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Image source: The Motley Fool. Thursday, Aug. 6, 2026 at 4:30 p.m. ET Senior Vice President of Corporate Affairs - Colleen Alabiso President and Chief Executive Officer - Ian Mortimer Chief Medical Officer - Christopher Kenney Chief Commercial Officer - Darren Cline Chief Financial Officer - Tucker Kelly Need a quote from a Motley Fool analyst? Email [email protected] Operator: Ladies and gentlemen, thank you for standing by. My name is Angela, and I will be your conference operator today. At this time, I would like to welcome everyone to the Second Quarter 2026 Xenon Pharmaceuticals, Inc. Earnings Conference Call. I'd like to remind everyone that this call is being recorded. [Operator Instructions] I would now like to turn the call over to Ms. Colleen Alabiso, Senior Vice President of Corporate Affairs at Xenon Pharmaceuticals, Inc. You may begin. Colleen Alabiso: Good afternoon. Thank you for joining us on our call and webcast to discuss Xenon's second quarter 2026 Financial and Operating Results. Joining me today are Ian Mortimer, President and Chief Executive Officer; Dr. Chris Kenney, Chief Medical Officer; Darren Cline, Chief Commercial Officer; and Tucker Kelly, Chief Financial Officer. After completing our prepared remarks today, we will open the call up for your questions. Please be advised that during this call, we will make a number of statements that are forward-looking, including statements regarding the timing of and potential results from clinical trials, the potential efficacy, safety profile, future development plans in current and anticipated indications, addressable market, regulatory success and commercial potential of our and our partners' product candidates, the strength of our clinical trial designs, our ability to successfully develop and achieve milestones in our clinical development programs, including the anticipated filing of INDs or equivalent and NDAs. The timing and results of those filings and our interactions with regulators, our ability to successfully obtain regulatory approvals, anticipated timing of top line data readouts for our clinical trials of Azetukalner and other candidates and our expectation that we will have sufficient cash to fund operations into 2029. Today's press release summarizing Xenon's second quarter financial results and the quarterly report on Form 10-Q will be made available under the Investors section of our website at xenon-pharma.com and filed with the SEC and SEDAR+. I'll now turn the call over to Ian. Ian Mortimer: Thanks, Colleen, and good afternoon to everyone joining us today. We are excited to recap another productive quarter for Xenon as we work toward our goal of becoming a fully integrated neuroscience company, delivering life-changing medicines to patients. In the second quarter, we remain focused on three key areas: First, preparing our new drug application for Azetukalner or AZK for focal seizures as well as sharing our exciting Phase 3 X-TOLE2 results with healthcare providers and preparing our go-to-market strategy. Second, advancing five additional Phase 3 studies of AZK in epilepsy and neuropsychiatry indications, which may help significantly expand the addressable patient population. And third, advancing and expanding our pain programs, including the Phase 1 studies of XEN1120 targeting Kv7 and XEN1701 targeting Nav1.7 as well as initiating clinical development of an additional Nav1.7 molecule, XEN1720, demonstrating our belief in and the importance of this target. I'll provide a bit more detail of our recent achievements before passing the call over to Chris, Darren and Tucker. First, we are making great progress towards submitting our NDA for AZK and preparing for launch. I'm happy to share that we've completed a successful pre-NDA meeting with the Food and Drug Administration, and we're on track for a submission later this quarter. We have continued to share our X-TOLE2 data with HCPs, including two important meetings for the epilepsy community. First, at the American Academy of Neurology meeting in April, where many of you will recall that the X-TOLE2 results were featured as a late-breaking science abstract and podium presentation. Then in June, we had another opportunity to present the top line X-TOLE2 results at the Epilepsy Foundation Pipeline Conference. This is attended by HCPs, researchers, industry and patient advocates. Beyond these congresses, our MSLs have been out in the community responding to HCP requests to learn more about our data. Overall, we continue to hear very positive feedback and excitement for both the X-TOLE2 results including the best placebo-adjusted efficacy in FOS to our knowledge and AZK's differentiated profile, including a novel mechanism of action, rapid onset of effect, once-daily dosing with no titration and no need for dose adjustments with other ASMs. We feel increasingly confident in AZK's potential to become a preferred add-on therapy for the significant number of patients who do not achieve seizure freedom with initial treatment. Darren will share a bit more on the excitement from the epilepsy community later in the call as well as the progress we continue to make on preparing for the launch of AZK. We also continue to focus on expanding the opportunity for Azetukalner, including through the X-TOLE3 study in FOS to support potential regulatory submissions outside the U.S. as well as the X-ACKT study in primary generalized tonic-clonic seizures to support regulatory submissions for an additional epilepsy indication. Through our ongoing Phase 3 X-NOVA2, X-NOVA3 and X-CEED studies, we continue to advance our work to broaden Azetukalner's opportunity to neuropsychiatry. There is strong rationale for Kv7 openers in major depressive disorder and bipolar depression, and AZK could deliver a novel mechanism where innovative treatments are urgently needed, especially treatments that may also impact anhedonia and that could offer differentiated tolerability profiles as well as rapid onset of action. We continue to expect our first Phase 3 MDD study results in the first half of 2027, and we will narrow that guidance as we get closer to the top line readout. Additionally, we're excited about the progress of our early clinical pipeline for pain. We are nearing completion of our Phase 1 studies for both XEN1701 and XEN1120, and data generated to date supports the initiation of Phase 2 proof-of-concept studies in acute pain for both programs. We have also recently advanced a second Nav1.7 candidate for pain into a Phase 1 clinical trial. So, this will give us multiple shots on goal for this important pain target. Success in any one of these three novel non-opioid pain programs would meaningfully increase value for Xenon and our opportunity to impact the lives of millions who live with chronic or acute pain. In line with our continued commitment to epilepsy, we also continue to invest in multiple high-quality candidates targeting various ion channels. This includes our preclinical Nav1.1 program for Dravet syndrome, where we are in IND-enabling studies with the intent of putting the best candidate into the clinic. It also includes our partnered program with Neurocrine, NBI-921355, an investigational selective inhibitor of Nav1.2 and Nav1.6 in development for the potential treatment of certain types of epilepsy, which continues to advance through a Phase 1b study with data expected in 2027. So, with that, now I'll turn over the call to Chris, who will provide additional clinical and regulatory updates. Chris? Christopher Kenney: All right. Thanks, a lot. It continues to be a very exciting time here at Xenon as we prepare the NDA for Azetukalner and share our data with the community through scientific exchange opportunities. The interactions our team has had at recent meetings as well as out in the field have been incredibly affirming of our belief in AZK's potential to meaningfully impact the FOS treatment paradigm and provide a therapeutic option with appeal to epilepsy specialists, general neurologists and advanced practice providers alike. As Ian mentioned, we have completed a productive and positive in-person pre-NDA meeting with FDA, where we gained alignment with the agency on components of the NDA package. We, therefore, remain on track to submit our NDA this quarter as planned and are encouraged by our continued engagement with the agency. Completing the NDA submission is our team's top priority, and I'm very pleased with our progress and look forward to updating you in the coming months. We also continue our focus on presenting and educating on our exceptional X-TOLE2 data and recently presented at two important conferences for the epilepsy community. First is a late-breaking science abstract and platform presentation at the AAN meeting in Chicago and second, at the EF Pipeline Conference in Leesburg, Virginia. In these presentations, we highlighted the following key points from our X-TOLE2 data. One, with regards to efficacy, the study met its primary endpoint and demonstrated what we continue to believe is the best placebo-adjusted response of any pivotal focal seizure study, which was highly significant and outperformed our Phase 2b X-TOLE study. This is even more meaningful when you consider the level of treatment resistance in the X-TOLE2 study population, which had failed a median of five prior antiseizure medications and 60% of those patients were on or had already tried and stopped cenobamate. Second, we also observed early dose-dependent MPC reductions in weekly FOS from baseline to week 1, reinforcing AZK's rapid and sustained antiseizure activity. Third, we observed dose-dependent increases in the proportion of patients with at least 75%, 90% and 100% reductions in monthly seizure frequency through the double-blind period as well as evidence of efficacy building over time as evidenced by improvements in the 100% responder rate in the last 8, 6 and 4 weeks of the study. Fourth, with regards to safety, AZK continued to demonstrate a generally well-tolerated profile, which was consistent with the X-TOLE study. The most common treatment-emergent adverse events across both studies in the AZK dose groups were dizziness, somnolence, headache and fatigue. With more than 800 patient years of safety and exposure data, we're comfortable that this profile is consistent with other well-tolerated antiseizure medications and with a drug that is potent and active in the central nervous system. We also had a tremendous opportunity to interact with general neurologists at AAN, where we highlighted our 48-month X-TOLE open-label extension data, demonstrating a 91% reduction in monthly seizure frequency for those treated for at least 48 months. In the same group, almost 40% were seizure-free for at least 12 months and one in four were seizure-free for at least two years. This is truly remarkable considering the level of treatment resistance in seizure frequency in the overall patient population at baseline. Now as we look ahead, we're excited to continue to share the AZK data at the 16th European Epilepsy Congress, or EEC, taking place between September 5 and 9 in Athens, Greece and at the Annual American Epilepsy Society or AES meeting taking place December 4 through 8 in Denver. With regards to EEC, our X-TOLE2 top line results are among the six abstracts accepted and planned for presentation. Also accepted is a new abstract that will highlight the mechanistic characterization of Azetukalner, including Kv7 binding, enhanced channel opening and rational polytherapy potential. In this presentation, we plan to share in vivo data demonstrating the potential additive effects of Azetukalner when used in combination with commonly prescribed antiseizure medications, reinforcing its opportunity to enhance seizure control through the application of rational polytherapy in clinical practice. Looking ahead, we're planning to have a significant Xenon presence at AES in December and multiple new AZK data presentations, including additional data from the X-TOLE2 study and continued follow-up from the X-TOLE open-label extension study. Moving on to neuropsychiatry. We continue to enroll patients in our three ongoing Phase 3 studies of AZK for Major Depressive Disorder or MDD and Bipolar Depression or BPD. Depression remains an area where the differentiated profile of AZK, including its novel mechanism of action, rapid onset of action and potential benefits on anhedonia could meaningfully benefit patients in a second category with a much larger patient population who continue to have unmet medical needs. There's a strong rationale for Kv7 openers in MDD and BPD. Several preclinical and clinical studies, including our own X-NOVA study have shown promising signals of antidepressive effects for the Kv7 mechanism. Additionally, in BPD, specifically, there are genetic links with Kv7, including evidence of Kv7 downregulation. AZK would deliver a novel mechanism to the MDD and BPD treatment paradigms where innovative treatments are urgently needed, especially those that may also impact anhedonia and that have the potential to offer differentiated tolerability profiles and rapid onset of action. Our clinical team has made great progress with X-NOVA2 and X-NOVA3 in MDD and X-CEED in BPD. Enrollment remains on track, and we anticipate sharing top line data from X-NOVA2 in the first half of 2027. Turning now to our pain portfolio. There remains a critical unmet need for non-opioid therapies given the limited efficacy of current options and substantial risk of abuse independency tied to opioids. At Xenon, we have more than 20 years of experience, both through collaborations and our own discovery research on novel pain targets, most notably the sodium channel, Nav1.7, which we view as the best genetically validated pain target. There's striking genetic data in patients with loss of function mutations that have no ability to feel pain and gain of function mutations have also been identified that drive pain disorders, further underscoring the critical role Nav1.7 plays in pain signaling. Our Phase 1 study of XEN1701, which targets Nav1.7 continues to advance. Consistent with what we shared earlier this year, we've seen exposures in both the single and multiple ascending dose portions of the study that are predictive of efficacy. Recall that nociceptive sensory neurons have processes that extend into peripheral tissue as well as behind the blood-brain barrier, such that channels are expressed in both peripheral and central compartments. Central Nav1.7 target engagement is therefore core to our therapeutic hypothesis. And in this Phase 1 study, we have confirmed central drug exposure via cerebrospinal fluid collection in healthy volunteers. Based on this, we believe we are achieving both peripheral and central receptor occupancies that exceed what is needed for efficacy based on our modeling and on human genetic data. We're looking forward to completing the Phase 1 study this year. In addition to advancing XEN1701, we've continued our discovery around Nav1.7 given our deep experience with the target and strong belief in its therapeutic potential. We've been working on several preclinical Nav1.7 compounds, continuing to refine our understanding of the biology and to develop novel chemistries. We're pleased to announce that we recently received CTA approval of XEN1720, which also targets Nav1.7 and have initiated a Phase 1 SAD/MAD study. XEN1720 provides us with an additional clinical candidate that further strengthens our leading position in Nav1.7, an important pain target with compelling genetic validation. Beyond Nav1.7, our Phase 1 SAD/MAD study of XEN1120, which targets Kv7 also continues to advance. Kv7 modulates neuronal hyperexcitability at multiple points along the pain pathway, and we believe Kv7 potentiators have the potential to treat a range of pain conditions. This is supported by high levels of Kv7 expression throughout the pain pathway and our preclinical data shows that Kv7 is enriched in the C- and A-delta pain subtypes of sensory neurons. In addition, Kv7 openers can block action potential firing in both DRG and spinal cord neurons, thereby significantly inhibiting pain signals from reaching the brain and evidence supports that dysfunction or downregulation of Kv7 activity has been observed in altered pain states. We've been pleased to see drug concentrations in both the single and multiple ascending dose portions of the study that are consistent with pain reduction in preclinical models. Like Nav1.7, exposure in both the peripheral and central nervous system is likely critical to success for a Kv7 opener in pain, and data so far support that we are achieving Kv7 target engagement in both compartments. We look forward to completing the Phase 1 study this year and continuing to lead on Kv7 science and its application to pain in addition to epilepsy and depression. With that, I'll turn it over to Darren to provide an update on our path to commercialization. Darren Cline: Thank you, Chris, and good afternoon, everyone. We're making strong progress as we prepare for a potential launch of AZK, our first commercial product and bring an important new treatment option to patients living with focal seizures. During the second quarter, we continued to execute our commercial build-out, adding key leaders across marketing, sales and field strategy and commercial operations. We've assembled an exceptional team that brings decades of epilepsy experience and successful launch execution. Their expertise, combined with a strong belief in AZK's potential, gives us confidence that we are building the capabilities needed to realize the significant commercial and patient impact opportunity ahead for AZK. Additionally, we continue to advance our launch readiness and refine our launch strategy informed by deep insights into the treatment landscape, prescribing dynamics and the healthcare professionals we expect to serve in both primary research and in advisory discussions with general neurologists, epilepsy specialists and advanced practice providers, we consistently hear strong enthusiasm for AZK and the recognition of the unmet needs that AZK would address, including compelling efficacy, a well-understood safety profile, rapid onset of action and ease-of-use attributes, all of which could make AZK a go-to add-on therapy. While we expect epilepsy specialists to lead early adoption of AZK, our market research supports the view that general neurologists can move to AZK sooner than historically has been the case for newly launched epilepsy therapies. To support these efforts, we continue to refine and validate our brand positioning, sharpen our key points of differentiation and develop tailored engagement strategies designed to resonate with specific customer segments. We also are increasingly focused on introducing payers to Xenon and communicating the potential value proposition of AZK through the lens of the unmet medical need. We've engaged with payers through several key conferences this year, helping to refine our market access strategy and strengthen our overall launch readiness. We also have started to build out our payer-facing field team with the expectation to fill all roles by the end of the year and deploy them in the field early next year. An important component of the AZK launch will be our distribution approach, and we continue to work to identify, engage our channel partners on the distribution and access side. We also continue to build awareness of Xenon as an emerging leader and committed partner to the epilepsy community between our customer engagement, MSL and patient advocacy teams as well as our presence at congresses, regional meetings, community events, we're making new connections, raising awareness of Xenon and the AZK data we've generated and deepening our relationship each day. As we move forward, I look forward to sharing more details on our go-to-market strategy and how we plan to bring innovation to the epilepsy landscape with a best-in-class antiseizure medication, enhanced channel and patient services and a strong value proposition for payers. We believe the strategy, capabilities and team we are assembling position us well for a successful launch, pending FDA approval and ultimately, the opportunity to improve outcomes for patients living with epilepsy. With that, I'll now turn the call over to Tucker to review our financial results and upcoming milestones. Tucker? Thomas Kelly: Thanks, Darren, and good afternoon, everyone. We ended Q2 with cash, cash equivalents and marketable securities of $1.2 billion, which, based on our current operating plans, provides cash to fund operations into 2029. Given our strong balance sheet, we are well positioned to support AZK's U.S. launch, multiple AZK registrational programs, the continued maturation of our pain pipeline and the advancement of other early-stage research and development programs. I would refer you to our press release and our 10-Q filed today for further details on our financial results. Overall, it's a very exciting time at Xenon as we continue to build momentum toward our first commercial launch and across our promising pipeline. As we head into the back half of the year, we remain focused on our upcoming NDA submission expected this quarter as well as the advancement of our commercial readiness activities to support a strong launch in FOS. We are also working to broaden the therapeutic opportunities for AZK beyond epilepsy, and we continue to make progress enrolling our studies in MDD and BPD. We look forward to the readout of our X-NOVA2 study in MDD anticipated in the first half of 2027. And lastly, we're excited about the progress we're making in pain with two Phase 1 studies for XEN1701 and XEN1120 approaching completion and now one additional Phase 1 study for XEN1720 underway and believe Xenon is well positioned to become a scientific leader in the development of novel non-opioid pain therapeutics. We remain very optimistic about the opportunity ahead as we transition to a fully integrated commercial stage company. And with that, we can open the call for questions. Operator? Operator: [Operator Instructions] And your first question comes from the line of Paul Matteis with Stifel. Paul Matteis: One quick one on AZK and one on pain. On AZK, maybe just recap for us this FDA pre-NDA meeting and if anything notable came out of it? And then second, on the pain program, maybe talk a little bit about the safety profile you've seen so far. Have you seen any cardiac AEs or anything noteworthy that has been dose-limiting for prior Nav1.7, not Kv7. And then just for Nav1.7, what's the rationale behind advancing a second product now? Ian Mortimer: Thanks, Paul. Chris, do you want to take the, maybe a little bit of color and commentary on the pre-NDA meeting, and then I'm happy to answer the pain questions. Christopher Kenney: Sure. Happy to do so, Ian. Thanks for the question, Paul. So we've had the pre-NDA meeting, as mentioned in the prepared remarks, it was an in-person meeting. It was very productive. We continue to appreciate the collaborative nature of the interactions with FDA. We covered the main questions that we wanted to cover with FDA as it pertains to the submission. We continue to believe that we have a very strong package and that overall, it's a pretty straightforward package that we're bringing to the agency. So we're in good shape at this point in time. We're on target to submit this quarter. Ian Mortimer: Thanks, Chris. And then, Paul, I think I've got all your pain questions down here, but if I miss one, just jump back in. So, as we think about, and your questions were related to Nav1.7, let's just focus on that target for a second. We had said earlier this year that based on some of the SAD data, we already thought that we were getting or we had profiled that we were getting up to enough exposures that we would see based on our predictions kind of that level of receptor occupancy that should show an analgesic effect. I would say we have even more confidence today because we're really nearing the completion of the study. So, we've gone through multiple SAD and MAD cohorts. And again, all of our modeling predicts that we're going to have enough exposure to have the receptor occupancy that is being taught by human genetics. So I think we feel like we're in a really good spot from the XEN1701 profile. There was a new piece of information that Chris disclosed today that I just don't want to miss, which is we've looked at CSF as well. So our hypothesis is that we want to get exposure both in the peripheral nervous system as well as the central nervous system. We can kind of model that based on our animal work and kind of predict what it's going to be in humans, but we did take extra cohorts just to actually do CSF and to make sure that we were getting central exposure. So I think that's another box that we've checked that, again, feel comfortable that we're getting this global receptor occupancy of the target. We haven't finished yet. So I'm not going to go into specific safety data. You asked around the cardiovascular effect. Again, today, what we see in the data is that it's a profile that we're very comfortable moving ahead into a Phase 2 proof-of-concept study. So that's taking everything into consideration. So I'm not going to go into very specific details, but we feel very comfortable on what we've seen so far, getting close to completion. [Technical Difficulty] Yes. Yes. Once we're complete, then I think we have an opportunity to just give you a little bit more information when we have all of the data unblinded and we can see both the placebo and the active groups. I think your last one was just around XEN1720 kind of the next molecule. Is that right? Yes. I don't know if you dropped off, Paul. But yes, I think you had a question just around 1720. So we have taken a second molecule into Phase 1 clinical development. When we think about the Nav1.7 program, and if you go back to the webinar we did almost a year ago, we've made a number of advancements that have overcome some of the limitations we've seen historically. So those were around selectivity and potency, around protein binding and around the kind of this PK or biodistribution and exposure both in the periphery as well as in the central nervous system. So when we look at 1720, it has some different analysis of those components that we're looking for when we compare it to 1701 and a differentiated chemistry profile. So I think that this is such a high-value target. We're going to continue to do preclinical work. We're going to continue to advance novel chemistries and move multiple molecules into the clinic just to get more opportunities to see what's the best molecule at the end of the day. Nothing changes with the lead molecule 1701. This is really just around a second molecule that has somewhat of a differentiated profile. Operator: Your next question comes from the line of Tessa Romero with JPMorgan. Tessa Romero: Ian, Chris, can you maybe talk a little bit about how you are thinking about what you would still like to get out into the public domain about the profile of Azetukalner in your Phase 3 X-TOLE2 trial and what the specific publication strategy looks like? I know there's a small epilepsy conference at the end of the year, but any other color you'd give us? Ian Mortimer: Thanks, Tessa. I'm happy to start, and Chris, you can add. So I think we've given a fair bit of information on X-TOLE2 already. So you've seen top line data. You've seen all of the key efficacy endpoints, including some that were outside of the statistical hierarchy. And you've seen kind of the broad safety profile. So we were able to show those data at AAN at the EF pipeline. We're going to have more data in Encore at EEC and then more, as you mentioned, at AES. If we look back to the X-TOLE data, we looked at certain different analyses that we're still going through, different seizure subtypes, different types of patients. So all of that work kind of ongoing, and you'll see that over time. The publication strategy is critical. So we have peer-reviewed publication of the X-TOLE and X-TOLE OLE data, and we are working hard to get the peer review of the X-TOLE2 data as well because we think that's really going to be important for the epilepsy community that we not only presented at congresses, but it's also peer reviewed. Chris, anything to add on kind of details on some of the other analyses you're looking at? Christopher Kenney: In the prepared remarks, we had talked about the fact that 60% of patients in X-TOLE2 were either on or had failed cenobamate. And so you may see data on that down the road. Operator: Your next question comes from the line of Andrew Tsai with Jefferies. Matthew Barcus: Congrats on the progress this quarter. This is Matthew Barcus on for Andrew Tai. Now you provided more color today on the progress of your Phase 1 SAD/MAD studies in pain. Can you just remind us like what additional data you plan on sharing later this year for those programs? And then at that time, will you be prepared to delineate which acute pain indications you'll be pursuing next for these studies as well? And then our understanding is that X-CEED started maybe 6 to 8 months after X-NOVA2. And with X-NOVA2 data in the first half of next year, how should we be thinking about the interim look from X-CEED, if you have any color on the timing for that? Ian Mortimer: Sure. I think Matt, I got them all. I'm happy to kind of walk through time lines and the pain stuff. Tucker, do you want to do the X-NOVA timelines? And then I'll, why don't I jump in on the data from the pain programs and the types of acute pain PoC studies? Thomas Kelly: Sure. So we've said on the call in the press release is that we'll have the X-NOVA2 data in the first half of next year. We haven't provided any guidance yet on either X-NOVA3, right, the second Phase 3 study in MDD. And I think you asked about the X-CEED study in bipolar depression. And again, as you said, both of those started after X-NOVA2, but we're still not far enough along in the enrollment curve to provide an updated time line for when those might read out, but they'll certainly be after, obviously, the first half readout for the MPD study, X-NOVA2. Ian Mortimer: And then on the pain stuff, yes. As I mentioned in the first question, we're getting close to completion of those Phase 1 studies, then we'll have the complete data package and then we can really talk about what we provide publicly. These are competitive targets. And so I think we may be balanced in terms of how much information we provide publicly. But I think we'll be able to at least walk you through kind of our decision process on why we believe we have enough exposure and the appropriate safety profile to move into a proof-of-concept study. The proof-of-concept studies are still being designed right now for both XEN1120, the Kv7 drug as well as 1701, the Nav1.7 drug, but these will be acute proof-of-concept studies, so things like a bunionectomy or an abdominoplasty study. We'll have the final trial designs for those in the coming months. And I think part of that rollout, we'll be able to talk about the specific indication in the acute pain proof of concept, but importantly, the trial design as well. Operator: Your next question comes from the line of Brian Skorney with Baird. Brian Skorney: My question is on the anticipated Phase 2 proof of concept in acute pain. How are you thinking about design right now? If we look at the path Vertex, they went head-to-head with low-dose oxycodone and placebo, but restricted rescue to ibuprofen, the TiVo program which was published the other week. We also went against low-dose oxycodone and placebo, but allowed use as Percocet as rescue and maybe because of Percocet's efficacy showed a pretty disparate result. Do you see any better value in one versus the other design in terms of using an opioid as a rescue? Or are you thinking about something completely different? Ian Mortimer: Thanks, Brian. I'm happy to start and then, Chris, if you've got anything to add. So Brian, we're not quite there yet, as I just kind of answered on the last question. I know you've been thinking about this a lot and you and I have had conversations about just the right design for a Phase 2 proof of concept. I'll take it a step further. You're looking at both what active comparators as well as kind of rescue. We also have to think just about how many active dose arms of the experimental medicine as we kind of really understand dose range finding and identifying doses to move forward in the future clinical development. So there's a number of things that we kind of want to answer within that Phase 2 proof-of-concept study. We're still in the design phase. I don't think that there's going to be anything in this study that's going to be unusual. So I think it would be reasonably standard. But as you said, a few different sponsors have taken slightly different approaches here. But I think we're only a few months away being able to kind of walk you through what the trial design is and why we've made certain decisions in the trial design. Chris, anything to add right now from your perspective? Christopher Kenney: I'll just say that we're following the field closely. And of course, the studies that have been done recently will serve as guides for what we do eventually. The advantage of using the opioid as a rescue is that you can show data with opioid sparing. So we're looking at that, but it's still in the works, Brian. Operator: Your next question comes from the line of Joseph Thome with TD Cowen. Joseph Thome: On the progress. Maybe first on depression. Can you remind us the powering assumptions on HAM-D for X-NOVA2? And maybe any changes in the baseline depression severity versus the patients that you were enrolling for X-NOVA? And then for AZK, this adoption by general neurologists seems to be a unique exciting opportunity. Can you go into a little bit more detail on when you expect general neurologists to start adopting the therapy and maybe specific education efforts you can do to make sure they have a good initial experience? Ian Mortimer: Thanks, Joe. Okay. Why don't we do, I'm happy to start just on the powering assumptions. And then, Chris, why don't we broaden that out? I mean, Joe's question is just on the HAM-D entry criteria from Phase 2 to Phase 3, but I think it might be helpful just to walk through a bunch of the changes that we've made from Phase 2 to Phase 3 because I think we learned a lot in the X-NOVA study that we're applying into X-NOVA2. And then Darren, jump in on your thoughts on general neuros and both adoption, but also, I think some of the profile of AZK that is really the feedback you're getting from the general neuro interaction, and I know you've done some ad boards on the general neuro side as well. But Joe, just to kick off on the HAM-D17, so we're appropriately powered for a Phase 3 study. So think about that kind of 90% for about a 2, 2.5 point separation in that range based on our expectation in terms of standard deviation. So I think we have really good powering in the study. It's 450 subjects. X-NOVA2 and X-NOVA3 are the same, meaning they're designed exactly the same as monotherapy studies, but I think well powered to see that separation between active and placebo. Chris, do you want to go through the X-NOVA to X-NOVA2 changes? Christopher Kenney: Yes, sure. Happy to. So obviously, one of the things that we changed is we're including a larger sample size, so the power is higher. We decreased the number of active treatment arms from two to one, which in general, saves you about one point on the placebo response. So that's favorable. We increased the cutoff a little bit so that we're collecting a little bit more of a slightly more impaired population with more depressive symptoms in Phase 3 relative to Phase 2. We're focusing on adherence by using an app that captures adherence and allows for real-time feedback for subjects who aren't adhering. And then just overall, we're scrutinizing patient randomization even closer in Phase 3 than we were in Phase 2, using the safer criteria and then keeping a real close eye on the data in real time to make sure that there isn't anything unexpected happening. But yes, we don't share baseline characteristics as the study is unfolding. As you know, every patient that's added changes that. So we'll share that once the study is complete. Darren Cline: Yes, Joe, regarding the general neuro, yes, we think it's a pretty exciting opportunity. If you look historically at the most successful antiseizure medications, Kv those were really embraced by the general neurologists. And we spent a lot of time understanding that history, but also then where does Azetukalner fit in with its unique characteristics. And Joe, you know better than anyone. It's a novel mechanism. We have ease of use attributes, really stellar safety and efficacy profile. So we've talked to a lot of general neurologists about this. And as Ian highlighted, through advisory boards and other one-on-ones. And when you couple the efficacy safety along with our open-label extension seizure freedom data, it really is a package that they're really compelled by. I think we have this opportunity to do that. We're doing a lot of work now kind of targeting, understanding where we're going to have our focus at launch. And so as you've noted, kind of how do we expedite that utilization, that's something we're tremendously highly focused on. The other piece of it is also how do you use the expression, make it a good experience for them. I think this is where we're trying to be and thinking about really being a little bit disruptive or innovative here because I think traditional antiseizure medication launches have gone a certain distribution route, have not really assisted the general neurologists in different things like prior authorization and helping patients get through obtaining the therapy. And also on the patient side, where they may show up at a retail pharmacy, for example, and really struggle there. So we're really evaluating a service that we can wrap around both the general neurologists and the patient to make that experience a good one out of the gate. We think that based on our research and discussions, those have been some of the barriers that they've encountered and that we hope to overcome. And so again, we still have a lot of work to do and over the next several quarters, but I think that we're in a really good position to really bend the curve if we can with the general neurologists. Operator: Your next question comes from the line of Brian Abrahams with RBC Capital Markets. Brian Abrahams: Two for me. First, can you characterize your payer conversations and just the latest views on the potential pricing benchmarks for Azetukalner and receptivity to potential premium pricing, just given all of its profile advantages? And then secondly, how might your commercial strategy be affected if there looks like there could be a Kv7 focal onset seizure fast follower competitor emerging? Ian Mortimer: Yes. Well, yes, both of them. Maybe I can start on a little bit, Darren, I'll start on the competitive landscape and then you can go into kind of the specific question from Brian on kind of a fast follower as well as on the payer stuff because I know you guys have done a huge amount of work already. Yes, Brian, look, there's more than 20 antiseizure medicines available. Patients do kind of cycle through drugs. We do see drugs. If you look at like sodium channel inhibition, multiple drugs of the same mechanism. And as Darren just talked about in the last answer, you have a drug like Vimpat, which is the same mechanism and did incredibly well, and there were attributes of that medicine that I think were really important specifically with the general neurologists. I think where we are today is we've set an incredibly high bar. So obviously, we will be the first Kv7 drug on the market. I think we have an incredible profile. And when you look at the four doses on label that we're talking to the agency about, you've got a clear dose response. You've got 10 and 15 milligrams that show separation, but quite frankly, have a really benign safety profile, very similar to placebo, a little bit higher in dizziness at the 15-milligram dose. And then if you go up to 20 and 25 milligrams, you get the opportunity in that dose response to see even better efficacy and seizure reduction. So, I think we've set an incredibly high bar, but we do see in the epilepsy space that this isn't a zero-sum game that multiple molecules can be successful together and even multiple molecules within the same mechanistic class. But I really like the setup for where we are right now. But Darren, happy for you to add your comments to that and then specifically on the payer side. Darren Cline: No, I think you've covered it on the potential other mechanisms. So, Brian, regarding payer and price, as I remind folks, by the time we're approved and commercializing, it will be almost a decade since the last focal onset seizure medication was approved. And so regarding the payer audience, our kind of our initial discussions really anchor around reeducating them about, A, focal seizures and B, most importantly, the unmet medical need. When we put the product profile in front of them, they're very impressed. They understand the difficulty in managing these patients, all the antiseizure medications that patients cycle through. And quite frankly, with Azetukalner and the new mechanism of action are excited. So, I think from that perspective, and we'll continue that dialogue with them as we get closer to launch. But I think it leads to the second part of your question is, okay, what's the value then that they perceive of this new antiseizure medication. So we have kicked off our pricing work. It's still ongoing. I think that I would characterize it that if you look at where we are today when we launch, the efficacy and safety that Azetukalner provides, meeting still a tremendous unmet medical need. We feel early days that there is an opportunity to ensure we get the value out of Azetukalner, while also, though, ensuring that patients can access the drug and physicians feel confident writing it. So it's one of these things. We'll assemble all that data. And when we ultimately launch it, we'll price it, but we'll have a good idea as we learn more as we continue our work. Operator: Your next question comes from the line of Myles Minter with William Blair. Myles Minter: Just a confirmatory one. In the pre-NDA meeting, did you confirm that you've got a sufficient amount of data for review in some of the lower doses that I think you're going to go on label with alongside the 25 milligram. That's the first one. And then the second one is actually on the X-CEED trial in bipolar. I know you're certainly getting patients in that have depressive episodes on type 1 and type 2. The type 1 patients, like there is always a reasonable chance that there may be some mania in the trial and you have a year open-label extension. How are you dealing with a patient that may experience mania? Do they drop out of the trial? Or do they go to like rescue medications like cariprazine? Ian Mortimer: Chris, these are, I think, all for you. Do you want to start with the pre-NDA and just our plan for four doses on label. Obviously, Myles, as you know, I think that's kind of where the question is coming from is that we have 10 milligrams was in the X-TOLE study, 15 in X-TOLE 2, 20 in X-TOLE and then 25 in both. So we do have different safety exposures at different doses, but obviously, a lot of open-label data at these kind of higher doses that would provide that coverage. But Chris, provide your perspective there. And then if you can go into the bipolar in terms of the patients that cycle into mania as well. Christopher Kenney: Yes. I mean, Myles, thanks for the question. A lot of this stuff will be dealt with in the review, but there were no concerns from the agency specifically about inadequate exposures in any way. So the details of that will be kind of discussed as we kind of go through the review process. But we think we have a pretty robust package for all these different doses that supports getting all four doses approved. I mean the 10-milligram dose was studied in a double-blind study, and it did separate from active, and it showed a really quite remarkable tolerability profile similar to placebo. So we think we're in pretty good shape as far as all the different doses go. It remains to be seen. We'll have to see how the review goes. The other topic, X-CEED BPD. I mean, that's starting to get into details about the protocol, but I'll just share with you that in general, most protocols deal with mania by defining it with a certain cutoff on the YMRS. And then if that's met, patients are discontinued. So we're taking kind of a standard approach to that. Operator: Your next question comes from the line of Paul Choi with Goldman Sachs. Unknown Analyst: This is Kevin Strang on for Paul. Just had a quick one on MDD. You talked about potential differentiation for AZK and sort of the rationale for Kv7 there. Can you just sort of book in what specific efficacy signals you might be looking for or thresholds when that trial reads out next year? Ian Mortimer: Sure. I'm happy to start. And Darren, maybe you can provide your perspective commercially as well. Kevin, in terms of the work that we've done with prescribers is obviously, there's a significant medical need here and they want different options for their patients. And so drugs that are approved, i.e., they've shown statistical data in clinical development, what we find it's less around a specific separation on HAM-D17 or MADRS or even kind of drug to drug, but much more about the profile of the patient and what therapy may be prescribed. And as we've talked a lot, the feedback that we're getting is where AVK could really stand apart is a novel mechanism. So most of these patients will have exposure to standard SSRIs or SNRIs atypicals, but it would be exposure to a novel mechanism. It would have the opportunity, what we've seen for this mechanism is to have an impact on anhedonia, which other mechanisms don't seem to have that impact. And so we are looking that as a key secondary endpoint in the study, looking at the SHAP scale. It does, what we see both across the epilepsy program as well as the psychiatry program is the rapid onset of effects. You do see the separation, whether it be in depression or epilepsy between active and placebo. at week 1. And so for, again, some of the mechanisms in depression that takes some time to work, this would work more quickly. And then a different tolerability profile. We don't, to date, haven't seen any notable sexual dysfunction or weight gain. So I think it's the kind of that package that the prescribers are talking to when we do DPP and market research to get the feedback and less around a specific efficacy measure. But Darren, I'm happy for you to provide your perspective as well. Darren Cline: Ian, I think you went through all the kind of the attributes other than it is still a tremendous unmet need. It's a big market, roughly 22 million Americans, a little bit more than half are treated with some kind of pharmacotherapy and one out of three of those are not adequately managed. So, and would be available for a branded and particularly a novel mechanism, which, again, most of these are SSRIs. So it's really, really a great opportunity. And there is a lot when we go talk to docs and do some market research, a lot of excitement around a new mechanism in this space. Operator: Your next question comes from the line of David Hoang with Deutsche Bank. David Hoang: So I just wanted to ask about some of these two questions. So for focal epilepsy for the adolescent population there, what additional work would be required to get a label and extend down to adolescent patients? And then to what extent is the PGTCS indication and label important for AZK's overall profile? And what would that contribute to the overall revenue opportunity? Ian Mortimer: Thanks, David. Chris, why don't we start with just the our pediatric plans, maybe I know David's question was around adolescents, but we could probably just expand to kind of the pediatric development that we've negotiated with FDA and EMA. And then Darren, can you address the patient population for PGGCS and how you see that commercially? Yes, sure. Chris, to start? Christopher Kenney: Yes, sure. So we have agreement on the pediatric plans for focal onset seizures with both FDA and EMA, as Ian has said. For those of you who aren't familiar with that, you're basically capturing data that pertains to safety and PK, not efficacy. And you sort of start at the older patients, the adolescents and then work your way down to patients who are younger over time based upon your being comfortable with the safety and the PK data. So we have all that agreed upon. That's exactly what we're intending to do to get sort of the extrapolation for the label down to a younger age than 18, which is what the studies are currently studying at least in focal onset seizures. Darren? Darren Cline: Yes. So regarding focal and then generalized, just to step back, there's roughly three million adults or folks with epilepsy in the U.S., about 1.8 million have focal and then roughly almost another one million have generalized seizures. From a development perspective, if you look at the most successful ASMs that I referenced earlier, focal is the entry and then you follow on with a generalized. I think in the marketplace, you do get some use in the generalized. But I think our development plan fits nicely with, if you think about Azetukalner being a broad-spectrum antiseizure medication, having that supplemental label expansion will be quite helpful, particularly down the road for general neurologists who want to treat their patients and want to have the comfort that it can cover a broad spectrum. So it's important. I know the development plan is going well. There's a lot of excitement for Azetukalner in this space, and it will be very beneficial for us. Operator: Your next question comes from the line of Ben Burnett with Wells Fargo. Benjamin Burnett: One question on X-TOLE3, just as this is enrolling, I think you've mentioned this has expanded to include Japanese patients. I guess what are you seeing in terms of baseline characteristics? Or what are you expecting in terms of baseline characteristics? Any differences that we should expect relative to X-TOLE2? Really just asking if the different geographies being included are associated with maybe different treatment paradigms. And of course, could that lead to differences in these characteristics and maybe a different effect on the drug? Ian Mortimer: Thanks, Ben. Chris, do you want me to start and then you can jump in as well. So Ben, I wasn't sure if you were referring to do we expect with the inclusion of Japanese subjects whether the baseline characteristics would change or just generally X-TOLE3 versus X-TOLE2. Was there something specific on the Japanese side you wanted to understand? Benjamin Burnett: No, more just generally. Ian Mortimer: Okay. Yes. I mean, as the study, I'll start and then Chris can provide additional detail. As these studies are ongoing, we don't comment and we didn't on X-TOLE or X-TOLE2 on baseline characteristics as we go along. Similarly, I think Chris answered this question as it relates to a different question earlier is that these things are changing all the time. Each patient has an impact on that. So we're not going to go into the specific details. As a reminder, X-TOLE2 and X-TOLE3 are an identical protocol. So by that definition, we expect a similar patient population in both. Once we unblind the data and we're done, would they maybe be slightly different depending on the jurisdiction and different sites? Yes, they might be. But I think generally, the expectation is that the patient baseline characteristics would be somewhat similar to X-TOLE2. Chris, anything to add to that? Christopher Kenney: Well, just that the inclusion/exclusion criteria were pretty similar between X-TOLE and X-TOLE2 and the baseline characteristics were nearly identical. So Ben, that's sort of the direction that we think we're heading in, but it's changing over time. Benjamin Burnett: Okay. So you're not really expecting major differences in sort of background medication with XCOPRI and other medications that can maybe influence the drug profile? Christopher Kenney: Well, from Phase 2 to Phase 3, the concomitant use of cenobamate went up because its usage went up within the medical community. But X-TOLE3 and X-TOLE 2 have been run in parallel. So I don't predict any significant differences between those studies. Operator: That concludes our question-and-answer session. I will now turn the conference back over to Mr. Ian Mortimer for closing remarks. Ian Mortimer: Thanks, operator, and thanks to everyone for joining us today. If we didn't get a chance to get to your questions during the allotted time, happy to reach out directly and connect. And we look forward to continuing to provide updates as we advance our programs and deliver on important milestones through the remainder of the year. So operator, we can now end the call. Operator: Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect. Before you buy stock in Xenon Pharmaceuticals, consider this: The Motley Fool Stock Advisor analyst team just identified what they believe are the 10 best stocks for investors to buy now… and Xenon Pharmaceuticals wasn’t one of them. The 10 stocks that made the cut could produce monster returns in the coming years. Consider when Netflix made this list on December 17, 2004... if you invested $1,000 at the time of our recommendation, you’d have $400,209!* Or when Nvidia made this list on April 15, 2005... if you invested $1,000 at the time of our recommendation, you’d have $1,375,393!* Now, it’s worth noting Stock Advisor’s total average return is 964% — a market-crushing outperformance compared to 215% for the S&P 500. Don't miss the latest top 10 list, available with Stock Advisor, and join an investing community built by individual investors for individual investors. See the 10 stocks » *Stock Advisor returns as of August 13, 2026. This article is a transcript of this conference call produced for The Motley Fool. While we strive for our Foolish Best, there may be errors, omissions, or inaccuracies in this transcript. As with all our articles, The Motley Fool does not assume any responsibility for your use of this content, and we strongly encourage you to do your own research, including listening to the call yourself and reading the company's SEC filings. Please see our Terms and Conditions for additional details, including our Obligatory Capitalized Disclaimers of Liability. The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy. Xenon Pharmaceuticals (XENE) Q2 2026 Earnings Call Transcript was originally published by The Motley Fool

This article first appeared on GuruFocus. Cash Position: Ended Q2 2026 with cash, cash equivalents, and marketable securities of $1.2 billion, providing funding into 2029. Revenue: No revenue was reported for the quarter, as the company is pre-commercial. Net Loss: The company did not disclose specific net loss figures during the call. R&D Expenses: Specific R&D expense figures were not provided in the call. SG&A Expenses: Specific SG&A expense figures were not provided in the call. Warning! GuruFocus has detected 5 Warning Signs with XENE. Is XENE fairly valued? Test your thesis with our free DCF calculator. Release Date: August 06, 2026 For the complete transcript of the earnings call, please refer to the full earnings call transcript. Xenon Pharmaceuticals Inc (NASDAQ:XENE) completed a successful pre-NDA meeting with the FDA and is on track to submit the NDA for azetukalner in focal seizures this quarter. The Phase III X-TOLD-2 trial demonstrated the best placebo-adjusted efficacy in focal seizures, with a highly significant primary endpoint and a differentiated profile including rapid onset and once-daily dosing. Long-term open-label extension data showed a 91% reduction in monthly seizure frequency at 48 months, with nearly 40% of patients seizure-free for at least 12 months. The company is advancing a broad pipeline with five additional Phase III studies for azetukalner in epilepsy and neuropsychiatry, including MDD and bipolar depression, with XNOVA-2 data expected in H1 2027. Xenon Pharmaceuticals Inc (NASDAQ:XENE) has a strong cash position of $1.2 billion, funding operations into 2029, and is making progress in its pain portfolio with two Phase I programs nearing completion and a third candidate initiated. Commercial readiness is progressing well, with strong enthusiasm from healthcare providers and payers, and a strategy to engage general neurologists earlier than typical for new epilepsy therapies. The NDA submission for azetukalner is still pending, and regulatory approval is not guaranteed, with potential delays or additional data requirements from the FDA. The company faces significant competition in the epilepsy market from over 20 existing anti-seizure medications, including potential fast followers in the KV-7 class. Phase I pain programs are still in early stages, and the company has not yet provided specific safety or efficacy data, with proof-of-concept studies not yet initiated. The MDD and bipolar depression programs are in Phase III, but there is uncertainty about the outcomes, and the company has not provided detailed baseline characteristics or interim data. The company is investing heavily in commercial infrastructure and multiple clinical programs, which could strain resources if milestones are delayed or if the launch underperforms. The transcript contains some inconsistencies in drug candidate names (e.g., XCN-1701 vs. XTN-1701), which could indicate potential confusion or errors in communication. Q: Can you recap the FDA pre-NDA meeting for AZK and any notable outcomes? Also, what is the rationale behind advancing a second NAV1.7 product (XEN1720) now?A: Ian Mortimer (CEO) and Christopher Kenney (CMO) stated the pre-NDA meeting was productive and collaborative, with alignment achieved on the NDA package components, keeping the submission on track for Q3 2026. Regarding XEN1720, the company is advancing a second NAV1.7 candidate with a differentiated chemistry profile to increase "shots on goal" for this high-value, genetically validated pain target. The lead molecule, XEN1701, remains unchanged, and the second molecule offers a different analysis of selectivity, potency, and biodistribution components. Q: What additional data do you plan to share later this year for the Phase 1 pain programs, and will you delineate which acute pain indications you'll pursue next? Also, what is the timing for an interim look from the XSEDE study in bipolar depression?A: Ian Mortimer (CEO) explained that the Phase 1 studies for XEN1701 (NAV1.7) and XEN1120 (KV7) are nearing completion. Once complete, the company will share the full data package and walk through the decision process on exposure and safety profiles. The Phase 2 proof-of-concept studies will be in acute pain settings like bunionectomy or abdominoplasty, with final trial designs expected in the coming months. Tucker Kelly (CFO) noted that XNOVA2 data is expected in H1 2027, but no guidance has been provided yet for XNOVA3 or XSEDE readouts, which will follow later. Q: How are you thinking about the design for the anticipated Phase 2 proof-of-concept studies in acute pain, particularly regarding the use of opioids as rescue medication?A: Ian Mortimer (CEO) stated the company is still in the design phase for the Phase 2 proof-of-concept studies. They are evaluating active comparators, rescue medications, and the number of active dose arms for dose-range finding. Christopher Kenney (CMO) added that the company is closely following recent studies in the field, noting that using an opiate as rescue could demonstrate opioid-sparing effects, but the design is still in development. Q: Can you remind us of the powering assumptions for XNOVA2 in MDD and any changes in baseline depression severity versus the Phase 2 X-NOVA study? Also, when do you expect general neurologists to start adopting AZK?A: Ian Mortimer (CEO) stated XNOVA2 is powered at approximately 90% for a 2.5-point separation on the HAM-D17, with 450 subjects. Christopher Kenney (CMO) detailed changes from Phase 2 to Phase 3, including a larger sample size, a single active treatment arm (saving about one point on placebo response), a higher cutoff for more impaired patients, and improved adherence monitoring. Darren Cline (CCO) noted that general neurologists could adopt AZK sooner than typical launches due to its novel mechanism, ease of use, and compelling efficacy/safety profile, with the company focusing on support services to ensure a positive initial experience. Q: Can you characterize your payer conversations and views on potential pricing benchmarks for AZK? Also, how might your commercial strategy be affected by a potential KV7 fast-follower competitor?A: Darren Cline (CCO) stated payer discussions are anchored on re-educating about focal seizures and the unmet medical need, with payers impressed by the product profile. Pricing work has kicked off, with early indications suggesting an opportunity to capture value while ensuring patient access. Ian Mortimer (CEO) noted that while AZK will be the first KV7 drug, the epilepsy market is not zero-sum, and multiple molecules can succeed. He highlighted AZK's clear dose response and benign safety profile at lower doses as setting a high bar. Q: Did you confirm sufficient data for the lower doses (10mg, 15mg) in the pre-NDA meeting for the label? Also, how are you handling patients who may experience mania in the XSEDE bipolar depression trial?A: Christopher Kenney (CMO) confirmed there were no concerns from the FDA about inadequate exposures for any dose. The 10mg dose was studied in a double-blind study, separated from placebo, and showed a tolerability profile similar to placebo. For the XSEDE trial, the company is taking a standard approach: mania is defined by a certain cutoff on the YMRS, and patients meeting that threshold are discontinued from the study. Q: What specific efficacy signals or thresholds are you looking for in the MDD trial when it reads out next year?A: Ian Mortimer (CEO) explained that prescribers are less focused on specific separation on HAM-D17 or MADRS and more on the patient profile. AZK's differentiation lies in its novel mechanism, potential impact on anhedonia (measured via the SHAP scale as a key secondary endpoint), rapid onset of action, and a tolerability profile without notable sexual dysfunction or weight gain. Darren Cline (CCO) added that the MDD market is large (~22 million Americans), with one in three treated patients inadequately managed, creating significant excitement for a new mechanism. Q: What additional work is required to extend the AZK label to adolescent patients, and how important is the PGTCS indication for AZK's overall profile?A: Christopher Kenney (CMO) stated the company has agreement with FDA and EMA on the pediatric plan for focal onset seizures, which involves capturing safety and PK data (not efficacy) starting with adolescents and working down to younger patients. Darren Cline (CCO) noted that while focal seizures are the entry point, the PGTCS indication is important for positioning AZK as a broad-spectrum anti-seizure medication, which will be helpful for general neurologists and contribute to the overall revenue opportunity. Q: For the XTOL3 study, what baseline characteristics are you expecting, and could different geographies (including Japan) lead to differences in treatment paradigms or drug effect?A: Ian Mortimer (CEO) stated the company does not comment on baseline characteristics during ongoing studies, as they change with each patient. XTOL2 and XTOL3 use identical protocols, so similar patient populations are expected. Christopher Kenney (CMO) noted that inclusion/exclusion criteria were similar For the complete transcript of the earnings call, please refer to the full earnings call transcript.

Interested in Xenon Pharmaceuticals Inc.? Here are five stocks we like better. Second-quarter revenue rose 3% to $149.4 million excluding non-recurring settlement revenue, as consumables growth was offset by a 47% decline in instrument revenue. Customers delayed purchases of existing spatial instruments while awaiting the new Atera platform. Atera orders have already exceeded expectations ahead of commercial shipments, though manufacturing capacity is limiting deliveries and the company still expects to ship about 40 systems in 2026. Shipments are expected to be concentrated in the fourth quarter, with a modest revenue decline anticipated in Q3 during the product transition. Gross margin improved to 74%, cash and marketable securities reached $552 million, and management raised full-year 2026 revenue guidance to $610 million–$630 million, representing 2%–5% growth excluding settlement revenue. Bristol Myers Squibb’s big buys: $18.1 billion in 2 biotech deals 10x Genomics reported second-quarter revenue of $151 million, including $1.6 million in license and royalty revenue tied to its settlement with Takara Bio. Excluding non-recurring settlement revenue in both periods, revenue was $149.4 million, up 3% from the prior-year quarter. Chief Executive Officer and Co-Founder Serge Saxonov said the quarter was marked by customer interest in Atera, the company’s new spatial biology platform. The company said booked Atera orders as of the end of the second quarter had already “greatly exceeded” its expectation to ship about 40 systems during 2026, although its shipment forecast remained unchanged as production ramps. → Meta’s Earnings Drop Shows Wall Street Wants More Than Ad Growth Total consumables revenue increased 7% year over year, with growth in both single-cell and spatial products. Single-cell consumables revenue rose 3%, supported by double-digit growth in reaction volumes, while spatial consumables revenue increased 16%. Chief Financial Officer Adam Taich said Xenium was the main driver of spatial consumables growth, though both Xenium and Visium consumables posted sequential growth. Saxonov said Xenium utilization remained strong during the quarter. → 4 Oil and Gas ETF Plays as Prices Stay Sky-High Instrument revenue, however, declined 47% year over year. Chromium instrument revenue fell 46%, while spatial instrument revenue declined 48%, primarily because of fewer systems sold. Management attributed the decrease in spatial instrument sales to customers holding off on purchases of existing products while awaiting Atera. Revenue performance varied by region. Excluding non-recurring license and royalty revenue, revenue in the Americas rose 6% and revenue in Europe, the Middle East and Africa increased 15%. Asia-Pacific revenue declined 19%, reflecting a comparison against roughly $4 million in China purchasing that had been pulled forward in the prior-year period ahead of potential tariff changes. → Sandisk Just Delivered a Blowout Quarter—Here's Why the Stock Is Falling Atera is designed to provide spatial whole-transcriptome profiling with single-cell sensitivity at scale. Saxonov said the company has received broad early interest from universities, academic medical centers and biopharmaceutical companies across oncology, neuroscience, autoimmune and inflammatory disease, cardiometabolic research, kidney biology and transplant research. “The constraint is actually shifting the manufacturing capacity to ship the units in the second half of the year,” Saxonov said in response to an analyst question about why the company was maintaining its approximately 40-unit shipment outlook. The company expects Atera shipments to be weighted heavily toward the fourth quarter. Taich said Atera instruments alone are expected to account for most of the implied sequential revenue increase from the third to the fourth quarter, with consumables and normal seasonal trends accounting for the remainder. Management expects a modest sequential decline in total revenue in the third quarter as the spatial product transition continues. Taich said the expected decline reflects lower demand for current spatial instruments and some consumables as customers prepare to receive Atera systems. 10x Genomics also plans to begin processing customer samples through its Catalyst Research Services program alongside Atera’s commercial availability. The program is intended to give customers access to the platform for pilot studies, ongoing research work and projects conducted by organizations that do not yet have an Atera instrument. Saxonov said the Atera roadmap includes workflow automation, base-by-base spatial sequencing and protein multi-omics. During the quarter, the company acquired Proteintech Genomics, which it said brings protein-measurement technologies that can be used in a multi-omic context. Management said adoption of Flex APEX has contributed to higher single-cell reaction volumes, particularly in biopharmaceutical and translational research applications involving large-scale perturbation experiments. Saxonov said the company expects the large majority of customers that plan to transition to Flex APEX from its other products to do so by year-end. He also said whole-blood workflows introduced by the company can support longitudinal studies, distributed sample collection and research involving archived samples. According to management, distributed sample collection can lead to more centralized processing at core laboratories and service providers, reducing the need to place instruments at individual laboratories. Taich noted that Chromium instrument revenue represents about 2% of company sales, distinguishing instrument placements from demand for the broader Chromium platform and consumables. 10x Genomics described artificial intelligence as a structural demand driver for its products, as researchers increasingly generate single-cell and spatial data to train biological models. Saxonov said AI-related demand is becoming pervasive across customer segments, though the company did not quantify revenue directly attributable to AI applications. The company said it sees potential for its technologies in AI-enabled drug discovery, particularly in target identification and patient selection. Saxonov also said advances in agentic AI may lower the bioinformatics barrier for researchers analyzing complex biological datasets. Second-quarter gross margin rose to 74% from 72% a year earlier. Taich said the improvement reflected lower manufacturing costs, including $2.6 million of tariff refunds, and lower inventory write-downs. Excluding non-recurring settlement revenue, gross margin increased to 74% from 67% in the prior-year quarter. Total operating expenses were $132.1 million, compared with $95 million in the prior-year period. The periods included gains from patent-litigation settlements of $3.4 million in 2026 and $40.7 million in 2025. Excluding those gains, operating expenses were approximately flat year over year. The company ended the quarter with $552 million in cash, cash equivalents and marketable securities, up $105 million from a year earlier and $12 million sequentially. 10x Genomics raised its full-year 2026 revenue outlook to a range of $610 million to $630 million. Excluding non-recurring patent-litigation settlement revenue in both 2026 and 2025, the outlook represents annual growth of 2% to 5%. Management said its guidance assumes that academic-market conditions remain broadly consistent with current trends. Saxonov said funding sentiment has improved somewhat, but purchasing conditions remain tenuous as funding allocation processes, grant reviews and order processing continue to delay spending decisions. Xenon Pharmaceuticals Inc is a clinical‐stage biopharmaceutical company dedicated to discovering and developing novel, small‐molecule drugs targeting ion channels in the central and peripheral nervous system. The company's research focus centers on neurological and pain disorders—including epilepsy, migraine, and neuropathic pain—by modulating key ion‐channel proteins to restore normal neuronal function. Xenon's scientific platform draws upon advances in ion‐channel biology and structure‐based drug design to identify and optimize therapeutic candidates with the potential for improved safety and efficacy profiles compared with existing treatments. The company's pipeline comprises multiple preclinical and clinical programs. This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to [email protected]. The article "Xenon Pharmaceuticals Q2 Earnings Call Highlights" was originally published by MarketBeat. View MarketBeat's top stocks for August 2026.

NDA submission for azetukalner on track for Q3 2026 following pre-NDA meeting with FDA Phase 3 X-TOLE3 study in FOS and X-ACKT study in PGTCS continue to enroll Three Phase 3 studies of azetukalner in neuropsychiatry continue to advance, with topline data from X-NOVA2 study in MDD expected H1 2027 Phase 1 studies of novel NaV1.7 (XEN1701) and KV7 (XEN1120) candidates expected to complete H2 2026; Phase 1 study underway for second NaV1.7 (XEN1720) candidate for pain Cash, cash equivalents and marketable securities of $1.2 billion with cash runway into 2029 Conference call at 4:30 pm ET today VANCOUVER, BC and BOSTON, MA, Aug. 06, 2026 (GLOBE NEWSWIRE) -- Xenon Pharmaceuticals Inc. (Nasdaq: XENE), a neuroscience-focused biopharmaceutical company dedicated to drug discovery, clinical development, and commercialization of life-changing therapeutics for patients in need, today reported financial results for the second quarter ended June 30, 2026 and provided a business update. “The second quarter of 2026 was marked by strong execution, including a successful pre-NDA meeting, and the NDA submission for azetukalner remains on track for the third quarter of 2026. Our X-TOLE2 data continue to be well-received by healthcare providers, specifically regarding azetukalner’s differentiated clinical profile and its potential to address significant unmet needs in epilepsy,” said Ian Mortimer, President and Chief Executive Officer of Xenon. “We also remain focused on broadening azetukalner’s opportunity to neuropsychiatry and expect topline Phase 3 X-NOVA2 data in the first half of 2027. Our clinical-stage pain pipeline also continues to grow with the recent Phase 1 study initiation for XEN1720, our second NaV1.7 clinical candidate.” Business Highlights and Anticipated Milestones Azetukalner Clinical Development Azetukalner is a novel, potent KV7 potassium channel opener in late-stage development for multiple potential indications, including two in epilepsy – focal onset seizures (FOS) and primary generalized tonic-clonic seizures (PGTCS) – as well as neuropsychiatric disorders, including major depressive disorder (MDD) and bipolar depression (BPD). Epilepsy Programs Xenon remains on track to submit its New Drug Application (NDA) for azetukalner in FOS in the third quarter of 2026, having completed a pre-NDA meeting with the U.S. Food and Drug Administration (FDA). The Company presented topline efficacy and safety results from the Phase 3 X-TOLE2 study of azetukalner in FOS at two important epilepsy congresses in the second quarter of 2026: the American Academy of Neurology (AAN) Annual Meeting in Chicago, Illinois from April 18-22, and the Epilepsy Foundation Pipeline Conference in Leesburg, Virginia from June 18-19. The Company submitted six abstracts for presentation at the upcoming 16th European Epilepsy Congress (EEC), taking place September 5-9, 2026 in Athens, Greece. The Phase 3 X-TOLE3 study of azetukalner in FOS continues to enroll and is intended to support regulatory submissions outside of the United States. X-TOLE3 enrollment outside of Japan is expected to complete in 2026. The Phase 3 X-ACKT study of azetukalner in PGTCS continues to enroll and is intended to support regulatory submissions for an additional epilepsy indication. Neuropsychiatry Programs Enrollment is ongoing in the Phase 3 X-NOVA2 and X-NOVA3 studies evaluating azetukalner in patients with MDD, with topline data from X-NOVA2 expected in H1 2027. Enrollment is ongoing in the Phase 3 X-CEED study evaluating azetukalner in patients with BPD I or II. Clinical Programs for Pain Xenon continues to expand its portfolio of potent, selective ion channel modulators using the Company’s strong heritage in human genetics, deep understanding of ion channel biology, and expertise in novel chemistries. This includes clinical-stage candidates targeting NaV1.7 and KV7, which are important novel targets for pain. NaV1.7 Programs The Phase 1 Single Ascending Dose (SAD)/Multiple Ascending Dose (MAD) study in healthy adult participants is ongoing for XEN1701 targeting NaV1.7. Study completion is expected in H2 2026 to support initiating a Phase 2 proof-of-concept study in acute pain. Xenon recently received approval of its Clinical Trial Application (CTA) to initiate a Phase 1 study of XEN1720 targeting NaV1.7. The Phase 1 SAD/MAD study in healthy adult participants is now underway. KV7 Program The Phase 1 SAD/MAD study in healthy adult participants is ongoing for XEN1120 targeting KV7. Study completion is expected in H2 2026 to support initiating a Phase 2 proof-of-concept study in acute pain. Early-Stage R&D and Partnered Programs for Epilepsy Beyond azetukalner, Xenon is committed to advancing additional novel treatment approaches to address significant unmet needs in epilepsy. IND-enabling studies are ongoing for the Company’s oral small molecule NaV1.1 program. Pre-clinical data suggest that targeting NaV1.1 could potentially address the underlying cause and symptoms of Dravet syndrome. In collaboration with Neurocrine Biosciences, a Phase 1b study is ongoing for NBI-921355, an investigational, selective inhibitor of voltage-gated sodium channels NaV1.2 and NaV1.6 in development for the potential treatment of certain types of epilepsy. Data from the Phase 1b study are expected in 2027. Upcoming Investor Conferences Xenon will attend three upcoming investor conferences in the third quarter of 2026, including the Stifel Biotech Summer Summit on August 10, the Wells Fargo Healthcare Conference on September 9, and the TD Cowen Novel Mechanisms in Neuropsychiatry & Epilepsy Summit on September 23. Q2 2026 Financial Results Cash, cash equivalents and marketable securities were $1,245.1 million as of June 30, 2026, compared to $586.0 million as of December 31, 2025. Based on current operating plans, Xenon anticipates having sufficient cash to fund operations into 2029. As of June 30, 2026, there were 96,752,884 common shares and 2,931,293 pre-funded warrants outstanding. Research and development expenses were $99.2 million for the quarter ended June 30, 2026, compared to $75.0 million for the same period in 2025. The increase in research and development expenses for the period was primarily attributable to the ongoing azetukalner Phase 3 clinical studies in the MDD and BPD programs and manufacturing activities to support our planned NDA submission, ongoing Phase 1 clinical studies of XEN1701 and XEN1120, as well as increased personnel-related costs due to an increase in employee headcount and stock-based compensation expense. General and administrative expenses were $23.9 million for the quarter ended June 30, 2026, compared to $19.2 million for the same period in 2025. The increase in general and administrative expenses for the period was primarily attributable to personnel-related costs due to an increase in employee headcount and an increase in professional and consulting fees. Other income was $11.8 million for the quarter ended June 30, 2026, compared to $8.9 million for the same period in 2025. The increase in other income for the period was primarily attributable to higher interest income. Net loss was $110.7 million for the quarter ended June 30, 2026, compared to $84.7 million for the same period in 2025. The increase in net loss for the period was primarily attributable to lower revenue from the collaboration with Neurocrine Biosciences, higher research and development expenses driven by the azetukalner and pain programs and higher personnel-related costs, higher general and administrative expenses driven by higher personnel-related costs and professional and consulting fees, partially offset by higher interest income. Conference Call Information Xenon will host a conference call and webcast today at 4:30 pm Eastern Time (1:30 pm Pacific Time) to discuss its second quarter 2026 results. A listen-only webcast can be accessed on the Investors section of the Xenon website, with a replay available following the event. Participants can access the conference call by dialing (800) 715-9871 or (646) 307-1963 for international callers and referencing conference ID 5286122. About Azetukalner Azetukalner is a novel, potent KV7 potassium channel opener currently in development for the treatment of epilepsy, major depressive disorder (MDD) and bipolar depression (BPD). It represents the most advanced, clinically validated potassium channel modulator in late-stage clinical development. Azetukalner is designed to open potassium channels in the central nervous system, allowing potassium ions to flow and hyperpolarizing neurons. This process helps reduce excessive neuronal firing, which is a key contributor to several neurologic and psychiatric disorders. Phase 3 Epilepsy Studies Xenon’s clinical development program for azetukalner in epilepsy includes three Phase 3 clinical studies in focal onset seizures (FOS) and primary generalized tonic-clonic seizures (PGTCS). The completed X-TOLE2 study and the ongoing X-TOLE3 study were both designed as multicenter, randomized, double-blind, placebo-controlled studies to evaluate the clinical efficacy, safety, and tolerability of 15 mg or 25 mg of azetukalner administered orally with food as adjunctive treatment in approximately 360 patients with FOS per study. The primary efficacy endpoint is median percent change (MPC) in monthly seizure frequency from baseline through the 12-week double-blind period (DBP) of azetukalner compared to placebo. X-ACKT is a multicenter, randomized, double-blind, placebo-controlled study evaluating the clinical efficacy, safety, and tolerability of 25 mg of azetukalner administered with food as adjunctive treatment in approximately 160 patients with PGTCS. The primary efficacy endpoint is MPC in monthly PGTCS frequency from baseline through the 12-week DBP of azetukalner compared to placebo. Upon completion of the DBP in the Phase 3 epilepsy studies, eligible patients may enter an open-label extension (OLE) study for up to six years. Phase 3 MDD Studies Xenon’s Phase 3 X-NOVA major depressive disorder (MDD) program includes three multicenter, randomized, double-blind, placebo-controlled clinical studies to evaluate the clinical efficacy, safety, and tolerability of 20 mg of azetukalner administered orally with food over the 6-week double-blind period (DBP) as monotherapy treatment in approximately 450 patients with moderate-to-severe MDD per study. The primary efficacy endpoint is the change from baseline in the HAM-D17 score at week 6 in patients who received azetukalner compared to placebo. Upon completion of the DBP, eligible patients may enter an open-label extension (OLE) study for up to 12 months. Phase 3 BPD Studies Xenon’s Phase 3 X-CEED Bipolar Depression (BPD) program includes two multicenter, randomized, double-blind, placebo-controlled clinical studies to evaluate the clinical efficacy, safety, and tolerability of 20 mg of azetukalner administered orally with food over the 6-week double-blind period (DBP) as monotherapy treatment in approximately 400 patients per study with BPD I or II. The primary efficacy endpoint is the change from baseline in the MADRS score at week 6 in patients who received azetukalner compared to placebo. Upon completion of the DBP, eligible patients may enter an open-label extension (OLE) study for up to 12 months. About Xenon Pharmaceuticals Inc. Xenon Pharmaceuticals (Nasdaq: XENE) is a neuroscience-focused biopharmaceutical company dedicated to drug discovery, clinical development, and commercialization of life-changing therapeutics for patients in need. Xenon’s lead molecule, azetukalner, is a novel, potent KV7 potassium channel opener in late-stage clinical development for the treatment of epilepsy, major depressive disorder and bipolar depression. Xenon is also advancing an early-stage portfolio of multiple promising potassium and sodium channel modulators, including KV7 and NaV1.7 programs in Phase 1 development for the potential treatment of pain. Xenon has offices in Vancouver, British Columbia, and Boston, Massachusetts. For more information, visit www.xenon-pharma.com and follow us on LinkedIn and X. Xenon and the Xenon logo are registered trademarks or trademarks of Xenon Pharmaceuticals Inc. in the US, Canada and elsewhere. All other trademarks belong to their respective owner. Safe Harbor Statement This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995 and Canadian securities laws. These forward-looking statements are not based on historical fact, and include statements regarding the timing of and potential results from clinical studies; the potential efficacy, safety profile, future development plans in current and anticipated indications, addressable market, regulatory success and commercial potential of our and our partners’ product candidates; the efficacy of our clinical study designs; our ability to successfully develop and achieve milestones in our azetukalner and other pipeline and development programs, including the potential timing of trial enrollment completion and the anticipated filing of INDs (or equivalent) and NDAs; the timing and results of our interactions with regulators, including the timing of any NDA submission; our ability to successfully develop, and obtain regulatory approval for, and commercialize azetukalner and our other product candidates; and anticipated timing of topline data readout from our clinical studies of azetukalner. These forward-looking statements are based on current assumptions that involve risks, uncertainties and other factors that may cause the actual results, events, or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: clinical studies may not demonstrate safety and efficacy of any of our or our collaborators’ product candidates; promising results from pre-clinical development activities or early clinical study results may not be replicated in later clinical studies; our assumptions regarding our planned expenditures and sufficiency of our cash to fund operations may be incorrect; our ongoing discovery and pre-clinical efforts may not yield additional product candidates; any of our or our collaborators’ product candidates, including azetukalner, may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; we may not achieve additional milestones in our proprietary or partnered programs; regulatory agencies may impose additional requirements prior to approval or delay the initiation or completion of clinical studies; the impact of market, industry, and regulatory conditions on clinical study enrollment; the impact of competition; the impact of expanded product development and clinical activities on operating expenses; the impact of new or changing laws and regulations; the impact of unstable economic conditions in the general domestic and global economic markets; adverse conditions from geopolitical events; as well as the other risks identified in our filings with the U.S. Securities and Exchange Commission and the securities commissions in British Columbia, Alberta, and Ontario. These forward-looking statements speak only as of the date hereof and we assume no obligation to update these forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements. Contacts For Investors:Tucker KellyChief Financial [email protected] For Media:Colleen AlabisoSenior Vice President, Corporate [email protected] XENON PHARMACEUTICALS INC.Condensed Consolidated Balance Sheets(Expressed in thousands of U.S. dollars) XENON PHARMACEUTICALS INC.Condensed Consolidated Statements of Operations and Comprehensive Loss(Expressed in thousands of U.S. dollars except share and per share amounts)

Xenon Pharmaceuticals XENE reported a loss of $1.17 per share in the first quarter of 2026, matching the Zacks Consensus Estimate. The company had incurred a loss of 83 cents per share in the year-ago quarter. In the reported quarter, Xenon did not generate any revenues, entirely missing the Zacks Consensus Estimate of $15 million. Due to the lack of a marketed product, the company recognizes only periodic collaboration revenues in its top line from its ongoing partnership with Neurocrine Biosciences NBIX. In the year-ago quarter, XENE recognized $7.5 million in revenues following a milestone payment from Neurocrine Biosciences in connection with the progress of NBI-921355 into a clinical-stage study. In the first quarter, research and development (R&D) expenses increased 45% year over year to $88.5 million. The uptick was primarily due to increased expenses related to Xenon’s ongoing azetukalner late-stage studies in epilepsy, major depressive disorder (MDD) and bipolar depression (BPD). Costs incurred in supporting the early-stage studies of XEN1701 and XEN1120, as well as increased personnel-related costs, also contributed to higher R&D expenses. General and administrative expenses totaled $23.8 million in the reported quarter, up 25% year over year due to higher personnel expenses from a larger workforce and increased professional and consulting fees. Xenon had cash, cash equivalents and marketable securities worth $1,339.6 million as of March 31, 2026, compared to $586.0 million as of Dec. 31, 2025. During the reported quarter, the company raised net proceeds of $130 million through its ATM program and an additional $707.6 million via a public offering. Based on its current operating plans, Xenon expects its existing cash position to support operations into 2029. Year to date, XENE shares have gained 24.9% against the industry’s 0.2% decline. Image Source: Zacks Investment Research In March 2026, Xenon announced positive top-line data from the phase III X-TOLE2 study, which evaluated its lead pipeline candidate, azetukalner, for treating focal onset seizures (FOS). The X-TOLE2 study evaluated the efficacy, safety and tolerability of 15 mg and 25 mg doses of azetukalner, given with food as an add-on treatment in patients with FOS. The study met its primary endpoint, showing a median percent change (MPC) in monthly FOS frequency from baseline to week 12 for both the 15 mg and 25 mg doses of azetukalner versus placebo. The placebo-adjusted MPC in the 25 mg group was -42.7%, which was better than the data from the earlier phase IIb X-TOLE study, in which the 25 mg dose showed a placebo-adjusted MPC of -34.6% over eight weeks. Treatment with azetukalner was generally well tolerated and demonstrated a safety profile similar to that seen in previous studies. Xenon plans to submit a new drug application to the FDA seeking approval for azetukalner to treat FOS in the third quarter of 2026. If approved, azetukalner would become the only KV7 potassium channel opener available for treating epilepsy. The identical phase III X-TOLE3 study is currently enrolling patients and is intended to support potential regulatory submissions for azetukalner for FOS in ex-U.S. jurisdictions. XENE is also evaluating azetukalner for primary generalized tonic-clonic seizures in a phase III X-ACKT study, which is currently enrolling patients. Xenon’s first two of three planned phase III clinical studies, X-NOVA2 and X-NOVA3, evaluating azetukalner in patients with MDD, are currently underway, with top-line data from X-NOVA2 expected in the first half of 2027. XENE’s first of two phase III clinical studies, X-CEED, evaluating azetukalner in patients with BPD I or II, is also currently ongoing. Xenon has initiated two separate early-stage studies evaluating XEN1120 and XEN1701 in healthy adult participants, targeting Kv7 and Nav1.7, respectively. Both studies are expected to be completed in the second half of 2026, potentially supporting the initiation of separate phase II proof-of-concept studies in acute pain. XENE, in collaboration with Neurocrine Biosciences, is currently evaluating NBI-921355, a Nav1.2/1.6 inhibitor, in a phase I study as a potential treatment for certain types of epilepsy. Top-line data is expected in 2027. Xenon Pharmaceuticals Inc. price-consensus-eps-surprise-chart | Xenon Pharmaceuticals Inc. Quote Xenon currently carries a Zacks Rank #3 (Hold). Some better-ranked stocks in the biotech sector are Amarin Corporation AMRN and Liquidia Corporation LQDA, each currently sporting a Zacks Rank #1 (Strong Buy). You can see the complete list of today’s Zacks #1 Rank stocks here. Over the past 60 days, estimates for Amarin’s 2026 loss per share have narrowed from $7.01 to $6.36. Over the same period, loss per share estimates for 2027 have also narrowed from $5.50 to $4.64. AMRN shares have risen 5.9% year to date. Amarin’s earnings beat estimates in three of the trailing four quarters and missed in the remaining one, with the average surprise being 50.02%. Over the past 60 days, estimates for Liquidia Corporation’s 2026 earnings per share have declined from $2.14 to $1.75. Over the same period, EPS estimates for 2027 have decreased from $3.79 to $2.91. LQDA shares have gained 22.6% year to date. Liquidia Corporation’s earnings beat estimates in two of the trailing four quarters, while missing the same on the remaining occasions, with the average surprise being 39.38%. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Neurocrine Biosciences, Inc. (NBIX) : Free Stock Analysis Report Amarin Corporation PLC (AMRN) : Free Stock Analysis Report Xenon Pharmaceuticals Inc. (XENE) : Free Stock Analysis Report Liquidia Corporation (LQDA) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research

Interested in Xenon Pharmaceuticals Inc.? Here are five stocks we like better. Xenon Pharmaceuticals plans to submit an NDA for azetukalner in Q3 2026 after positive Phase 3 focal onset seizure data, with a potential U.S. launch targeted for late 2027 or early 2028. The Phase 3 X-TOLE2 study met its primary endpoint in both dose groups, showing meaningful seizure reductions and a safety profile the company said was consistent with prior studies, supporting its commercialization plans. Xenon ended Q1 with $1.3 billion in cash after a recent financing, which management says should fund operations into 2029 and support its broader epilepsy, depression and early-stage pain pipeline. Bristol Myers Squibb’s big buys: $18.1 billion in 2 biotech deals Xenon Pharmaceuticals (NASDAQ:XENE) said it is preparing to submit a new drug application to the U.S. Food and Drug Administration in the third quarter of 2026 for azetukalner, its investigational anti-seizure medicine, after reporting positive Phase 3 data in focal onset seizures during the first quarter. On the company’s first-quarter 2026 earnings call, President and Chief Executive Officer Ian Mortimer said the results from the Phase 3 X-TOLE2 study “exceeded our expectations” and reinforced Xenon’s plans to move toward commercialization. Mortimer said the company’s base-case assumption is a standard FDA review period followed by Drug Enforcement Administration scheduling, which would put a potential launch “at the end of 2027 or early 2028.” → Insider Sales: Top AST SpaceMobile Insider Cuts Postion Over 30% Azetukalner, also referred to as AZK, is a Kv7 potassium channel opener being developed for epilepsy and depression. Xenon is also studying the drug in primary generalized tonic-clonic seizures, major depressive disorder and bipolar depression. Mortimer said the X-TOLE2 study in focal onset seizures demonstrated, to the company’s knowledge, “the highest placebo-adjusted median percent change in monthly focal seizure frequency ever seen in a pivotal FOS study.” The company presented the data as a late-breaking oral presentation at the American Academy of Neurology annual meeting. → Light Speed Returns: Corning Cashes In on NVIDIA Growth Dr. Chris Kenney, Xenon’s chief medical officer, said the study met its primary endpoint in both the 25 mg and 15 mg azetukalner dose groups compared with placebo. He said the median percent reduction in monthly focal seizure frequency was 53.2% for 25 mg, 34.5% for 15 mg and 10.4% for placebo. Kenney said patients in X-TOLE2 were highly treatment-resistant at baseline, with a median of 13 seizures per month, a median of five prior anti-seizure medicines and more than half using three concomitant anti-seizure medications. He added that about 60% were either taking cenobamate or had previously tried and discontinued it. → Years in the Making, AMD’s Upside Movement Has Just Begun Xenon executives also highlighted long-term open-label extension data from the earlier X-TOLE program. Kenney said patients treated for at least 48 months had a 91% reduction in monthly seizure frequency. He said nearly 40% of those patients were seizure-free for at least 12 months, and one in four were seizure-free for at least two years. Kenney said the safety profile remained consistent across X-TOLE and X-TOLE2, with the most common treatment-emergent adverse events in the azetukalner groups including dizziness, somnolence, headache and fatigue. He said the company has more than 800 patient-years of safety and exposure data. Chief Commercial Officer Darren Cline said physicians at AAN and other forums have shown strong interest in azetukalner’s profile, including its novel mechanism, once-daily dosing, expected effective starting dose, no titration and no dose adjustments with other anti-seizure medicines. Cline said Xenon believes azetukalner has the potential to become “the preferred branded ASM for general neurologists,” citing feedback that ease-of-use attributes could make it more practical in community neurology settings. He said launch readiness remains a key company priority, with Xenon expanding field-based capabilities, adding medical science liaisons and initiating discussions with payers. The company also discussed how azetukalner may compare with cenobamate, sold as XCOPRI, though executives emphasized the limitations of cross-trial comparisons. Mortimer said Xenon’s focal onset seizure studies involved a more refractory patient population, while Kenney said longer-term seizure freedom is the more meaningful measure for clinicians and patients. Xenon is continuing to enroll three Phase 3 depression studies: X-NOVA2 and X-NOVA3 in major depressive disorder and X-CEED in bipolar depression. Mortimer said top-line results from X-NOVA2 are expected in the first half of 2027. Kenney said depression remains an area of unmet need and that azetukalner’s Kv7 mechanism, potential rapid onset and possible benefits on anhedonia are key elements of the company’s rationale for development in major depressive disorder and bipolar depression. The company also highlighted progress in earlier-stage pain programs. Mortimer said Xenon expects to complete first-in-human studies later this year for XEN1701, targeting NaV1.7, and XEN1120, targeting Kv7, with the intent to advance both into Phase 2 proof-of-concept studies in pain. In response to analyst questions, Mortimer said Xenon feels it can safely dose XEN1701 and achieve the therapeutic index needed to test the mechanism in Phase 2. He said the company is considering acute pain models such as bunionectomy or abdominoplasty but has not finalized the study designs. Xenon also continues to advance a NaV1.1 program in Dravet syndrome, with investigational new drug-enabling studies ongoing. Mortimer said the company sees an opportunity for an oral small molecule that could potentiate the remaining functional NaV1.1 channel in patients with Dravet syndrome. Chief Financial Officer Tucker Kelly said Xenon ended the first quarter with $1.3 billion in cash, cash equivalents and marketable securities, compared with $586 million at the end of 2025. The increase followed a $747.5 million public financing completed after the X-TOLE2 results. Kelly said the company’s cash position is expected to fund operations into 2029 based on current operating plans. He said the balance sheet positions Xenon to support a potential U.S. launch of azetukalner, multiple registrational programs and continued development of its early-stage pipeline. Mortimer said Xenon does not plan to build commercial infrastructure outside the United States. He said the company is conducting clinical development designed to meet global regulatory requirements, including steps to support Japan through the incorporation of Japanese sites and patients in X-TOLE3, and would look to potential partners for ex-U.S. markets at the appropriate time. Xenon Pharmaceuticals Inc is a clinical‐stage biopharmaceutical company dedicated to discovering and developing novel, small‐molecule drugs targeting ion channels in the central and peripheral nervous system. The company's research focus centers on neurological and pain disorders—including epilepsy, migraine, and neuropathic pain—by modulating key ion‐channel proteins to restore normal neuronal function. Xenon's scientific platform draws upon advances in ion‐channel biology and structure‐based drug design to identify and optimize therapeutic candidates with the potential for improved safety and efficacy profiles compared with existing treatments. The company's pipeline comprises multiple preclinical and clinical programs. The article "Xenon Pharmaceuticals Q1 Earnings Call Highlights" was originally published by MarketBeat. View MarketBeat's top stocks for May 2026.

Image source: The Motley Fool. May 7, 2026 President and Chief Executive Officer — Ian Mortimer Chief Medical Officer — Christopher John Kenney Chief Commercial Officer — Darren S. Cline Chief Financial Officer — Thomas Kelly Head of Investor Relations — Colleen Alabiso Need a quote from a Motley Fool analyst? Email [email protected] Colleen Alabiso: Good afternoon. Thank you for joining us on our call and webcast to discuss Xenon Pharmaceuticals Inc.’s first quarter 2026 financial and operating results. Joining me today are Ian Mortimer, President and Chief Executive Officer; Christopher John Kenney, Chief Medical Officer; Darren S. Cline, Chief Commercial Officer; and Thomas Kelly, Chief Financial Officer. After completing our prepared remarks today, we will open the call up for your questions. Please be advised that during this call, we will make a number of statements that are forward-looking, including statements regarding the timing of and potential results from clinical trials; the potential efficacy, safety profile, future development plans in current and anticipated indications; addressable market, regulatory success, and commercial potential of our and our partner’s product candidate. The strength of our clinical trial designs; our ability to successfully develop and achieve milestones in our clinical development programs, including the anticipated filing of INDs and NDAs; the timing and results of those filings and our interactions with regulators; our ability to successfully obtain regulatory approval; anticipated timing of top line data readouts for our clinical trials of AZET2 calendar and other candidates; and our expectation that we will have sufficient cash to fund operations into 2029. Today’s press release summarizing Xenon Pharmaceuticals Inc.’s first quarter financial results and the accompanying quarterly report on Form 10-Q will be made available under the Investors section of our website at xenon-pharma.com and filed with the SEC on SEDAR+. I will now turn the call over to Ian. Ian Mortimer: Thanks, Colleen, and good afternoon to everyone joining us today. We are excited to recap an exceptional quarter for Xenon Pharmaceuticals Inc., where we made tremendous progress toward our goal of becoming a fully integrated neuroscience company delivering life-changing medicines to patients. In March, we reported results from our Phase 3 XTOL-2 study of azetu calder, or AZK, in focal onset seizures that exceeded our expectations. Now with these positive data in hand, we are focused on our NDA submission to the FDA expected in 2026, and we also continue to work on increasing AZK awareness and education through our scientific engagement amongst HCPs, as well as our commercial readiness activities. In addition, we continue to broaden the therapeutic opportunities for AZK beyond epilepsy with potential neuropsychiatric indications where we have strong preclinical, clinical, and genetic evidence. Our three Phase 3 depression studies in major depressive disorder and bipolar depression continue to enroll and we are on track to deliver top line results from EXNOVA-2 in 2027. Successful studies in MDD, BPD, or both would serve to benefit patients and substantially expand the commercial opportunity for AZK. Finally, we remain focused on expanding our pipeline through the advancement of our promising earlier-stage ion channel programs, with exciting candidates that provide the potential to drive our long-term growth. This includes completion of our first-in-human studies for XEN1701, targeting Nav1.7, and XEN1120, targeting Kv7, later this year, with the intent to advance both programs to Phase II proof-of-concept studies in pain. As we continue to execute our clinical programs and prepare for the anticipated approval and launch of AZK, we also continue to prioritize maintaining a strong balance sheet. So today I am going to focus most of my comments on AZK and epilepsy, and then I will turn the call over to Chris, Darren, and Tucker. As you all know, in Q1 we announced positive top line results from the XTOL-2 study in focal onset seizures, which exceeded our expectations by surpassing the already strong results from the Phase 2b XTOL study and, to our knowledge, demonstrated the highest placebo-adjusted median percent change in monthly focal seizure frequency ever seen in a pivotal FOS study. Similar to XTOL, we observed a rapid onset of efficacy, strong and dose-dependent responder rates, and a consistent safety and tolerability profile. Following the top line announcement, we were excited to present the data as a late-breaking oral presentation at the American Academy of Neurology Annual Meeting in Chicago. Around these two milestones, we have engaged with hundreds of epileptologists and neurologists and the feedback we have received has been incredibly positive. HCPs are enthusiastic about the magnitude of the efficacy benefits seen in our two randomized trials; the breadth and consistency of our safety and tolerability data; the impressive rates of seizure freedom in the OLE; and the key differentiating attributes of AZK. This includes a novel Kv7-targeting mechanism of action, no titration, once-daily dosing, and no dose adjustments for other ASMs. If approved, this profile would add a meaningful new medicine to their toolkit and provide the opportunity for rational polytherapy. We feel increasingly confident in AZK’s potential to become a preferred ASM for the significant number of patients who do not achieve seizure freedom with initial treatment. We are working hard to submit our new drug application to the U.S. Food and Drug Administration in 2026. Our base case assumption is a standard review period followed by DEA scheduling, which would put the anticipated launch timing at 2027 or early 2028. At the same time, we are focused on building out our commercial infrastructure and finalizing our go-to-market strategy, and Darren will speak to this a little bit later on the call. Beyond FOS, we are encouraged by the potential of AZK in primary generalized tonic-clonic seizures, and our Phase 3 EXACT study continues to enroll. Positive results in EXACT would enable us to submit a supplemental NDA for an additional epilepsy indication, which would meaningfully increase our addressable patient population. Outside of epilepsy, we are making good progress enrolling our three ongoing neuropsychiatry studies: EXNOVA-2 and EXNOVA-3 in major depressive disorder, and EXEDE in bipolar depression. There is strong rationale for Kv7 openers in depression. Several preclinical and clinical studies, including our own NOVA study, have shown promising signals of antidepressive effects for the Kv7 mechanism. Additionally, in bipolar depression, there are genetic links with Kv7, including evidence of Kv7 downregulation. We look forward to sharing our first top line Phase 3 data set in MDD in the first half of next year. We also continue to progress our early-stage programs, including our first-in-human studies with XEN1701, targeting Nav1.7, and XEN1120, targeting Kv7. These are both compelling targets to treat pain with non-opioid approaches. These programs are exciting as they leverage our deep expertise in ion channel science and the strength of our discovery capabilities, and would address large unmet medical needs. Acute and chronic pain affects more people than diabetes, heart disease, and cancer combined, yet effective non-opioid options are scarce. There is a significant opportunity for Xenon Pharmaceuticals Inc. to be a leader in unlocking the next generation of pain therapeutics. We are also excited about our early-stage epilepsy programs, including our Nav1.1 program in Dravet syndrome. IND-enabling studies are ongoing, and we continue to showcase our encouraging preclinical findings at large congresses, such as the recent AAN meeting. Our collaborators at Neurocrine are also progressing a Phase 1b study for 121,355. This is an investigational selective inhibitor of voltage-gated sodium channels Nav1.2 and Nav1.6, which is being investigated as a potential treatment for certain types of epilepsy. Data from this study are expected next year. Finally, I want to highlight another major accomplishment for Q1, which was the completion of our $747.5 million financing. It significantly extends our cash runway into 2029, allowing us to transition to a commercial-stage company and advance our depression and pain programs to key data milestones. Now with that overview, I will turn it over to Chris to provide an update on our activities at AAN and our broader clinical program. Chris? Christopher John Kenney: It has been a really exciting time at Xenon Pharmaceuticals Inc. since we reported our top line XTOL-2 data. As you would imagine, there is a great deal of enthusiasm in the epilepsy community with the prospect of a new anti-seizure medicine that could address many of the gaps in today’s treatment paradigm, including the limited number of mechanisms available. With the strong XTOL-2 data that exceeded all expectations, coupled with the long-term OLE data showing sustained effects and impressive seizure freedom, I am incredibly excited about the potential for AZK to positively impact the lives of patients in the near future and for decades to come. Recently, our team spent a week in Chicago at the American Academy of Neurology Annual Meeting, where we gave several important clinical, preclinical, and real-world data presentations, which collectively underscored the significance for AZK and our growing leadership within epilepsy. I will start by highlighting the XTOL-2 data that were featured as a late-breaking science presentation. Every year, AAN receives more than 300 late-breaking science submissions, and this year they selected just 18 abstracts for data that they viewed as warranting expedited presentation and publication to their neurologists. Dr. Jackie French of NYU and chair of the XTOL-2 steering committee presented the XTOL-2 data in both an oral platform presentation as well as a poster. The reactions were very positive, with the session moderator from Harvard University and Massachusetts General Hospital characterizing the data as outstanding, and Dr. French highlighting rapid onset of efficacy and no titration as key differentiating aspects of AZK that will appeal to physicians. Our XTOL-2 presentation reinforced the positive top line data we announced in March, including that the study met its primary endpoint of median percent change in monthly FOS frequency from baseline to Week 12 in both the 25 mg and 15 mg AZK dose groups compared to placebo. Specifically, we observed an MPC reduction of 53.2% for 25 mg, 34.5% for 15 mg, and 10.4% for placebo, results which were highly statistically significant and actually outperformed the Phase 2b XTOL study. We also observed early dose-dependent MPC in weekly FOS from baseline to Week 1, which was sustained through the double-blind period with both AZK doses, reinforcing AZK’s rapid and sustained anti-seizure activity. These efficacy results are even more impressive when you consider that XTOL and XTOL-2 included the most treatment-resistant FOS population ever trialed. At baseline, patients in XTOL-2 were experiencing a median of 13 seizures per month, had been treated with a median of five prior ASMs, and more than half were already using three concomitant anti-seizure medications. About 60% were on or had already tried and stopped cenobamate, and still they had not achieved seizure control. We also provided additional data from our responder rate analysis, where we observed dose-dependent increases in the proportion of participants with at least 75% and 90% reductions in monthly seizure frequency through the double-blind period. We also presented 100% responder rate data, which demonstrated that a 100% reduction in seizures over the double-blind period was attained by a greater proportion of participants with AZK 25 mg than placebo, results which were highly consistent with the results of XTOL. While AZK has a rapid onset of efficacy, it also takes a few weeks to reach steady-state levels, and we have seen in other instances, such as the XTOL OLE, that efficacy continues to build over time. Therefore, we also conducted a post hoc analysis of the XTOL-2 data to see if a greater proportion of participants experienced a 100% reduction in seizures over time. Indeed, the 100% responder rate increased steadily over the last eight, six, and four weeks. For example, the 100% responder rate over the 12-week double-blind period for 25 mg was 6.5%, but over the last six weeks it increased to 11.3%, and over the last four weeks it increased further to 13.7%. We are looking forward to continuing to follow this trend in the Phase 3 OLE. This brings me to our other key AZK presentation at AAN: our 48-month XTOL OLE data, where the trend of efficacy building over time is even more compelling. The OLE is also where we are best positioned to evaluate whether patients are truly achieving seizure freedom, which has been a consensus definition of no seizure for 12 months or more. This definition also aligns to practical, real-world outcomes for patients, as in many states 12 months without seizures means they are able to drive again. Our long-term OLE data demonstrated continued reductions in focal seizures, with a 91% reduction in monthly seizure frequency for those treated for at least 48 months. Those who entered the study taking one or two ASMs demonstrated a 100% reduction in monthly seizure frequency, compared with an 82% reduction in seizure frequency among those taking three ASMs at baseline. With regard to seizure freedom, among patients treated for at least 48 months, almost 40% were seizure-free for at least 12 months, and one in four were seizure-free for at least two years. If you consider how treatment-resistant the overall patient population was at baseline, this is truly remarkable. Based on feedback from our investigators, we understand some of these patients have never experienced seizure freedom before taking AZK, and their stories fuel our desire to bring AZK to patients and clinicians as quickly as possible. Finally, I will also note that our AZK data at AAN continue to support a generally well-tolerated profile. The safety data are remarkably consistent between XTOL and XTOL-2 in terms of types of treatment-emergent adverse events, the frequency at which they occurred, the number and types of serious adverse events, and the events that led to discontinuations. The most common treatment-emergent adverse events across both studies in the AZK dose groups were dizziness, somnolence, headache, and fatigue. With more than 800 patient-years of safety and exposure data, we are comfortable that this profile is consistent with other well-tolerated ASMs and with a drug that is potent and active in the central nervous system. We will continue to add to these robust safety and tolerability data with our ongoing Phase 2 and Phase 3 OLEs in epilepsy. Another focus for Xenon Pharmaceuticals Inc. at AAN was education around unmet needs in epilepsy care, including the impact that titration has on both patients and HCPs, the opportunity for no-titration options to improve treatment experiences, outcomes, and healthcare resource utilization. We presented real-world data that captured the challenges reported by patients around medication schedules, daily life, and quality of life during titration periods, while physicians reported challenges related to treatment complexity and cross-titration. When questioned on their perceptions of ASMs without titration, most patients noted that they either agree or strongly agree that initiating an ASM without needing to titrate to a stable dose would boost their confidence, reduce anxiety, and improve adherence. Physicians noted that no titration would increase simplicity, as many patients are already on complex drug regimens. These findings suggest using ASMs that do not require titration may reduce stress and simplify FOS management, and we heard this echoed in our discussions at AAN as well, especially for general neurologists who value ease-of-use attributes in prescribing decisions. We rounded out our AAN scientific program with an oral presentation of preclinical data from our Nav1.1 program in Dravet syndrome. These data demonstrated that selective potentiation of Nav1.1 channels in Dravet mice improves motor function, suppresses spontaneous seizures, prevents sudden unexpected death from epilepsy, increases long-term potentiation (which is a potential cellular correlate of learning and memory), and produces more mature dendritic spine morphology. The data continue to support our belief that targeting Nav1.1 with a small molecule could potentially address the underlying cause and symptoms of Dravet syndrome. IND-enabling studies for this program are currently ongoing. All in all, we are very proud of our scientific contributions at AAN, as well as how positively they were received by the community. Moving on to our other clinical programs, we have had a lot of activity as we continue to enroll three Phase 3 studies in depression and two Phase 1 programs in pain. Depression is an area where the differentiated profile of AZK, including its novel mechanism of action, rapid onset of action, and potential benefits on anhedonia, could meaningfully benefit patients. Like epilepsy, the depression landscape has experienced a dearth in innovation for some time, and new mechanisms are urgently needed. Our clinical development team has made great progress with EXNOVA-2 and EXNOVA-3, which are ongoing and enrolling patients with major depressive disorder. As Ian previously stated, we anticipate sharing top line data from EXNOVA-2 in 2027. In addition, EXEDE, a Phase 3 clinical study evaluating AZK in patients with bipolar I and bipolar II depression, also continues to enroll. This is another area where there is significant unmet need for safe and effective therapies due to nonadherence related to side effects and other factors. The physicians that we have spoken with are keenly interested in AZK’s novel selective Kv7 mechanism of action, potential benefit on anhedonia, rapidity of onset, and differentiated safety profile. To round out my remarks, pain continues to be an area of growing focus and we are looking forward to completing our first-in-human studies for our novel pain programs this year. There remains a strong desire for non-opioid pain therapies given the limited efficacy of current options and substantial risk of abuse and dependency tied to opioids. We know that analgesics can act along multiple different points of the pain pathway and interrupt the pain signal on its way to the brain, and we believe in the potential for Nav1.7 inhibitors and Kv7 potentiators to play important roles at multiple points in this pathway, including in the initial transduction of pain stimuli into pain signals, the transmission of those pain signals along nociceptive neurons, and the relay from peripheral sensory neurons to spinal cord neurons in the central nervous system. We believe Nav1.7 is the best genetically validated pain target, with striking genetic data in patients with loss-of-function mutations that have no ability to feel pain. Gain-of-function mutations have also been identified that drive pain disorders, further underscoring the critical role Nav1.7 plays in pain signaling. With XEN1701, as well as other Xenon Pharmaceuticals Inc. programs in preclinical development, we believe we have solved for some of the critical limitations of prior Nav1.7 compounds. Kv7 is also a compelling target to modulate neuronal hyperexcitability at multiple points along the pain pathway, and we believe Kv7 potentiators have the potential to treat a range of pain conditions. This is supported by high levels of Kv7 expression throughout the pain pathway, and our preclinical data show that Kv7 is enriched in the C and A-delta subtypes of sensory neurons. In addition, Kv7 openers can block action potential firing in both DRG and spinal cord neurons, thereby significantly inhibiting pain signals from reaching the brain. Evidence supports that dysfunction or downregulation of Kv7 activity has been observed in altered pain states. We are excited to be advancing an optimized Kv7 opener with our XEN1120 program. We are really encouraged by our Nav1.7 and Kv7 work in pain and look forward to providing more details later in the year. With that, I will turn it over to Darren to provide an update on our path to commercialization, including interactions and discussions at AAN. Darren? Darren S. Cline: Thank you, Chris. I would like to reinforce the comments from Ian and Chris regarding the strong interest in our XTOL-2 data since we first reported the results in early March. Since then, we have seen sustained engagement and interest from a broad group of epileptologists and neurologists attending AAN. Across these interactions, they reiterated the strength of our XTOL-2 and OLE datasets and AZK’s differentiated profile, and we consistently heard enthusiasm about the potential to use AZK in clinical practice. Physicians highlighted the importance of efficacious therapies that are also straightforward to incorporate into routine patient care. AZK’s unique mechanism and its expected profile of once-daily dosing, an effective starting dose, no drug interactions, and no dose adjustments with other ASMs remain among the most frequently cited and most compelling attributes. Looking ahead, we plan to increase our understanding through primary research, advisory boards, and one-on-one meetings as we continue to deepen our insight of AZK in advance of potential approval and launch. Based on our growing engagements with this audience, we believe AZK has the potential to become the preferred branded ASM for general neurologists. We also continue to hear that AZK’s profile may support greater confidence in treating a broader range of epilepsy patients within community practices, rather than referring patients to a level three or four epilepsy center after exhausting existing available options, which could contribute to broader adoption, improve patient outcomes, and meaningful prescription growth over time. Launch readiness remains a key enterprise priority. Over the past several months, we have focused on increasing our scientific engagement with epilepsy specialists, neurologists, and advanced practice providers, while continuing to expand our field-based capabilities, including the recent addition of several medical science liaisons. In parallel, we have initiated discussions with payers to introduce Xenon Pharmaceuticals Inc., better understand unmet needs, and communicate the potential value proposition of AZK. In March, we attended the Pharmaceutical Care Management Association, or PCMA, meeting for the first time and held a number of productive introductory discussions with pharmacy benefit managers and payers. The timing of these conversations alongside our XTOL-2 data release helped drive interest and momentum. We plan to participate in several national payer meetings this year, and in the coming months, we expect to expand our field-based payer team to continue dialogue with this important constituency and further strengthen our launch preparedness. As we execute on these launch readiness priorities, we remain focused on building an experienced launch and lifecycle management organization, advancing innovation across channels and patient services, and increasing awareness across our customer universe. Our commercial objective is to establish Xenon Pharmaceuticals Inc. as a leader in epilepsy, and we believe we are making meaningful progress toward that goal. We are highly motivated by the opportunity to deliver meaningful benefits to patients and the physicians who care for them. With that, I will turn the call over to Tucker to review our financial results. Thomas Kelly: Thank you. As Ian mentioned, the exceptional results in XTOL-2 allowed us to complete a highly successful public offering of nearly $750 million, which fortified our balance sheet as we move toward potential approval and launch. We ended Q1 with cash, cash equivalents, and marketable securities of $1.3 billion, compared to $586 million as of December 31. Based on our current operating plans, this provides cash to fund operations into 2029. Given our strong balance sheet and fiscal management, we are well positioned to support AZK’s U.S. launch, multiple registrational programs for AZK, and the continued maturation of our early-stage pipeline. I would refer you to our press release and our 10-Q filed today for further details on our financial results. Overall, it is a very exciting time at Xenon Pharmaceuticals Inc. as we continue to build momentum in our pipeline spanning epilepsy, depression, and pain, and make progress against our critical priorities, with our first priority being the submission of our NDA for AZK to the FDA in 2026, as well as the advancement of our commercial readiness activities to support a strong launch in FOS. We also remain focused on broadening the therapeutic opportunities for AZK beyond FOS, and we continue to make good progress enrolling our studies in major depressive disorder and bipolar depression, with the readout of our first depression study anticipated in 2027. Lastly, we are pleased with the momentum in our early-stage pain programs, and we anticipate completing the first-in-human studies for 1701 targeting Nav1.7 and 1120 targeting Kv7 later this year, and we seek to advance both programs to Phase II proof of concept. We are in an excellent position to execute our priorities due to our strong cash position, and we are feeling very optimistic about a bright future as we begin to transition to a commercial-stage company delivering meaningful medicines to patients. With that, we will now open the call for questions. Operator: At this time, I would like to remind everyone that in order to ask a question, please press star then the number one on your telephone keypad. We will pause for just a moment. Your first question comes from the line of Paul Matteis with Stifel. Your line is open. Paul Matteis: Great. Thanks very much. Congratulations on everything from the first quarter. I wanted to ask a couple of questions on the pain programs, if that is okay. First, as it relates to the Nav1.7 compound, I was wondering if you could talk about where you have gotten to in your Phase I program at this point, and how much you feel like you have de-risked some of the safety issues that have plagued other drugs? And then separately, can you maybe speak to more specifics around these Phase II plans in acute pain? What would the size and scope of those studies potentially look like, assuming the Phase I data later this year lets you advance? Thank you. Ian Mortimer: Thanks, Paul. Chris, I am happy to start and then you can provide your perspective, especially on the future clinical development. At JPMorgan earlier this year in January, we discussed progress we had made on both Nav1.7 and Kv7. You asked specifically around Nav1.7. At that time, we said that we already felt that we were at high enough exposures to get receptor occupancy that would mimic the human genetics, so we had already made good progress in those early cohorts of dose escalation. Bringing it forward to today, we have continued to enroll additional healthy volunteers in that Phase 1 study. Sitting today, we feel really good that we can safely dose, have the appropriate therapeutic index, and give this mechanism a real shot to show proof-of-concept data in Phase II. Based on what we know today, our plans are to move forward into a Phase II acute pain proof-of-concept study. Obviously, on the acute pain side, we are looking at studies like bunionectomy or abdominoplasty. We have not yet fully designed the studies. We would want to have them of sufficient size and power, and these would be placebo-controlled studies to show a difference between active and placebo. The question we continue to think about internally is how many arms, active comparators, how many doses—those things we are still planning. That will become clearer as we finish Phase 1 and we have a really good idea of what we are seeing in terms of the dose response and safety profile in those Phase 1 healthy volunteer studies. Chris, any color to add on additional details for future development? Christopher John Kenney: I will just double down on your point that we think we have what we need to go forward into Phase II on both programs, and we have not worked out exactly what the plan would be after the proof of concept that would be with abdominoplasty and/or bunionectomy. Paul Matteis: Alright. All good. Thank you very much. Unknown Speaker: Thank you. Operator: Your next question comes from the line of Tessa Thomas Romero with JPMorgan. Your line is open. Tessa Thomas Romero: Hey, thanks so much for taking our question, and congratulations from us on all the progress. Ian and Chris, I was wondering if you could provide your perspectives on how the seizure freedom data that you have shared at 12 weeks from XTOL-2 compares to what we know about XCOPRI on a cross-trial basis numbers-wise. How do you think doctors will approach thinking through the seizure freedom data that we have for these two assets, given that nearly 60% of the patient population were taking or had already discontinued XCOPRI in XTOL-2, and, of course, that XCOPRI has to be titrated? Thank you. Ian Mortimer: Thanks, Tessa. I will start. Chris can provide perspective, but I also want Darren to weigh in because we have had a huge amount of interaction with HCPs and the feedback that they are providing us. Chris mentioned in the prepared remarks that the consensus definition of seizure freedom is really having no seizure for 12 months, and so when we talk about our seizure freedom data with prescribers, we focus more on our open-label data than our double-blind data. In the double blind, you will hear us use terms like RR100, which is the percentage of patients that had a 100% reduction over the double blind. You asked for a comparison between AZK and cenobamate. It is a cross-trial comparison and it is challenging, but I will make a couple of comments. One, it was a materially different patient population. As Chris walked through and as you have seen in our publications and posters, we believe that both in XTOL and XTOL-2 this was the most refractory population ever trialed in a pivotal FOS study. When we look at the cenobamate double-blind trials done over a decade ago, that was a significantly less refractory population. So we are comparing two different clinical populations within FOS. You also mentioned another key factor, which is because cenobamate is titrated, when they look at their RR100 during their double blind, they only report over the maintenance period, which is the last six weeks of dosing. One of the reasons why we provided a breakdown of the last eight, six, and four weeks is to enable a better comparison. Another point on the cross-trial comparison is that often they show their data at their 400 mg dose, which—based on feedback and real-world data—patients rarely reach. If you look at their 200 mg dose and you look at the last period within our double-blind period—within the last six weeks or four weeks of our data—I would actually say that our RR100 is higher than the cenobamate data seen at their 200 mg dose. Then the last point you made is important: we actually had a cenobamate-refractory population in our trial, with close to 40% of patients on background cenobamate and approximately another 20% who had tried it and failed it either for efficacy or tolerability and were no longer on the drug. Overall, I think our data stack up really well, and I have not even talked about the open-label data. That is just a cross-trial comparison during the double-blind period. I will pass it to Chris to talk about the open-label seizure freedom data and then to Darren on how that is being pulled through into the real world. Christopher John Kenney: Thanks, Tessa. In the epilepsy field, there is a bit of a disconnect. If you talk to epileptologists and neurologists and ask them what they are hoping to achieve, they talk about seizure freedom on a long time horizon—at least six months, more like a year, sometimes more. Yet, in the same conversation, they will ask what was your seizure freedom over a month or two or three months. As you make comparisons, the details matter. If you are talking about seizure freedom with cenobamate at 400 mg, with hardly anybody taking 400 mg, and many patients treated at 200 mg or lower, it is important to think about dose. Also, when they talk about seizure freedom in cenobamate, they are excluding the first six weeks of the trial period, which is why we provided those different cuts of seizure freedom to allow a better comparison. Zooming out, general neurologists want something easy to use. With AZK, you do not have to worry about titration, drug-drug interactions, or manipulating other medications to reach therapeutic dose. To wrap up on seizure freedom, what really matters is what happens in the long term. In the data we just presented at AAN, among patients treated for four years or more, we are seeing about 40% with seizure freedom for a year or more. That is what really matters—not so much what happened over one, two, or three months. Thanks. Darren S. Cline: Thanks, Tessa. I would reiterate what Ian and Chris said. When we engage with physicians—both epileptologists and general neurologists—at AAN and other forums, XCOPRI is largely an epileptologist drug. When we query about seizure freedom at 400 mg, very few, if any, patients get to the 400 mg dose. As it relates to their own experience, seizure freedom at those doses is not as compelling in the real world. XCOPRI does add benefit, but physicians are not seeing anywhere near what is shown at 400 mg. General neurologists have struggled with using it; many try it once and are done. What differentiates AZK—and what we believe will make this a tremendous opportunity—is the ease-of-use attributes: lack of titration, once-daily dosing, and no DDIs. These really resonate, and general neurologists look forward to incorporating AZK in their practice. Operator: Your next question comes from the line of Cory William Kasimov with Evercore. Your line is open. Cory William Kasimov: Hi. This is Addy on for Cory. Just on the earlier question asked on the pain assets, can you confirm if investors should anticipate any data this year? I believe earlier it was mentioned that maybe Phase 1 SAD/MAD data might be presented. Should we anticipate that data? Thank you. Ian Mortimer: Thanks. We are very comfortable saying that the Phase 1 healthy volunteer studies for both 1701 and 1120 will complete this year. In terms of how much of those data we provide publicly—for competitive reasons—we will certainly communicate that we believe we have enough receptor occupancy, exposure, and coverage to have a really good shot at seeing an analgesic effect in a proof-of-concept study. It is to be determined whether we will broadly show the Phase 1 data publicly. We are comfortable that those studies will wrap up this year. Operator: Your next question comes from the line of Analyst with TD Cowen. Your line is open. Analyst: Hi, thanks for taking our questions. Have you scheduled or had a pre-NDA meeting yet? If you have had the meeting, can you talk about any feedback you have received from the FDA? Then on scheduling, can you walk us through the timeline and your expectations for DEA scheduling if you get approved? Christopher John Kenney: What we have guided is that we had top line XTOL-2 in March. We expect about a six-month period between that and submitting the NDA. We are expecting a standard review of 12 months, and then DEA scheduling is expected to be three months, which is why Ian stated that we expect approval in 2027 or early 2028. Pre-NDA meetings are standard. We expect that to occur between the top line data and the NDA submission in the fall, but we have not provided specifics on timing. We have had thoughtful and timely interactions with FDA, we think we have a good reputation with them, and we have not foreseen any problems up to this point. We look forward to future interactions. Analyst: Great. Thank you. Operator: Your next question comes from the line of Andrew Tsai with Jefferies. Your line is open. Andrew Tsai: Hey, good afternoon. Thanks for taking my questions. This is Matt Barkis on for Andrew Tsai. Can you give us a little flavor on what other Phase 3 data analyses you might share later this year, especially at AES in December, which can further showcase AZK’s potential differentiation? Ian Mortimer: Thanks. Chris, do you want to walk through our thinking around AES and additional analyses? Christopher John Kenney: We have spent a lot of time digging into the Phase 3 data and are working through what we intend to submit as potential abstracts at AES. As you know, you submit and they may or may not be accepted. We are focusing on analyses that combine efficacy and safety from our two pivotal FOS trials—XTOL and XTOL-2. We may also revisit seizure subtypes as we did in XTOL. And of course, we will update the XTOL OLE data, as we do each year. Those will happen for sure; we are working through whether there will be anything else. Ian Mortimer: That was great. Thanks, Chris. Operator: Your next question comes from the line of Brian Skorney with Baird. Your line is open. Brian Skorney: Hey, thanks for taking the question. This is Charlie on for Brian. Thinking about your Nav1.1 in Dravet—obviously a preclinical space—how do you see this compound and mechanism differentiating from the field, especially considering there are other therapies out there addressing this issue in epilepsy? And one more on pain: what are you thinking about long term in terms of chronic pain versus acute pain, and how each asset might fit into that paradigm? Thank you. Ian Mortimer: Thanks. I can start on Nav1.1 and then Chris can add, and we can touch on pain strategy. In Dravet syndrome, these children are haploinsufficient in Nav1.1, so they have about 50% of the protein. Currently approved drugs address seizures—like clobazam, Epidiolex, or FINTEPLA—aim to reduce seizure burden. We believe the field is also moving toward correcting the underlying genetics. There are ASO approaches you are aware of. We see an opportunity for a small molecule that is orally administered and can be titrated or weight-based dosed across a wide range of pediatric weights. By potentiating the channel and increasing current through the wild-type channel, there is potential to correct underlying disease physiology. The preclinical data Chris described—presented at AAN, including in haploinsufficient genetic models that mirror the human phenotype with spontaneous seizures and SUDEP—are quite remarkable. We see not only seizure reduction but also potential disease modification, including protection from death and improvements in long-term potentiation. We are now in tox studies. There is a huge need for better therapies in Dravet, and we think this could fit in nicely, though it is still early days. On pain, our first proof-of-concept studies will be in acute pain—bunionectomy or abdominoplasty. There is nothing in the genetics of Nav1.7 or the mechanism of Kv7 that suggests they should only work in acute versus chronic, or nociceptive versus neuropathic pain. If these programs look promising in PoC, the plan would be to go broad in late-stage development. Christopher John Kenney: Maybe it is slightly crowded, but this is a devastating disorder and it is good that multiple groups are working on it. We think we are differentiated because we are advancing a small molecule that addresses pathophysiology in a manner analogous to ASOs targeting the mechanism, but delivered orally rather than intrathecally. Think about the SMA analogy: gene therapy, ASOs, and then orals—all played roles. We think we can offer something meaningful. On pain, we are focused on getting out of first-in-human and into PoC; we still need to figure out chronic versus acute and other parameters in the coming months. Brian Skorney: Great. Thank you for all the color. Really helpful. Operator: Your next question comes from the line of Myles Minter with William Blair. Your line is open. Myles Minter: Thanks for taking the question. One on the commercial side: it is interesting that we are all comparing to XCOPRI when that is not the number one branded product—BRIVIACT is, and I think that went generic at the start of the year. Is that a headwind to marketing a newly branded ASM because costs are coming down in general neurology, or is it a tailwind because you no longer have to compete for that branded slot and can come in and take the market within general neurology? Darren S. Cline: Thanks, Myles. On the contrary, we think AZK’s attributes—particularly the novel mechanism—stand out after generations of SV2A, sodium channel blockers, and GABAergic approaches. The novel Kv7 mechanism is a benefit. Our ease-of-use attributes that we have outlined and receive positive feedback on—no titration, once-daily dosing, no DDIs—are compelling. Considering the timing, when we ultimately launch it will be almost a decade of what I would characterize as stagnation in focal epilepsy innovation. Along with our clinical data and profile, we see a great opportunity. BRIVIACT is another “me too” mechanism following a wildly successful parent in Keppra; that is a completely different market and opportunity than what we have with AZK as we look to the future and prepare to launch. Operator: Your next question comes from the line of Analyst with Deutsche Bank. Your line is open. Analyst: Hi, thanks for taking my questions. On the commercial side, given the strong balance sheet you have now, how do you think about leveraging that to ensure the best commercial launch for AZK in focal epilepsy? For example, would you increase the number of sales reps you field? And a competitor is doing a monotherapy study, arguing that weaning patients off background meds could allow earlier-line use. Have you thought of a study like that, and would it be helpful for AZK? Ian Mortimer: Thanks. I am happy to start with a bit of historical context, and then Darren can go through launch preparation details, and Chris can address monotherapy and labeling. Since the XTOL data in 2021, we have invested in commercial preparation at risk. This is a generational, paradigm-shifting opportunity. Given our confidence heading into the XTOL-2 Phase 3 readout, we started commercial prep already. Darren was hired almost a year ago. We have had field medical—MSLs—engaging in scientific exchange; this summer it will be two years since that team has been in the field. Darren’s leadership team is in place. We have had access personnel in place for years. Early investment gives us an opportunity for real success in the early days of commercialization. Darren? Darren S. Cline: Thanks. Successful launches share a few ingredients. First is early investment, which was in place when I joined. Second is the team: we have commercial leaders with deep epilepsy experience, relationships, and launch experience—which gives us a leg up. Third, we will be a highly desirable place for epilepsy-dedicated professionals; there has been little new for years, so when we post roles we expect the best talent. On the product, from brand positioning to pricing commensurate with value to services and distribution, we are thinking creatively to extract value and, most importantly, deliver the best patient and physician experience. Creating demand is only part of it; converting to paid scripts, persistency, and compliance complete the equation. All those variables are being put in place, and with AZK’s clinical profile, we are extremely excited and bullish on the launch. Chris, on monotherapy? Christopher John Kenney: To be blunt, I do not see the upside of doing a monotherapy study. From a labeling perspective, current labels do not specify adjunctive; they state the indication. I do not see upside from a labeling perspective. If, for whatever reason, I did see upside, I would design a pure monotherapy study—drug versus placebo—from the start. Manipulating background ASMs, trying to back off, and then interpreting efficacy and safety is likely very challenging. Operator: Your next question comes from the line of Analyst with Wells Fargo. Your line is open. Analyst: Yes, this is Orpheus on for Ben. Good afternoon, and congrats on the progress. As we look forward to XTOL-3 data and a potential ex-U.S. launch, how are you thinking about commercialization in ex-U.S. territories? I know in the past you have shared you would look to partner in such geographies. Any updates you can share? Thank you. Colleen Alabiso: I am happy to address that. Ian Mortimer: We are conducting clinical development to meet regulatory requirements around the world. We have been clear that the clinical program should meet requirements in Europe. An update over the last couple of quarters was our interaction with PMDA and the incorporation of Japanese sites and subjects into XTOL-3 to meet requirements in Japan without having to run a separate Phase 3 program there. We have done what is needed to drive global clinical development and value. We have also been clear that we are not going to build market access and commercial infrastructure outside the U.S. When the time is right, we will engage with potential partners to access those markets. Right now, we are focused on global clinical development. Analyst: Very helpful. Thank you very much. Operator: I will now turn the call back over to Ian Mortimer for closing remarks. Ian Mortimer: Thanks very much, operator, and thanks to everyone for joining us today. I know there were other questions in the queue, so if we did not get to yours, we will reach out to you directly to connect. We look forward to providing continued updates as we advance our programs and deliver on important milestones throughout the remainder of the year. Operator, we can now end the call. Operator: Ladies and gentlemen, that concludes today’s call. Thank you all for joining. You may now disconnect. Before you buy stock in Xenon Pharmaceuticals, consider this: The Motley Fool Stock Advisor analyst team just identified what they believe are the 10 best stocks for investors to buy now… and Xenon Pharmaceuticals wasn’t one of them. The 10 stocks that made the cut could produce monster returns in the coming years. 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As with all our articles, The Motley Fool does not assume any responsibility for your use of this content, and we strongly encourage you to do your own research, including listening to the call yourself and reading the company's SEC filings. Please see our Terms and Conditions for additional details, including our Obligatory Capitalized Disclaimers of Liability. The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy. Xenon (XENE) Q1 2026 Earnings Transcript was originally published by The Motley Fool

Reported positive topline data from Phase 3 X-TOLE2 study of azetukalner in FOS in March and anticipate NDA submission in Q3 2026 Five additional Phase 3 studies of azetukalner continue to enroll in epilepsy and depression indications with Phase 3 X-NOVA2 MDD topline data expected in H1 2027 Phase 1 studies of novel NaV1.7 (XEN1701) and KV7 (XEN1120) candidates expected to complete H2 2026 to support Phase 2 proof-of-concept studies in pain Cash, cash equivalents and marketable securities of $1.3 billion extends cash runway into 2029 Conference call at 4:30 pm ET today VANCOUVER, British Columbia and BOSTON, MA, May 07, 2026 (GLOBE NEWSWIRE) -- Xenon Pharmaceuticals Inc. (Nasdaq: XENE), a neuroscience-focused biopharmaceutical company dedicated to drug discovery, clinical development and commercialization of life-changing therapeutics for patients in need, today reported financial results for the first quarter ended March 31, 2026 and provided a business update. “In the first quarter of 2026, we announced positive results from our X-TOLE2 study, which exceeded expectations and reinforced azetukalner’s significant potential to provide a new therapeutic option for FOS patients with uncontrolled seizures. The strong X-TOLE2 results have paved the way for us to submit an NDA to the FDA in the third quarter of 2026 and our commercial preparedness activities are well underway, supported by our strong balance sheet with cash runway into 2029,” said Ian Mortimer, President and Chief Executive Officer of Xenon. “We remain enthusiastic about broadening the opportunity for azetukalner beyond FOS and are making good progress advancing multiple additional Phase 3 studies in epilepsy and neuropsychiatry indications. Additionally, we are looking forward to completing the first-in-human studies for our novel programs targeting NaV1.7 and KV7 in pain later this year.” Business Highlights and Anticipated Milestones Azetukalner Clinical Development Azetukalner is a novel, potent KV7 potassium channel opener in Phase 3 clinical development for multiple indications, including two in epilepsy – focal onset seizures (FOS) and primary generalized tonic-clonic seizures (PGTCS) – as well as neuropsychiatric disorders, including major depressive disorder (MDD) and bipolar depression (BPD). Epilepsy Programs Xenon announced positive topline data from the Phase 3 X-TOLE2 study in March 2026. The study met its primary endpoint of median percent change (MPC) in monthly FOS frequency from baseline to week 12 in both the 25 mg and 15 mg azetukalner dose groups compared to placebo (MPC of -53.2%, -34.5% and -10.4%, respectively; p<0.0001 for both 25 and 15 mg vs. placebo). The placebo-adjusted MPC in the 25 mg group was -42.7%, outperforming the previously completed Phase 2b X-TOLE study and demonstrating the highest placebo-adjusted efficacy ever observed in a pivotal FOS study, to the company’s knowledge. The safety and tolerability profile of azetukalner was consistent with data from the X-TOLE study. Based on the positive results from X-TOLE2 and X-TOLE, Xenon anticipates submitting a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the third quarter of 2026. X-TOLE2 topline efficacy and safety results were featured as a Late Breaking Science oral and poster presentation at the American Academy of Neurology (AAN) Annual Meeting in Chicago, Illinois, April 18-22. Also at AAN, Xenon presented 48-month data from the ongoing X-TOLE open-label extension study, which demonstrated continued reductions in monthly FOS frequency with longer azetukalner treatment, greater seizure reductions in less refractory patients and sustained periods of seizure freedom. Xenon also presented real-world data regarding unmet needs in epilepsy, including the need for no-titration options. The Phase 3 X-TOLE3 study of azetukalner in FOS continues to enroll and is intended to support regulatory submissions outside the United States. X-TOLE3 enrollment outside of Japan is expected to complete in 2026. The Phase 3 X-ACKT study of azetukalner in PGTCS continues to enroll and is intended to support regulatory submissions for an additional epilepsy indication. Depression Programs Enrollment is ongoing in the Phase 3 X-NOVA2 and X-NOVA3 studies evaluating azetukalner in patients with MDD, with topline data from X-NOVA2 expected in H1 2027. Enrollment is ongoing in the Phase 3 X-CEED study evaluating azetukalner in patients with BPD I or II. Early-Stage R&D Xenon continues to expand its portfolio of potent, selective ion channel modulators using the Company’s strong heritage in human genetics, deep understanding of ion channel biology and expertise in novel chemistries. This includes clinical-stage candidates targeting NaV1.7 and KV7, which are important targets for pain. NaV1.7 and KV7 in Pain The Phase 1 Single Ascending Dose (SAD)/Multiple Ascending Dose (MAD) study in healthy adult participants is ongoing for XEN1701 targeting NaV1.7. Study completion is expected in H2 2026 to support initiating a Phase 2 proof-of-concept study in acute pain. The Phase 1 SAD/MAD study in healthy adult participants is ongoing for XEN1120 targeting KV7. Study completion is expected in H2 2026 to support initiating a Phase 2 proof-of-concept study in acute pain. NaV1.1 in Epilepsy IND-enabling studies are ongoing for the Company’s NaV1.1 program. Pre-clinical data suggest that targeting NaV1.1 could potentially address the underlying cause and symptoms of Dravet syndrome. The Company presented pre-clinical data for its NaV1.1 program in an oral session at the AAN meeting, demonstrating that selective potentiation of NaV1.1 channels in Dravet mice improves motor performance, suppresses spontaneous seizures, prevents Sudden Unexpected Death in Epilepsy (SUDEP), increases long-term potentiation (a potential cellular correlate of learning and memory), and produces more mature dendritic spine morphology. Partnered Program In collaboration with Neurocrine Biosciences, a Phase 1b study is ongoing for NBI-921355, an investigational, selective inhibitor of voltage-gated sodium channels NaV1.2 and NaV1.6 in development for the potential treatment of certain types of epilepsy. Data from the Phase 1b study are expected in 2027. Upcoming Investor Conferences Xenon will present at three upcoming investor conferences in the second quarter of 2026, including the Bank of America Global Healthcare Conference on Thursday, May 14, the RBC Capital Markets Global Healthcare Conference on May 19, and the Jefferies Global Healthcare Conference on June 4. Details about the presentations, including webcast information, can be found on the Investors section of Xenon’s website. Q1 2026 Financial Results Cash and cash equivalents and marketable securities were $1,339.6 million as of March 31, 2026, compared to $586.0 million as of December 31, 2025. During the quarter ended March 31, 2026, $130.0 million of net proceeds was raised under the Company’s ATM and $707.6 million of net proceeds was raised through a public offering. Based on current operating plans, Xenon anticipates having sufficient cash to fund operations into 2029. As of March 31, 2026, there were 96,624,123 common shares and 2,931,293 pre-funded warrants outstanding. Research and development expenses were $88.5 million for the quarter ended March 31, 2026, compared to $61.2 million for the same period in 2025. The increase in research and development expenses for the period was primarily attributable to the ongoing azetukalner Phase 3 clinical studies in the MDD and BPD programs, ongoing Phase 1 clinical studies of XEN1701 and XEN1120, as well as increased personnel-related costs due to an increase in employee headcount and stock-based compensation expense. General and administrative expenses were $23.8 million for the quarter ended March 31, 2026, compared to $19.0 million for the same period in 2025. The increase in general and administrative expenses for the period was primarily attributable to personnel-related costs due to an increase in employee headcount and an increase in professional and consulting fees. Other income was $7.5 million for the quarter ended March 31, 2026, compared to $8.1 million for the same period in 2025. The decrease in other income for the period was primarily attributable to lower interest income. Net loss was $102.3 million for the quarter ended March 31, 2026, compared to $65.0 million for the same period in 2025. The increase in net loss for the period was primarily attributable to lower revenue from the collaboration with Neurocrine Biosciences, higher research and development expenses driven by the azetukalner and pain programs and higher personnel-related costs, higher general and administrative expenses driven by higher personnel-related costs and professional and consulting fees, and lower interest income. Conference Call Information Xenon will host a conference call and webcast today at 4:30 pm Eastern Time (1:30 pm Pacific Time) to discuss its first quarter 2026 results. A listen-only webcast can be accessed on the Investors section of the Xenon website, with a replay available following the event. Participants can access the conference call by dialing (800) 715-9871 or (646) 307-1963 for international callers and referencing conference ID 7898598. About Azetukalner Azetukalner is a novel, potent KV7 potassium channel opener currently in Phase 3 clinical trials for the treatment of epilepsy, major depressive disorder (MDD) and bipolar depression (BPD). It represents the most advanced, clinically validated potassium channel modulator in late-stage clinical development. Azetukalner is designed to open potassium channels in the central nervous system, allowing potassium ions to flow and hyperpolarizing neurons. This process helps reduce excessive neuronal firing, which is a key contributor to several neurologic and psychiatric disorders. It is the only KV7 potassium channel opener in development for multiple indications that is backed by long-term efficacy and safety data in epilepsy patients and proof-of-concept data in MDD patients. Phase 3 Epilepsy Studies Xenon’s clinical development program for azetukalner in epilepsy includes three Phase 3 clinical studies in focal onset seizures (FOS) and primary generalized tonic-clonic seizures (PGTCS). The completed X-TOLE2 study and the ongoing X-TOLE3 study were both designed as multicenter, randomized, double-blind, placebo-controlled studies to evaluate the clinical efficacy, safety, and tolerability of 15 mg or 25 mg of azetukalner administered orally with food as adjunctive treatment in approximately 360 patients with FOS per study. The primary efficacy endpoint is median percent change (MPC) in monthly seizure frequency from baseline through the 12-week double-blind period (DBP) of azetukalner compared to placebo. X-ACKT is a multicenter, randomized, double-blind, placebo-controlled study evaluating the clinical efficacy, safety, and tolerability of 25 mg of azetukalner administered with food as adjunctive treatment in approximately 160 patients with PGTCS. The primary efficacy endpoint is MPC in monthly PGTCS frequency from baseline through the 12-week DBP of azetukalner compared to placebo. Upon completion of the DBP in the Phase 3 epilepsy studies, eligible patients may enter an open-label extension (OLE) study for up to six years. Phase 3 MDD Studies Xenon’s Phase 3 X-NOVA major depressive disorder (MDD) program includes three multicenter, randomized, double-blind, placebo-controlled clinical studies to evaluate the clinical efficacy, safety, and tolerability of 20 mg of azetukalner administered orally with food over the 6-week double-blind period (DBP) as monotherapy treatment in approximately 450 patients with moderate-to-severe major depressive disorder (MDD) per study. The primary efficacy endpoint is the change from baseline in the HAM-D17 score at week 6 in patients who received azetukalner compared to placebo. Upon completion of the DBP, eligible patients may enter an open-label extension (OLE) study for up to 12 months. Phase 3 BPD Studies Xenon’s Phase 3 X-CEED Bipolar Depression (BPD) program includes two multicenter, randomized, double-blind, placebo-controlled clinical studies to evaluate the clinical efficacy, safety, and tolerability of 20 mg of azetukalner administered orally with food over the 6-week double-blind period (DBP) as monotherapy treatment in approximately 400 patients per study with BPD I or II. The primary efficacy endpoint is the change from baseline in the MADRS score at week 6 in patients who received azetukalner compared to placebo. Upon completion of the DBP, eligible patients may enter an open-label extension (OLE) study for up to 12 months. About Xenon Pharmaceuticals Inc. Xenon Pharmaceuticals (Nasdaq: XENE) is a neuroscience-focused biopharmaceutical company dedicated to drug discovery, clinical development, and commercialization of life-changing therapeutics for patients in need. Xenon’s lead molecule, azetukalner, is a novel, potent, selective KV7 potassium channel opener in Phase 3 clinical trials for the treatment of epilepsy, major depressive disorder (MDD) and bipolar depression (BPD). Xenon is also advancing an early-stage portfolio of multiple promising potassium and sodium channel modulators, including KV7 and NaV1.7 programs in Phase 1 development for the potential treatment of pain. Xenon has offices in Vancouver, British Columbia, and Boston, Massachusetts. For more information, visit www.xenon-pharma.com and follow us on LinkedIn and X. Xenon and the Xenon logo are registered trademarks or trademarks of Xenon Pharmaceuticals Inc. in the US, Canada and elsewhere. All other trademarks belong to their respective owner. Safe Harbor Statement This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995 and Canadian securities laws. These forward-looking statements are not based on historical fact, and include statements regarding the timing of and potential results from clinical studies; the potential efficacy, safety profile, future development plans in current and anticipated indications, addressable market, regulatory success and commercial potential of our and our partners’ product candidates; the efficacy of our clinical study designs; our ability to successfully develop and achieve milestones in our azetukalner and other pipeline and development programs, including the potential timing of trial enrollment completion and the anticipated filing of INDs and NDAs; the timing and results of our interactions with regulators, including the timing of any NDA submission; and our ability to successfully develop and obtain regulatory approval of azetukalner and our other product candidates. These forward-looking statements are based on current assumptions that involve risks, uncertainties and other factors that may cause the actual results, events, or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties, many of which are beyond our control, include, but are not limited to: clinical studies may not demonstrate safety and efficacy of any of our or our collaborators’ product candidates; promising results from pre-clinical development activities or early clinical study results may not be replicated in later clinical studies; our assumptions regarding our planned expenditures and sufficiency of our cash to fund operations may be incorrect; our ongoing discovery and pre-clinical efforts may not yield additional product candidates; any of our or our collaborators’ product candidates, including azetukalner, may fail in development, may not receive required regulatory approvals, or may be delayed to a point where they are not commercially viable; we may not achieve additional milestones in our proprietary or partnered programs; regulatory agencies may impose additional requirements or delay the initiation or completion of clinical studies; the impact of market, industry, and regulatory conditions on clinical study enrollment; the impact of competition; the impact of expanded product development and clinical activities on operating expenses; the impact of new or changing laws and regulations; the impact of unstable economic conditions in the general domestic and global economic markets; adverse conditions from geopolitical events; as well as the other risks identified in our filings with the U.S. Securities and Exchange Commission and the securities commissions in British Columbia, Alberta, and Ontario. These forward-looking statements speak only as of the date hereof and we assume no obligation to update these forward-looking statements, and readers are cautioned not to place undue reliance on such forward-looking statements. Contacts For Investors: Tucker Kelly Chief Financial Officer [email protected] For Media: Colleen Alabiso Senior Vice President, Corporate Affairs [email protected]