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spk04: 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.
spk03: 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.
spk09: 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.
spk00: Chris. Briefly, by way of background, prior to the XTOL top-line readout, we conducted primary market research in a blinded fashion with 50 clinicians ranging from academic epileptologists to high-volume prescribing neurologists and epileptologists across the U.S. This earlier market research underscored the enduring unmet need that remains despite the availability of numerous anti-seizure medications for the treatment of adult FOS. Physicians emphasize that high clinical unmet need exists, particularly among patients who are not well controlled despite being treated with multiple drugs in a polypharmacy approach. The results of our prior market research suggested that the potential profile of XEN1101 was compelling, given an anticipated efficacy profile that at the time was in line with current standard of care. We modeled a 35% reduction in the 25 milligram treatment group, a comparable safety tolerability profile to existing ASMs, along with differentiated ease-of-use attributes such as QD dosing and no titration. Then, following the EXTOL results, we surveyed 148 prescribing epileptologists and neurologists in the U.S. to understand their perspectives on the anticipated XEN-1101 product profile based on the EXTOL data. The surveyed sample following the EXTOL results had prescribing behaviors consistent with the broader U.S. market, and surveyed physicians noted that the efficacy and safety are the most important factors contributing to the treatment decisions for ASMs. Overall, the profile of XEN1101 was very well regarded, and both neurologists and epileptologists viewed the efficacy and tolerability of XEN1101 as potential differentiators. In particular, differential efficacy was cited as a driver of use for XEN1101 across all lines of therapy. Beyond efficacy, QD dosing, no titration, and the novel mechanism of action were viewed favorably to highly favorable compared to current ASMs. In light of the strong efficacy in the overall product profile, physicians indicated comparable utilization of Exxon 1101 to Vimpat, competing for the first branded opportunity for patients with residual seizure burden. Given the substantial efficacy demonstrated in the XTOL results, combined with all we have learned from our market research, We believe the profile of XEN-1101 has the potential to significantly improve the standard of care for patients with residual seizure burden and, if approved, would represent a meaningful advancement in the therapeutic armamentarium for this disease. I'd now like to turn the call over to Sherry, who will provide some financial highlights and a summary of our important milestones ahead. Sherry?
spk04: Thanks, Chris. Today I will focus on some highlights from this quarter's financial statements and would refer you to our news release and 10Q report for further details. Cash and cash equivalents and marketable securities as of September 30, 2021 were $249.6 million compared to $177 million as of December 31, 2020. Subsequent to the quarter, we raised additional net proceeds of approximately $324.3 million net of underwriting discounts and commissions, but before offering expenses in a public offering. As Ian noted, following the XTOL data, we thoroughly analyzed our product portfolio and revisited our cash runway guidance, focusing on our most important programs. Based on current assumptions, which include fully supporting the planned XCN 1101 clinical development program, our XCN 496 Epic Phase III clinical trial, and our preclinical and discovery programs, we anticipate having sufficient cash to fund operations into at least 2024, excluding any revenue generated from existing partnerships or potential new partnering arrangements. Guided by our focus on our proprietary KV7 potassium channel programs, we believe we are in a strong position to execute against our corporate goals. I would refer you to today's press release and our 10Q filing for other specific details from this quarter's financial statements. I'll give you a quick update on our partner programs before reviewing upcoming milestones from our proprietary pipeline. Our two key partners, Neurocrine and Flexion, have made important progress this year. Under our Neurocrine collaboration, there are now two ongoing phase two clinical trials with NBI 921352, including one study in adolescent patients aged 12 years and older with SCN8A developmental and epileptic encephalopathy, and a second study has recently been initiated in adult patients with focal onset seizures. We are excited for these studies to test our hypotheses of selective NAV1.6 inhibition and the impact on seizures in both the genetic gain-of-function patients as well as the broader population of focal epilepsy. Turning to our partners at Flexion, following the decision to expand the study with an additional cohort, Flexion anticipate data in the first quarter of 2022 from a Phase 1B proof-of-concept trial evaluating the safety and tolerability of FX301 in patients undergoing bunionectomy. In addition, looking ahead, key objectives and milestone opportunities in our proprietary pipeline include... Our activities at AES 2021 and the release of additional Phase IIb EXOLE data within a scientific poster presentation and at a scientific symposium. Conducting an end of Phase II meeting with the FDA in the second quarter of 2022 to help guide our Phase III development program for Exxon 1101, which will be initiated in the second half of 2022. continued support for the ongoing investigator-led study examining Exxon 1101 in MDD and the initiation of a larger company-sponsored MDD clinical study in the first half of 2022, continued evaluation of other epilepsy indications well-suited for the future development of Exxon 1101, and the ongoing advancement of our EPIC Phase III clinical trial in pediatric patients with KCNQ2-DEE with estimated completion in the first half of 2023. On behalf of the entire executive team, we are proud of the hard work that led us to this exciting point in Xenon's history. As we look ahead to 2022, we have multiple ongoing Phase II and III clinical trials underway from both our partnered and proprietary programs. I'm excited to keep you updated on our progress as we continue to advance Exeon 1101 and the rest of our neurology-focused pipeline. I'll now ask the operator to open the line for any questions.
spk01: Thank you, Sherry. As a reminder to our audio attendees, if you would like to register a question, please press star followed by the number one on your telephone. If your question has been answered and you would like to withdraw your registration, please press the pound key. Also, please limit yourselves to one question at a time, then re-enter the queue. One moment, please, for the first question. And our first question is from Paul Mattis from Stifel. Your line is now open.
spk11: Hey, thanks for taking our question. This is Alex on for Paul. A couple on 1101 and then one on 007 if that's all right. I guess moving forward with 1101, is your expectation that you would only run one phase three study or are you planning on running two? How are you thinking about that? And then I'll ask a couple follow-ups if that's okay.
spk03: Sounds good, Alex. I'll pass it to Chris Kenny just to talk about... kind of what our proposal will be in front of FDA and the Phase III program in focal epilepsy.
spk09: Yeah, sure. Thanks, Ian. We're certainly going to be going out next year with more details about this, but we're of the opinion that simply conducting one more randomized controlled trial will probably not be sufficient to have a large enough safety database at the time of the NDA submission to increase our chance of success. So we're planning on doing... you know, more than that, and the details of which will be forthcoming. You can imagine, I mean, these are pretty straightforward in terms of their design, and so what you're seeing, you'll see a repeat of what was already done to a large extent, and then something beyond that to return.
spk03: Yeah, I was just going to maybe add to that before you jump in on 007. You know, look, we believe strongly in the strength of the XTOL data, so we will be making our arguments in front of the FDA that this is one of two registration studies, which is, I think, maybe a bit of a nuance on your question. But as Chris mentioned, expect that the Phase III program overall will be broader than just one Phase III trial.
spk11: Yep, makes sense. And then one more on 1101 before 007. But I guess, is there anything gating for your own Phase II MBD study out of the Mount Sinai study, or are you planning to... you know, start that before you might see any more data out of that.
spk03: Chris, do you want to just go through our thought process on our own company-sponsored MDD site?
spk09: Sure. I mean, the quick answer to your question is that there is something gating. The MDD trial at Mount Sinai just began screening and randomization, and we're going to be doing the same shortly. So we're not waiting for any data to initiate.
spk11: Makes sense. And then quickly on 007, I guess, has your view of the molecule changed over the last quarter or so? I mean, any more color that you can give on sort of the prioritization of 1101 and 496 next year? Thanks.
spk03: No, not at all. It's really about prioritization. As you can imagine, a lot of the focus on the 1101 program, we talk about what the Phase III trials will look like, but we're gearing to moving as quickly as we can to get this drug filed and approved. And so there's a massive amount of work both in TOCS as well as ClinPharm, other clinical trials we'll need to run, and all of the CMC work. And those are the competing resources to put those resources on other programs. And so to us, you know, 496 is ongoing, and the broad 1101 development program is the most important objective that we're focused on. So it's really a focus on prioritization and effort there rather than anything specific around 007. We believe the drug's active. We've seen that. We've talked about that publicly. And obviously the investigator-led study has gone slowly, and I think a lot of that was due to COVID impacts that we've seen across clinical development. But we absolutely believe that we're seeing drug activity for 007. Right now we just need to focus our efforts on 1101 and 496.
spk11: Makes sense. Thanks so much.
spk01: Reminder again to limit yourself to one question and one follow-up on. Thank you. Next, we have Andrew Cha from Jefferies. Your line is open.
spk05: Okay, great. Thanks for taking my questions. Good afternoon. So my first one is on AES when you present the full data set. You know, you did mention responder analysis, more safety. I mean, I guess my question is could you share more, and if so, I guess, what would you encourage us to focus on as it relates to kind of understanding 1101's competitive profile? And I also want to ask, you know, could we see seizure freedom data, for instance, or even kinetics around efficacy? Just maybe talk a little bit more about that. That would be helpful. And I have a follow-up.
spk03: Thanks. Sure. Maybe, Chris, maybe I'll give a couple comments on AES, and then you jump in as you're close to the details. So, you know, I know you suggested, Andrew, kind of the full data set. The full data set would come in a publication later, but there's definitely going to be more information at AES than in our top-line press release. And we're still receiving, you know, additional data in terms of PK and other things from the study. You know, I had mentioned in my prepared remarks that we'll break down the responder analysis. So to answer your question very specifically, yes, you'll see seizure freedom data and also kind of those bins of those that responded more than 50%, more than 75%, and other bins as well. There's some additional subgroup efficacy analysis that we're interested in that we're running right now also, so you'll probably see some more efficacy data in subgroups as well as more detailed AE tables and overall safety. I think my overall comment, and then I'll pass it to Chris to add, is that nothing changes our view here. I think it's always great to do additional analyses and have additional information presented in scientific forums and at medical meetings, but nothing's changed in terms of our overall view. The top line efficacy, you know, in terms of the dose dependency and the efficacy and what we would expect to see on the safety side, nothing's changed in our views as we get deeper into the data. Chris, anything to add? Oh. Okay, sorry, I just got a note that Chris Kenney just lost connection. So we'll carry on, Andrew. Do you want to go on your second question?
spk05: Hey, thanks. Yeah, thank you for the details. My second one is actually I would love your latest thinking and kind of your appetite around partnerships for 1101. I'm curious if you're keen on licensing out U.S. rights or is it ex-U.S. you're interested in and then A corollary to that is just as I think about EU development and tying that with your upcoming FDA meeting, I don't know. I mean, could there be a scenario where you run one phase three U.S., one phase three global, and then together that's how you can file both an NDA and an MAA down the road at the same time, I guess. Maybe talk about those two dynamics. Thanks. Thanks.
spk03: Yeah, I mean, there's a fair bit there. So I'll give a couple of comments. And maybe, Chris, once again, you can talk a little bit about some of our thinking on the commercial side also. So, Andrew, we don't give guidance on partnering and when we may be in partnering discussions or not. But we are, in terms of our strategic objectives, our goal is to launch 1101 just like to launch 496 in the U.S. market ourselves. We have focused our comments today on an end-of-Phase II meeting and getting feedback from FDA, but we will be doing the same thing with European regulators. We will be going through the process to receive scientific advice, and I think as we get through those meetings, we can answer one of your questions more directly, which is what are going to be the requirements for the NDA and the filing in the U.S. versus the requirements in Europe. And so we'll be able to get into more of those details in 2022. But that's our overall thinking and overall strategy. Chris Fonseca, maybe you can comment a little bit as we think about U.S. commercialization and our forward integration.
spk00: Yeah, Ian, happy to. So when we think about the FOS opportunity on a global basis, the U.S. represents the lion's share of the commercial opportunity, predominantly driven by the differential pricing that one can achieve in the U.S. market. It's our belief that we have the capacity to bring this product to the market in the U.S., built on the backbone of the commercial infrastructure that we'll first have with XEN496. And it's our intention to be able to build and execute within the U.S. market. The European market is a much more challenging one, but also a very meaningful commercial opportunity in its own right for FOS products, and that's an area where we still have work to do to think through the best commercialization strategy to optimize the opportunity in that market as well.
spk05: Thanks for all the color. Congrats on all the progress. Thanks, Andrew.
spk01: Before we proceed, I'd like to ask the speakers first, how is your audio? Is everything fine? Can you hear the questions perfectly?
spk03: The audio is good on our side. We did drop one of our speakers got disconnected, Chris Kenny. So if you can reconnect him, I think he was trying to dial back in. But we can continue on with the Q&A.
spk01: Thank you for confirming that. Sorry, Ian. Our next question is from Mark Goodman, SVB Living. Your line is open.
spk03: Mark, are you there?
spk01: Mark with your question. Next is Brian Abraham from RBC Capital Markets. Your line is open.
spk10: Hey, guys. Thanks so much for taking my questions. On 1101, I'm sort of curious if you've done any additional PKPD and safety analyses since the top-line XTOL data and maybe where that's steering you with respect to potential Phase III dosing as well as dosing for the MDD study. And then I had a quick follow-up.
spk03: Sure, Brian, I'll take that because I think – oh, actually, Chris Kenney, are you back online now? I am. Okay, did you hear the question? Maybe you can, if you heard the question, maybe you can address kind of the PKPD. I know a lot of that stuff is still coming in, and then you're thinking around dose selection for Phase 3 and MDD.
spk09: Yeah, sure. So obviously, you know, the information that we already have is suggestive of which doses we could bring into Phase 3. We're in a very fortunate situation where I think you could make an argument that you could bring any or all of those three doses forward, and we're just trying to figure out which dose or doses would be best. PKPD is certainly a part of that. We're in the process of having that information come in right now. Regarding the safety, we are also spending a lot of time evaluating all the safety data, and much of that will be presented at AES in a more granular format than what you saw in the press release. So we're bringing in all the information, and next year we're going to be more forthcoming about exactly which dose or doses we're bringing into Phase III.
spk10: Got it. And then maybe just a quick follow-up, if I could. You've maybe alluded to broadening out the 1101 program, epilepsy program, given the strength of the data. Just curious if you could expand a little bit on some of the possible other epilepsy indications you might consider, and might this also include going down in age to a pediatric population? Thanks.
spk03: Yeah, Brian, good questions. I'll start, and then Chris Kenney, if you want to join as well. You know, we did a webinar on 1101 in the summer where one of our KOLs talked a lot about the preclinical data. And I think what's fascinating about the KV mechanism and 1101 is just its broad spectrum activity. And so that gives us a lot of confidence combined with the EXTOL data to go into other epilepsy indications in addition to adult focal. We're doing that evaluation right now. There are other large epilepsy markets to give you a bit of an idea. And then specifically around pediatrics, that's another part of our planning. Again, I think many of you will know kind of what the extrapolation guidance is from FDA in terms of expanding the label into younger patients with focal epilepsy, and that's something we're working through right now and we'll be submitting definitely our formal pediatric plans to both FDA and European regulators. Chris, Kenny, anything to add kind of on your thought on expansion?
spk09: Yeah, I mean, it's a similar answer to what I said about doses. I mean, we have the luxury of broad-spectrum activity and preclinical models in conjunction with really robust clinical data and focal-onset seizures. So we're looking at all potential avenues, you can be sure. We'll be sort of specifying what our plans are again next year. Great. Thanks, Chris. Thanks, Ian, for your help.
spk01: Next we have Laura Chico from Wedbridge Securities. Your line is now open.
spk07: Hi, this is Sam. I'm for Laura Chico. Thanks for taking the question. I'm wondering if you can tell me what the communication around the 101 open label extension study. So I'm just curious about how you're thinking about additional updates from that study.
spk03: Thanks, Sam. That's a good question. As we had mentioned in our remarks, you know, it's very common to have 12-month OLEs, but we did extend for XTOL, our open label extension, to three years to generate some of that longer-term safety data. We're not going to have any cuts of the OLE data at AES, so maybe I can just be clear on kind of the near term. And then I expect that we will have some updates from the OLE in 2022. We haven't quite mapped out exactly where that is, but we will be wanting to share some of that data with FDA at the end of phase two meeting. But exactly where that fits in the medical meeting schedule, we haven't mapped out yet. But I would expect that we'll see, we'll be disclosing some additional open label extension data during 2022. Makes sense.
spk07: Thank you. Yeah.
spk01: Next we have Mark Goodman from SVP Living. Your line is open.
spk08: Sorry about that. Not sure what happened, but can you just talk a little bit about the upcoming meeting with FDA that you're planning on having and what are your goals? What are kind of the key questions that you feel like you need to get answered there? Thanks.
spk03: Chris, do you want to address that?
spk09: Sure. One of them Ian already alluded to. So as you take a look at the X-toll data, it's really quite robust, right? And if you take a look at the size of that study and the convincing nature of the efficacy data, we think that there's a reasonable chance that we're considering it as a pivotal trial. We just don't know if FDA agrees with that position or not. So that'll be an important topic. And then the rest of it is sort of the typical stuff that you would expect. So We're planning on doing, you know, at least we're going to do at least one more randomized controlled trial in focal onset seizure, and so we want to run the study design by them for that, although it's pretty basic from study to study, so not expecting any sort of surprises there. We've already talked about, you know, considering other areas of epilepsy besides focal onset seizures, so we're going to want to go through you know, all the implications of that in terms of making sure that they're on board with the study design and what implications there would be from a label perspective. And then, of course, there's toxicology, making sure that you're going to be coming to the NDA with everything that they're going to need to be able to support the clinical program from the tox perspective. And then, of course, clinical pharmacology. So we have a clinical pharmacology plan with several NDA-enabling studies, and we want to make sure that they're They think that what we're doing is sufficient.
spk08: And just so I'm clear, your plan is to do probably two studies, but that's not necessarily because you feel like you need two studies. You really think, and obviously they'll confirm it, but you feel X toll is a pivotal. You only need one more pivotal. The reason you do two studies is not for efficacy. It's really more for just enough safety data. Is that correct?
spk09: The primary driver there is that, you know, if you take a look at the other anti-seizure medications in terms of what they brought to the table at the time of approval, you know, they're fairly robust safety databases. So we don't think that just doing another randomized controlled trial in epilepsy, we think that there would be, you know, a certain amount of regulatory risk there, that it would be a very thin NDA. So we're planning on doing more. And what we're trying to figure out is, you know, what exactly that means and so does that you know what what other areas and epilepsy would we consider etc next all right next we have Yatin Saneha from Guggenheim your line is now open thanks this is Eddie on for Yatin appreciate you guys taking the question on
spk02: So thanks for the IP update. Can you remind us when the composition of matter patent and polymorph patents expire? And do you have any additional patents pending that could extend protection beyond 2040? And then when do you think we could see some MDD data from either the investigator or company-generated studies? Are there any post-hoc analyses from the EXTOL study to support the MDD indication?
spk03: Thanks. Thanks, Eddie. So, yeah, I mean, thanks for the question on IP. I think we've done. an excellent job really identifying other ways to extend exclusivity, and obviously some of the work we've done over the last couple of years is now coming to fruition with some of these patents being issued. So I think many people on the call know the base composition of matter when we acquired the drug with median hatch waxman took us into the 2030s, but we wanted to extend that, and obviously we've had a strategy that so far has been successful focus on the food effect as well as on polymorph. And the polymorph is, you know, polymorphs are compositions in terms of the polymorph patent that's now being issued that gets us out to, you know, 2039, 2040, absent any patent term extension there. We do have other ideas that we are working on, but nothing yet that would take us past that timeframe. We're really focusing on that timeframe. In terms of your MDD question, We haven't guided on this. We believe, although the Sinai study is up and running, meaning that they are screening and they've randomized patients, so that's a really nice progress in the last quarter. And our study will start later, but we expect our study would probably go more quickly because it will be at multiple centers rather than just two. And when we've looked at other companies that have run kind of these phase two proof of concept studies, they've often had data in a reasonable period of time. So if we can get the study up and running, which is our expectation in the first half of next year, I think we could see MDD data in 2023. Appreciate it.
spk02: Thanks for the call.
spk09: There was also a question there about whether XTOL data is needed to inform those studies. I mean, the major driver for the MDD trials is the preclinical data and then the clinical data. The preclinical data with 1101 and then the clinical data with the Zogabine. So we don't necessarily need XTOL data to inform what we want to do.
spk01: Next, we have Tim Lago from William Blair. Your line is now open.
spk12: Hey, guys. This is Lago on for Tim. Thanks for taking the questions. So on the topic of the MDD trials, I realize it's early in the investigator-initiated studies, generally enroll pretty slowly, but is there anything you can say about the enrollment progress or trends there that you're seeing in that study? And then on the company-sponsored one, Have you made progress on the design for that in terms of, you know, I know dosing has been mentioned earlier. Are you going to allow concomitant therapies, any sort of high-level criteria like that that you've decided on?
spk03: Sure, Lachlan. I'll give a couple comments, and then Chris can add as well. You know, we don't give guidance on any of our studies in terms of where we are with enrollment, but I will give the caveat that the investigator study is just up and running now, so it's very, very early days for that, but they have randomized, which is great. And in terms of our study, you know, we've given a little bit of color previously. I think one of the things that we have kind of paused on, although we're making good progress, is just trying to now incorporate our thinking with the XTOL data. So that's really around kind of the final dose selection for our company-sponsored study. In terms of the endpoints, we will not have a functional MRI endpoint, which is the primary endpoint in the IST with Sinai. We'll be focused on the clinical endpoints of depression and anhedonia, and it's currently being designed as a monotherapy study. Chris, any additional color in your thinking?
spk09: I think you covered it. Nothing to add.
spk03: Okay, great.
spk01: Next, we have David Huang from SMBC. Your line is now open. I'll click David to answer the question. Our last question is from Serge Belanger from Needham & Company. Your line is now open.
spk06: Hi. Thanks for squeezing me in. A couple questions. First one on 007. Do you still plan to report results from the ongoing investigator study? And is that a program you could eventually partner? And then secondly, regarding the flexion collaboration, just curious if there's any changes in the economics of that collaboration with the expected change in control of that company. Thank you.
spk03: Thanks, Serge. I'll answer the second one first. So no changes to any of the economics as Flexion is going through their transactions. So the new company would just step into their shoes in terms of the economics. So no change there. In terms of 007, so the IST is continuing and will really be driven by the investigator in terms of her plan to publish data or present data at medical meetings. So I do expect at some point we will see more data from that 007 study. And as I had answered in one of the questions earlier, you know, we believe that the drug is active based on what we've seen. This is an open label study. And so in terms of what our strategic optionality for that asset, I still think we have some Really, today's decision in communication and what we've been focused on internally in our planning is the work that is coming for 1101 and 496 and the focus on that. But we absolutely feel that 007 is an active drug, and we'll continue to support the investigator as she finishes off her study.
spk01: And there are no further questions, and that concludes the Q&A session. I will now turn the call back to Sherry Allen for closing remarks.
spk04: I just wanted to say thank you, everyone, for joining us today. And, operator, we will now end the call.
spk01: And this concludes today's conference call. Thank you all for your participation. Enjoy the rest of your day. Keep safe, and you may now disconnect.
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