Xenon Pharmaceuticals Inc.

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 third quarter 2021 financial results and the accompanying quarterly 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, and thanks for joining us today. Xenon marked an incredibly important milestone last month when we announced the positive top-line results from our Phase IIb X-Toll clinical trials. Exxon 1101 demonstrated impressive efficacy in difficult-to-treat adult patients with focal epilepsy. With its differentiated potassium channel mechanism of action, strong efficacy data, and ease-of-use attributes, including once-a-day evening dosing and no titration, we believe Exxon 1101 could play an important role in treating adult focal epilepsy. These data exceeded our expectations with consistent, dose-dependent, and statistically significant efficacy across the key primary and secondary seizure reduction endpoints. With these positive data in hand, we conducted a detailed analysis of our product pipeline, including the evaluation of additional indications for XCN 1101. Moving forward, we intend to sharply focus our efforts on the finalization of clinical development plans for XCN 1101, including a planned end of phase two meeting with FDA anticipated in the second quarter of 2022. and the initiation of our Phase III program in adult focal epilepsy anticipated in the second half of 2022. We look forward to providing more details on the final XCN 1101 clinical development plan in the first half of 2022, including the final design of our Phase III program and our plans to evaluate other epilepsy indications, as well as supporting Phase II development in major depressive disorder, or MDD. In addition to XEN-1101, our XEN-496 EPIC Phase III trial continues to enroll patients with KCNQ2 developmental and epileptic encephalopathy, or KCNQ2-DEE. Further, this portfolio focus on XEN-1101 and XEN-496 has helped shape our decision around our XEN-007 program. To date, a total of eight subjects have been enrolled in an investigator-led Phase II proof of concept study examining the potential clinical efficacy, safety, and tolerability of XEN007 as a treatment in patients diagnosed with treatment-resistant absence seizures, including childhood and juvenile absence epilepsy. As disclosed previously, we believe XEN007 is demonstrating efficacy in these patients with absence seizures. However, given the focus and resources required to advance XEN1101 and XEN496, We do not intend to allocate any resources to company-sponsored XEN007 development activities in 2022. So looking forward, you will see that our company objectives and activities are centered around our KV7 potassium channel programs and advancing our proprietary neurology pipeline. In addition to our clinical advancements, we have also focused over the past few years on expanding our intellectual property portfolio for XEN1101. and we have made excellent progress on this front. Over the past few months, two new U.S. patents were issued to Xenon. The first contained claims related to four distinct crystalline forms of XEN-1101 drug substance, including the form that we intend to use in our Phase III development and for commercialization, along with methods for their preparation. The second patent relates to the methods of enhancing the bioavailability of XEN-1101 by administration with food, and this is consistent with the dosing of XEN-1101 in our clinical studies. Absent any extensions of patent term, these U.S. patents are expected to expire in 2039 and 2040, respectively, providing us with an extensive runway protecting XEN-1101. Turning now to our other KV potassium channel program, XEN-496, new sites and jurisdictions continue to come online to support our EPIC study, which is a phase three, randomized, double-blind, placebo-controlled, parallel group, multi-center clinical trial, evaluating the efficacy, safety, and tolerability of XCN496 in approximately 40 pediatric patients aged one month to less than six years with KCNQ2DEE. Based on its KV7 mechanism of action, as well as published physician case studies, we believe that XCN496 has the potential to address an important unmet medical need for these patients. We anticipate that the EPIC study will be completed in the first half of 2023, and we look forward to keeping you updated on its progress. Before turning the call over to Chris Kenney, I want to remind everyone that we're planning a significant presence at AES 2021. This is the annual meeting of the American Epilepsy Society held in December. We look forward to presenting additional EXTOL data at this event, including sub-analyses of the responder analysis as well as more detailed safety data in a late-breaking poster presented by Dr. Jackie French, as well as during our sponsored scientific symposium. Activities at AES 2021 include scientific posters related to Exxon 1101, including the late-breaking Extol poster, as well as 496 and Xenon's other earlier-stage preclinical work. We will be participating in a joint industry scientific exhibit relating to rare genetically-defined epilepsies and we will also be sponsoring a scientific symposium featuring a panel discussion with key opinion leaders in adult focal epilepsy space to discuss XTN1101 and the KV mechanism. For those of you who are unable to join us in Chicago this year, we expect to host a conference call and webcast to discuss our presentations at AES, specifically focused on the new analyses within our XTOL data. We will circulate details in a news release closer to the event, and we look forward to connecting with you either in person or virtually. So with those invitations extended, I'd now like to turn the call over to Chris Kenney, and Chris will touch upon some of the highlights from the XTOL data and our XEN 1101 plans moving forward.

Chris? Thanks, Ian. Today I'm going to hit on some of the highlights of the XTOL data, so I encourage listeners to also review the October 4th news release, or you can listen to our webinar from that date as we went into considerable detail around the XTOL top-line results. As a reminder, XTOL was designed as a randomized, double-blind, placebo-controlled ACE2B study to evaluate the clinical efficacy, safety, and tolerability of XCN1101, administered as once-daily adjunctive treatment in adult patients with focal epilepsy. The study results include a total of 325 randomized and treated subjects in the safety population and 323 subjects in the modified intent to treat population for the efficacy analyses. Of the 285 subjects who completed the double-blind period, 96.5% entered the open-label extension to evaluate the long-term safety, tolerability, and effectiveness of XCN 1101. This high rollover rate provides important insight into the comfort of clinicians and their patients with the overall benefit and tolerability profile of XEN-1101. The trial met its primary endpoint with XEN-1101 demonstrating a statistically significant dose-dependent reduction from baseline in monthly focal seizure frequency when compared to placebo, a monotonic dose response with a p-value of less than .001. Key secondary efficacy measures included a pairwise comparison of each active dose to placebo and the proportion of patients who achieved a 50% or greater reduction in monthly focal seizure frequency from baseline. Median percent reduction in monthly focal seizure frequency was 52.8% in the 25 milligram group, 46.4% in the 20 milligram group, and 33.2% in the 10 milligram group compared to 18.2% in the placebo group. These data suggest a clinically meaningful dose-response relationship for XEN-1101 in the adjunctive treatment of focal seizures in adult patients. We believe these data are even more impressive when we take into consideration the history of these patients in terms of their exposure to previous anti-seizure medications and the concomitant anti-seizure medications while on study. In this context, XEN-1101 demonstrated a statistically significant reduction from baseline in monthly focal seizure frequency compared to placebo for all three XEN-1101 doses in pairwise comparisons between each dose and placebo with two-sided p-values of p less than .001 for 25 milligrams versus placebo, p of less than .001 for 20 milligrams versus placebo, and a p-value of .035 for 10 milligrams versus placebo. These efficacy data strongly suggest that XEN-1101 is highly active in the central nervous system. XEN-1101 was generally well tolerated in the study with adverse events consistent with other commonly utilized anti-seizure medications. There were no pigmentary abnormalities reported during the double-blind study or during the open-label extension to date, with 70 subjects now treated more than 12 months. The most common treatment emergent adverse across all XCN 1101 dose groups were dizziness, somnolence, fatigue, and headache. The treatment emergent adverse events rates were consistent with other anti-seizure medications and at rates that were expected. Overall, the safety and tolerability profile of XCN 1101 is in line with other anti-seizure medications and what would be expected given XCN 1101 appears highly active in the central nervous system. To summarize, The EXTOL results demonstrate impressive efficacy of Exxon 1101 for adult patients with focal epilepsy, including those with seizures that are deemed difficult to treat when compared to other clinical trials. In addition, we believe physicians and patients could benefit from Exxon 1101's other important attributes, such as once a day dosing in the evening with no titration. Given Exxon 1101's unique potassium channel mechanism of action and the strength of these we believe Xeon 1101 could play a very important role in treating focal epilepsy in the future. Since announcing the top line data, we have focused on building out our phase three development plans. We anticipate having an end of phase two meeting with FDA in the second quarter of 2022 to support the initiation of our phase three clinical program in adult patients with focal epilepsy, anticipated in the second half of the year. In addition, the Extol open label extension, which has been extended to three years, is expected to continue to generate important long-term data for XCN1101. As Ian noted, we're also expanding the development of XCN1101 to MDD, major depressive disorder. We have a strong scientific rationale based on promising preclinical data, as well as clinical results from both an open-label study and a randomized placebo-controlled clinical trial that explored the targeting of KCNQ2 channels as a treatment for MDD using azogabine, and earlier generation KB7 potassium channel opener that's no longer commercially available. We're collaborating with the School of Medicine at Mount Sinai to conduct an investigator sponsored phase two proof of concept randomized placebo control clinical trial of XEN-1101 for the treatment of major depressive disorder with patient screening and randomization currently underway. Approximately 60 patients with MDD will be randomized in a one-to-one fashion to XEN-1101 or placebo with subjects taking 20 milligrams once a day of either XCN 1101 or placebo over the course of eight weeks. The primary objective is to investigate the effect of XCN 1101 on brain measures of reward using functional magnetic resonance imaging. Secondary endpoints include clinical measures of depression and anhedonia. In addition, we're planning a larger company-sponsored clinical study in major depressive disorder with XCN 1101, which is expected to be initiated in the first half of 2022. Now, a few months ago, I joined Xenon based in part on the promise of Xenon's maturing neurology pipeline, and I couldn't be more excited that the XTOL results exceeded our expectations, which allowed us to accelerate our phase three development program for XEN-1101. As Ian noted, we're committed and focused on advancing XEN-1101, as we believe it could benefit a large number of patients suffering with adult focal epilepsy. With that, I'd like to turn the call to Chris Von Sager, who will share some market research insights shaping our current plans for Axion 1101. Chris, turn it to you.