material for medical meeting and just kind of where the thinking is on that? And then sort of what sort of medical meeting or forum might be a potential opportunity for looking at the results in detail.

Sure. So yes, we've been -- we've done this a few times. So we've been pretty consistent in terms of what we put in a top line press release and then the opportunity to continue to build on that story at subsequent medical meetings and congresses, which is really important, right? It's really important that the Xenon brand and azetukalner becomes part of the medical community and our communication there. So we've been -- I don't think we're going to deviate much from what we've done in the past, which is you'll get enough information in that top line press release on the key endpoints to know the overall profile of the drug. I would say we probably disclose a little bit more in that top line press release because our perspective is that we're very balanced in our disclosure and we want to give a complete picture of the molecule as we see it. Obviously, at that top line data, we can't complete every analysis. There's always a balance between speed and how deep we can go in that first analysis. And so there's always an opportunity to do subsequent analyses that can be presented at medical congresses and we'll continue to do that. In the epilepsy space, there really is 1 key meeting. I know there's some. Yes, there's some regional meetings and there's a European meeting. But the American Epilepsy Society meeting in December of each year is really the key medical meeting in epilepsy where that entire community comes together. Really, the entire community globally comes together. There are some other smaller regional meetings that do take place. That's really important for us, and we think about that as we think about the cadence of things moving forward. Obviously, on the psychiatry space, it's a little bit broader than that.

Okay. Great. Assuming clinical success, which I think most investors think is pretty likely here based on your Phase II X-TOLE results. Can you maybe just remind us what your regulatory package broadly would look like. I think you've indicated that guidance from the FDA or suggestion that X-TOLE could serve as one of your confirmatory trials. With X-TOLE2, you'll have a package put together. But what other things are needed in terms of either a safety database or things like that? Is that adequately sizing, how long you have to track these patients for in terms of establishing the safety profile? Just maybe some comments there.

Yes, happy to. And I think it's a good question because we often -- we and I'm saying, kind of both companies and investors focus a lot on the efficacy data and the top line data, but the packages you suggest at the time of NDA is quite broad. So obviously, key efficacy studies will be X-TOLE and X-TOLE2. But this is a large market opportunity. And what I mean by that is we need to meet ICH guidelines in terms of the safety database. And so that's driven by just a number of unique exposures and then as you mentioned, long-term follow-up as well. One of the benefits that we have, which is really unique to where we are and a clear differentiator when we think about the competitive space is just the long-term exposures we've already accumulated with the molecule. That gives us a tremendous amount of comfort on the profile of the molecule. It gives us an opportunity to engage with physicians on an annual basis because we keep maturing that data. But we started that open-label extension as a 1-year study and then we extended it to 3 years, then to 5 years, it's now been extended to 7 years. And so we're generating this huge amount of long-term safety data. So again, as we think about the overall package, whether it be -- on the safety side, as you've mentioned, clinical pharmacology, toxicology, CMC, all of those things we're really comfortable with. And it's really that X-TOLE2 data, which is on the critical path to us getting that entire package together.

Okay. I want to touch maybe briefly just on the competitive landscape because there are other molecules in this class on development and just good management teams, hopefully are not paranoid, but they do think about the competitive landscape. And so just as you think about your time lines where you're clearly further along versus some of the other drugs in the category, just what do you watch for in terms of the competitive landscape, whether it's Biohaven or who else and what are you monitoring for?

Yes. And I'll maybe talk a little bit about -- on the clinical side and then Chris can talk about. And there's lots of drugs that are commercially available for epilepsy. So we need to think about the competitive space and where we think azetukalner could fit in, in the treatment paradigm as well. And Chris can walk through that. Yes, obviously, we're always monitoring what else is happening in the field. I mean we're in this very unique position. We're only -- we're the only potassium channel modulator that has any efficacy data. And I think we have a very unique and compelling profile of azetukalner. So we're really proud of the work we've done. We're proud of the leadership position. There's really no other late-stage clinical development that has a molecule with the profile and the data that we've generated to date. And so I think we're clearly differentiated from the field and it's really us to execute, and we believe we'll get there. I didn't want to lose, one of your points, as the epilepsy is we do see high consistency and reproducibility across studies. So we have the confidence as well the Phase II has a very high probability of being successful and this being a really important medicine in the community. And that's a good transition to Chris because we hear that time and again from the physicians that we spend time with. Although there's lots of available therapies, there's still the significant need. And to come forth with a novel mechanism with the profile we have, I think, is going to be extremely important for patients.

Yes. Building on what Ian has said, we think about the competitive space as being reasonably favorable for azetukalner. More than 2 dozen drugs approved here in the U.S. to treat focal onset seizures and yet more than half of the patients still have very substantial unmet medical need. We often focus on branded competitors, of which there are very few. And -- but you have to think about the competitive set as being more of the generic therapies that are earlier lines of therapy. We're not thinking that this product is going to displace levetiracetam or lamotrigine as a first or a second line therapy. But with more than half of the patients progressing to third line or more there is ample opportunity for a product that has the differentiating features that we have to play a really compelling role in that space. Historically, a product like lacosamide or Vimpat actually did quite well is what was really the first branded opportunity in the space. And when we think about azetukalner's profile, same ease-of-use attributes, but much more compelling efficacy and the potential to address depressive symptoms, offer something that's really unique. Vimpat, on more than $1 billion products here in the U.S. in -- but with the addition of a depression benefit for this profile, you can start to think about potentially Lamictal or lamotrigine as being a better analog for where we likely could end up in that treatment paradigm. Preferential use in patients who have known underlying depressive symptoms in addition to the very compelling efficacy attributes that azetukalner brings to the table.

And just how do you monitor companies like whether it's a Biohaven or recently debuted companies like Rapport that are looking into the space as well.

Sure. I'll start and I think, Chris can go into detail where we've seen multiple branded drugs coexist and be successful, right? So again, there's a lot of patients here, right? Just going to even the EPI data. There's 3 -- over 3 million Americans that have epilepsy, 60% have focal onset seizures. That's 1.8 million, about half of them are not getting good seizure control on current therapy. So there's lots and lots of patients that need better drugs, and Chris can talk about how these drugs can kind of coexist. But again, I'll just reemphasize the point I made earlier is we are the only company that has double-blind data where we've shown a significant statistical separation between active and placebo. Actually on a placebo-adjusted basis. It's the best data ever seen in focal epilepsy in the most severe population ever trialed. And so we just have such a unique position on where we are right now. There's lots of other companies and molecules that are going to be in the space that's I think our data and our leadership is going to [ Berlin ] competition and that's fine. And I think we're significantly different and if you just look at the overall open-label package, right, just the amount of safety data and long-term exposure, you can't shortcut that stuff, right? This is -- this takes time to build up this type of experience in the field and the type of profile that we have with azetukalner.

Yes. What I would add to Ian's point is we don't shy away from competition. Again, the profile that we have with azetukalner is incredibly compelling. The value attributes that we've shown to date are going to be hard to match and we are very clearly ahead both from a time line and a total data package as well as some of the unique attributes that we haven't spent as much time on today, but the dosing, the lack of DDIs, other attributes that are really unique to this molecule. It's not just about matching efficacy, it's about the complete picture. And again, in a polypharmacy environment with a product that plays well with other mechanism, it gives you a really unique potential to differentiate against the mainstay of therapy that might be more sodium channel focused or the SV2As. Our product plays well with those mechanisms and as a stand-alone mechanism.

Okay. I want to maybe in our remaining time, touch on some corporate matters, just reflecting maybe questions on spend levels versus your cash runway, which as you mentioned, will take you out a few more years, but -- and embeds running Phase III programs for both FOS and MDD. But I want to ask just is this sort of burn rate sort of -- what we should sort of think about for the near to intermediate term, just given you are running so many late-stage programs. And then as FOS completes its pivotal studies here and you get to the commercial stage, maybe either for you or for Chris, how do you think about launching an FOS, whether it's -- want to -- going it alone or partnering and maybe just some comments there?

Sure. I'll start a little bit on the spend and Chris can talk about our commercial strategy in the U.S. and outside the U.S. as well. Yes, so we're -- I mean, again, maybe a bit of a theme today is how we differentiate in the marketplace. We talked a lot about the molecule. I think the balance sheet differentiates as well, right, having cash runway into 2027, which fully funds our Phase III epilepsy program, our Phase III depression program and things continuing to mature in the pipeline. That's a very unique position to be in and I think that's a statement that very few companies can make. We don't give specific OpEx guidance on an annual or on a quarterly basis. But yes, as we do more and more late-stage clinical development, you'll see an increase in spend. And you can see that if you just look at our cash runway and kind of back out what the spend would be supporting that cash runway and the balance sheet. So yes, it's things -- there's always these ins and outs. X-NOVA is complete now, if we thought about some of the spend and then this year, we've got the Phase III epilepsy programs ongoing and then we'll see the spend from the Phase III depression program as we get into that later this year.

It's been clear that we plan on bringing this product forward ourselves in the United States based by comparison to other neurologic arenas. This is a much more confined call point with a much more narrow field team that's needed in order to be successful. So the analog products have been launched and supported with, call it, 100 to 125 field-facing folks. On the commercial side much more manageable for a company that looks and feels like Xenon and one where with the profile attributes that we have as well as the lead time we have to build relationships in the community, we feel as if we can certainly differentiate in this space. We've also been clear that we -- eventually we'll seek an ex-U.S. partner for this product. We believe there's a meaningful commercial opportunity and clinical unmet need beyond the United States. But from an infrastructure standpoint, Xenon today and it's our belief that there will be partners for the time is ready, who will be very interested in this product ex-U.S.

We have about a minute left, and I just want to touch on the early-stage pipeline, which I think you continue to do obviously very high-quality work in terms of sodium channel drug development and just sort of what time lines are and just sort of how to think about the cadence of INDs for 1.7 as well as to the next Kv7 drug that you mentioned earlier?

Yes. So we haven't gone -- given very granular guidance, but there's the 3 targets that we've talked about that we're really interested in Kv, Nav1.1 and Nav1.7. And what we've stated is that we're kind of at the candidate selection. And we look at multiple chemistries and multiple molecules on target, but we're a candidate selection across those 3 targets. Candidate selection to us is a reasonably high bar. So we do a fair bit of non-GLP toxicology work to try to risk mitigate those tox studies moving forward. That means we're going to see multiple molecules over this year and next, move into GLP toxicology studies. And so starting in 2025 and beyond is when you'll start to see some of those IND filings.

Okay. Great. We're almost up on time here. So maybe we'll end it on that note. My thanks to Ian and Chris are joining us from Xenon. Thank you very much.

Thanks, Paul.