Earnings Call: Q2 2020

Aug 6, 2020

Good day, ladies and gentlemen, and welcome to Quarter 220 Sudden 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 instructions will be given at that time. Would now like to turn the call over to Ms. Jodi Rates. Ma'am, the floor is yours. Thank you. Good afternoon. Thanks everyone for joining us on our call and webcast to discuss our second quarter 2020 financial and operating results. Joining me on today's call are Doctor. Simon Pimstone, Xenon's Chief Executive Officer and Ian Mortimer, Xenon's President and Chief Financial Officer. Following this introduction, Simon will give an overview of Xenon's clinical programs and then Ian will provide some high level financial commentary. After that, we will open up the call to your 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 the COVID-nineteen 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 including those related to XEN496, XEN1101, XEN007, and other proprietary products and those related to NBI 921352, FX301 and other partnered product candidates. The potential efficacy, safety profile, future development plans, addressable market, regulatory success and commercial potential of our proprietary and partnered product candidate, 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 and achieve milestones in our proprietary development programs the timing and results of our interactions with regulators, the potential to advance certain of our product candidates directly into phase 2 or later stage clinical trials, the timing and anticipated enrollment in our clinical trials, the progress and potential of our other ongoing development programs, the potential receipt of milestone payments and royalties from our collaborators our expectation of having sufficient cash to fund operations into 2022 and the timing of potential publication or presentation of future clinical 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 Xenon's second quarter of 2020 and the accompanying quarterly report on Form 10 Q are available under the Investors section of our website at www.xenonpharma.com and filed with the SEC and on SEDAR. Now, I would like to turn the call over to Simon. Thank you, Jody, and good afternoon, everyone, and thanks for joining us today. I hope everyone is staying well. Here at Xenon, we continue to manage well as we respond to the global impacts of the COVID-nineteen pandemic. Importantly also have the cash runway to support our near term business objectives. We're looking forward to several key milestone events over the next 12 months including top line data from our XEN1101 Phase IIb clinical trial. The anticipated start of a Phase III clinical trial with XEN496, data from our phase 2 proof of concept trial with XEN007, the expected initiation of a Phase II trial in our partnered program with Neurocrine and the expected initiation of clinical development with FX-three zero one under our agreement with Flexion. Today I'll provide a brief status report on each of our proprietary and partnered programs. First XEN1101, which is a differentiated next generation Kv7 potassium channel modulator that's currently in our phase 2bX Toll clinical trial in the U. S, Canada and Europe. Briefly, this trial is a randomized double blind placebo controlled multicenter study to evaluate the clinical efficacy, safety and tolerability of N1101 administration 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 treatment period of active versus placebo. In the context of the COVID-nineteen pandemic and its impact on ongoing clinical studies, we're in close collaboration with each of the XEN1101 clinical sites in North America and Europe, taking specific direction from their respective clinical guidelines as they relate to new stole clinical trial to include new sites in both existing and new jurisdictions. Although new patients screening and randomization were significantly impacted in the spring due to COVID-nineteen. We have seen a recent increase in screening over the past number of weeks And while screening is not yet back to where it was pre COVID, we believe our presence in multiple jurisdictions with new sites opening is helping to mitigate for expected top line data in the first half of twenty twenty one. Of course, dependent on the ongoing impacts of the COVID-nineteen pandemic on patient enrollment rates in the coming months. In the EXHOLD trial, dropout rates continue to be low with good tolerability continuing to be reported and rollover into the open label extension portion of the study continuing to be very high at over 90% of subjects at a completed the double blind portion of the trial. We also continue to explore potential indications outside of epilepsy that may be well suited for the unique mechanism of action of XEN1101. And we do intend to outline our plans for a phase 2 proof of concept trial as details are firmed up in the is a Kv7 potassium channel modulator that contains the active pharmaceutical ingredient ezogabine, also known as retigabine that we have now reformulated and are developing as a treatment for a rare pediatric neurodevelopmental disorder called KCNQ2 developmental and epileptic encephalopathy or KCNQ2DE. This is a severe pediatric condition for which no medicine has been approved to date. KCNQ2DE is characterized by multiple daily refractory seizures presenting within the 1st week of life with significant neuro developmental impairment that follows. Recent epidemiology statistics indicate 1 in 17,000 live births compared to approximately 112,000 for Dravet syndrome. We have developed our XEN496 program based on a strong genetic rationale, the mechanism of action of XEN496 enhancing the inhibitory muscarinic current through the KCNQ2 channel suggests that ezogabine may be efficacious as a treatment for KCNQ2 DEE which is caused by loss of function mutations in this very channel. This genetic validation is further supported by data from clinical surveys as well as from anecdotal parental and physician feedback that have suggested ezogabine may reduce seizure burden with the potential to improve development and cognition in the severe pediatric population. We have made considerable progress towards our goal to initiate a Phase III clinical trial examining XEN496 in patients with KCNQ2DE. On the regulatory front, the FDA has granted Xenon Fast Track designation for the investigation of XEN496 for the treatment of seizures associated with KCNQ2DE and orphan drug designation for the treatment of KCNQ2DE. The results from our recent pharmacokinetic or PK study of XEN496 and 24 healthy adult volunteers supports our phase 3 development plans. These PK data are comparable to historical PK data for immediate releases ogabine tablets with XEN496 showing similar absorption and elimination curves. We achieved another important milestone recently with the filing of our XEN496 Phase III protocol with the FDA, having implemented recommendations made by the agency in previous interactions, Based on the entirety of the FDA's feedback to date, we anticipate initiating a randomized double blind placebo controlled Phase III clinical trial to evaluate the clinical efficacy, safety and tolerability of XEN496 in pediatric patients with KCNQ2DE. The primary endpoint is expected to be the median is anticipated that approximately 40 patients will be randomized in a blinded manner to either an active treatment group or to placebo. After screening, patients will enter a baseline period to assess the frequency of seizures followed by a titration then a maintenance treatment period and then a post treatment follow-up period. It is expected that there will also be an open label extension period after the double blind portion of the trial. With site selection well underway, we have completed a number of the steps necessary to prepare for the Phase III clinical trial. Including the selection of a CRO, the establishment of a global steering committee, determining the principal investigator for the study is Doctor. John Miller Chap. We're also planning regulatory submissions outside of the U. S. To support the broader clinical development of XEN496. This is an exciting point in a pediatric epilepsy in the KCNQDE population. Before turning From our KB7 programs, I would note that we continue to be present in a virtual format at the premier epilepsy related conferences and meetings I presented an overview of our XEN1101496 programs at the recent Allot Conference on new antiepileptic drugs and devices. And Xenon will present a similar overview on August 27th at the upcoming 2020 epilepsy pipeline conference presented by the epilepsy foundation. Turning now to XEN007 with the active ingredient flunarizine, which is a CNS acting calcium channel modulator that modulates CAF 2.1 and T type calcium channels. Position led single site phase 2 proof of concept study is examining the potential clinical efficacy, safety and tolerability of XEN007 as an adjunctive treatment in pediatric patients diagnosed with treatment resistant childhood absence epilepsy or CAE. Due to the impact of COVID-nineteen on clinical trial enrollments and in particular, the multi month closure of our clinical sites the top line results from the study are now expected in the first half of twenty twenty one. Depending on the final results, CAE may represent an exciting potential orphan indication for future development of XEN007. We're also proud of the progress made by our collaborators. We have an ongoing collaboration with Neurocrine Biosciences to develop treatments for epilepsy. Neurocrine is an exclusive license to XEN901, now known as MBI 921352. A clinical stage selective NAB 1.6 sodium channel inhibitor with potential in SCNHA developmental epileptic encephalopathy or SCN8A DEE as well as other forms of epilepsy. Neurocrine is in indicated that it anticipates filing an IND application with the FDA in the very near term in order to start a Phase 2 clinical trial in SCN8ADE patients in the second half of twenty twenty. This important milestone would trigger a $25,000,000 milestone payment to Xenon upon the FDA acceptance of the IND for NBI 921352 with 55 percent of the amount in the form of an equity investment in Xenon at 15% premium to the 30 day trailing average share price and 45% of the amount in cash. Moving now to our partnership with Flexion Therapeutics who acquired the global rights to develop and commercialize XEN402 an NAB 1.7 inhibitor also known as Funipide. Flexion's preclinical product candidates, which they've termed FX301, consists of XEN402 formulated for extended release from a thermosensitive hydrogel. The initial development of FX301 is intended to support administration as a peripheral nerve block for control of postoperative pain. Flexion anticipates initiating human clinical trials next year in 2021, and we look forward to keeping you informed about this partnered program. Before turning the call over to Ian, I'd also like to take a moment to welcome a new member to the Xenon Leadership team. Earlier this week, Sheila Grant joined us as our Senior Vice President of R&D Operations Reporting To Doctor. Ernesto Akady, our Chief Medical Officer. Sheila has more than 20 years of senior level experience in the pharmaceutical industry most recently at Correvio Pharma Corp. With responsibilities that have encompassed global regulatory, manufacturing and supply chain operations for multiple commercial stage drugs registered in numerous countries. I'm confident Sheila's expertise will support Xenon's growth and maturation as we advance our neurology programs into late stage clinical developments and increase our commercialization efforts. Sheila joins us at a time when I truly believe Xenon is one of the most exciting epilepsy pipelines currently in development. I'm extremely proud of our I believe we at Xenon also have an opportunity to provide leadership by example within our community as we continue to help Employers and employees plan for transitions back to the workplace while safely managing the risks associated with COVID-nineteen. At this point, I'll ask Ian to recap our financial position and to provide some closing commentary before opening up the call to your questions, Ian. Thanks, Simon, and good afternoon, everyone. Specific details within our financial statements are covered in today's press release and our 10 Q filing. But I will provide an overview and conclude with a summary of upcoming milestones. In the second quarter, we reported total revenue of $13,400,000, related to the recognition of $11,900,000 from the license and collaboration agreement we have with Neurocrine. There was no revenue recognized for the same period in 2019. R and D expenses for the quarter were $10,700,000 compared to $8,200,000 for the same period in 2019. The increase of $2,500,000 is primarily attributable to increased spending 1101 and to a lesser extent increased spending on preclinical discovery and other internal program expenses. This was partially offset 2 as clinical development costs are now borne by Neurocrine. G and A expenses for the quarter were $3,300,000 compared to $2,300,000 for the same period in 2019. The increase primarily attributable to increased stock based compensation expense salaries and benefits, insurance premiums and business development expenses, partially offset by a decrease in legal fees for intellectual property protection. This provides a net loss for the The change is primarily attributable to revenue recognized in the quarter ended June 30, 2020, pursuant to the agreement with Neurocrine, partially offset by an increase securities as of June 30, 2020 were $202,800,000 compared to 141 point $4,000,000 as of December 31, 2019. Based on our current assumptions, which include fully supporting the planned clinical development of XEN1101, XEN496 and XEN007. We anticipate having sufficient cash to fund operations into 2022, excluding any revenue generated from existing partnerships or potential new partnering arrangements. Importantly, we believe we have the cash runway to support the business objectives we have outlined today and we continue whole milestone events. We expect to initiate a phase 3 clinical trial for XEN496 in KCNQ2DE later this year. Anticipate a $25,000,000 milestone payment upon FDA acceptance of an IND to be filed by our partner Neurocrine in the near term in order to start a phase 2 clinical trial for MBI-nine twenty one-three fifty two in SCN ADA DE pediatric patients. In the first half of twenty twenty one, we anticipate results from our Phase 2b ex toll clinical trial, examining XEN1101 in adult focal epilepsy. We look forward to the results from the physician led Phase 2 open label study in treatment resistant childhood absence epilepsy with XEN007 anticipated in the first half of twenty twenty one, and we anticipate Flexion's continued development of FX301 to support of up to $9,000,000 through At this point, We have your first question from Mr. Paul Matteis from Stifel. Your line is open. Hey, this is Alex on for Paul. Thanks for taking our questions. A couple from us. I guess the first you mentioned that you're exploring the potential of 1101 in other neurological indications, TPD, just curious if you could give us any more detail there. And if this sort of signals a strategic shift or just some strategic looking into outside of epilepsy moving forward. And then on 7, curious if you could just give us an idea of what the bar is, what you're looking for out of the Phase 2 proof of concept related to sort of standard of care and what you're looking for there in order to move forward? Thanks. Sure. I'll take a stab at this and E and P's comment, it's Simon. Yes, I think in terms of the first question, no, we've been communicating for some time now. We're exploring indications outside of the focal epilepsy indication, which remains our primary indication for this drug. But there's a tremendous amount of literature that's building in the role of the KAV72 and or 3 channel, in neuronal hyper excitability that underlies a number of interesting neurological disorders where hyper excitability appears to perhaps drive, for example, apoptosis in motor neuron disease, in hyper excitability through this channel, mediating pain signaling, hybrid scalability through this channel, thought to have potentially a role in anhedonia and a major depressive disorder. And we know these channels are also expressed in the ear and the hair cells in particular and the potential for treatment. Using a Kv7two modulator for tinnitus is also of interest. So we're looking at a number of these types of disorders. We've been talking about this for some time. It's been an extremely active activity at the company. And we expect pretty soon, I think, to be able to communicate what that plan is. It remains so. The trial continues to progress well, as was updated, tolerability seems very good. We get a high rollover rate, a low dropout rate. So of course, everything's blinded, but data seems consistent with hypothesis going in, the preclinical data, the TMS data, very supportive of epilepsy as an important indication. And of course, there's precedent with ezogabine being the 1st generation drug working very well in focal epilepsy. So, no, the strategy hasn't changed, but we do see some very exciting opportunities outside of focal epilepsy including, by the way, within epilepsy, but outside of epilepsy, how that may impact long term from a commercial standpoint, obviously, that's something we would discuss publicly at the right time, but we certainly don't see any shift in our plan today in developing the structural focal epilepsy primarily clearly furthest ahead. In that indication as well. Yes. Look, it's a this is a single investigator led study, single site study. It isn't it's a non controlled study in the sense that there isn't a, a placebo, but this is an open label study compared to baseline. These are highly refractory patients. So there really is 2 drugs that are primarily used in these patients with childhood absence epilepsy, ethosuximide and sodium valproate. These would be children and adolescents in which those drugs either have not worked to suppress abs on seizures or are not tolerated, which is generally thought to be the case in about a third of these kids. Remember this is a condition that's actually quite prevalent to fix about 40,000, 45,000 kids in the U. S. And it's deemed about 25% to 30% are either refractory or have tolerability concerns with the known drugs. So I think overcoming the refractory nature of this disease given the highly refractory nature of these children, I think, is important. I think the question really goes down to, well, what are we deeming to be potentially clinically meaningful. And I think that's, that's, you know, I think what we'll certainly have more detailed updates over time. But I would say I think in general for disorders like this and similar Sydney for focal epilepsy as well. Clinical meaning meaningful effect is generally one that's deemed to be more than 30% in terms of seizure frequency reduction. And certainly with focal epilepsy, that spread we see in addition with CAE, the spread we see in terms of seizure frequency reduction is median is generally in that 30%, 40% range. And so seeing a reduction in seizures in that range in this refractory population I think would be deemed to be clinically meaningful Of course, seizure freedom rates is important, but this is a relatively small study as we've talked about with about 20 subjects. So we're very excited by this. We think preclinical study data is supportive for flunarizine in this condition. And, we really look forward to data coming out of the study. As I noted in my update, there will be a bit of a delay. This, again, single site study multi month closure with COVID just coming back online, and starting to see patients. And it's just these types of studies, unfortunately, will be impacted in the setting, but I don't think it's going to be a major delay to the program. Great. Thanks so much. The next question from Jefferies. Congrats on the progress. Two questions. The first one is on 1101. I'm curious, can you remind us about the the inpatient visits required for safety assessments and how frequently patients are coming in per the protocol And maybe can you talk about what kind of safety assessments are being done, eye exams, urinary retention, so forth? Any color here would be helpful given I acknowledge we're in a COVID environment. Thanks. And I have a follow-up as well. Yes. I'll take a stab at this and bring you in. It's a tough question. I don't have an exact answer for you, but certainly offline can come back and happy to discuss this further. But we're we're, we've essentially and the reason I say that is, you know, different sites have different requirements. And so as you can imagine, we're not able to implement sort of standard protocols across every site because sites, some are open, some are partially open, some are not open, some are seeing patients back in the clinic. Others are seeing them remotely. And so, and of course, related to that is the fact that I think as I've said earlier with Ian on a call with an investor, I've really never seen actually a clinical study with such incredible gymnastics and the clinical team has done an incredible job in such a short period of time If you think about all the elements here, you mentioned a few. Obviously, questionnaires need to be done. Patients need to be examined. Blood needs to be taken. To be taken, EKGs, blood pressures need to be done, eyes need to be examined, and drug needs to arrive to patients. Now, all of that in the context of sites having different openings, closings, and different protocols. So we've had to really adapt on a, I'd say, not just country by country, but sort of site by site basis. And so I can't give you an exact breakdown of exactly what's being done where and how, but what we feel is that we've maintained the integrity of data in the study, such that we don't believe there's any material impact in the clinical trial from an outcome standpoint or numbers outcome based on maintenance of data integrity. And so we've been able to question subjects. We've been able to examine as needed. We've got nurses coming into homes. We needed to measure blood pressure to do mobile EKGs to take blood, to take urine. We've got drug being delivered by courier from sites into patients' homes, But I think in general, the integrity of the data we feel is sound. There will be obviously a few gaps here and there. We that in every study, let alone in a COVID environment, but none that we believe are going to be materially impacting the outcome integrity of the study in. So comments? Yes. I mean, Andrew, I can provide you a little bit of the detail, on what, the way the protocol was designed. And then, as Simon mentioned, there's a number of adjustments, but none of the adjustments do we believe are, have any impact on the integrity of the data or what the results going to be at the end of the day. So I think really important is that we do have patient visits at screening and baseline because we do need those baseline characteristics Then during the study, there would have been normally weekly, weekly visits. A number of those visits we've moved to the telemedicine visits, but we do want those baseline characteristics. And that's why we saw very few patients, kind of going through screening And remember after your last baseline visit is when you get into the randomization, that's a very important visit to do. And so during Exactly. So during, you know, kind of March, April, May, that's where we saw a significant, kind of reduction, on that. And that's where that's starting to pick up a little bit as sites reopen. And then, and so we have the detailed examination, including an eye exam at that time. So we have those baseline characteristics and the randomization visit then the other ones during the study, a lot of those can be done, remotely and don't all have to be done on-site. Yeah. And then the final visits, of course, we will be getting eye exams done and there may be some instances where there might be a few weeks off again just because of sites opening and closing. But we again, we're not aware of of cases where they're materially measurements are off from a timing standpoint such that we think there won't be a there'll be loss of data integrity It's actually been remarkably well managed. So, you know, look, when sites were closed, which all sites were for a few months, the focus of the trial shifted from screening and randomization to remote monitoring and drug supply and maintenance of data integrity. Now as Ian said, we are seeing sites open. I actually think Europe is probably going to do better than the U. S. In the next few months. I think we've got more of a concern in the U. S. In the development landscape broadly, not just from Xenon. But I think Europe is certainly. And so as we focus new sites, a lot of that new site activity was actually in Europe. That's great to hear. It sounds like you have a great handle on the situation, so I promise to you guys. Maybe if I can ask a follow-up? Sure. In your prepared remarks, I think you said dropout rates continue to be a low tolerability, good, rollover, good. So that's great. So that led us to think I'm curious how often can you guys monitor the blinded safety data? Is it on a can you do it whenever you want or is it just like once per quarter? And then maybe I mean, the team has access to blinded data, obviously, for safety monitoring, it's very important. We need to know sort of once patients drugged and once once blood is drawn, do they have any lab abnormalities once EKGs are done? You don't wait till the end of the study. You don't wait 6 months. So this kind of data is available real time. It's not that we necessarily check every minutes of every day, but no, it's real time. The team is very much on top of this as is the CRO providing oversight. So yeah, I mean, it's this is current as we disclosed to you observations, this is current. Great, great to hear. Your next question comes from the line of Lara Chico from Wedbush. Good afternoon. Thanks for taking the question. I have one with regards to 496. So now that the protocol has been submitted, could you reaffirm your powering assumptions that you've incorporated here. I think also just could you talk a little about your assumptions on subject recruitment and perhaps the pace? I think there's also some early stage gene therapy efforts that are starting to progress towards the clinic, but curious on how you think about the potential impact to recruitment specific to the KCNQ2 space. And then I have one follow-up for you. Laura, I think we're pretty close, we think, in terms of getting kind of final FDA feedback. And our preference has been from the get go is to really set up a call and go through the study in a lot more detail once we've got a final protocol. Again, I always just don't like being in a position where I'm giving you a perspective that may or may not change based on FDA feedback So I would just and given this is not like months months months months away, I would just prefer to hold off on discussions around stats and discussions around design until we've got that feedback. We're optimistic that what we've submitted should be given the go ahead, but we need to see that and we need to see minutes. So we're not far from that. We will definitely communicate in a way that I think will be satisfactory to you and others. In terms of the competitive environment, yes, look, I mean, I think every of these monogenic epilepsies is going to face multiple, administrative modes and multiple modes of treatments. So, yes, there's going to be competition, there's going to be competition in ADA in KCNQ, in Dravet. We see oligo antisense work, gene therapy work, I think, you know, the way I think about Oligo intrathecal or, I think about those modalities probably with 2 two points in mind. One is I think they're going to be pretty long term development programs, meaning I think they're going to have to be very, very cautiously tested in very sort of select patients and they'll have to build a data set over quite a long period of time. I mean, remember you're giving single dose of a drug and you don't have a reversal agent. And so we know, and I've said this publicly many times, we know that most, if not all, anti seizure meds, if given at high enough doses, cause seizures We know that they're dose limiting toxic that observed in animals. And so when we think particularly about ion channels and ion channel biology, We speak about the so called Goldilocks phenomenon. You've got to get it just right. The porridge has to be warm, but not too hot and not too cold. And I think that's very important. As we think about being able to modulate these channels with small molecules, we believe at least it's the approach we've taken. That's not to say oligos and gene therapies don't have a place. I'm sure they do, and I think it's going to take a bit of time. But I think the other point pre patient. I cannot imagine patients who are have not tried drugs, that are designed for these indications I cannot imagine these patients will be going into that type of therapeutic approach early in their epilepsy I have to believe just like the surgery option for very refractory patients, this is probably going to be a later stage option. Now over time, these modalities may show to have a remarkable effect. They may cure the disease. They may do all sorts of things that are positive. We don't know. And if they do, this will be a great outcome for patients. But I think for at least the foreseeable future, there is a place. I think it's limited. I think it's going to be limited very, very, very severe, most refractory and certainly won't be used for a second or third line. Yes. And then Laura, maybe to add to that, so that's good context and background. And then what we're doing to, I would call it maybe more control our own destiny is, you know, we have a very close relationship with the advocacy group with key KOLs in the space. We've identified a number of sites, probably more sites than we'll need. We have a relationship with Invitae on the testing side. There's a number of databases, both within the advocacy group and with some academics that are tracking these children. So we've got multiple angles to identify children and sites to be able to get the study. And if everything goes according to plan, we should be up and running by the end of the year. That's great. And I guess maybe one follow-up to the 1101 study could you maybe walk us through the timeframe in which subjects enter for screening and the elapsed time it takes for them to reach their final visit if they're accepted in the study. And I guess what I'm trying to get at is maybe what's your confidence in hitting that target for first half twenty one readout? Thank you. Going to take that? Yes. The 1 in Guyan, I'll add if needed. Yes. So I'll walk you through kind of the schematic that a patient goes through. What that funnel looks like. And then, you know, your last question on confidence is really, I think it's less about the schematic and more about the pandemic and how enrollment is going to be over the next number of months as we kind of can narrow those confidence intervals on when top line data is going to be. But patients are screened, obviously, sites that we've identified will go through their patient records and identify patients from a screening perspective, if patients meet, you know, essentially all of the criteria in screening, then they'll go into baseline. And the baseline, mirrors the double blind portion. So it's an 8 week baseline. And really one of the main things we're looking at in the baseline period is the number of seizures. So there need a minimum of, of 4 seizures in 28 days and they can't be seizure free for more than 3 weeks of any given period. And so we're just making sure that anything that is from their charts or in the screening actually shows through in the baseline because that's what our statistics are based off of. And then once they go to a randomization visit, the random to active, 1 of the 3 active arms are placebo and then there's 8 weeks of treatment. And then they have an option at the end of the double blind period. They can either roll directly into open label extension. And that would happen immediately or if they choose not to, but we're seeing a very high percentage, as Simon had mentioned previously. If they don't, then there's a 6 week follow-up visit, which is kind of the last piece of data that we need in order to, to complete the study. I think one of the benefits of the study is we are using an electronic diary to capture the efficacy endpoints. And so, you know, much more so than in the paper diary world, we can track when there's missing data points real time So we do expect kind of that cleaning up of the data, you know, and scrubbing and locking the database and getting to top line, should be more efficient than maybe other studies because we should be doing a lot of that or we are doing a lot of that real time throughout the study and not waiting to the end, to see where we are from a quality of data perspective. Your next question comes from the line of Yatin Suneja from Guggenheim Partners. Your line is open. Hey guys, this is Eddie on for Yatin. So just a follow-up on a previous question about sort of collecting metrics and endpoint data in this sort of quarantine teleworking or telemedicine environment, do you have an agreement on how you're accounting for missed data points in the study? And then do you think you'll be able to give more updated or granular guidance before the end of the year on the progress as you get a sense of how the enrollment is going? And then I have a question of 496. So to your second question, yes, we probably will be able to give, updated guidance by end of the, I think as Ian said, I think what's really going to be key for us and everyone else in this industry is is what's going to happen in, you know, over the next 6 months in terms of sites. And, you know, we are certainly on track, in terms of our predictive curves. You know, we've been conservative, we think, in those curves, but you know, sites are closing, all over the world again. You know, we and others are obviously going to be impacted. So, I think by the end of the year, we'll probably have the kind of visibility we'd need based on numbers of recruited subjects and, and guidance, I think, can be narrowed. So in terms of your first question. I do not believe we have a formal regulatory agreement on, as I'll just term the data gaps. But I think we spent a ton of time on this internally and with regulatory advisors, and we feel very, very confident including with the CRO, we have actually 2 CROs involved, 1 in Europe and 1 in the U. S. We feel very confident based on all of this review that we don't believe there is going to be any material that immateriality concerns in the, in terms of adequacy of data. Again, there will be some data gaps. I mean, the data gaps in every clinical trial, but we don't believe the data gaps are going to be meaningful to impact regulatory decision being able to be made on the endpoint or the safety assessments for this drug. To add to that, I mean, as I said on the last question, because we have an e diary to measure the efficacy endpoints, it's it's, it's kind of, you know, COVID hasn't been relevant there. So we don't expect any gaps from. So when you think about our primary endpoint as an efficacy endpoint, we don't expect a gap other than, as Simon mentioned, any gaps that you just have in a normal study that someone forgets to fill it out. Yeah. The Wi Fi is down and they can load up it. But then that'll be caught up later. So really any of the moving in person visits to telemedicine, you're going to miss some safety assessments there, right? You know, if you do a telemedicine visit, you're not gonna draw blood unless we have a home health visit. So, we may be missing a couple, you know, some safety points along the way, but I, but I don't again, this is where we've always been clear on the integrity of the efficacy readout. We don't believe that's going to be affected by COVID. And remember, it's a Phase 2 clinical trial as well. So the study is is really the significance is built around and the statistics built around the endpoint as Ian has described, which is I think, you know, extremely low if any risk because of its electronic capability. And so while there might be some gaps in the safety and Alice of blood pressure here or there that may not have been done in time or a missed eye exam in the patient. Those in the context of a study this size, again, firstly, they're always observed. And I don't think we're going to have much different from COVID. And certainly it's not going to impact the ability to read the study and determine sort of safety parameters of the drug to allow us to make a decision to proceed or not to proceed to phase 3. Great. Thanks. And just quickly on 496, if the FDA does come back with additional suggestions on the final protocol. What is the timing look like there? Does that sort of reset the clock and then you have to go back to the drawing board or Is there a chance that you could still get started this year? Look, I didn't know. I don't want to sort of I don't want to get specific on this, I just don't know. Look, we do have some drug designation and we've, you know, we've got Fast Track and these of course provide opportunities to go back. Without necessarily having to wait every time for a 30 or 60 day cycle. So there are advantages. That's where the key advantages are of those designations really And of course, we'll use them. Look, we've tried to actually implement in the submission what the FDA guidance has been to us in 2 prior meetings. We had a pre IND meeting. We had a Type C meeting and and I believe a Type B meeting. And I think those gave us good feedback, which we felt was the relevant feedback we needed. So I think I think the risk of there being sort of a really material difference in what we've submitted to what the FDA asked us for I think it's quite low. There may be nuances, but often those can be amended in the final protocol without the study being on hold. So we'll have to just wait and see. I don't think this is a high risk. There's some risk always, but remember, we have had 2 prior meetings with the agency. Great. Thank you so much guys. Yes. And we are planning in terms of the operations of the study. We are planning to initiate that study at least start in the second half of this year. So as we've guided, Could we accommodate a month or 2 delay possibly? I just don't know, it's going to depend. Thanks. Yes, we have your next question from Antonia Moravino from Blum Burton. Your line is open. Hi, there. Just two questions for me. For the new sites that you've opened for 1101, You mentioned that most of the new sites are in Europe. I'm just wondering if you could specify what territories you've opened new sites in. And also how confident are you that the baseline standard of care and patient outcomes will be consistent between sites? And then, my second question, I don't know if you want to disclose at this time, but I'm just wondering for the 496 study in addition to seizure reduction, are you looking at any secondary endpoints that may indicate an improvement in developmental delay in these patients? Or will that not be looked at in this study? Yes. So Antonio, in terms of territories, we haven't disclosed kind of where, but I will say, these territories are well known jurisdictions for epilepsy trials. I said, some of those new sites will be in the US, but there are some in Europe and probably the majority are in Europe, as I said. And but we're very comfortable with the site selected, the region selected. There was a lot of thought that went into it also based on COVID and how sites are doing in those countries. So the team, I think, again, was very thoughtful in the approach here as to what to select. You know, we'll probably be adding ultimately 10 to 20 new sites probably 15 to 20 at the end of the day, which is going to be a good number based on our initial target in and above that. In terms of and so we're comfortable that baseline exams and ability to follow protocol, etcetera, will be will be maintained. I mean, again, these are not sites that have this is their first focal epilepsy trial. That's part of our screening criteria. The not just the quantity of studies, but the quality of studies, obviously, we look at audits, regulatory audits before we look at deviations from a regulatory standpoint at these sites. So we have a, I'd say, a pretty comprehensive checklist as we go into this with our QA clinical group in site selection. In terms of 496, you know, yes, we are interested in secondary endpoint outside of seizure frequency. The study itself, I think, just set expectations is a relatively short study, over a few months. And we're unlikely certainly our expectation is it's unlikely to see an impact in the development cognition, intellectual behavior in a 3 or 4 month clinical setting. But as we talked about earlier, there is this, a high likelihood and certainly we are hoping to have an open label extension as part of the protocol. And we, we will certainly be continuing to follow developmental outcomes, not just throughout trial, but through the open label extension. So again, yes, we are monitoring a number of other outcomes, so what we call comorbidities, not just seizures, impression of change in the parents, behavior, intellect, etcetera, developmental milestones, But I think probably the relevance of those readouts will only be, better understood through and, throughout the open label attention period of the trial. That concludes the Q And A session. I will now turn the call over to Jodi Rates for closing remarks. Thanks everyone for joining us today. Operator, we will now end the call. This concludes today's conference call. Thank you everyone for joining. You may now disconnect.