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

Okay. Good morning. We'll continue with our next session. I'm Paul Choi, and I cover the small and mid-cap biotechnology sector here at the firm. And we'll continue with our next session, which is with Xenon. We're very pleased to have CEO, Ian Mortimer to my immediate left; and CFO, Sherry Aulin, to my far left. What we'll do is some Q&A with the team. If along the way, anyone has questions in the audience or online, please raise your hand or shoot me an e-mail, and we'll read the questions anonymously over the path -- over the time. But maybe what we'll do, let's start with Ian, with -- maybe with some sort of high-level questions, which is for investors who may not be familiar or new to the Xenon story.

Can you maybe give us a quick overview of the company and then maybe a little bit on the sort of basic science that underpins your pipeline and developmental efforts with regard to the potassium channel and so forth.

Yes, for sure, happy to. And thanks very much for you and for Goldman for hosting us today. We really appreciate it. So yes, for those that are less familiar with the Xenon story, we're a neurology company. Really deep expertise in drug and ion channels in the CNS. We've been doing this for about 15 years, and you'll see that as a theme that runs through our pipeline and portfolio. Deep clinical experience in developing drugs in epilepsy and obviously an interest in depression as well, which we'll talk about. The lead program, which we'll spend our time on today is called XEN1101. So this is a potassium channel modulator. So it targets Kv7.2 in the CNS. And really, I won't get into deep science today, but we're trying to break on hyperexcitability in the brain to treat seizure disorders and depression as well. And our excitement around XEN1101 came from the data that we had about 18 months ago. It was called our X-TOLE trial, it's the Phase IIb study in patients -- adult patients with focal epilepsy. This was a 4-arm study, 3 active dose of placebo, and we were able to show in that study when we unblinded the data that we were statistically significant at every seizure reduction endpoint at all doses and a clear dose response as well. And what was interesting when we unblinded the data is just how severe or refractory the patient population was. So we measure that by the number of drugs that these patients had failed before coming on study, the number of drugs that they were on during the study. So they're con meds as well as their baseline seizure burden. And when we look back at the literature, it's likely the most difficult trial population ever in focal epilepsy. And so we have to really put our compelling efficacy in the context of the patient population. So we believe we have one of the most important drugs in development in focal epilepsy, and we look at that based on not only the compelling efficacy. We're going to have an only in class mechanism. These patients are treated with polypharmacy will be the only potassium channel modulator available. The drug doesn't need to be titrated. Many of these drugs in epilepsy and in the CNS have to be titrated slowly. 1101 has really gets to steady state over a period of time so it doesn't need titrated. So you're on your dose on day 1. And what we found based on that is we have statistically significant efficacy at week 1. So these patients are coming into study with significant seizure burden and they are getting relief from their seizures almost immediately, which is really important. Over the last year, 1.5 years, we've done a number of things to get into a broad Phase III program. Initially, we engaged with FDA at an end of Phase II meeting about a year ago where we anchored the Phase III program, as well as what's going to be required at the time of NDA filing. And now we're in 3 Phase III clinical trials. So there's 2 Phase III clinical trials in focal epilepsy called X-TOLE2 and X-TOLE3. The nomenclature is very purposeful there. This is the same inclusion, exclusion criteria as we have in the X-TOLE study. So we're trying to replicate that Phase IIb data in our Phase III program. And then the third Phase III clinical trial is in a separate epilepsy indication called primary generalized tonic-clonic seizures. So this is the old grand mal seizure, and we're running a single Phase III trial, which we discussed with FDA as well. So all of those studies have been initiated over the last number of months and are ongoing. We have broadened the indication, and I know we'll talk about today our work in major depressive disorder. So we have a Phase II clinical trial ongoing called our X-NOVA study in MDD and that study will read out later this year. And I know we'll spend some more time there. Maybe Sherry can just review upcoming milestones, balance sheet, cash runway, and then we can get into your Q&A.

Sounds good.

Great. Thanks, Ian. So we're actually entering a fairly data-rich period in the second half of this year, we're going to have a couple of important presentations at upcoming conferences. So at the International Epilepsy Congress later in September, which is held in Dublin, we're going to provide some additional data from our X-TOLE study, specifically the open-label extension. In addition, we'll have presentations at this year's 25 -- 2023 AES or American Epilepsy Society meeting in December. And then as Ian mentioned, we have 2 important data readouts as well in the fourth quarter. So our Phase II X-NOVA study in major depressive disorder will read out in the fourth quarter, as well as we have a partnered program with Neurocrine, where they licensed from us a selective sodium channel inhibitor and that Phase II readout in focal onset seizures will also happen in Q4. From a balance sheet perspective, we're going into this period with a very strong balance sheet. We ended the first quarter with $687 million in cash, which gives us runway into 2026, and that fully funds our very ambitious Phase III epilepsy program, which Ian outlined, which includes 3 studies as well as an open-label extension. And so we're very much looking forward, Paul, to exiting on that program.

Great. Thanks, Sherry. So investors may be somewhat familiar with the space in 1101, but there was formally an on-market drug in the potassium channel category. And in your view, or what were particular strengths and weaknesses and sort of what is the white space in your view for 1101, maybe starting with FOS.

Sure. So let's take a bit of a step back and review some of the history. So Paul is referring to a drug. The brand name was Potiga, the generic name was ezogabine retigabine. So all use ezogabine, that's the nomenclature that we normally use. So this was a drug that was developed by GSK. And it was -- had success in focal epilepsy, so had numerous successful studies and the drug was approved. The drug didn't do well commercially, and the drug is no longer available. It was removed from the market for commercial reasons. So the first reason that it didn't do well is just the pharmacokinetic profile of the drug. It's a TID drug. It gets cleared very quickly. And when these patients are on polypharmacy, and they're on drug for decades, when most of the drugs are BID or QD, it's difficult to have a TID drug, especially when the adverse event profile of all the drugs that are active in the CNS are the Cmax related adverse events. And when you dose the drug 3 times a day, you get that Cmax 3 times a day and you really have an effect of that. They also had some very specific liabilities based on the chemistries related to discoloration and had some impact on urinary retention as well.

This is the Smurf syndrome blue.

Yes. So the -- yes, it was really an unfortunate part of the chemistry that under oxidative conditions, the drug dimerize and that dimer had color associated with it, and that dimer had high affinity for melanin. And so over a cumulative dosing over quite some period of time, you would see some blue discoloration show up in certain melanin-rich parts of the body. So 1101 is taking advantage of known pharmacology with a much better molecule. So we're significantly more potent than ezogabine on target. So when we look preclinically, both in vitro and in vivo, we're about 15 to 20x more potent on drug -- sorry, more potent on target. We do not have the chemistries that give rise to the discoloration. We've been able to show that preclinically. We also now have patients that have been dosed, a number of patients more than 3 years. So if that risk was to show up, it would have shown up already. So we feel very confident that we have a very different molecule in XEN1101. So really, it's taking advantage of known pharmacology with a better molecule. And it looks like the data overall are better. Obviously, we're a QD drug, not TID, more potent, much less dose. And it looks like the efficacy profile, again, with the caveat of cross trial comparisons, it does look like the efficacy of 1101 is better than the efficacy of ezogabine. Now let's go back to how that's actually going to be used. So we're not competing against ezogabine because it's not on the market, but there are a number of other anti-seizure medicines that are available. But as I mentioned, for the patients that were treated, they get branded medicines, they're treated in polypharmacy. So like many therapeutic indications when we combine drugs together, we do want to combine drugs with different mechanisms. And when XEN1101 is commercially available, it will be the only potassium channel modulator available. So we believe that gives us an advantage in terms of being combined with other drugs that are used broadly.

As you think about the epilepsy market and some of the trends that we've seen in the last couple of years, obviously, COVID was a bit of a market factor, but you also mentioned ezogabine was not commercially successful due to its particular profile I guess, how do you think about the room for a later line drug here? And what are maybe some of the trends you're seeing currently with regard to patient behavior in the population that you guys are initially developing 1101 for what are the compliance and duration trends like potentially here?

Yes. So maybe I'll start, Paul, a little bit higher level and talk about the epi data as well as the treatment paradigm, and then Ian can comment on some of the specifics around compliance and where 1101 would treat -- fit into the treatment paradigm. So at the highest level, there's about 3 million adult epilepsy patients in the U.S. and 60% of those patients experience focal onset users. The next largest segment of that population are patients who are diagnosed with generalized epilepsy, and that makes up about 30% of the population. When we think about that group, actually a significant number still experience breakthrough seizures and have a need for additional therapies because the seizures are not well controlled. And that actually makes up about 30% to 50% of the population. So the branded epilepsy market, if you think about that group could be upwards of about 1 million adult patients in the U.S. From a treatment paradigm perspective, so typically, just given the payer environment, patients will have to go through 1 or 2 generics before being put on a branded agent. So generally, patients will be on a drug like levetiracetam, is frequently used or Keppra, lamotrigine. Those typically will form the backbone of therapy in these patients. And then patients will -- generally, physicians will sort of bake on trial and error, adjust medications for either breakthrough seizures or tolerability issues. And that's where you get into polypharmacy and adding additional agents like 1101 with a novel mechanism can be very attractive to physicians. When you think as well about how these patients are treated, this isn't really a space where patients are getting an episodic treatment like depression. Patients are going to be on medication for the entire duration of their lifetime. Even if they are not experiencing seizures, they will still remain on medication. When we get into later lines of therapy, again, as I mentioned, it's really about trial and error and figuring out what specific sort of cocktail or combination of medications work for each patient. With respect to COVID, maybe just one final comment before I pass it to Ian. We haven't seen anything significant impacts with respect to COVID from patient visits or really from a treatment perspective, with the exception of -- during this period of time, we've seen the launch of XCOPRI, which is a drug that's fairly recent, and we'll be the only branded agent when 1101 -- when we expect 1101 will launch, as well as Vimpat, which is a drug that's been highly used in the space has recently gone generic.

So just to add to Sherry's comments, if we look at the 1101 profile, we will be, based on the payer environment and medical practice, we're going to be competing for those first branded patients in polypharmacy environment. And we look at the profile of 1101 with a novel mechanism, the early onset to efficacy, the compelling efficacy, no titration are all of the things that we believe, when we're out speaking with KOLs and treating physicians that they resonate and that the struggle do well. From a compliance point of view, maybe one comment is when you talk to the prescribers and the epileptologist, usually, their understanding is that the greatest reason of breakthrough seizure is drug compliance, right? These patients are not having seizures necessarily every day. And when they don't take their medications, they are having breakthrough seizures. One of the benefits of 1101 is it does have a very long PK. So if you just look at the half-life of the drug, it does stay above, we believe, based on our modeling above some semen or minimal concentration required for efficacy for some period of time. So if there is a situation where a patient does miss a dose, I think on a drug that has the PK profile of 1101 could be beneficial for those patients.

Okay. Great. Sherry, I wanted to return to you for a moment because you did talk about some updated 1101 data that's coming at the Dublin meeting, the International Epilepsy meeting as well as AES, particularly with regard to the open-label extension data. And maybe if you were to direct investors as to how to think about that? And what to expect as with this additional follow-up, just what sort of trends or patterns you'd have us focus on with the updated data?

Yes, absolutely. And so as a reminder, we had an open-label extension as part of the X-TOLE study. So that open-label extension actually initially started as 1 year. And based on physician feedback, we actually extended that open label to 3 years and then subsequently to 5 years based on feedback from physicians that had patients that were doing really well on the drug. And we did actually have quite high turn -- rollover from the X-TOLE study into the open-label extension, upwards of 97% of patients went into the OLE. So we're going to have some really interesting data coming out of that OLE, which we're continuing to generate more efficacy and safety data. We're going to have that data come out later this year, as I mentioned earlier, at both the IEC conference, where we're going to specifically be focusing on -- in addition to some data that we've already presented, there's going to be some quality-of-life data that we're going to present at that conference. Again, as you see, these patients continue to have periods of seizure freedom and continued seizure reduction. There is an impact of quality of life on these patients. So we're going to present that data. And then at the American Epilepsy Society meeting in December, we're going to do a more recent cut of the OLE. So just as a reminder, last year at AES, we did an 18-month cut of the OLE data. So there, we showed some really impressive data with respect to efficacy. So we continue to see really strong efficacy at later time points, actually as high as 80% to 90% efficacy for patients on the OLE and then as well as some seizure freedom data, which was really impressive. So these patients are experiencing periods of seizure freedom. We reported close to 20% seizure freedom for 6 consecutive months as well as 10% for 12 consecutive months, which is really impressive when you think about the baseline seizure burden that the average patient had coming into X-TOLE, which was about 13.5 seizures per month. So that's going from a seizure every other day to having periods of 6 months of seizure freedom or 12 months of seizure freedom. So we'll just do an additional cut of that data, which will be further progress. It will be an additional 12 months, and so it's a 30-month cut of that data, and we're looking forward to those presentations later this year.

Great. you're doing both the U.S. and international conference. Could you maybe speak to how like maybe there are some regional differences in the approach to treating epilepsy? And what does that potentially mean for the regulatory path in sort of the major geographies?

Yes. Most of the drugs that are available to treat epilepsy are used in multiple jurisdictions. And this isn't a geographic disease, we see the disease globally. When we go back to our X-TOLE study, we had both U.S. sites as well as European sites in that study, 60% of the enrollment came from Europe, 40% from the U.S. And as a reminder, because of the success in X-TOLE, we're really trying to replicate that, especially in X-TOLE2. So we're going back to a lot of the same sites and investigators as we go -- as we get into the X-TOLE2 program. So we don't see massive regional differences on how these patients are treated. And when we look at the drugs that they failed or on, based on geographies, you see a lot of the same drugs show up. From a regulatory point of view, so the nice thing about epilepsy is in terms of the regulatory path, it's really well understood. So in the U.S., the primary endpoint for all of these studies is called the MPC. So we're looking at these percent changes on a monthly basis. We actually do a median analysis. So the studies are run where you do a baseline period. You look at the seizure burden over baseline, you make that into a monthly number, you normalize it. And then the patients are randomized. You count seizures in a seizure diary through the double-blind period and then you can combine -- or compare for individual patients, the number of seizures they had in the double-blind period versus the baseline period and do your statistical analysis that way. And as we mentioned in the X-TOLE study, we had really compelling efficacy at that primary MPC, where we had over a 50% reduction for the high dose. And as Sherry mentioned, when we follow those patients in open-label extension, we get even more seizure reduction over time as they get into open-label extension. From Europe, the primary endpoint is different. It's a responder analysis. It's called the RR50. So it's the percentage of patients that have at least a 50% reduction in seizures. Those things track really well. It's the same patients if they're getting benefit, they're going to show benefit on both MPC in RR50. Practically, we deal with that is we design the studies the same. We have sites in both jurisdictions. And the primary endpoint is MPC and the secondary endpoint is RR50 for the U.S. And then at the statistical analysis plan level, we just switched the primary and the secondary for Europe. So we've had significant regulatory interaction with both major jurisdictions and feel comfortable. And as I mentioned, the nice thing about epilepsy is the regulatory path and the endpoints are really well understood.

That's great. With regard to X-TOLE2, which you mentioned as well as X-TOLE3, can you maybe give us just an update on where you guys are tracking with regard to enrollment? And when you might be prepared to start talking about data timelines and so forth and as well as for Exact?

Yes. So maybe just taking a little bit of a step back and talking about the X-TOLE2 and X-TOLE3 study designs and how they compare to X-TOLE. We've really designed those studies to essentially mirror as closely as possible X-TOLE given the success we had with that study. So when we think about the key factors such as inclusion/exclusion criteria, the general number of sites that we're including in those studies as well as the key primary and secondary end points. Those are all the same between X-TOLE2. X-TOLE3 as 2 X-TOLE. There are some slight differences. So the Phase III studies are a little bit larger at 360 patients versus 325 patients, and the double-blind period is also slightly longer at 12 weeks versus 8. But generally speaking, these studies are very -- the Phase III studies are designed very similar to X-TOLE. So for that reason, from our perspective, we feel very confident around our ability to execute on the Phase III FOS studies, given our experience with X-TOLE. In addition, we have those relationships with a lot of the investigators. And we are, in fact, leveraging many of the X-TOLE sites in our Phase III program. And so the investigators have experience with the drug. They know it's an active agent based on the results of our Phase II study. And so we feel, again, confident about our ability to execute on that. So given that it's early days, we initiated -- both of those studies are now underway. X-TOLE2 started late last year with a little bit of a stagger in the start for X-TOLE3, but we will be in a position, Paul, to provide more formal guidance later this year as we continue to get sites initiated and look to see how patient screening and randomization is progressing against our internal timelines, we'll be able to provide some guidance there. And then with respect to Exact, so again, just some high-level comments on that study. So we agreed with FDA on a single Phase III study, which has now initiated. That study is running in parallel to X-TOLE2 and X-TOLE3. Important, again, to remember, as I had mentioned earlier, that PGTCS or primary generalized epilepsy is less prevalent than FOS. So although the study is smaller at 160 patients, it will take a little bit longer to recruit. And we don't have that direct experience as we do in the focal onset seizure space. But irrespective, the study is running in parallel. And so how we -- what path we progress from a regulatory perspective will depend on timing of readout. It will either be part of the NDA, if the readout is at the same time as the FOS studies or it could be as part of an sNDA shortly thereafter. But again, importantly, this is a unique development path that we're pursuing. So a lot of companies will actually -- and what we've seen with ASMs is that drugs will get approved for FOS. And then quite some time later, actually, they may broaden their label to PGTCS. So we will be quite early in the life cycle of 1101 in pursuing this additional indication.

Okay. Great. Let's maybe turn to MTD and talk about sort of the rationale for your NOVA study here. Can you maybe remind us what the ezogabine data showed previously? And how this underpins -- or has your thinking has adopted on the NOVA trial design based on what the ezogabine data has shown previously?

Yes. So the -- I'll talk a little bit about the preclinical mechanistic rationale in some of those data. And then as you mentioned, ezogabine ran a Phase II clinical trial in major depressive disorder that was published recently a couple of years ago. So we're basing it off of that as well. So there's some early work done a number of years ago in a chronic social defeat stress model, where you can put animals in a stressful environment, and you can see whether they are resilient to that environment or to that stress or they're susceptible. And it was found that the animals that were resilient had a natural upregulation of potassium channels in the CNS or in the brain that protected them, or at least that was the gene that from an expression point of view, seems to be up-regulated the greatest. What I think was really elegant based on the science and the work that was done is you could take the susceptible animals and you can make them resilient pharmacologically. You could actually do it with gene expression as well, but pharmacologically, you could do with ezogabine. So that gave some academic investigators and a group at Mount Sinai and collaborators at Baylor, the interest in running clinical development. So they've run 2 clinical studies with ezogabine. The first was run in an open-label manner, the second was a placebo-controlled study. So we'll focus on the placebo-controlled study. It was a small study, it was at 2 centers, but they saw clear separation on clinical scales of depression, which they use MADRS as the endpoint there, as well as the clinical scale of anhedonia. And the anhedonia or the lack or loss of pleasure, was something that was important when we go back to the preclinical mechanistic rationale. So that study was very successful. That group out of Mount Sinai came and approached us because they wanted to do future clinical development, but ezogabine, as we mentioned earlier, was no longer available. So they're running an IST right now with XEN1101 in a study that's a little bit larger than the study that they had run previously. And it's a 1:1 randomization using 20 milligrams of 1101 versus placebo. If we go back to the ezogabine work on MADRS, they had a 7.9-point separation, so very active between the active arm and placebo. And they use the dose of 300 milligrams of ezogabine, 300 milligrams TID, which is a dose that was used. We call it the mid dose that they used in their epilepsy development. So we do know, at least from an exposure point of view, you're in the range when you're seeing an antiseizure effect as you're seeing the antidepressive effects for ezogabine. Now when we look at 1101, as I mentioned, there's an IST ongoing and then we're doing our own study, which we call X-NOVA, we have 2 active doses in placebo of 50 subjects per arm. So 150 subjects in total, 1:1:1. We're using -- we're looking at the 10-milligram dose and the 20-milligram dose. The lease in epilepsy, the 20-milligram dose of XEN1101 was more efficacious than the 300-milligram dose of ezogabine. So I think we've got good preclinical rationale. We've got good clinical data with ezogabine. I think we're in the right dose range to potentially see an effect. And the study has gone really well. We've been running the study for about the last year. We will complete patient screening in the near term here with data later this year in Q4.

Great. Probably one of the biggest concerns that investors always have when it comes to MDD studies is thinking about placebo variability. And can you maybe talk about how you've thought about your trial design, powering and so forth to account for this, given that we have seen a wide range of placebo performances in historical MDD studies, just kind of how you think about the staff plan there?

Yes. So let's talk -- I'll talk about powering first, how we've designed the study and then let's talk specifically around the conduct of the study and some of the things that we're trying to do to manage the placebo rate and make sure that this is a well-conducted study. So on the powering side, as I had mentioned, we did use ezogabine as a bit of a guide here. So we are looking at a similar patient population. So these are patients that are going to have moderate to severe depression. So our expectation at baseline is that those MADRS scales will be kind of in the high 20s to low 30s, and we'll be looking at the primary endpoint of MADRS. As I mentioned with ezogabine, they had a 7.9-point separation. We've designed our study for half that effect size. So a 4-point separation, we have 80% power. We obviously have power as you move to an effect size that are smaller than that, but your power goes down as the effect size gets smaller as well. In terms of managing just the overall conduct of the study, I think we're doing a number of the things that you would expect us to do. These are -- this is a U.S.-only clinical study. So we're not looking at sites outside of the U.S. We are obviously using a CRO that we've gone through a significant process to choose. And with our CRO, we believe we've chosen good sites with investigators that have experience here. In addition, we are using the SAFER criteria. That's the criteria through mass Gen where you have independent adjudication. So each -- every individual patient is adjudicated by a third party to try to make sure that we're identifying the right patients. And we see that a little bit in the screen failure rate as well. The last thing is the entry criteria coming into the study. As I mentioned, the primary endpoint is MADRS, but the entry criteria coming in is actually HAM-D17. So you can use the different entry criteria coming in versus your primary endpoint, and you can manage just that interaction between the patient and the physician as well. There's a number of different things that we're trying to manage across the board to, like I mentioned, to have the best study that we can.

Okay. Great. So you mentioned your data will be coming in the fourth quarter. So your last patient is coming up relatively soon here. And so you'll be in the later innings for the study. Can you maybe just sort of walk through what the mechanics will be in terms of as you go into data, top line and so forth, data cleaning, what kind of level of details you would potentially disclose with the press release if the study is successful and so forth?

Yes, that's a great question. So yes, as you mentioned, Paul, we've said that we're going to complete patient screening this month. So once that last patient is screened and randomized, they would go through a 6-week double-blind period followed by a follow-up period. And then at that point, we would be able to lock our database, clean the data and present our top line. As we did with X-TOLE, we probably expect that we'd be in a position over the next quarter or 2 to provide maybe a little bit more granular guidance around when that data is going to be within Q4. So that's something to look forward to as well. And then expectations from a top line data release, I'd say at this stage, we're comfortable saying that we're going to obviously include efficacy data from our primary and then key secondary endpoints as well as some data around tolerability in this patient population.

Great. We have a few minutes left, so I want to give the audience a chance to ask any questions, if there are any. There's a mic available, so just raise your hands if you'd like to raise a -- raise your hand and we can ask a question. So if NOVA is successful here, how do you think about next steps? You mentioned it is sort of -- it is a U.S.-only study. How do you think about pursuing it independently, what would you sort of ask maybe FDA in terms of next steps? And maybe you could elaborate on that in remaining few minutes here.

Sure. And to build on Sherry's comments on what we'll see in the top line press release, not only will be clear, as Sherry mentioned on some of the endpoints and disclosure you'll see there. But we'll also talk about what the next steps for the program are for MDD. So we have different options here. I think one of the things that we just want to be -- that we want everyone to be aware of is that depression is a really important comorbidity in epilepsy. So it's the most common comorbidity in patients that have epilepsy. There's up to a 50% lifetime risk of depression if you're an epilepsy patient. So the ability to have all of the attributes that we talked about 1101 in epilepsy, but also potentially have a mood benefit would also differentiate in the epilepsy space. So generating any data on depression and mood, I think, could be beneficial as we think about our Phase III program and our commercial aspirations in epilepsy. When we think specifically around the primary indication of major depressive disorder, obviously, we'll see the data later this year. And based on the totality of the data, there is an opportunity for us to do continued clinical development in MDD. As you mentioned, we would need to engage with regulators post Phase II at an end of Phase II meeting. We deal with a different division for depression than we do for epilepsy. So we would engage with regulators and discuss what that program would look like. So right now, we're thinking we have multiple options available to us. We continue to generate data, which is important for epilepsy. We have the opportunity to do continued clinical development in major depressive disorder. And being an ion channel company and a drug discovery company in addition to what we do on the development side, we also have other molecules that we've looked at preclinically. So we've got other drugs that are differentiated from XEN1101. There're still KV drugs but have different profiles.

Okay. Great. We're coming up on time here, but maybe just as you think about that further down the road and potentially becoming a commercial stage company. Can you maybe outline for us how you're maybe thinking about approaching a potential launch, you'll initially be obviously an FOS most likely? And just sort of how you think about the shape and build out of a commercial Xenon versus a clinical stage Xenon?

Yes. So focusing our comments on FOS or on epilepsy specifically because we don't have the data yet from X-NOVA and haven't announced our next steps. But when we think about the epilepsy space from a commercial infrastructure perspective, I mean, the call point there is going to be epileptologists and neurologists. And so we're confident that we would be able to appropriately scale and build the necessary commercial infrastructure to be able to address that call point, thinking about a field force of somewhere between kind of 100 to 150 sales reps. We are already starting to build out our commercial team. We have our Chief Commercial Officer, who joined us a couple of years ago and building some of the key functions under the commercial group such as market access and marketing. Obviously, medical affairs is also an additional area where we're continuing to build our capabilities as we think forward to commercialization. Our strategic objective is really to focus on the U.S. market that is 80% of the global market. And we think that, that's within a range for us. We do expect that we're going to be thinking about possibly some strategic alternatives for ex U.S. markets and exactly what that looks like is to be determined, Paul.

Okay. Great. We're up on time here. So my thanks to Ian and Sherry for joining us for this session, and we'll end it on that note.

Thank you.

Thank you.