Xenon Pharmaceuticals at Goldman Sachs Conference: Strategic Clinical Advances

On Tuesday, 10 June 2025, Xenon Pharmaceuticals (NASDAQ:XENE) presented at the Goldman Sachs 46th Annual Global Healthcare Conference 2025. The company outlined its strategic focus on advancing clinical programs for its lead molecule, Zeto counter, in epilepsy and major depressive disorder (MDD). While the company is optimistic about its clinical and commercial prospects, challenges remain in executing its ambitious plans.

Key Takeaways

• Xenon is advancing its lead molecule, Zeto counter, with a focus on epilepsy and MDD.
• The company expects Phase III data for Zetucalder in focal onset seizures by early 2026.
• Xenon plans to build a commercial infrastructure in the US, seeking partners for ex-US markets.
• A strong cash position extends the company’s financial runway into 2027.
• Xenon is exploring the potential of Zeto counter in bipolar depression.

Financial Results

• Cash Position and Runway:

- Xenon ended Q1 with just under $700 million.

- The company projects a cash runway extending into 2027, covering all planned clinical trials and drug discovery efforts.

• Commercialization Strategy:

- Plans to establish a US commercial infrastructure for AZET2 Calynur.

- Seeking partnerships for market access outside the US.

Operational Updates

• Zeto Counter (Epilepsy):

- EXTOL-2 (Phase III in focal onset seizures) nearing completion, with data expected in early 2026.

- XTOL-3 enrolling at various centers, similar criteria as XTOL-2.

- EXACT (Phase III in Primary Generalized Tonoclonic Seizures) facing longer enrollment due to patient scarcity.

• Zeto Counter (MDD):

- ExNova 2 (Phase III) active in approximately 50 US centers, with guidance expected soon.

- ExNova 3 to start at different centers, including some outside the US.

• Zeto Counter (Bipolar Depression):

- Phase III program set to begin mid-year.

Future Outlook

• Clinical Data Readouts:

- Significant milestones expected during the cash runway, with epilepsy data anticipated in early 2026.

• Pipeline Development:

- Focus on advancing KV7 molecules, Nav1.7 inhibitors, and Nav1.1 potentiators.

• Market Expansion:

- Exploring partnerships for ex-US markets.

• Commercial Launch:

- Aiming for AZET2 Calynur commercialization by late 2026 or 2027.

Q&A Highlights

• Commercial Strategy:

- Xenon to build US infrastructure and seek ex-US partners.

- Investment in MSLs to enhance presence in the epilepsy community.

• Pricing:

- Epilepsy drugs typically priced in the specialty neurology range.

- Similar pricing expected for branded drugs in epilepsy and depression.

• Competition:

- Xenon anticipates being one of two branded drugs available, alongside XCOPRI.

For more detailed insights, readers are encouraged to refer to the full conference call transcript.

Full transcript - Goldman Sachs 46th Annual Global Healthcare Conference 2025:

Paul Choi, Analyst, SmithCat: Okay. We’ll continue with the next session, which is Xenon Pharmaceuticals. I’m Paul Choi, I cover the SmithCat 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, 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 and A.

Ian Mortimer, CEO, Xenon Pharmaceuticals: That sounds great. And thanks, Paul, for hosting us. Always good to be here. So 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.

But 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 and A, so our lead molecule is at two counter, in a broad phase three epilepsy program, so we’ll talk about that. We’ve also moved into neuropsychiatry, both in major depression as well as bipolar depression. And that late stage clinical program is starting and getting up and ramped up over the remainder of this year. And then 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. And then over the next few months, we’ll get our Nav1.7 inhibitor into the clinic as well. And I know we’re starting to get some attention there. But if we focus on is that to calendar in epilepsy, obviously we have a Phase III program ongoing.

That’s our next big clinical readout, XTOL-two, which is a Phase III clinical trial in focal onset seizures that we’ve guided to data in early twenty twenty six. And we can spend more time going into the details. But we really think the profile of the Zet2 calendar based on the phase two data, I think is really impressive. And we’re excited to get to that phase three data because that’s on the critical path to moving towards filing an NDA and becoming a commercial organization. And then as we’ve moved into psychiatry, our is that to counter phase three MDD studies up and running.

We’ll have our phase three up and running here shortly around midyear, and then our bipolar depression study as well. So a busy year for us in terms of clinical execution. And then 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.

Paul Choi, Analyst, SmithCat: Okay, great.

Ian Mortimer, CEO, Xenon Pharmaceuticals: Thanks for

Paul Choi, Analyst, SmithCat: 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? You can reference a prior market drug like Potiga and so What at least at a clinical level your initial XTOL study as well as the Exnova study have shown in terms of efficacy and safety for those two indications.

Ian Mortimer, CEO, Xenon Pharmaceuticals: Yeah. 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. So we’ve been a company that’s been around for some time, but we’ve really built these core capabilities of drug channels in the CNS. So we work on validated targets, either they have genetic validation or pharmacologic validation. We’re an ion channel company.

We’re very focused in neurology. So I think those are the things where we believe we can have a competitive advantage. And you’ll see those themes run throughout the pipeline. But to your question on is that two calendar, so this is a potassium channel modulator. So 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.

And as you mentioned, I think the phase II data were very robust. This was our XTOL 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.

Paul Choi, Analyst, SmithCat: It’s been several years now.

Ian Mortimer, CEO, Xenon Pharmaceuticals: Yeah, it’s been several years. And actually, there’s an annual medical meeting that’s really important in our space, which is the American Epilepsy Society meeting, takes place every December. And we’ve been able to, every December, show another year of mature data. So this past year, we had our three year data on the open label extension. And what we found for Zetucalder 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 efficacy seen in a clinical trial for patients with focal onset seizures. The drug doesn’t need to be titrated. And so the patients are treated with one pill once a day. And 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 two program and we’re continuing to monitor that also in phase three. And then if you look at the long term efficacy and safety data, it’s really strong as well. So we’re seeing patients have longer periods of seizure freedom. That’s very important in terms of the quality of life of these patients. And then in terms of safety, we now have amassed over seven hundred patient years of exposure.

We have our patients that have been dosed more than five years. So we have a really good handle on the safety profile of the drug as well.

Paul Choi, Analyst, SmithCat: Okay, great. Maybe turning to your phase 3s. Can you maybe just update us on how trial execution and trial operations are going in terms of enrollment with EXTOL-two? And then when would you potentially be in a position to announce last patient in?

Ian Mortimer, CEO, Xenon Pharmaceuticals: Sure. EXTOL-two is our phase three clinical trial in focal onset seizures. And we started this program a couple of years ago. We’re getting close to the end. So 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 in a baseline period before randomization, and then it’s a twelve week double blind period. And so that puts us on track for data in early twenty twenty six. The real approach to XTOL-two was to have consistency with our XTOL study. So the inclusion exclusion criteria in the phase three program is exactly the same. Because we had a really nice outcome in phase two, we’ve gone to a lot of the same investigators, a lot of the same clinical sites.

And so we have a relationship with them. We’re using a lot of the same sites and geographies that we’ve used in phase two. So a lot of consistency between the phase two program and the phase three program.

Paul Choi, Analyst, SmithCat: Okay, great. I think at least based on my investor discussions, investors have a lot of confidence on the efficacy side. And so a lot of the conversations often shift to the commercial side and just post data, post filing, and so And sort of what sort of commercial considerations and modeling factors can go into the thinking. And so maybe just starting with pricing here. And how are you thinking about pricing given the state of the market?

And as you think about lifecycle management, you are also looking at multiple indications. And so are you thinking about indication specific pricing? Does one pricing model work for multiple indications? Maybe just can you

Ian Mortimer, CEO, Xenon Pharmaceuticals: help us frame that analysis? Sure. And 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 I’ll start with epilepsy. So there’s about three million Americans that have epilepsy.

About sixty percent have focal onset seizures, the most common form of epilepsy. And we know it depends on which literature you look at, but somewhere between thirty percent and fifty percent of patients are not getting to good seizure control. So 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 a million patients roughly in The US that are still looking for better medicines where we think a profile like a Zetu counter could fit in. In terms of pricing, so again, not that we have given any guidance on pricing, but the nice thing about epilepsy, these are specialty neurology priced drugs. So it’s in a pretty narrow band and we feel very comfortable with that.

And 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.

Paul Choi, Analyst, SmithCat: Okay, great. Potentially at a time of launch, it’s maybe late twenty six, ’27 or up, thereabouts you and XCOPRI will be only sort of a 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 as a columnar will bring to the market versus those currently available therapies and how much you try to position your product?

Ian Mortimer, CEO, Xenon Pharmaceuticals: Yeah. So there’s a number of drugs to treat focal onset seizures. Many, many of those are obviously generic drugs now. So 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 locosamide usage now that VIMPAT has lost exclusivity as well. And so those patients are going on to a monotherapy generic drug. And for the patients that are doing well on that generic monotherapy, they’ll continue. For those that are either having tolerability issues or having still 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.

And that’s where we believe a zetu counter would be appropriate. As you mentioned, there is a drug, a branded drug that’s currently on the market called XCOPRI or Sunobamate, launched a few years ago. And you’re right, based on our analysis, we will be the only two branded drugs when we’re ready to commercialize at two counter. 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 Vazet two counter 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 X CoPre. And obviously, we still have the Phase study to complete and the Phase III data to unblind. But so far, based on the profile of a Zet2 counter, we’ll have really good discussions with the prescribing community and the opportunity for this to be an important new medicine.

Paul Choi, Analyst, SmithCat: Great. Maybe just touching on the filing strategy briefly. You obviously had a very strong result You’ll be in a position to unblind XTOL II in the early part of next year. Assuming 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 XOL3 if XOL2 is positive?

Ian Mortimer, CEO, Xenon Pharmaceuticals: Yeah. And I think it’s actually useful to just talk about some of the other components of a new drug application as well. 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. So from our perspective, XTOL-two is on the critical path to filing an NDA. So we’ve had that regulatory interaction.

And so you’re right, we plan to file with XTOL and XTOL II. 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. So 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 XTOL-two. One is XTOL-three, as you’ve mentioned.

XTOL-three is a carbon copy of the XTOL-two study, so the same inclusionexclusion 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 US. The other thing is we can use the safety data from XTOL3, or a study, which I’ll come to in a minute, called EXACT, 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.

And then the clinical trial, as I mentioned, is called EXACT. That’s in a different epilepsy indication called Primary Generalized Tonoclonic Seizures. That study will take a little bit longer. The condition is not as prevalent as focal epilepsy. So these patients have fewer seizures, often more severe, but those studies take a little bit longer to run.

Paul Choi, Analyst, SmithCat: Classically called grand mal.

Ian Mortimer, CEO, Xenon Pharmaceuticals: Yeah, that’s exactly right. The old nomenclature was the grand mal seizure, and now we call it a generalized tonic clonic seizure. But yeah, it’s the same indication.

Paul Choi, Analyst, SmithCat: I want to follow a little bit up on your EXOL3 study, which is still enrolling as you mentioned here, but in different study centers and geographies versus EXOL2. Just in terms of The US 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 the clinical regulatory focus in other major markets versus The US?

Ian Mortimer, CEO, Xenon Pharmaceuticals: So all of the data that we generated in XTOL and XTOL two and XTOL three, but if you’re talking about jurisdictions outside of The US, we’ll still use the EXTOL and the EXTOL2 data in those jurisdictions as well. So if we look at the two big jurisdictions of The US 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. So in The US, we focus on what’s called the MPC as the primary endpoint, where in Europe it’s a responder analysis. So it’s the percentage of patients that have at least a fifty percent reduction in their seizures from baseline to the double blind period. So we run the exact same protocol, whether it be XTOL-two, XTOL-three.

We have clinical centers both in The US and in Europe in both studies. And then when we get to the SAP level, just change the statistical hierarchy to meet the requirements of the individual jurisdiction.

Paul Choi, Analyst, SmithCat: Okay, great. I want to continue maybe a little bit on the ex US strategy as well as plans. 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 US 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 U.

S. Approval, just what does that mean for your U. S. Pricing strategy, just given some of this Washington discussion on MFN and so Sure. Maybe just help us put that picture together.

Ian Mortimer, CEO, Xenon Pharmaceuticals: Yes, absolutely happy to. So yes, I’ll talk about kind of what our strategy is overall and how we’re thinking about partnering. Today, think it’s important to know that we own 100% of this asset globally with no partners and no trailing economics. So the benefit in the position we’re in right now is we have total flexibility. So we’ve been really clear in terms of our strategy.

We only want to build the commercial infrastructure here in The US. And 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 invested in MSLs. So we have medical science liaisons that are out interacting with the community. And we’re starting to build not only in the profile of AZET2 Calynur, but the profile of Xenon as a trusted partner in the epilepsy community. So 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. So we’re already building the profile of Xenon. We’ve made a corporate and strategic decision not to build commercial infrastructure outside of The US. So 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.

Paul Choi, Analyst, SmithCat: Okay, great. I want to shift gears maybe a little bit to the MDD side and talk about Exnova. And maybe what did you learn as now that you’re operationalizing your Phase three programs in MDD, what did you learn from Exnova that you’re applying now in Exnova two? And anything you’d want to highlight in terms of specific changes with your go forward clinical plan?

Ian Mortimer, CEO, Xenon Pharmaceuticals: So this is the same molecule as Etucallna that we’re running in depression. We ran our phase two, which is the ex Nova study that you’re referencing, was a bit of a smaller study. And we did that purposely because we really wanted 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. So we wanted to go out and gain that experience.

So in ExNova, we ran a three arm study, two active doses in placebo, ten milligrams, twenty milligrams versus placebo. And 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 ten milligrams and then more of a drug effect of twenty milligrams, so that was really positive.

We saw separation on both clinical scale depression and anhedonia as well. But it was a smaller study. It was just over 160 subjects for the three arms, so just above 50 subjects per arm. So I would say we’ve actually made quite a few changes in going from that ex nova readout, which was at the end of twenty twenty three, to where we are today up and running in our Phase III clinical trial. So I’ll highlight some of them now.

So we moved in terms of the primary endpoint from MADRS to HAM D17. So both are well validated clinical scales of depression. And from a regulatory point of view, you can use either endpoint. What we saw with HAM D17, which is consistent with literature, we looked at both of those endpoints in phase two, is that we saw less variability in the data. And so that’s the endpoint that we’re taking forward.

So the primary endpoint in phase three is HAM D17 at week six. We also have changed the sample size materially. So as I said, there was just over 50 subjects per arm in phase two. We’re going to be two twenty five subjects per arm in phase three, and it’s going to be a one to one randomization. So we’re looking at twenty milligrams versus placebo.

We also know as you add additional active arms in a depression study, that can have an impact on your placebo rate. So 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. And so, 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.

So we’ll be looking at both a depressed population as well as an anhedonic population in phase three. And in phase three, like in phase two, one of the key secondary endpoints is looking at hedonia. We look at a scale called CHAPS. And then there’s a number of other criteria that we look at in terms of how the study is conducted. So that comes down to the CRO selection, to the site selection, the investigators we’re working with, as well as using a party through MassGen that they provide some of that party oversight and adjudication.

So there was a number of things that we learned in phase two that we’re taking into the phase three program. Great. Maybe this is a bit

Paul Choi, Analyst, SmithCat: of a Wall Street artifact, but it seems to be a bit of a recurring theme, is just placebo responses in these types of studies. And so maybe what else can you say in terms of trial design or trial execution that you implemented to sort of minimize placebo effects? And how is that factored into your statistical assumptions here?

Ian Mortimer, CEO, Xenon Pharmaceuticals: Yeah, look, I think in all of the psychiatry studies, to get the right types of patients and trying to manage placebo rate is absolutely critical to success. And so 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. So, 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. And we have a lot of oversight there, both internally at Xenon as well as through the CRO, as well as through a party. So 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

Paul Choi, Analyst, SmithCat: 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. Single center studies are always fraught with risks and so And so just can you maybe help us contextualize that study result, which unfortunately missed, but just contextualize that versus maybe what was different versus ex Nova?

Ian Mortimer, CEO, Xenon Pharmaceuticals: Yeah. I think we’ve been really consistent with our messages around this, whether we’re talking today or we’re talking six months ago or twelve months ago. We had always said that what was decision critical for us was the Exnova result. Quite frankly, we’re already in a Phase III program before this IST read out. As you say, a small academic center I think is difficult to interpret.

And so we have been very consistent whether the data were good or bad. It really wasn’t going to have an impact. But I think overall the data are really consistent. The primary endpoint was actually not a clinical endpoint of either depression or Yeah, was an imaging endpoint. And that was really the purpose.

This was NIH funded work and they wanted to look at neuroimaging. So 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, twenty milligrams of azetucalna versus placebo.

And actually at week six, they had quite a good separation on MADRS. It was over four points. And again, if we look at this study and we look at our ex 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 twenty milligrams outperformed placebo at every endpoint on both MADRS and on CHAPS. And 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. But I think it was really positive to see consistency in what we expected in terms of the is that to counter performance versus placebo.

Paul Choi, Analyst, SmithCat: Great. Maybe turning to your phase three program and the ex NOVA2 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?

Ian Mortimer, CEO, Xenon Pharmaceuticals: Sure. So ExNova two, that’s our phase three clinical trial in MDD is up and running. That got started just at the end of last year. So I’d

Paul Choi, Analyst, SmithCat: say we’re like a quarter, quarter and

Ian Mortimer, CEO, Xenon Pharmaceuticals: a half into this. So we haven’t yet provided formal guidance on top line data. So far everything’s going fine. This is gonna be a US only study. It’s gonna be at approximately 50 medical centers in The US.

Most of those are up and running now and we’re well into the early part of the study in terms of screening. So, so far everything we’ve seen is kind of what we would expect. And 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 gonna have what we call ExNova three, which is the phase three clinical trial. That should start.

It’s going to be the same clinical trial design, obviously at different medical centers. And I think we’re going to have some ex US centers in that trial as well. That’ll be up and running in the next couple of months. And then the new information that we provided a few months ago is that we’re going to run a phase three program in bipolar depression as well. And that bipolar depression study will be up and running around mid year also.

So yeah, a fair bit of work on the psychiatry side. And then if we look at the phase, maybe to answer your question a little bit more directly, if we looked at the phase II ex nova, the number of centers and length of time, these studies should take about two years to enroll. Okay.

Paul Choi, Analyst, SmithCat: Maybe just one related note on that is how competitive is it to find these patients and 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? Then I had a question on bipolar.

Ian Mortimer, CEO, Xenon Pharmaceuticals: Sure. Yeah, specifically in depression, again, for us, our experience is comparing this to epilepsy. And the depression studies, 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. But 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. But so far, no concerns in terms of finding the patients on the depression side.

Paul Choi, Analyst, SmithCat: Great. You, not too long ago, made the announcement that you’re also going to explore bipolar. And so 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?

Ian Mortimer, CEO, Xenon Pharmaceuticals: Yeah, I mean the benefit is that to counter into any other indication is we know a huge amount about the safety profile of the drug. So that’s very helpful. So if you look at, and we’ve seen this both pre clinically and now we’ve seen it in the clinic, both in epilepsy and in depression, is that we know what the pharmacologic range is. So 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. So all of that information allowed us to make a decision clinical development. We didn’t need to do dose range finding. So we haven’t 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’ll go through the sizing and powering assumptions and endpoints and everything. Stay tuned for that.

But given that we believe this mechanism in this molecule has an impact, a positive impact and antidepressant impact, we think that should translate both from MDD into bipolar depression. And remember, we’re only looking at those bipolar patients that are in a depressive episode, not that are in a manic episode. So we’re looking at the depression side of bipolar. There’s 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.

Paul Choi, Analyst, SmithCat: Okay, great. You’re running a fairly fulsome phase three program or late stage clinical program that are some sizable trials. And the question I think with regard to timelines and your balance sheet has come up periodically. And so can you maybe just remind us where does your current

Ian Mortimer, CEO, Xenon Pharmaceuticals: cash

Paul Choi, Analyst, SmithCat: runway assumption here? And how do you think about funding what is a very large scale sort of impressive, I guess, as well clinical development plan here?

Ian Mortimer, CEO, Xenon Pharmaceuticals: Yeah, so we ended Q1 with just under 700,000,000 on the balance sheet. We’re guiding that has cash runway into 2027. So obviously, yes, we have an ambitious clinical program for a Dutch accounting in epilepsy and psychiatry. And now we’re starting to see some of our preclinical molecules mature into clinical development as well. But everything we’ve talked about today in terms of the AZETRA calendar 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. And as I mentioned at the outset, maybe this is a nice transition to say we’re going have a huge number of clinical milestones during that cash runway starting with the Phase III epilepsy data early next year.

Paul Choi, Analyst, SmithCat: Okay, great. We’re coming up on time, so I also do want to touch on your early stage pipeline as well. You talked about a couple of different assets earlier on. And I guess in terms of the cadence of advancing these drugs in the clinics and potential initial readouts from phase one or phase two studies, just can you maybe remind us how you’re thinking about development timelines for these assets?

Ian Mortimer, CEO, Xenon Pharmaceuticals: Sure. There’s really three targets that we have been a focus priority for us over the last couple of years. And we’re doing some other earlier stage drug discovery. But the three targets that we’ve really emphasized publicly is additional molecules on KV7. So these are follow on molecules to a zetu counter, 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’ll go kind of in reverse order. On Nav1.1, we’ve identified molecules that I think are looking really interesting preclinically. We highlighted, I won’t go through today in the interest of time, but we highlighted all of the work we’re doing on Nav 1.1 at the AES meeting at the end of last year. So there’s some really nice posters that people can go and look at. But we should get into toxicology studies for the Nav1.1 program this year, which would put us in a position to transition to clinical development next year.

The other two targets are a little bit more advanced. So on KV7, our next molecule, which is called XEN110, that’s now in a Phase I 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. So that’ll likely initiate next year. And then 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, but 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. So both our KV71120 and our Nav1.7, and we call our lead molecule there XEN1101, those should both be in pain proof concept studies next year. Great. And maybe just quickly, do you

Paul Choi, Analyst, SmithCat: think about focusing on in terms of clinical development, whether you’re an acute population since that’s easier or shorter trials? How are you thinking about the chronic strategy there?

Ian Mortimer, CEO, Xenon Pharmaceuticals: Yeah. So the proof of concept studies will be on the acute side. So the two proof of concept studies that I think most companies focus on is either Bunyectomies. Exactly, it’s either a bunionectomy study or an abdominoplasty study. So those are the two ones that most companies focus on.

We will as well. So the 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.

Paul Choi, Analyst, SmithCat: Okay. We’re out of time now, so we’ll end it there. My thanks to Ian and Xenon for joining us.

Ian Mortimer, CEO, Xenon Pharmaceuticals: Great. Thank you.

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