Xenon Pharmaceuticals Inc.

Thank you for standing by. My name is Rebecca and I'll be your conference operator today. At this time, I would like to welcome everyone to the first quarter 2026 Xenon Pharmaceuticals Earnings Conference Call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, Simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one again. Thank you. I will now turn the call over to Colleen Alabisco, Senior Vice President of Corporate Affairs at Xenon. Please go ahead.

Good afternoon. Thank you for joining us on our call and webcast to discuss Xenon's first quarter 2026 financial and operating results. Joining me today are Ian Mortimer, President and Chief Executive Officer, Dr. Chris Kenney, Chief Medical Officer, Darren Klein, 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 in 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 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 a Zet2 calendar and other candidates, and our expectation that we will have sufficient cash to fund operations in 2029. Today's press release summarizing Zenon's first quarter financial results and the accompanying quarter we report on Form 10Q will be made available under the investor section of our website at zenon-pharma.com and filed with the SEC on CDAR+. I'll now turn the call over to Ian.

Thanks, Colleen, and good afternoon to everyone joining us today. We are excited to recap an exceptional quarter for Xenon, 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 XTOL2 study of azetucalner, 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 the third quarter of 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 three depression studies in major depressive disorder and bipolar depression continue to enroll, and we're on track to deliver top-line results from Exnova 2 in the first half of 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 two 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'm going to focus most of my comments on AZK and epilepsy. And then I'll turn the call over to Chris, Darren, and Tucker. As you all know, in Q1, we announced positive top-line results from the XFOL2 study in focal onset seizures, which exceeded our expectations by surpassing the already strong results from the Phase 2b XFOL 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've 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 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 the third quarter of 2026. Our base case assumption is a standard review period followed by DEA scheduling, which would put the anticipated launch timing at the end of 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're encouraged by the potential of AZK in primary generalized tonic-clonic seizures, and our phase three 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're making good progress enrolling our three ongoing neuropsychiatry studies, ex nova 2 and ex nova 3 in major depressive disorder, and exceed in bipolar depression. There is strong rationale for KV7 openers in depression. Several preclinical and clinical studies, including our own ex-novus 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 III dataset 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 XEN 1701 targeting NAV 1.7 and XEN 1120 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 to be a leader in unlocking the next generation of pain therapeutics. We're 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 in Neurocrin are also progressing a phase 1B study for MBI921355. 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. So now with that overview, I'll turn it over to Chris to provide an update on our activities at AAN and our broader clinical program.