Xenon Pharmaceuticals Inc.

welcome you to the Q4 2024 Seed and Farmers Utilities, Inc. Earnings Conference Call. All lines have been placed in view 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. I would now like to turn the conference over to Chad Pugier. Please go ahead.

Good afternoon. Thank you for joining us on our call and webcast to discuss Xenon's fourth quarter and full year 2024 financial and operating results. Joining me are Ian Mortimer, Xenon's President and Chief Executive Officer, Dr. Chris Kenney, Xenon's Chief Medical Officer, and Sherry Allen, Xenon's Chief Financial Officer. After completing their 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 plan, and current and anticipated indications, addressable market, regulatory success, and commercial potential of our and our partner's product candidate. The efficacy of our clinical trial design, our ability to successfully develop and achieve milestones in our clinical development program, including the anticipated filing of INDs and NDAs, the timing and results of our interactions with regulators, our ability to successfully obtain regulatory approval, anticipated timing of top-line data readout for clinical trials of the Z2 calendar, and our expectation that we'll have sufficient cash to fund operations in 2027. Today's press release summarizing Xenon's fourth quarter and full year 2024 financial results and the accompanying report on Form 10Q will be made available under the Investors section of our website at xenon-pharma.com. and filed with the FCC and on CEDAR+. Now, I would like to turn the call over to Ian.

Thank you, Chad, and good afternoon, everyone. Thanks for joining our call today. I'll begin with a brief review of our accomplishments in 2024 and then look ahead to what promises to be an exciting year in 2025, highlighted by our first Phase III epilepsy readout and the continued progress of our growing neuroscience-focused pipeline. After that, I'll turn the call over to Chris, who will share more details on our clinical development programs. And then later, Sherry will comment on the potential of Zetucalner in the bipolar depression treatment landscape and close with a summary of our financial results. Looking back at this past year, I am proud of the numerous advancements across our pipeline, including the advancement of Zetucalner in our broad Phase III epilepsy program, the launch of our Phase III MDD program, considerable planning around further indication expansion of a ZetuCalendar in bipolar depression and significant progress in our discovery portfolio with several molecules across multiple targets placed to enter the clinic this year. 2024 was a year of execution for Xenon and the progress made across our business has positioned us well to deliver on our three key strategic priorities. Number one, driving towards phase three data NDA submission, and commercializing the use of azetucalner in focal onset seizures in the U.S. Number two, broadening the azetucalner opportunity across additional epilepsy and neuropsychiatric indications. And number three, expanding our product portfolio through advancement of our promising early-stage ion channel programs. We believe Xenon's leadership in the KV7 landscape is unmatched. And our lead asset is that your calendar is the only KV7 opener in development backed by long-term efficacy and safety data from clinical studies of patients living with epilepsy. We now have amassed over 700 patient years of exposure in focal epilepsy patients. There remains a substantial need for new, efficacious, and well-tolerated epilepsy therapies, especially for those patients who continue to experience the debilitating impacts of focal seizures even while taking multiple anti-seizure medications. Based on the significant body of compelling clinical evidence that we have generated to date, along with azetucalner's other important attributes, such as once-daily dosing without the need for titration, a rapid onset of effect, novel mechanism of action, and potential mood benefit, we believe that azetucalner represents a potentially best-in-class anti-seizure medication that could be paradigm shifting in the future treatment of epilepsy. As we near the completion of our first phase three epilepsy readout, which will enable the completion of an anticipated NDA filing, we are excited about the potential for Xenon's first commercial launch. Over the last 12 months, it culminated in a strong presence at the American Epilepsy Society meeting, or AES, which took place in December. This is the marquee medical congress in epilepsy that hosted over 6,000 attendees, and we were able to present new long-term AZETA calendar data from our ongoing XTOL open label extension study, showing a sustained monthly reduction in seizure frequency, impressive seizure freedom rates in patients with epilepsy, and improved quality of life measures. Xenon has led some of the latest surveys and research to understand in more detail the high burden of illness within the epilepsy community. And AES provided us with an opportunity to highlight some of these findings around the mental health burden and comorbidities of epilepsy. We believe that an enhanced understanding of the burdens of focal onset seizures and the association between these comorbidities, particularly mental health comorbidities like depression, may enable better treatment options and help in improving patient outcomes. Chris will provide more detail about our AES data presentations and activities in his prepared remarks. Within our Phase III MDD program, we are pleased to be enrolling patients in our ExNova 2 study, and we expect that the second of three planned studies, ExNova 3, will initiate around midyear. Further, we're in an incredibly fortunate position in that azetucaliner's attributes may enable significant utility beyond epilepsy, and we believe that azetucaliner has broad potential in neuropsychiatric indications. Supported by strong scientific rationale, today we announced our plans to initiate a registrational program studying the use of azetucaliner in bipolar depression. Both Chris and Sherry will provide further details on the current unmet patient needs and market research that supported our decision to pursue this new neuropsychiatric program. This is an exciting opportunity for Isetukalner. With the launch of this new program, Isetukalner will be in registrational trials across four distinct epilepsy and neuropsychiatric indications, truly a pipeline and a product opportunity. We also continue to expand our pipeline by leveraging our extensive discovery knowledge and expertise in developing potassium and sodium channel therapeutics. This past year, we made significant progress within our early stage portfolio, progressing multiple drug candidates targeting KV7 and NAV1.7 into IND enabling studies. Recognizing the potential broad applicability of the KV7 mechanism of azetucalner, we have identified multiple chemically diverse KV7 development candidates, and we believe that this mechanism may have utility in a broad range of therapeutic indications, including seizure disorders, pain, as well as neuropsychiatric disorders such as MDD and bipolar depression. Further, I'm incredibly excited that we continue to make meaningful progress within our NAV1.7 sodium channel program. Our pioneering work around the NAV1.7 target has formed a core part of Xenon's heritage. Given its importance as a pain-related target with strong human genetic validation, we believe NAV1.7 could represent a new class of medicines without the limitations of opioids. We are now in a position where we expect multiple regulatory filings in 2025 coming out of our early stage portfolio to support the initiation of first in human trials across multiple targets. We also expect a lead candidate within our NAV11 program will enter IND enabling studies this year. We presented some of our preclinical findings at AES this past December. Briefly, these results showed that dosing with an orally available small molecule, CNS penetrant, highly selective NAV1.1 potentiator suppressed induced seizures and improved motor performance, supporting the potential for improvements in dravet patient motor function. Further, in these animal models, chronic dosing suppressed spontaneous seizures, protected against sudden unexpected death in epilepsy or SUDEP, and increased long-term potentiation, a potential cellular correlate of learning and memory. These preclinical data are incredibly exciting and suggest that targeting NAV1.1 could potentially address the underlying cause and symptoms of Dravet syndrome. Later this year, we are planning to host an investor webinar to showcase various xenon early stage programs, including deeper dives into the mechanism, underlying human genetics, preclinical, and other supporting data generated today, as well as an overview of the unmet medical needs and commercial opportunity, and more details to come at a later date. Finally, we're pleased to confirm that as part of our collaboration with Neurocrine Biosciences, A promising selective inhibitor of sodium channels NAV1.2 and NAV1.6 that was discovered in Xenon's labs has progressed into a Phase I study, and this triggered a milestone payment to us. This important achievement is a testament to our world-class discovery team and a direct result of Xenon's deep expertise and pioneering work in the sodium channel space, with our research work contributing to the discovery of new molecules and a further understanding of how mutations in the genes that encode for both NAV1.2 and NAV1.6 cause irregular neuronal activity associated with several forms of epilepsy. Neurocrine has guided that this first in human study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of investigational compound MBI 921355 in healthy adult participants to support its development for the potential treatment of certain types of epilepsy. Looking ahead, we expect the next 12 to 24 months will represent a catalyst rich period for Xenon as we continue to advance our deep and expanding pipeline of promising late and early stage programs. We anticipate a number of important milestones. Most importantly, the first phase three top line readout of a Zetacalner in focal onset seizures expected in the second half of 2025, representing a major inflection point for Xenon as we evolve from a clinical to commercial stage organization. This is an incredibly exciting time at Xenon, and I look forward to keeping you updated on our progress. So I'll now turn the call over to Chris to provide some additional detail around our development programs.