Xenon Pharmaceuticals Inc.

Thank you for standing by. My name is RG, and I will be your conference operator today. At this time, I would like to welcome everyone to the Q3 2025 Stephen Pharmaceuticals, Inc. 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 would now like to turn the call over to Colleen Sinon, Senior Vice President of Corporate Affairs. Please go ahead.

Good afternoon. Thank you for joining us on our call and webcast to discuss Sinon's third quarter 2025 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, our Chief Financial Officer. After completing our prepared remarks today, we will open the call up for 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 efficacy 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 the top-line data readout for our clinical trials of a ZET2 calendar, and our expectation that we will have sufficient cash to fund operations into 2027. Today's press release summarizing Zenon's third quarter financial results and the accompanying quarterly report on Form 10Q will be made available under the investor section of our website at zenon-pharma.com and filed with the SEC and on CDAR. I'll now turn the call over to Ian.

Great. Thank you, Colleen, and good afternoon, everyone. Thanks for joining us on our call today. We're excited to share the considerable progress we have made over the past quarter as we remain focused on our three critical priorities. First and foremost, completing our Phase 3 XTOL2 study of azacucalner for the treatment of focal onset seizures, the top-line data readout in early 2026, followed by the filing of our first NDA for the approval of azacucalner in the U.S. Second, broadening the therapeutic opportunities for Zetucalner beyond epilepsy with potential neuropsychiatric indications where we have identified strong preclinical, clinical, and genetic evidence supporting the development in major depressive disorder and bipolar depression. And third, expanding our pipeline through the advancement of our promising earlier stage NAV1.7, KV7, and NAV1.1 ion channel programs with recent progress of our novel NAV1.7 and KV7 modulators moving into phase one studies. I will focus most of my comments on our AZK phase three epilepsy program. And Chris will provide additional details across our clinical stage portfolio. As a reminder, AZK remains the only KV7 channel opener and the only ASM in development that is backed by long-term efficacy and safety data from clinical studies of patients living with epilepsy, having demonstrated highly compelling placebo-adjusted efficacy in focal onset seizure patients in our Phase IIb XTOL trial, and durable and sustained efficacy over time through our open-label extension study, with greater than 800 patient years of exposure and safety data. As we disclosed in today's press release, the final patients in our XTOL2 study have completed the baseline period, and all patients have now been randomized. The final number of patients randomized is 380, which is a significant milestone, and we remain on track for top-line data readout in early 2026. As a reminder, XTOL2 was designed and powered to randomize approximately 360 patients, so we are very pleased to have randomized more than the target in the study design. This will result in good power across the critical endpoints in this study. From the outset, we have prioritized working with high-quality, experienced clinical sites to maximize study success, while diligently monitoring key metrics throughout the study. These metrics are tracking as we expect, and as we disclosed previously, patient baseline demographics and the open label extension rollover rate are consistent with our successful Phase 2bx tool study. Therefore, we remain confident in XTOL2 and share the epilepsy community's excitement as we progress towards top-line data readout. Two topics that we often get questions on with respect to XTOL2 are the final steps between now and top-line data, as well as our expectations going into this important readout. So I'm happy to address both of these topics. As I mentioned, the final patients in XTOL2 have recently been randomized. That means all patients have completed their eight-week baseline period and their randomization visit. These final patients are now in the 12-week double-blind portion of the study. For those patients who complete the double-blind portion, they have an opportunity to enter the open-label extension. The OLE rollover rate has been high in XTOL2, consistent with XTOL, where we saw greater than 95% of patients roll over to open-label. For those patients who don't enroll in the OLE, there is an eight-week safety follow-up visit. Therefore, the final timing of the top-line data will be determined based on the last few patients and whether they enter OLE. After the final patients have completed the double-blind period, we will finalize data cleaning, unlock the database, complete the statistical analysis and medical review, and be ready for top-line data release. we will be in a position to narrow guidance about the specific timing for top-line data in the coming months. We are optimistic for a positive outcome, and we believe that XTOL2, together with the strong results from XTOL, will serve as the basis for a new drug application for AZK in focal onset seizures. As we prepare for the XTOL2 readout, we have completed a detailed review of prior FOS studies, And we find that there is high reproducibility of results from phase two to phase three. ASMs that have strong efficacy results in earlier studies demonstrated similar positive results in subsequent phase three studies. Although there is some reduction in effect size, which is not unusual when moving from phase two to phase three. Over the last 20 years, Anti-seizure medicines that have been approved in adult FOS in the U.S. have shown a placebo-adjusted seizure reduction percentage ranging from the teens into the low 30s. Interestingly, some of the more successful ASMs, including Vimpat, are on the lower end of this range, and often the drugs on the higher end of the range have other challenges, either around tolerability or an onerous titration or DDI profile. This reinforces what we consistently hear from physicians, although efficacy is an important component, the overall profile of the ASM drives prescribing decisions to address a broad range of unmet needs for their patients. And it is this overall profile where we believe is that you counter is differentiated and has a compelling set of attributes at launch. We believe AZK will be an only-in-class KV7 mechanism of action with strong short and long-term efficacy, QD dosing with no required titration, no adjustments for DDIs, the potential for mood benefit, and an overall favorable safety and tolerability profile. It is this profile that we believe will drive adoption and commercial success. So again, we have high confidence and we expect that a positive XTOL2 readout combined with the impressive efficacy from our XTOL study will form compelling profile supportive of our MDA submission. We remain excited as we look forward to the potential of bringing an important new medicine to the epilepsy community. So I'll now turn the call over to Chris, who will share more details on our clinical development programs across epilepsy, depression, and pain. Chris. Over to you.