Xenon Pharmaceuticals Inc.

efficacy of our clinical trial designs, our ability to successfully develop and achieve milestones in our Exxon 1101 and other development programs, the timing and results of our interactions with regulators, our ability to successfully develop and obtain regulatory approval of Exxon 1101 and our other product candidates, anticipated enrollment in our clinical trials and the timing thereof, and our expectation that we will have sufficient cash to fund operations into 2026. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected on today's call. We undertake no obligation to publicly update any forward-looking statement. Today's press release summarizing Xenon's first quarter financial results and the accompanying annual report on Form 10-Q will be made available under the investor section of our website at www.xenon-pharma.com and filed with the SEC and on CDAR. Now I would like to turn the call over to Ian.

Thanks, Sherry, and good afternoon, everyone, and thanks for joining us on our call today. We are excited about the continued progress across our broad XEN 1101 Phase III epilepsy program. including the recent initiation of XTOL3. All planned phase 3 epilepsy clinical trials are now actively recruiting patients, including XTOL2 and XTOL3 in patients with focal onset seizures, or FOS, and EXACT in patients with primary generalized tonic-clonic seizures, or PGTCS. XCN1101 is the only potassium channel modulator in late-stage clinical development, and we continue to build on our leadership position in the KV field. driving our mission to provide new therapies for patients with epilepsy and other neurological conditions. Based on our experience with our XTOL Phase 2b study, which was similar in size to both XTOL 2 and XTOL 3, and supported by our continued relationships with key investigators, many of whom already have familiarity and experience with XTN 1101, we maintain a high degree of confidence in our ability to execute on our XTN 1101 Phase 3 program And we are pleased with our progress to date. In addition to our ongoing phase three epilepsy program in adults, we recently obtained feedback from the FDA that has shaped our strategy for our pediatric development plans for XCN 1101. Progress and highlights from our XCN 1101 pediatric plans include ongoing work on a pediatric formulation of XCN 1101 for younger patients. We also expect to take advantage of the FDA's pharmacokinetic extrapolation rule for focal onset seizures, which allows us to, over time, move into cohorts of progressively younger patients with focal onset seizures with XCN1101 in an open-label setting. And finally, we're in the process of expanding the exact Phase III clinical trial to include patients as young as 12 years of age, and this was driven by feedback from FDA. We believe XCN 1101 has the profile and attributes to support broad development, including moving into younger patients with epilepsy, where there continues to be considerable need for new medicines. And so, after careful consideration, we are prioritizing our XCN 1101 pediatric epilepsy development plans and will no longer pursue the clinical development of XCN 496. We wish to extend our sincere gratitude to the patients and their families who participated in the epic clinical trial. We intend to work with study investigators to offer an option for continued access through a transition period for those patients currently on XCN496. Turning to non-epilepsy indications, our Phase II XCN1101 ex nova study in major depressive disorder, or MDD, continues to make good progress. Our decision to examine XCN1101 in MDD was based on encouraging published clinical results with azogabine as well as promising preclinical data with XCN 1101. We were further interested in gathering additional data, given that depression is a common comorbidity within the epilepsy patient population. Exnova, which as a reminder was initiated only 12 months ago, has progressed well, and we expect to screen the last patient next month in June. After the last patient goes through a screening period lasting up to four weeks and is then randomized, There is a six-week treatment period and a four-week follow-up visit, after which the database can be locked and the data analyzed. Given these steps, we are looking forward to a top-line data readout for Exnova in the fourth quarter of this year, which is a slight shift in our previous guidance of top-line data in the third quarter. These data will help guide our future plans for Exeon 1101 in MDD. In summary, we remain laser-focused on the continued advancement of our Phase 3 XEN 1101 program, including XTOL 2 and XTOL 3 clinical trials in focal onset seizures and exact clinical trial in PGTCS, as well as executing on our pediatric development plans. We are also looking forward to the important data from our Phase 2 Ex Nova study in MDD later this year. Lastly, we continue to generate important long-term data from our ongoing XTOL open-label extension study that affirms the XTOL Phase IIb results, supporting our position that XCN 1101 presents a novel, compelling product profile with the potential to address some of the currently unmet needs of patients with epilepsy. And as Chris and Sherry will highlight in their remarks later in the call, we are excited to be entering a data-rich period for Xenon. Between now and the end of the year, we will present additional XCN 1101 XTOL open label data focused on quality of life measures at the International Epilepsy Congress in September, and 30-month OLE data at the American Epilepsy Society annual meeting in December, as well as the two Phase II readouts in the fourth quarter of this year, including data from our XEN1101-XNOVA study, as well as data from our collaboration with Neurocrin. So I'd now like to turn the call over to Chris Kenney, who can provide additional details on the progress made within our Phase III XEN1101 program, as well as recent and upcoming data presentations for XCN 1101. Chris, over to you. Okay, thanks, Ian.

I would echo that we believe the clinical data generated to date support a very compelling product profile for XCN 1101, and that the efficacy data from the Phase 2b EXTOL study and the ongoing EXTOL open label extension compare favorably to medicines currently available for focal onset epilepsy patients. to briefly review the XEN1101 clinical trials within our robust phase three program. As Ian mentioned, we now have initiated XTOL3, which is running in parallel to our XTOL2 study. Each of these studies will enroll approximately 360 subjects with focal onset seizures who will be randomized one to one to one with once daily dosing of either 15 or 25 milligrams of XEN1101 or placebo. The primary efficacy endpoint is the median percent change, or MPC, in monthly seizure frequency from an eight-week baseline through the 12-week double-blind period with Exxon 1101 compared to placebo. We've also successfully executed our plans to pursue another epilepsy indication. Our phase three exact clinical trial is expected to enroll approximately 160 subjects with primary generalized tonic-clonic seizures. Subjects will be randomized one-to-one for once daily dosing of either 25 milligrams of Exxon 1101 or placebo. The primary efficacy endpoint is the MPC and monthly PGTCS frequency from an eight-week baseline to the 12-week double-blind period of Exxon 1101 compared to placebo. I've noted that this parallel approach in both focal onset seizures and primary generalized tonic-clonic seizures at this stage of development is unique. Our rationale is based on the KD mechanism and the photosensitive proof-of-concept model of generalized epilepsy, favorable data in multiple preclinical epilepsy models, and clinical data, including activity we saw across all focal seizure subtypes in the Phase IIb XTOL study. Our hope is that we're setting the groundwork for potentially broader use of exe and 1101 in both of the most common forms of epilepsy, should it be approved. We recently met with physicians and epileptologists at the annual meeting of the American Academy of Neurology, who continue to assert the need for new therapeutic options with differentiated mechanisms of action to improve upon existing anti-seizure medications. At AAN, in addition to a poster outlining our exact clinical trial design, we were thrilled that the XEN 1101 program was selected for an oral presentation at this important neurology-focused meeting. Dr. Jackie French, one of the preeminent leaders in the epilepsy field, presented data from our ongoing open-label extension study with XEN 1101. she outlined how these data build upon the strong efficacy data generated in the Phase IIb XTOL clinical trial. Importantly, she spoke about the data demonstrating continued seizure reduction and extended periods of seizure freedom experienced by patients in the open-label extension study. Her podium presentation outlined several key takeaways. During the open-label extension, there was a sustained monthly reduction in seizure frequency specifically 80% to 90% seizure reduction as measured by median percent change from the double-blind period baseline. Also, seizure freedom for greater than or equal to six months and greater than or equal to 12-month consecutive durations was achieved in 17.5% and 10.5% of patients, respectively. XEN-1101 continues to be generally well-tolerated in the open-label extension with adverse events consistent with prior results and other anti-seizure medications. Dr. French expressed that these data are encouraging for prescribing physicians who continue to seek new, differentiated therapeutics that improve upon existing options and may provide further hope for the many patients who experience the debilitating impacts of focal seizures, even while taking multiple anti-seizure medications. Looking ahead, Our team is excited to continue to showcase XEN 1101 at medical conferences later this year, including our presence at the upcoming 35th International Epilepsy Congress in Dublin in September and at the American Epilepsy Society meeting in December. At IEC in September, we have multiple podium and poster presentations highlighting our XEN 1101 Phase 3 program, as well as new quality of life data from the ongoing XTOL open label extension. In addition, we're in the process of submitting abstracts to the American Epilepsy Society meeting, including 30-month open label extension data from XTOL, supporting the long-term use of XEN-1101, as well as important seizure freedom data. We look forward to keeping you updated on our progress on the XEN-1101 Phase III Epilepsy Program as well as continuing to build the profile of XEN 1101 with physicians and the medical community. I'll now turn the call over to Sherry, who will give us a brief update on our partnered program with Neurocrin before summarizing our first quarter financial results and upcoming milestones. Sherry.