Xenon Pharmaceuticals Inc.

Ladies and gentlemen, thank you for standing by and welcome to the first quarter 2021 Zenon Pharmaceuticals Earnings Conference Call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press the star then the one key on your touchtone telephone. Please be advised that today's conference is being recorded. If you recall all your assistants, please press star then zero. I would now like to hand the conference over to your speaker host. Jody Rex, please go ahead.

Thank you. Good afternoon. Thank you for joining us on our call and webcast to discuss our first quarter 2021 financial and operating results. 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 a reminder, 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 Xenon's Board. At the same time, Ian will be appointed President and Chief Executive Officer, while Sherry will be appointed Chief Financial Officer. 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 the 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 profile, future development plans, addressable market, regulatory success, and commercial potential of our proprietary and partnered 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 partnered 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 statements. Today's press release summarizing Zenon's first quarter financial results and the accompanying quarterly report on Form 10Q 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 Ian.

Thanks, Jody, and good afternoon. Thanks, everyone, for joining us. I hope everyone is healthy and well. We have made significant progress over this past quarter and I'm excited to provide an update today as we enter a period of important clinical data readouts over the coming quarters. I'll focus on our two proprietary KV7 programs, XEN 1101 and XEN 496. Later in the call, Simon will update you on our XEN 007 CAE program as well as partner programs with academic and industry collaborators followed by a financial update from Sherry. We'll then open the call up for your questions. So I'll begin with XCN 1101, which is a novel next-gen KV7 modulator being developed for the treatment of epilepsy and potentially other neurological disorders. We are very encouraged about the compelling product profile that is emerging for XCN 1101. In addition to my comments on XCN 1101, Simon will provide some commentary on our work examining XCN 1101 in indications outside of epilepsy. In the near term, Our focus is on the upcoming data readout from our Phase IIb XTOL study. As a reminder, XTOL is designed as a Phase IIb randomized, double-blind, placebo-controlled, multicenter clinical trial to evaluate the efficacy, safety, and tolerability of XCN1101 administered as adjunctive treatment in approximately 300 adult patients with focal epilepsy. The primary endpoint is the median percent change in monthly focal seizure frequency from baseline compared to the treatment period of active versus placebo. We believe that this is a well-powered and well-run study, which gives us confidence in the integrity of the key efficacy endpoints as captured by eDiary. I am pleased to report that we have now completed patient screening with the final patients now in the baseline period of the study. Patient randomization is expected to be complete in June, with top-line data anticipated by the end of the third quarter of this year. Given our current numbers already randomized and those last subjects in baseline, we expect we will randomize more than 300 subjects. This upcoming data readout represents a notable inflection point for Xenon and an opportunity to drive XEN 1101 forward into a late-stage pivotal program. Given this importance, I'd like to expand upon the unique properties and potential advantages associated with XCN 1101. First, some comments on the potential efficacy of XCN 1101. XCN 1101 is based on a previously proven KV mechanism of action with broad anti-seizure activity. We reported strong target engagement in our phase 1B transcranial magnetic stimulation study. Interestingly, from our interviews and research with KOLs and community healthcare providers, we understand that the efficacy of many anti-seizure medications is perceived to be roughly equivalent and that the other ease of use and tolerability attributes are important in prescribing decisions. Therefore, if we obtain efficacy measures that are statistically significant and within the range of other anti-seizure medications, there are a number of other positive attributes of XEN1101 that we believe could further differentiate it within the adult focal epilepsy market. We believe that XEN1101 has the potential to address some key ease of use considerations for physicians, and XEN1101's KV7 mechanism would represent the only drug in its class available on the market. From our discussions, we believe that this unique mechanism of action and currently apparent low DDI risk may be leveraged in a rational polypharmacy approach. We believe Exxon 1101's one pill, once daily dosing may be attractive to both physicians and patients with a forgiving PK profile that may provide coverage for missed doses. Additionally, no drug dose titration is envisaged, which compares favorably to the majority of other therapies used to treat adult focal seizures. Further, given that ASMs are generally perceived as having non-differential efficacy, the safety and tolerability profile is another key treatment driver. XEN-1101 was reported as safe and well-tolerated in a Phase I clinical trial. When taken as an evening dose, the drug CMAX is reached during sleeping hours, and thus patients may avoid some CMAX-related CNS AEs. Additionally, based on the lower than model dropout rates and high conversion to open label extension and extol, we have further reasons to believe that XCN1101 could have competitive safety tolerability properties. Digging in a little deeper into the potential mood benefits of XCN1101, we have strong scientific rationale to further explore major depressive disorder or MDD based on preclinical data and clinical work to date. that supports the use of KV7 modulators for the treatment of depression and anhedonia. If XEN1101 could present a mood benefit beyond its impact on seizures, this added positive effect would also be a key differentiator. And if XEN1101 has a good safety and tolerability profile without psychiatric AEs, this too could potentially encourage its use. On the whole, taking into account our conclusions from preclinical studies and clinical results to date, along with the market research exploring the current gaps in the adult focal epilepsy space, we believe XEN-1101 has a product profile that could be meaningfully differentiated from other anti-seizure medications. Turning now to XEN-496, which is a proprietary pediatric formulation of the active ingredient azogabine, that we're developing for the treatment of KCNQ2 developmental and epileptic encephalopathy, or KCNQ2-DEE, a rare severe pediatric neurodevelopmental disorder. Now in phase three development, XEN496 represents our most advanced program in the clinic, and we have received fast track designation and orphan drug designation in the U.S., as well as orphaned medicinal product designation from the European Commission. Our Phase III EPIC clinical trial is evaluating the efficacy, safety, and tolerability of XCN496 administered as adjunctive treatment in approximately 40 pediatric patients aged one month to less than six years with KCNQ2-DEE. Designed as a randomized, double-blind, placebo-controlled parallel group, multicenter clinical trial enrollment is underway. Our team continues to collaborate with KOLs, physicians, and patient advocacy groups to identify potential patients. We recently hosted a webinar in partnership with the KCNQ2 Cure Alliance Foundation, which featured Dr. John Millichap, our principal investigator of the EPIC study, who outlined study details and answered questions about the clinical trial from the families of the KCNQ2 DEA patients. Based on its KV7 mechanism of action, as well as published physician case studies, we believe that XEN496 has the potential to address an important unmet medical need for these young patients. And we look forward to keeping you updated on the progress of the EPIC study. At this point, I'll ask Simon to provide an update on our work with academic collaborators and industry partners, including the investigator-led studies with both XEN007 and XEN1101. Simon?