Xenon Pharmaceuticals Inc.

Good morning, ladies and gentlemen, and welcome to the Q4 2020 San Antonio Pharmaceuticals Incorporated Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session, and instruction will follow at that time. If anyone should require assistance during the conference, please press star then zero on their touchtone telephone. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host today, Ms. Jody Rates. Ma'am, please go ahead.

Thank you. Good afternoon, everyone. Thanks for joining us on our call and webcast to discuss our financial and operating results for the year ended December 31, 2020. Joining me on today's call are Dr. Simon Pimstone, Xenon's Chief Executive Officer, Ian Mortimer, Xenon's President and Chief Financial Officer, and Sherry Olin, Xenon's Vice President, Finance. As announced in January, this coming June, at the time of the company's annual meeting of shareholders, Simon will be transitioning to his new role as executive chair of Zenon's board. At the same time, Ian will be appointed president and CEO, while Sherry will be appointed chief financial officer. On today's call, you will hear from both Simon and Ian as they provide a corporate update and overview of our clinical development programs. Sherry will provide some high-level financial commentary, and we will then open up your call for questions. Please be advised that during this call, we will make a number of statements that are forward-looking, including statements regarding the anticipated impact and timing of COVID-19 pandemic on our business, research and clinical development plans, and timelines and results of operations, the timing of and results from clinical trials and preclinical development activities of our proprietary and partnered product candidates, the potential efficacy, safety profiles, future development plans, addressable market, regulatory success, and commercial potential of our proprietary and partner product candidates, the anticipated timing of IND or IND equivalent submissions, and the initiation of future clinical trials for our proprietary products and those related to other partner candidates, the efficacy of our clinical trial designs, our ability to successfully develop our proprietary development programs, the timing and results of our and our collaborators' interactions with regulators, the timing and anticipated enrollment in our clinical trials, the potential receipt of milestone payments and royalties from our collaborators, our expectation of having sufficient cash to fund operations into 2023, and the timing of potential publication or presentation of future clinical data. 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 the results of Zenon's 2020 year-end financial results and the accompanying annual report on Form 10-K will be made available under the investor section of our website at www.zenon-pharma.com and filed with the SEC and on CDAR. Now, I would like to turn the call over to Simon.

Thank you, Jody, and good afternoon, everyone, and thank you all for joining us today. I hope everyone is staying safe and well. I would also like to welcome Sherry to today's call. Over the coming months leading up to her transition to CFO in June, you'll have an opportunity to hear her comments on our business and plans moving forward. For my part, as you know, I'm moving into the new role of Executive Chair of Xenon's Board. In this capacity, I'll continue to be very active in the company as Ian leads the day-to-day operations. I couldn't be more excited in making the transition at this time when Xenon is at the strongest point in our history with a talented and capable management team, a neurology pipeline that is one of the most robust in our industry, and meaningful clinical data readouts in the near term. Ian and I have a shared strategic vision, and we are looking forward to the next stage of growth at Xenon. With two of our most advanced proprietary product candidates, XEN1101 and XEN496, currently in phase two and three clinical trials respectively, and numerous earlier clinical and non-clinical assets in development, I'm excited to provide a progress update today. I'd like to begin with some corporate and partner updates, followed by an overview of our clinical development programs. I will then ask Ian to spend some time focusing on XEN1101 including a summary of the new XEN 1101 preclinical data that was presented recently at the Ascent 2021 virtual meeting and how we are thinking about next steps for this program. Before diving into our program updates, I'd like to take a moment to thank Dr. Ernesto Arcadi, our Chief Medical Officer, who will be moving on at the end of April to lead global development for a pharmaceutical company. Ernesto joined us at a time when we began concentrating our clinical efforts on neurological disorders with a particular focus on epilepsy. Perhaps his most impactful legacy will be his work building up our clinical development organization with an experienced team capable of supporting multiple mid- to late-stage clinical trials, and we are grateful for his contributions. With the XEN1101 Phase IIb XTOL study on track for top-line data readout in the third quarter of this year, and with XEN496 Phase III EPIC study now underway, we are looking forward to a very smooth transition. I'm also delighted to announce that Dr. Kenneth Somerville will serve as our interim chief medical officer. A board-certified neurologist, Ken is one of the most experienced epilepsy drug developers in the pharmaceutical industry today, with over 20 years of experience at companies including Abbott, GW, Pfizer, King, UCB, and Schwartz Pharma. He has led phase two and phase three epilepsy trials in the U.S. and made major contributions to multiple successful NDA submissions. In addition to leading the development of Epidiolex to a successful NDA submission for GW Pharmaceuticals, Ken was highly involved in the clinical development of sodium valproate, tyagabine, and lacosamide. Ken's leadership and development experience will be a tremendous asset as we move our clinical development programs forward especially at a time when we are anticipating important data readouts from the EXTOL study and the continued advancement of our Phase III EPIC study. Turning briefly to the latest guidance from our partnered programs, Neurocrine Biosciences anticipates initiating a Phase II clinical trial for NBI 921352 in adolescent patients aged 12 years and older, who have SCN8A developmental and epileptic encephalopathy, otherwise known as SCN8A-DEE, in the third quarter of 2021, and the trial protocol will be amended to include younger pediatric patients aged 2 to 11 years with SCN8A-DEE as soon as the FDA has reviewed and approved additional non-clinical information. In parallel, Neurocrine Biosciences is advancing clinical plans to develop the molecule NBI921352 for the treatment of adult focal epilepsy and expects to initiate a Phase II clinical trial this year. We look forward to keeping you updated on NBI921352 and its progress. Flexion Therapeutics is developing FX301, which consists of XEN402, a xenon NAV1.7 inhibitor, formulated for extended release from a thermosensitive hydrogel to support administration as a peripheral nerve block for control of postoperative pain. Recently, the FDA cleared an IND for FX301, resulting in a milestone payment due to xenon. Flexion has guided that it anticipates initiating a Phase 1B proof-of-concept clinical trial of popliteal fossa block with FX301 in patients undergoing bunionectomy in the first half of 2021, with top-line results potentially available later this year. Moving to our proprietary programs, XEN007 is a CNS-acting CAV2.1 and T-type calcium channel modulator that is being studied in treatment-resistant childhood absence epilepsy, or CAE, in a physician-led Phase II proof-of-concept study. At AES 2020, we presented promising interim data from a small number of patients with all three CAE subjects having completed their maintenance phase of dosing and exhibiting a significant reduction in seizures as measured by seizure diary and confirmed by EEG. In response to COVID-19's impact on recruitment in the study which is ongoing, we are working with our study collaborator to include additional sites and we have adjusted guidance to expect results from a larger data set in the second half of 2021. While the AES 2020 presentation represents a small data set, we believe we are seeing drug activity and seizure reduction and on EEG that is supportive of a broader development plan for XEN007, and we expect to make a decision this year regarding XEN007 in CAE. XEN-496, a proprietary pediatric formulation of the active ingredient izogavine, is being developed for the treatment of KCNQ2 developmental and epileptic encephalopathy, or KCNQ2-DEE. To provide the regulatory backdrop for this program, Xenon has received fast-track designation and orphan drug designation for XEN-496 for the treatment of seizures associated with KCNQ2-DEE from the US FDA, as well as orphan medicinal product designation from the European Commission. We recently initiated a Phase III randomized double-blind placebo-controlled multicenter clinical trial called the EPIC study, evaluating the efficacy, safety, and tolerability of XEN496 administered as adjunctive treatment in approximately 40 pediatric patients aged one month to less than six years with KCNQ2-DEE. We believe XEN496 may be efficacious and address a significant unmet need in this rare, severe pediatric neurodevelopmental disorder based both on its KV7 mechanism of action as well as published case reports from physicians who used izogabine to treat infants and young children with KCNQ2DEE. Advancing this program into phase three is such an important milestone for Xenon, and we believe it is also significant for the physicians, caregivers, families, and patients with KCNQ2DEE. We look forward to keeping you updated on the progress of this epic study. Before I turn the call over to Ian, I'll provide a few comments on XCN1101. We know that the KV mechanism is important in the CNS, and there has been supportive data in a wide variety of therapeutic approaches, including seizure disorders, pain, motor neuron disease, depressive disorders, and tinnitus. This is very common. Many CNS drugs work in a variety of neurological conditions. Within the KV mechanism, we have also seen strong clinical validation with the approval of fluopatine in pain and izogabine in adult focal epilepsy. And in the near term, there will be published randomized clinical data in the high-impact American Journal of Psychiatry related to the use of izogabine in major depressive disorder and anhedonia. There is tremendous validation of the KV mechanism, but to date, a drug with the right pharmaceutical properties has not been developed. We believe that XEN1101, with this drug, we have an opportunity to be the only in-class drug in adult focal epilepsy with the potential to broaden the opportunity into other neurological disorders given XEN1101's attributes following the strong KV scientific and mechanistic rationale and Isogabine's clinical validation. This is an extremely exciting time for the profile of the KV mechanism and for XEN1101. And Ian will provide more details on our approach and future plans. Ian?