Xenon Pharmaceuticals Inc.

Thank you for standing by, and welcome to Sinon Pharmaceuticals' 2021 Year-End Financial Results Call. At this time, all participants are in 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 star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star 0. I would now like to hand the conference over to your host, Sherry Olin, Chief Financial Officer of Xenon Pharmaceuticals. Please go ahead.

Good afternoon. Thank you for joining us on our call and webcast to discuss Xenon's year-end 2021 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 Dr. Chris Von Sageren, Xenon's Chief Commercial Officer. Please be advised that during this call, we will make a number of statements that are forward-looking, including statements regarding the 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 at least 2024, 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 Xenon's year-end 2021 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'd like to turn the call over to Ian.

Thanks, Sherry. Good afternoon, everyone. Thanks for joining our call. Today I'll provide a high-level update on our partnered and proprietary programs, and then I'll turn the call over to Chris Kenney, who will provide additional color around our plans for XEN 1101 moving forward. Sherry will conclude our call by briefly summarizing our financial results and anticipated key milestone events ahead. Chris Von Zegern is also on the call to provide his perspective during Q&A. Overall, when we look back on 2021, we are proud of the significant progress we made across our proprietary drug development pipeline and partner programs, including the transformational event of the positive readout of strong efficacy data from our XEN 1101 Phase 2b XTOL clinical trial. We enter 2022 with incredible momentum, with multiple mid- to late-stage clinical programs and important milestone opportunities throughout the year, which we'll discuss today. I'll start by briefly touching on our partner programs. In November, Pacira Biosciences completed its acquisition of Flexion Therapeutics, along with the rights to develop and commercialize XEN402, a NAV1.7 inhibitor. XEN402 is being formulated for extended release from a thermosensitive hydrogel and is now known as PCRX301. PCR has indicated that they expect data in the second quarter of this year from a phase 1b proof of concept trial that is evaluating the safety and tolerability of PCR X301 administered as a single dose in patients undergoing bunionectomy. In addition, I'm pleased to report that our partner programs with Neurocrine Biosciences also continue to advance through development. In January, we received a $15 million regulatory milestone under our collaboration. and Neurocrin now has two separate Phase II clinical trials underway evaluating MBI 921352 in adult patients with focal onset seizures and pediatric patients with SCN8A-related epilepsy. We look forward to keeping you updated as these partner programs reach important milestones. Within our proprietary pipeline, we continue to enroll patients in our pediatric SCN496 Phase III EPIC clinical trials. This phase three randomized double-blind placebo-controlled parallel group global multicenter clinical trial is evaluating the efficacy, safety, and tolerability of XCN496 in approximately 40 pediatric patients aged one month to less than six years with KCNQ2DE. Based on published physician case studies with azogabine and its KV7 mechanism of action, we believe that XCN496 has the potential to address an important unmet medical need for these young patients. As the EPIC trial continues to expand through the onboarding of new sites and new geographical jurisdictions, our clinical team is anticipating the study completion in the first half of 2023. We also continue to make meaningful progress within our XTN 1101 program and have spent considerable time from our XTOL top line data in October 2021, analyzing and presenting additional subgroup analyses, building out a robust PKPD model, evaluating interim safety data in the EXTOL open label extension study, and completing our planning for our Phase 3 program. This is all in preparation for our anticipated end of Phase 2 meeting with FDA in Q2 of this year, and expected initiation of our Phase 3 program in the second half of the year. Before passing the call to Chris, we have had some questions recently from investors on the Biohaven-Kanop preclinical KB deal. We haven't discussed the XEN-1101 preclinical data in some time, but we're happy to provide our perspective as these questions have come up. The first question we've received is the activity of XEN-1101 on GABA-A. XEN-1101 has no activity on GABA-A at 10 micromolar. These experiments on XEN-1101 have been conducted at established CRO labs and are also included in our regulatory filings supporting our clinical studies. And just to put this into context, 10 micromolar is approximately 50-fold higher than the concentrations we reach clinically, so we have no reason to believe that XCN1101 has any GABA activity in a human contributing to either the efficacy or the tolerability of XCN1101. The second question we've received is around in vivo pharmacology and therapeutic index. Comparison across experiments are always challenging, and the data presented on their KB compound, BVH7000, is in a different preclinical species and with different toxological measures than the data they showed for XTN1101 or azogabine. We have chosen to use a much broader number of preclinical efficacy models, and we focused on data generated in the mouse MES model. As the EC50s in this model predicts well the concentrations required to see efficacy in human clinical trials, and this is now being validated with both the Zagabine and XCN1101. The BVH7000 efficacy data presented is in the rat MES model. Rats are known to show efficacy in this model at significantly lower concentrations for the KV mechanism than the mouse. we see roughly a four-fold leftward shift in our EC50s in the rat MES model for the KB mechanism. So bottom line, data generated using different preclinical species and different experimental endpoints cannot be compared. But now moving back to our XTN1101 clinical program, in summary, we have considerable data supporting the role that XTN1101 could play in treating adult patients with focal epilepsy. The XTOL clinical results demonstrated substantial efficacy in a difficult-to-treat patient population, with even more impressive efficacy in some subgroup analyses of patients with less severe disease. A tolerability profile consistent with an active CNS drug, additional clearly differentiating attributes, including an only-in-class mechanism, dosing of one pill once a day with no titration required. Feedback from KOLs and from our proprietary market research shows supports our belief that XTN 1101 has the potential to significantly improve the current standard of care for patients with residual seizure burden, and if approved, would represent a meaningful advancement in the therapeutic armamentarium for this disease. On that note, I'd like to turn the call over to Chris Kenney, who can provide an update on where we are with our phase three plans for XTN 1101, and also on our other phase two proof of concept studies running in parallel. Chris?