Okay, we'll continue with the next session, which is Xenon Pharmaceuticals. I'm Paul Choi, and I cover the mid-cap biotechnology sector here at the firm. It's my pleasure to have Ian Mortimer, to my immediate left here, CEO of Xenon. What we'll do is what we've been doing in other sessions, which is let Ian kick it off with maybe a high-level overview of Xenon, sort of where the company is, its key programs, and the overall strategy, and then we'll get into Q&A.
That sounds great. Thanks, Paul, for hosting us. Always good to be here. Yeah, I'll give a bit of an overview. I know we have lots of things that we can cover over the next half hour or so. For many folks that know the Xenon story, obviously we're a neurology company. Kind of a couple of big focuses for us, and I know we'll get through this in Q&A. Our lead molecule, Azetukalner, is in a broad phase III epilepsy program, so we'll talk about that. We've also moved into neuropsychiatry, both in major depression as well as bipolar depression. That late-stage clinical program is starting and kind of getting up and ramped up over the remainder of this year. I would say we're starting to talk a little bit more about our early-stage pipeline as well, which has been maturing nicely.
We'll be in the clinic with two molecules this year. One is a potassium channel modulator that just started in clinical development recently. Over the next few months, we'll get our first NaV1.7 inhibitor into the clinic as well. I know we're starting to get some attention there. If we focus first on Azetukalner and epilepsy, obviously we have a phase III program ongoing. That's our next big clinical readout, X-TOLE 2, which is a phase III clinical trial in focal onset seizures that we've guided to data in early 2026. We can spend more time going into the details, but we really think the profile of Azetukalner based on the phase II data, I think, is really impressive. We're excited to get to that phase III data because that's on the critical path to moving towards filing an NDA and becoming a commercial organization.
As we've moved into psychiatry, our first Azetukalner phase III MDD study is up and running. We'll have our second phase III up and running here shortly around mid-year, and then our first bipolar depression study as well. A busy year for us in terms of clinical execution. Obviously, over the next couple of years, it's going to be a really data-rich period with a lot of clinical data coming in 2026, 2027, and for the years to come.
Okay, great. Thanks for that, Ian. Maybe just one more point of overview for people who are newer to the Xenon story or maybe listening on the webcast. Can you maybe just remind us in terms of what mechanistic validation you have here? Obviously, you can reference a prior market drug like Potiga and so forth, but just sort of what, at least at a clinical level, your initial X-TOLE study as well as the X-NOVA study have shown in terms of efficacy and safety for those two indications.
Yeah, I mean, maybe this is a good opportunity for me actually to take a little bit of a step back and talk a little bit about what I think we're building at Xenon. We've been a company that's been around for some time, but we've really built these core capabilities of drug and ion channels in the CNS. We work on validated targets, either they have genetic validation or pharmacologic validation. We're an ion channel company and we're very focused in neurology. I think those are the things where we believe we can have a competitive advantage. You'll see those themes run throughout the pipeline. To your question on Azetukalner, this is a potassium channel modulator. It opens or potentiates a potassium channel in the brain, and that can have an impact on reducing hyperexcitability and have the opportunity to treat epilepsy.
As you mentioned, I think the phase II data were very robust. This was our X-TOLE study we read out a few years ago, although we're still continuing to treat patients in the open label extension part of that study.
It's been several years now.
Yeah, it's been several years. Actually, there's an annual medical meeting that's really important in our space, which is the American Epilepsy Society Meeting, which takes place every December. We've been able to, every December, show another year of mature data. This past year, we had our three-year data on the open label extension. What we found for Azetukalner in epilepsy, and really what the value proposition or what we differentiate and how we speak with the physicians in the epilepsy community is this is a novel mechanism. There are no potassium channel modulators that are currently available. On a placebo-adjusted basis, we believe that this is the best efficacy seen in a clinical trial for patients with focal onset seizures. The drug doesn't need to be titrated, and the patients are treated with one pill once a day.
We see early onset, because you're on a therapeutic dose on day one, we actually see really strong efficacy. It was statistically significant at week one in the phase II program, and we're continuing to monitor that also in phase III. If you look at the long-term efficacy and safety data, it's really strong as well. We're seeing patients have longer periods of seizure freedom. That's very important in terms of the quality of life of these patients. In terms of safety, we now have amassed over 700 patient years of exposure. We have our first patients that have been dosed more than five years. We have a really good handle on the safety profile of the drug as well.
Okay, great. Maybe turning to your phase IIIs, can you maybe just update us on how trial execution and trial operations are going in terms of enrollment with X-TOLE 2? And then when would you potentially be in a position to announce sort of last patient in?
Sure. XTOLE-2 is our first phase III clinical trial in focal onset seizures. We started this program a couple of years ago. We're getting close to the end. We were able to announce in our Q1 financial results in May that we believe we're a few months away from the completion of patient screening. Patients do have to go through a screening and a baseline period before randomization, and then it's a 12-week double-blind period. That puts us on track for data in early 2026. The real approach to XTOLE-2 was to have consistency with our XTOLE study. The inclusion-exclusion criteria in the phase III program is exactly the same. Because we had a really nice outcome in phase II, we've gone to a lot of the same investigators, a lot of the same clinical sites. We have a relationship with them.
We're using a lot of the same sites and geographies that we've used in phase II. So a lot of consistency between the phase II program and the phase III program.
Okay, great. I think at least based on my investor discussions, investors have a lot of confidence on the efficacy side. A lot of the conversations often shift to the commercial side and just post data, post filing, and so forth. What sort of commercial considerations and modeling factors can go into the thinking? Maybe just starting with pricing here, and how are you thinking about, I guess, pricing given the state of the market? Are you thinking about, as you think about lifecycle management, you are also looking at multiple indications? Are you thinking about indication-specific pricing? Does one pricing model sort of work for multiple indications? Maybe just can you help us frame that analysis?
Sure. Before we get into some of the more detailed pricing questions, I think it would be helpful even just to talk about the epidemiology and what we think the opportunity is, at least let's start with epilepsy. There are about 3 million Americans that have epilepsy. About 60% have focal onset seizures, so the most common form of epilepsy. We know it depends on which literature you look at, but somewhere between 30%-50% of patients are not getting to good seizure control. If we look at that and then we look at there are patients, adolescent patients and pediatric patients that also have focal onset seizures, we believe it's about 1 million patients roughly in the U.S. that are still looking for better medicines where we think a profile like Azetukalner could fit in.
In terms of pricing, again, not that we have given any guidance on pricing, but the nice thing about epilepsy, these are specialty neurology priced drugs. It is in a pretty narrow band, and we feel very comfortable with that. Actually, interesting, if you look at the most recent branded drugs in both epilepsy and the recent branded drugs in depression, those price points are very similar.
Okay, great. Potentially at time of launch, who knows, maybe late 2026, 2027, or thereabouts, you and Xcopri will be the only sort of branded anti-seizure medications on the market at that time. So there's a comp out there, but can you maybe speak to the value proposition that you think Azetukalner will bring to the market versus those currently available therapies and how you try to position your product?
Yeah. So there's a number of drugs to treat focal onset seizures. Many, many of those are obviously generic drugs now. We know a newly diagnosed patient is going to get a generic drug. Often they get exposure to drugs like levetiracetam or lamotrigine. We're seeing a little bit more lacosamide usage now that Vimpat has lost exclusivity as well. Those patients are going on to a monotherapy generic drug. For the patients that are doing well on that generic monotherapy, they'll continue. For those that are either having tolerability issues or still having breakthrough seizures, that's when polypharmacy is introduced and physicians are looking at combining different drugs with different mechanisms of action. That's where we start to see the introduction of the branded medicines. That's where we believe ezetucalner would be appropriate.
As you mentioned, there is a drug, a branded drug that's currently on the market called Xcopri or cenobamate, launched a few years ago. You're right, based on our analysis, we will be the only two branded drugs when we're ready to commercialize as Azetukalner. I think Xcopri is a good drug. There's some really good data there, and they've had some good commercial success. What I think we're really proud of in terms of the profile of Azetukalner is it will be a novel mechanism. Because the drug doesn't need to titrate, as I mentioned earlier, I think those are some key differentiating features between us and Xcopri. Obviously, we still have the phase III study to complete and the phase III data to unblind.
So far, based on the profile of zetucalner, we'll have really good discussions with the prescribing community and the opportunity for this to be an important new medicine.
Great. Maybe just touching on the filing strategy briefly, you obviously had a very strong result with X-TOLE. You'll be in a position to unblind X-TOLE 2 in the early part of next year. Assuming that that study is positive, which I think is probably most people's base case, can you maybe just remind us, can you file on those two data sets and then what happens with X-TOLE 3 if X-TOLE 2 is positive?
Yeah. Yeah, and I think it's actually useful to just talk about some of the other components of a new drug application as well, right? Obviously, there's a lot of focus on the clinical data, but we can't lose sight of the importance in having the non-clinical package ready and the CMC package and clinical pharmacology as well. From our perspective, X-TOLE 2 is on the critical path to filing an NDA. We've had that regulatory interaction. As you're right, we plan to file with X-TOLE and X-TOLE 2, and then everything else, and there's still a huge amount of work that's being completed, but none of that other work, either from a CMC perspective or a clinical pharmacology perspective, is on the critical path. That work is well in hand, and we feel very comfortable in terms of bringing all that together.
We have two other phase III clinical trials outside of X-TOLE 2. One is X-TOLE 3, as you've mentioned. X-TOLE 3 is a carbon copy of the X-TOLE 2 study. So the same inclusion-exclusion criteria. We're running that at different medical centers, but the protocol is exactly the same. We believe that study is going to be required for filing in other jurisdictions outside of the U.S. The other thing is we can use the safety data from X-TOLE 3 in terms of the number of exposures. And whether you're in X-TOLE 2, X-TOLE 3, or a third study, which I'll come to in a minute called X-ACT, all of those patients go into open label extension. That continues to add to the overall safety database, not only in terms of us being able to communicate to the epilepsy community, but also for using in our filings with regulators as well.
The third clinical trial, as I mentioned, is called X-ACT. That is in a different epilepsy indication called primary generalized tonic-clonic seizures. That study will take a little bit longer. The condition is not as prevalent as focal epilepsy. These patients have fewer seizures, often more severe, but those studies take a little bit longer to run.
Classically called grand mal.
Yeah, yeah, that's exactly right. The old nomenclature was the grand mal seizure, and now we call it a generalized tonic-clonic seizure. Yeah, it's the same indication.
I want to follow a little bit up on your X-TOLE 3 study, which is still enrolling it, as you mentioned here, but in different study centers and geographies versus X-TOLE 2. Just in terms of the U.S. filing requirement versus other geographies, is there a different focus, let's say in Europe and other geographies in terms of freedom from seizures, seizure intervals, severity? Just sort of what is sort of the clinical regulatory focus in other major markets versus the U.S.?
All of the data that we generated in X-TOLE and X-TOLE 2 and X-TOLE 3, but if you're talking about jurisdictions outside of the U.S., we'll still use the X-TOLE and the X-TOLE 2 data in those jurisdictions as well. If we look at the two big jurisdictions of the U.S. and in Europe, the primary endpoint for approval, we capture those data in all of our studies, but the statistical analysis plan is a little bit different. In the U.S., we focus on what's called the MPC as the primary endpoint, where in Europe, it's a responder analysis. It's the percentage of patients that have at least a 50% reduction in their seizures from baseline to the double-blind period. We run the exact same protocol, whether it be X-TOLE 2, X-TOLE 3. We have clinical centers both in the U.S. and in Europe in both studies.
When we get to the SAP level, we just change the statistical hierarchy to meet the requirements of the individual jurisdiction.
Okay, great. I want to continue maybe a little bit on the ex-US strategy as well as plans. And just what can you say, I guess, at this point on commercialization and/or partnering for ex-US markets? I know you've previously identified the U.S. as your primary focus, but just I guess, just what is the state of things and potentially partnering? And then my other question is, if you have an ex-US approval, just what does that mean for your U.S. pricing strategy, just given some of this Washington discussion on MFN and so forth? Maybe just help us put that picture together.
Yeah, absolutely. Happy to. Yeah, I'll talk about kind of what our strategy is overall and how we're thinking about partnering. Today, I think it's important to know that we own 100% of this asset globally with no partners and no trailing economics. The benefit in the position we're in right now is we have total flexibility. We've been really clear in terms of our strategy. We only want to build the commercial infrastructure here in the U.S. We can do that if we look at the type of sales force and the commercial infrastructure that we need to build. We're very comfortable in doing that in the U.S. Actually, because we haven't commercialized previously, we've already done some of that work. We have people in our commercial organization already. Even last year, we invested in MSL.
We have medical science liaisons that are out interacting with the community. We're starting to build not only the profile of Azetukalner, but the profile of Xenon as a trusted partner in the epilepsy community. We've been on that path for many, many years, and we're continuing to do that. Just as one small data point and an aside is at the American Epilepsy Society Meeting in December, we had 50 Xenon employees there representing clinical development, clinical science, as well as our commercial organization and medical organization. We're already building the profile of Xenon. We've made a corporate and strategic decision not to build commercial infrastructure outside of the U.S. You're absolutely right. At some point, we will need partners for market access.
Just to your last question and the last discussion we had a few minutes ago, we believe we're doing the clinical development to access those markets, but we're not going to build the commercial infrastructure. As it relates to your specific question around timing and around potentially some policy changes, obviously right now, we're not rushing out to do any partnering. We're continuing to do the clinical development and generating the data, and we can make those decisions in the future.
Okay, great. I want to shift gears maybe a little bit to the MDD side and talk about X-NOVA. Maybe what did you learn now that you're operationalizing your phase III programs in MDD? What did you learn from X-NOVA that you're applying now in X-NOVA 2? Anything you'd want to highlight in terms of specific changes with your go forward clinical plan?
This is the same molecule as Azetukalner that we're running in depression. We ran our phase II, which is the X-NOVA study that you're referencing, was a bit of a smaller study. We did that purposely because we really wanted to understand. We felt that there was some good mechanistic rationale for a potassium channel modulator in depression, but we didn't have that experience yet. We wanted to go out and gain that experience. In X-NOVA, we ran a three-arm study, two active doses and placebo, 10 mg, 20 mg versus placebo. I think we saw some really interesting data. We saw a clear separation between active and placebo. We saw that there was a dose response. We saw an impact on 10 mg and then more of a drug effect at 20 mg. That was really positive.
We saw separation on both clinical scale depression and anhedonia, as well. It was a smaller study. It was just over 160 subjects for the three arms, so just about 50 subjects per arm. I would say we've actually made quite a few changes in going from that X-NOVA readout, which was at the end of 2023, to where we are today, up and running in our first phase III clinical trial. I'll highlight some of them now. We moved in terms of the primary endpoint from MADRS to HAM-D17. Both are well-validated clinical scales of depression. From a regulatory point of view, you can use either endpoint. What we saw with HAM-D17, which is consistent with the literature, we looked at both of those endpoints in phase II, is that we saw less variability in the data.
That's the endpoint that we're taking forward. The primary endpoint in phase III is HAM-D17 at week 6. We also have changed the sample size materially. As I said, there was just over 50 subjects per arm in phase II. We're going to be 225 subjects per arm in phase III. It's going to be a one-to-one randomization. We're looking at 20 mg versus placebo. We also know as you add additional active arms in a depression study, that can have an impact on your placebo rate. The one-to-one randomization, I think, is an important decision as we move into phase III as well. We've also increased the entry criteria from a disease severity perspective. We'll have a more severe depressed population in phase III when we compare that to phase II.
We have entry criteria both on clinical scales of depression as well as anhedonia. We will be looking at both a depressed population as well as an anhedonic population in phase three. In phase three, like in phase two, one of the key secondary endpoints is looking at anhedonia. We look at a scale called CHAPS. There are a number of other criteria that we look at in terms of how the study is conducted. That comes down to the CRO selection, to the site selection, the investigators we are working with, as well as using a third party through MassGen that provides some of that third party oversight and adjudication. There were a number of things that we learned in phase II that we are taking into the phase III program.
Maybe this is a bit of a Wall Street artifact, but it seems to be a bit of a recurrent theme, which is just placebo responses in these types of studies. What else can you say in terms of trial design or trial execution that you've implemented to sort of minimize placebo effects? How is that sort of factored into your statistical assumptions here?
Yeah, look, I think in all of the psychiatry studies, trying to get the right types of patients and trying to manage placebo rate is absolutely critical to success. A lot of the things I talked about, moving from a two-to-one randomization to one-to-one, increasing the entry criteria, it's actually often those milder patients that you see more variability in the data, and they often have a very good response on the placebo arm as well. Going to a more severe entry criteria, a more depressed population, is another one that was important to us, as well as all of the things that we have in terms of the oversight of the study, how you actually identify these patients and the types of patients that we enroll that eventually get through screening and are randomized.
We have a lot of oversight there, both internally at Xenon, as well as through the CRO, as well as through a third party. A number of different ways that we, like everybody on the sponsor side, are trying to run an incredibly high-quality study with the right patients being enrolled.
Great. Now that we've had a few weeks of perspective on this, I just want to maybe get your latest thoughts or updated thoughts on the IST trial that was run on MDD here. Just single center studies are always fraught with risks and so forth. Can you maybe help us contextualize that study result, which unfortunately missed, but just contextualize that versus maybe what was different versus X-NOVA?
Yeah, and I think we've been really consistent with our messages around this. Whether we're talking today or we were talking six months ago or 12 months ago, we had always said that what was decision critical for us was the X-NOVA result. Quite frankly, we're already in a phase three program before this IST readout. As you say, a small academic center, I think, is difficult to interpret. I think we've been very consistent. Whether the data were good or bad, it really wasn't going to have an impact. I think overall, the data are really consistent. The primary endpoint was actually not a clinical endpoint of either depression or anhedonia. It was an imaging endpoint. That was really the purpose. This was NIH-funded work, and they wanted to look at neuroimmaging.
It was a functional MRI endpoint, and that's the way the study was designed. It was on the smaller side. It was about 30 subjects per arm, one dose, 20 mg of Azetukalner versus placebo. Actually, at week six, they had quite a good separation on MADRS. It was over four points. If we look at this study and we look at our X-NOVA study, what I really like is we saw consistency. We saw separation between active and placebo at every single time point, between active and placebo. The active drug, 20 mg, outperformed placebo at every endpoint on both MADRS and on CHAPS. We absolutely saw some variability in the data. We can see that when you have a small academic center with the sample size that they had.
I think it was really positive to see consistency in what we expected in terms of the Azetukalner performance versus placebo.
Great. Maybe turning to your phase three program and the X-NOVA 2 study, can you maybe just update us on how the cadence of study centers and IRB approvals is proceeding? How many sort of what the cadence and potential timeline for enrollment is, or just sort of what the latest thinking is there?
Sure. So X-NOVA 2, that's our first phase III clinical trial in MDD, is up and running. That got started just at the end of last year. I'd say we're like a quarter, quarter and a half into this. We haven't yet provided formal guidance on top line data. So far, everything's going fine. This is going to be a US-only study. It's going to be at approximately 50 medical centers in the US. Most of those are up and running now. We're well into the early part of the study in terms of screening. So far, everything we've seen is kind of what we would expect. I think probably within the next quarter or two, we'll have enough information to provide that guidance to top line data.
Coming behind that, we're going to have what we call X-NOVA 3, which is the second phase III clinical trial. That should start. It's going to be the same clinical trial design, obviously at different medical centers. I think we're going to have some ex-U.S. centers in that trial as well. That'll be up and running in the next couple of months. The new information that we provided a few months ago is that we're going to run a phase 3 program in bipolar depression as well. That first bipolar depression study will be up and running around mid-year also. Yeah, a fair bit of work on the psychiatry side.
If we look at the phase, maybe to answer your question a little bit more directly, if we looked at the phase II X-NOVA, the number of centers, and the length of time, these studies should take about two years to enroll.
Okay. Maybe just one related note on that is how competitive is it to find these patients versus other sponsors who may be running MDD trials? Just curious, are these patients hard to find? Just sort of what's going on there? I had a question on bipolar.
Sure. Yeah, specifically in depression, again, for us, our experience is comparing this to epilepsy and the depression studies, I think, a little bit different. So finding these patients is not hard. It's quite a prevalent indication. I think finding the right patient and making sure that they meet all of the screening criteria is really important here, as we talked about earlier. Yeah, I don't think that we're going to be concerned about finding the MDD patients. Obviously, on the epilepsy side, it does take a little bit longer just based on the prevalence of that disease. So far, no concerns in terms of finding the patients on the depression side.
Great. You not too long ago made the announcement that you're also going to explore bipolar. Can you maybe help us understand? Obviously, we've seen very good evidence to date in FOS, as well as MDD, but just sort of how are you able to make the leap into bipolar and proceed with sort of a mid to late stage program in that indication and population?
Yeah, I mean, the benefit of Azetukalner into any other indication is we know a huge amount about the safety profile of the drug, right? That's very helpful. If you look at, and we've seen this both preclinically and now we've seen it in the clinic, both in epilepsy and in depression, we know what the pharmacologic range is, right? We know at what range in terms of what dose are we seeing activity, and we're seeing the same overlapping pharmacology in terms of that dose and exposure from both depression and in epilepsy, and we don't expect anything different in terms of bipolar depression. All of that information allowed us to make a decision in clinical development. We didn't need to do dose range finding.
We have not yet given all of the details on bipolar depression, but soon, over the next couple of months, as that study gets up and running, we will go through the sizing and powering assumptions and endpoints and everything. Stay tuned for that. Given that we believe this mechanism and this molecule has an impact, a positive impact and antidepressant impact, we think that should translate both from MDD into bipolar depression. Remember, we are only looking at those bipolar patients that are in a depressive episode, not that are in a manic episode. We are looking at the depression side of bipolar. There is actually some interesting genetics and some other literature out there that also supports Kv7 modulation in bipolar depression as well.
I don't think we have time today to go into those details, but there's some literature out there that supports us moving into bipolar depression.
Okay, great. You're running a fairly fulsome phase III program or late stage clinical program. There are some sizable trials. The question, I think, with regard to timelines and your balance sheet has come up periodically. Can you maybe just remind us what is your current cash runway assumption here? How do you think about funding? What is a very large scale, sort of impressive, I guess, as well clinical development plan here?
Yeah, so we ended Q1 with just under $700 million on the balance sheet. We're guiding that has cash runway into 2027. Obviously, yes, we have an ambitious clinical program for Azetukalner in epilepsy and psychiatry. Now we're starting to see some of our preclinical molecules mature into clinical development as well. Everything we've talked about today in terms of the Azetukalner clinical program, as well as both our drug discovery efforts and our early clinical development efforts on the pipeline, is all included in that runway. I think we have a good balance sheet. We've been well supported by our investors. As I mentioned at the outset, maybe this is a nice transition to say we're going to have a huge number of clinical milestones during that cash runway, starting with the phase three epilepsy data early next year.
Okay, great. We're coming up on time. I also do want to touch on your early stage pipeline as well. You talked about a couple of different assets earlier on. I guess in terms of the cadence of advancing these drugs in the clinics and potential initial readouts from phase I or phase II studies, just can you maybe remind us how you're thinking about development timelines for these assets?
Sure. There are really three targets that have been a focus priority for us over the last couple of years. We are doing some other earlier stage drug discovery, but the three targets that we have really emphasized publicly are additional molecules on Kv7. These are follow-on molecules to Azetukalner, molecules on a target called NaV1.7, which is a well-validated genetic pain target, and molecules that potentiate a channel called NaV1.1. Maybe I will go kind of in reverse order. On NaV1.1, we have identified molecules that I think are looking really interesting preclinically. We highlighted—I will not go through today in the interest of time—but we highlighted all of the work we are doing on NaV1.1 at the AES meeting at the end of last year. There are some really nice posters that people can go and look at.
We should get into toxicology studies for the NaV1.1 program this year, which would put us in a position to transition into clinical development next year. The other two targets are a little bit more advanced. On Kv7, our next molecule, which is called XEN1120, that's now in a phase one human clinical trial. What we'd like to do as we get through our safety studies, that's in healthy volunteers, is we'd like to move into a pain proof of concept study. That'll likely initiate next year. On NaV1.7, which is probably where we're getting a little bit more interest and questions on NaV1.7, obviously this is a highly validated target. It has been a challenging target for sure. I think we have some very interesting chemistries that are now through the toxicology studies.
We're just actually in the next couple of months, we'll file a CTA and get that into a human clinical trial as well. Both our XEN1120 and our NaV1.7, and we call our lead molecule there XEN1701, those should both be in pain proof of concept studies next year.
Great. Maybe just quickly, do you think about focusing on, in terms of clinical development, more the acute population, since that's sort of easier, shorter trials? How are you thinking about the chronic strategy there?
Yeah, so the first proof of concept studies will be on the acute side. The two proof of concept studies that I think most companies focus on is either.
Bunionectomy.
Exactly. It's either a bunionectomy study or in a dominoplasty study. Those are the two ones that most companies focus on. We will as well. The first proof of concept will be in acute pain. I think then longer term, as we think about the development strategy after those proof of concept studies, that's when you start to make the decision on additional work in acute pain and also starting to think about chronic pain.
Okay. We're at time now, so we'll end it there. My thanks to Ian and Xenon for joining us.
Great. Thank you.