Q2 2021 Xenon Pharmaceuticals Inc Earnings Call

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Operator: Good day, ladies and gentlemen, and welcome to the Xenon Pharmaceuticals Inc. Earnings Conference Call. At this time, all participants are

Good day, ladies and gentlemen, and welcome to the Q2.2021, Xenon Pharmaceuticals, Inc, earning.

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 follow at that time, if anyone should require assistance. During the conference. Please press Star then zero on your Touchtone telephone as a reminder, this conference call is being recorded.

Operator: and more in a listen-only mode. Later, we will conduct a question-and-answer session.

Operator: Any instructions...

Operator: All of these will follow at that time. If anyone should require assistance...

Operator: I would now like to turn the conference over to your host, Ms. Joanne.

Joanne: Good afternoon. Thanks for joining us on our call and webcast to discuss our second quarter 2021 financial and operating results. Joining me on today's call are Ian Mortimer, Xenon's President and Chief Executive Officer, Simon Pimstone, Executive Chair of Xenon's Board, Sherry Aulin, Xenon's Chief Financial Officer, and Christopher Seggern, Xenon's Chief Commercial Officer. Please be advised that during this call, we will make a number of statements that are forward booking, including statements regarding the anticipated impact and timing of the COVID-19 pandemic on our business, research and clinical development plans and timelines and results of operations, the timing of and results from clinical trials and preclinical development activities of our proprietary and partnered product candidates, the potential efficacy, safety profile, future development plans, addressable market, regulatory success, and commercial potential of our proprietary and partnered product candidates, the anticipated timing of IND or IND equivalent submissions, and the initiation of future clinical trials for our proprietary products and those related to our other partnered candidates.

I would now like to turn the conference over to your host Ms. Jodi rates. Thank you. Please go ahead.

Thank you good afternoon, and thanks for joining us on our call and webcast to discuss our second quarter 2021 financial and operating results. Joining me on today's call are President and Chief Executive Officer, Simon Pinto Executive Chair Xenon Sport Sherri, one nuance Chief Financial Officer.

And Chris one seven <unk> 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 anticipated impact and timing of the COVID-19 pandemic on our business research and clinical development plans and timelines and results of operations.

The timing of and results from clinical trials and preclinical development activities of our proprietary and partnered product candidates the potential efficacy safety profile future development plans addressable market regulatory success and commercial potential of our proprietary and partnered product candidates the anticipated.

The timing of IMD or IND equivalent submissions and the initiation of future clinical trials for our proprietary products and those related to our other partnered candidates the efficacy of our clinical trial designs, our ability to successfully develop our proprietary the proprietary development programs the timing and results of our in our call.

Joanne: 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 loyalty from our collaborators, our expectation of having sufficient cash to fund operations into 2023, and the timing of potential publication or presentation of future clinical data. Four of the statements is 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.

I believe those interactions with regulators the timing and anticipated enrollment in our clinical trials the potential receipt of milestone payments and royalties from our collaborators our expectation of having sufficient cash to fund operations into 2023, and the timing of potential publication or presentation of future.

Cynical 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.

Joanne: Our results may differ materially from those projected on today's call. We undertake no obligation to publicly update any forward-looking statements. Today's press release summarizing Xenon's second 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 FEC and on CDAR. Now, I would like to turn the call over to Ian.

Our results may differ materially from those projected on today's call. We undertake no obligation to publicly update any forward looking statements.

Today's press release summarizing xenon second quarter 2021 financial results and the accompanying quarterly report on Form 10-Q will be made available under the investors section of our website at www Dot two noncash pharma dot com and filed with SEC and on SEDAR now.

Ian C. Mortimer: Jody, and good afternoon everyone, and thanks for joining us today. We continue to make strong progress across our portfolio of proprietary and partnered neurology-focused therapeutic programs. Importantly, we remain on track to report top-line data from our XCN 1101 Phase 2b X-Toll Study in late September or mid-October. In anticipation of this important milestone, we will focus the majority of our attention on Xenon 1101. I will, however, begin with a brief overview of the rest of our proprietary and partner programs.

I would like to turn the call over to him.

Jodi and good afternoon, everyone and thanks for joining US today, we continue to make strong progress across our portfolio of proprietary and partnered neurology focused therapeutic programs.

Accordingly, we remain on track to report topline data from our <unk> 11 O. One phase to be X Tole study in late September to mid October and.

In anticipation of this important milestone we will focus the majority of our attention on actually on 11 to one today I will however, it begin with a brief overview of the rest of our proprietary and partnered programs, although not Simon to provide an update on our <unk> 11 O. One X tole clinical trial, and then I'll provide some commentary on the study design and such.

Ian C. Mortimer: I'll then ask Simon to provide an update on our XEN11-01 XTOL clinical trial, and then I'll provide some commentary on the study design and statistical assumptions. And Chris will provide an overview of the work we've done on the commercial assessment of XEN11-01 and where XEN11-01 could fit into the treatment of adult focal epilepsy. Sherry will provide a financial update, and then we'll open the call up for your questions.

Mr Cola assumptions and Chris will provide an overview of the work we've done on the commercial assessment of <unk> hundred one and were <unk> 11 O one could fit into the treatment of adult focal epilepsy Sherry will provide a financial update and then we'll open the call up for your questions.

Ian C. Mortimer: So I'll start with an update on our non-XEN 1101 programs and partnered assets. Briefly, in our XEN-496 program, site initiation, as well as patient identification and enrollment, continue in our phase three randomized, double-blind, placebo-controlled, parallel-group, multi-center clinical trial called the EPIC study to evaluate the efficacy, safety, and tolerability of XEN-496 in approximately 40 pediatric Based on its KV7 mechanism of action, as well as published physician case studies, we believe that XEN496 has the potential to address an important unmet medical need for these young patients, and we look forward to keeping you updated on the progress of the EPIC study.

So I'll start with an update on our non <unk> hundred one programs and partnered assets briefly in our <unk> for 96 program.

Initiation as well as patient identification and enrollment continue in our phase III randomized double blind placebo controlled parallel group multicenter clinical trial called the epic study to evaluate the efficacy safety and Tolerability of <unk> hundred 96, and approximately 40 pediatric patients.

H, one months to less than six years with KFC in Q2 developmental and epileptic encephalopathy.

Based on its <unk> mechanism of action as well as published physician case studies, we believe that <unk> hundred 96 has the potential to address an important unmet medical need for these young patients and we look forward to keeping you updated on the progress of the epic study.

Ian C. Mortimer: Patient enrollment also continues in the investigator-led Phase 2 proof-of-concept study examining the potential clinical efficacy, safety, and tolerability of XEN007 as a treatment in pediatric patients diagnosed with treatment-resistant absence seizures. This study has enrolled different conditions with Abstinence Seizures, including Jevon Syndrome, Childhood Abstinence Epilepsy, or CAE, and Juvenile Abstinence Epilepsy, or J

Patient enrollment also continues in the investigator led phase II proof of concept study examining the potential clinical efficacy safety and Tolerability of <unk> seven as a treatment in pediatric patients diagnosed with treatment resistant absence seizures. This study has enrolled different conditions with absence.

<unk>, including <unk> syndrome childhood absence, epilepsy, or CAE, and juvenile absence epilepsy or Jay based on the initial data and promising signs of drug activity in three patients with CAE, which we presented at Aes at the end of last year. The goal is to focus future enrollment on childhood in juvenile Epsilon.

Ian C. Mortimer: Based on the initial data and promising signs of drug activity in three patients with CAE, which we presented at AES at the end of last year, the goal is to focus future enrollment on childhood and juvenile absence seizures. The lead investigator has also expanded the study to include an additional Canadian site which is currently screening patients and is also evaluating the addition of other... Additional results from a larger cohort are anticipated by the end of this year, which will help inform our decision regarding the future development of Xenon 007.

Seizures. The lead investigator has also expanded the study to include an additional Canadian site, which is currently screening patients and is also evaluating. The addition of other sites additional results from a larger cohort are anticipated by the end of this year, which will help inform our decision regarding the future development of <unk>.

Zero seven.

In addition to the clinical progress. We have also recently received both orphan drug designation and rare pediatric designation for CAE and these are important milestones for this program.

Ian C. Mortimer: In addition to the clinical progress, we have recently received both orphan drug designation and rare pediatric designation for CAE, and these are important milestones for this program. Moving to our partner programs, where we also expect important milestone events in 2021. NeuroCurrent Biosciences is anticipating the advancement of MBI-921352 into Phase II clinical development, with two efficacy studies expected to initiate this year, one in adult focal seizures, and second in patients older than 12 years of age with SCN8A developmental and epileptic encephalopathy.

Moving to our partnered programs, where we also expect important milestone events in 2021, Neurocrine Biosciences is anticipating the advancement of <unk> 90 to 135, two into phase II clinical development with two efficacy studies expected to initiate this year one in adult focal seizures and second in.

Older than 12 years of age with SPN, eight a developmental and epileptic encephalopathy.

In addition, inflection therapeutics is expecting top line results from its phase one be FX 301 clinical trial in Bunionectomy. Later this year, we look forward to keeping you updated on our collaborators progress.

So now, let's turn our attention to <unk> 1100, one which is a novel Nextgen kv seven modulator being developed for the treatment of epilepsy and potentially other neurologic neurological disorders, where we're looking forward to our topline data from our phase <unk> clinical trial expected in late September to mid October we are in.

Ian C. Mortimer: In addition, Flexion Therapeutics is expecting top-line results from its Phase 1b FX-301 clinical trial in bunionectomy later this year. We look forward to keeping you updated on our collaborators' progress. So now let's turn our attention to XEN11-01, which is a novel next-gen KV7 modulator being developed for the treatment of epilepsy and potentially other neurological disorders, where we're looking forward to our top-line data from our Phase IIb X-Toll clinical trial, expected in late September to mid-October. We are encouraged by the compelling product profile that is emerging for XEN11-01.

<unk> by the compelling product profile that is emerging for <unk> hundred one.

Last month, we hosted a webinar with two leading key opinion leaders in the epilepsy space to discuss the focal epilepsy landscape. The X tole clinical trial and the important attributes of <unk> hundred 11 in one and its potential in the treatment of adult focal epilepsy.

We also disclosed in our quarter today, an update on our strategy to continue to expand the intellectual property protection of <unk> hundred one.

We have recently received allowance of a U S patent application with claims directed to four distinct crystalline forms of <unk> hundred 11 O one and any patent issued from this allowed application is expected to expire in 2040.

In addition, we have a number of pending patent applications, which we believe will continue to provide added protection to <unk> 1100, one. So overall, we're very pleased with the progress we've made on our <unk> 11 O one intellectual property portfolio.

Ian C. Mortimer: Last month, we hosted a webinar with two leading key opinion leaders in the epilepsy space to discuss the focal epilepsy landscape, the ECTL clinical trial, and the important attributes of XCN 1101 and its potential in the treatment of adult focal epilepsy. We also disclosed in our quarterly earnings release today an update on our strategy to continue to expand the intellectual property protection of Xenon 1101. We have recently received allowance of a U.S. patent application with claims directed to four distinct crystalline forms of Xenon 11-01, and any patent issued from this allowed application is expected to expire in 2040.

So at this point I'd like to turn the call over to Simon and he'll provide an overview of our clinical experience to date and the trial design of our phase <unk> study and what we can expect in our topline data press release Simon.

Thank you, Ian and hi, everyone.

As you noted in the near term our focus is on the upcoming data readout from our phase <unk> study.

Today I'll provide a brief overview of some of the clinical development highlights to date that have led us to this important readouts and I'll also discuss our plans regarding the X Tole study top line data release.

Our phase one studies with HCN 11 O one showed a promising drug profile.

<unk> from Phase, one sad and Mad studies demonstrated favorable PK supporting once daily dosing exceeding 1100, one was well tolerated in phase one studies, including at the doses currently being tested in a phase <unk> clinical trial with the majority of Aes being reported as mild and CNS related.

Ian C. Mortimer: In addition, we have a number of pending patent applications, which we believe will continue to provide added protection for XCN 1101. So overall, we're very pleased with the progress we've made on our XCN 1101 Intellectual Property Portfolio. So at this point, I'd like to turn the call over to Simon, and he'll provide an overview of our clinical experience to date and the trial design of our Phase 2b X-Toll study and what we can expect in our top-line data press release.

These dose dependent aes provide additional support of drug activity in the CNS.

In addition to the phase one sad Mad cohorts. We also completed a phase one b transcranial magnetic stimulation or Tms Pharmacodynamic study that showed <unk> 1100, one reduces corticospinal excitability with a strong PK PD relationship.

Simon N. Pimstone: Thank you, Ian, and hi to everyone. Ian, as you noted, in the near term, our focus is on the upcoming data readout from our Phase 2b XTOL study. Today I'll provide a brief overview of some of the clinical development highlights to date that have led us to this important readout, and I'll also discuss our plans regarding the XTOL study top-line data release. Our Phase 1 studies with XEN11-01 showed a promising drug profile.

Although not annualized hit to hit if it was more robust spring compared to that of <unk> in the literature.

Data from the phase one sad Mad and Tms studies together with numerous non clinical in vivo studies inform dose selection in the phase <unk> trial.

<unk> is designed as a double blind placebo controlled multi center phase <unk> clinical trial to evaluate the efficacy safety and Tolerability of <unk> hundred one administered as adjunctive treatment in adult patients with focal epilepsy.

Simon N. Pimstone: Results from Phase 1 SAD and MAD studies demonstrated favorable PK, supporting one's daily dose. Exxon 1101 was well tolerated in Phase 1 studies, including at the doses currently being tested in our Phase 2b clinical trial, with the majority of AEs being reported as mild and CNS-related. Those dependent AEs provide additional support of drug activity in the CNS. In addition to the Phase I SADMAD cohorts, we also completed a Phase Ib transcranial magnetic stimulation, or TMS, pharmacodynamic study that showed Xen 1101 reduces corticospinal excitability with a strong PK-PD relationship. Although not analyzed head-to-head, the effect was more robust when compared to that of Isogavine in the literature.

The primary endpoint is median percent change of MPC in monthly focal seizure frequency from baseline to the eight week double blind treatment period for <unk> compared to placebo.

I'm pleased to report that we have completed the randomization of 326 patients in late June.

Patients have been randomized in a blinded manner to one of three active treatment groups or placebo in a two to one to one to two fashion that being <unk> and 1100.125 milligrams.

And 11 to 120 milligrams extremely liberal on 10 milligrams in placebo in a two to one to one to two fashion with <unk>.

Randomization now complete we anticipate anticipate topline results from the phase <unk> clinical trial and as guided in late September to mid October.

Simon N. Pimstone: Data from the Phase 1 SADMAD and TMS studies together with numerous non-clinical in vivo studies informed dose selection in the Phase 2b EXTOL trial. EXTOL is designed as a double-blind, placebo-controlled, multi-center Phase 2b clinical trial to evaluate the efficacy, safety, and tolerability of XEN1101 administered as adjunctive treatment in adult patients with focal epilepsy. The primary endpoint is the median percent change, or MPC, in monthly focal seizure frequency from baseline to the eight-week double-blind treatment period for XEN1101 compared to placebo.

I would also like to provide a little more detail and what's at minimum we expect to include in the topline press release.

Firstly, we willing to the median percent change each of the four arms of the study and the P values associated with different statistical analyses that Ian will walk through.

In addition, we will present, the 50% responder analysis for the forms of the study is this is a key secondary endpoints we.

We will also provide commentary on the overall safety and Tolerability and given the history with these <unk> discuss any observed urinary aes and pigmentation.

So overall, we expect that we will be in a position upon receipt of top line data to provide information on the key efficacy and tolerability measures in the study and provide our perspective on these data in the context of the opportunity for <unk> and 11 O one to be a novel mechanism for the treatment of refractory focal epilepsy.

Simon N. Pimstone: I'm pleased to report that we have completed the randomization of 326 patients in late June. Patients have been randomized in a blinded manner to one of three active treatment groups or placebo in a 2 to 1 to 1 to 2 fashion, that being XCN1101, 25 milligrams. XEN 1101 20mg, XEN 1101 10mg, and placebo in a 2 to 1 to 1 to 2 fashion. With randomization now complete, we anticipate top-line results from the Phase 2b extra-clinical trial as guided in late September to mid-October. I would also like to provide a little more detail on what, at minimum, we expect to include in the top-line press release.

Yes, I'll ask Ian to comment further on the study design and our modeling and powering assumptions as well as the statistics in back to you great. Thanks Simon.

I will begin with how we design the <unk> study and our powering assumptions as we have discussed previously placebo rates have been going up over time in adult focal epilepsy clinical trials and in this study we modeled at 20% reduction in the MPC in the placebo arm for the active arms, we have modeled a dose response and use the historical as aquavit in clinical data.

As our guide and we've modeled a 25% reduction in MPC for the 10 milligram arm, a 30% reduction for the 20 milligram arm and a 35% reduction for the 25 milligram arm. Our primary statistical analysis takes into consideration all subjects in the study and a monotonic dose response, where the null hypothesis.

Simon N. Pimstone: Firstly, we will include the median percent change, each of the four arms of the study, and the p-values associated with different statistical analyses that Ian will walk through. In addition, we will present the 50% responder analysis for the forms of the study, as this is a key secondary endpoint. We will also provide commentary on overall safety and tolerability and, given the history with Isogabine, discuss any observed urinary AEs and pigmentation

As there is no change between placebo and the active dose groups in the alternative hypothesis is there is a positive dose response, the rejection of the null hypothesis and a statistically significant outcome, which include one dose was better than placebo under these assumptions in our modeling we have good power in the 80% to 90% range.

After this analysis, we will then run pairwise statistical analyses, comparing 25 milligrams to placebo for both MPC and the 50% Responder analysis and then we will move to the other two dose groups. So overall, we feel the study as well conducted and well designed with good power and we're looking forward to the topline data I'd now.

Simon N. Pimstone: So overall, we expect that upon receipt of top-line data to provide information on the key efficacy and tolerability measures in the study and provide our perspective on these data in the context of the opportunity for XN1101 to be a novel mechanism for the treatment of refractory focal epilepsy. I'll pause here.

I'd like to introduce Chris <unk>, Chief Commercial officer, Chris joined Xenon last year as our first CTO previously he was a partner at clear view health care partners, where he oversaw a number of commercial engagements as well as strategic due diligence on in licensing and M&A opportunities. Chris has done an immense amount of work analyzing the commercial opportunity.

<unk> for <unk> hundred one both from primary and secondary market research sources.

So she will share some of those insights today Chris.

Simon N. Pimstone: I'll ask Ian to comment further on the study design and our modeling and powering assumptions as well as the statistics. Ian, back to you. Great.

Thanks, Ian I'm pleased to share some more information from our market research on <unk> one on the call today by way of background, we conducted market research in a blinded fashion with 50 clinicians ranging from academic epileptic logistics to high volume prescribing neurologists in epilepsy.

Ian C. Mortimer: Thanks, Simon. I will begin with how we designed the XTOL study and our driving assumptions. As we've discussed previously, placebo rates have been going up over time in adult focal epilepsy clinical trials, and in this study, we modeled a 20% reduction in the MPC in the placebo arm. For the active arms, we have modeled a dose response and used the historical azogavine clinical data as our guide. We modeled a 25% reduction in MPC for the 10-milligram arm, a 30% reduction for the 20-milligram arm, and a 35% reduction for the 25-milligram arm.

The U S with the goals of pinpointing the drivers of their clinical decision, making understanding the unmet medical need and focal onset seizures and identifying the key attributes desire for future anti seizure medications.

I'll briefly summarize some of the key findings.

First at a high level, our findings indicate that an enduring unmet need remains despite the availability of numerous ASM.

Physicians emphasize that high clinical unmet need exists, particularly among patients who are not well controlled despite being treated with multiple drugs and a polypharmacy approach.

Looking at the <unk> profile opportunity actually on <unk> hundred one is based on our previously proven <unk> mechanism of action with validated anti seizure activity and if approved would be the only drug in its class available on the market.

Ian C. Mortimer: Our primary statistical analysis takes into consideration all subjects in the study in a monotonic dose response, where the null hypothesis is that there is no change between placebo and the active dose groups, and the alternative hypothesis is that there is a positive dose response. The rejection of the null hypothesis and a statistically significant outcome would conclude that one dose is better than placebo. Under these assumptions in our modeling, we have good power in the 88 to 90 percent range. After this analysis, we will then run pairwise statistical analysis, comparing 25 mg Siplicebo for both MPC and the 50% responder analysis, and then we'll move to the other two doses.

From our research we understand that the efficacy of many anti seizure medications is perceived to be roughly equivalent and that other ease of use and tolerability attributes are important in prescribing decisions.

Therefore, if we obtain efficacy measures that are within the range of other anti seizure medications. There are a number of other positive attributes of <unk> 11, and one that we believe could further differentiate it within the adult focal epilepsy market.

From our discussions we believe that this unique mechanism of action and currently apparent low TDI risk may be leveraged and rational polypharmacy approach.

We believe <unk> hundred one's one pill once daily regimen may be attractive to both physicians and patients with a forgiving PK profile that may provide coverage for <unk>.

Christopher E. Von Seggern: So overall, we feel the study is well-conducted and well-designed, with good power, and we're looking forward to the top-line data. I'd now like to introduce Chris von Seggern, Xenon's Chief Commercial Officer. Chris joined Xenon last year as our first CCO. Previously, he was a partner at Clearview Healthcare Partners where he oversaw a number of commercial engagements as well as strategic due diligence on in-licensing and M&A opportunities. Chris has done an immense amount of work analyzing the commercial opportunity for XEN 1101, both from primary and secondary market research sources. And he'll share some of those insights today. Chris.

Additionally, no drug dose titration as anticipated, which compares favorably to the majority of other therapies used to treat adult focal seizures.

Further given that ASM are generally perceived as having non differential efficacy safety and tolerability profile is another key treatment driver.

<unk> was reported as well tolerated in phase one clinical studies when taking isn't evening dose the drug C. Max has reached during the sleeping hours, which made blunt potential C. Max related CNS aes.

Another very important differentiator might be the potential benefits of <unk> hundred one.

We have strong scientific rationale to further explore in major depressive disorder based on preclinical data and clinical work to date that supports the use of <unk> modulators for the treatment of depression and anhedonia.

Christopher E. Von Seggern: Thanks, Ian. I'm pleased to share some more information from our market research on XEN 1101 during the call today. By way of background, we conducted market research in a blinded fashion with 50 clinicians ranging from academic epileptologists to high-volume prescribing neurologists and epileptologists across the U.S. with the goals of pinpointing the drivers of their clinical decision-making, understanding the unmet medical need and full-blown seizures, and identifying the key attributes desired for future antiseizure medications. Today, I'll briefly summarize some of the key findings.

If X again 11, one could present, a mood benefit beyond its impact on seizures. This added positive effect would be a striking differentiator given that many ASM sort of associated with negative symptoms and depression is a common core morbidity and focal onset patients.

Sure.

I Hope this provides us a snapshot of some of our important findings where <unk>. One is clearly differentiated based on its novel mechanism of action.

<unk> low DDI risk one pill once a day no titration potential mood benefits and evening dosing.

We believe these combined attribute stack up well against other ASM is currently available to treat adult focal epilepsy, and we are looking forward to our top line phase <unk> data in the near term.

Ian C. Mortimer: First, at a high level, our findings indicate that an enduring unmet need remains despite the availability of numerous ASM. 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. Looking at the XEN 1101 profile opportunity, XEN 1101 is based on a previously proven KB mechanism of action with validated anti-seizure activity and, if approved, would be the only drug in its class available on the market.

Ian I'll turn things back to you. Thanks.

Thanks, Chris on the hall, taking into account our findings and conclusions from preclinical studies and clinical results to date, along with the market research exploring the current gaps in the adult focal epilepsy space. We believe <unk> hundred 11, <unk> hundred one has a product profile that could be meaningfully differentiated from other anti seizure medications I'll now ask Sherri.

To recap our financial position.

Thanks, Ian and I will.

I'll focus on some highlights from this quarters financial statements and we refer you to our news release and 10-Q report for further details.

Cash and cash equivalents in marketable securities as of June 32021 were $216.5 million compared to 177 million as of December 31, 2020.

Ian C. Mortimer: From our research, we understand that the efficacy of many anti-seizure medications is perceived to be roughly equivalent, and that other ease-of-use and tolerability attributes are important in prescribing decisions. Therefore, if we obtain efficacy measures that are within the range of other anti-seizure medications, there are a number of other positive attributes of XEN-1101 that we believe could further differentiate it within the adult From our discussions, we believe that this unique mechanism of action and currently apparent low EDI risk may be leveraged in a rational polypharmacy approach.

Based on current assumptions, which include fully supporting the <unk> X Tole trial and company sponsored Mbd proof of concept study.

<unk> epic trial, the <unk> seven investigator led proof of concept study as well as funding our preclinical and discovery activities, we anticipate having sufficient cash to fund operations into 2023, excluding any revenue generated from existing partnerships or potential new partnering arrange.

Ian C. Mortimer: We believe XEN 1101's One Pill, Once Daily regimen may be attractive to both physicians and patients, with a forgiving PK profile that may provide coverage for myths. Additionally, no drug dose titration is anticipated, which compares favorably to the majority of other therapies used to treat adult focal seizures. Further, given that ASMs are generally perceived as having non-differential efficacy, the safety and tolerability profile is another key treatment driver. XEN11-01 was reported as well-tolerated in Phase I clinical studies.

We plan to revisit our cash runway guidance post actual data with increased visibility on our spend in 2022 and beyond we expect to have more clarity on partnership milestone revenue in the coming months as well.

Bolstered by our strong balance sheet, we continue to have a lot of flexibility as we manage our business and continue to advance our product candidates.

As of June 32021, there were $41 million 117, 568 common shares 1 million 80, 181 pre funded warrants and 1.016 million series one preferred shares outstanding I would refer you to today's press release, and our 10-Q filing for other.

Ian C. Mortimer: When taken as an evening dose, the drug CMAX is reached during sleeping hours, which may blunt potential CMAX-related CNS AEs. Another very important differentiator might be the potential mood benefits of Xenon 1101. We have a strong scientific rationale to further explore major depressive disorder based on pre-clinical data and clinical work to date that support the use of KB7 modulators for the treatment of depression and anhedonia. If Xenon 1101 could present a mood benefit beyond its impact on seizures, this added positive effect would be a striking differentiator, given that many ASMs are associated with negative mood symptoms, and depression is a common core morbidity in focal onset patients.

Details from this quarter's financial statements at this point I'll turn the call back to Ian who will summarize the key milestone events for anticipating for the remainder of this year.

Thanks, Jerry as we look ahead, our key corporate objectives include importantly, within our <unk> <unk> hundred one phase <unk> clinical trial, we anticipate top line data in late September to mid October the.

The continued advancement of our epic phase III clinical trial in pediatric patients with Casey on Q2 D. A development decision and results from a larger patient cohort by year end from the investigator led <unk> 007 proof of concept study in absence seizures continued support from our partner programs with Neurocrine Biosciences.

Including the anticipated initiation of two phase II clinical trials with MBIA 90 to 135, 2% in 2021 and results from collections FX 301 phase <unk> clinical trial anticipated in late 2021, and we anticipate the initiation of an investigator led phase II proof of concept study as well as ongoing.

In planning for a company sponsored clinical trial examining <unk> hundred one in major depressive disorder, we're incredibly proud of the breadth and depth of our neurology pipeline and equally excited about our upcoming release of topline data from our <unk> hundred one phase <unk> clinical trial I'll now ask the operator to open the line for questions.

Ian C. Mortimer: This focus provides a succinct snapshot of some of our important findings where Xenon 1101 is clearly differentiated based on its novel mechanism of action, apparent low DDI risk, one pill once a day, no titration, potential mood benefits, and evening doses. We believe these combined attributes stack up well against other ASMs currently available to treat adult focal epilepsy, and we are looking forward to our top-line Phase IIb XTOL data in the near term. Ian, I'll turn things back to you.

Operator.

Thank you, Sir ladies and gentlemen, if you have a question at this time. Please press. The Star then the number one key on your Touchtone telephone. If your question has been answered or you wish to remove yourself from the queue. Please press the pound key we ask you to limit yourself to one question and one follow up.

Your first question is from Paul Matthews from Stifel. Your line is open.

Yes.

Ian C. Mortimer: Thanks, Chris. On the whole, taking into account our findings and conclusions from preclinical studies and clinical results to date, along with market research exploring the current gaps in the adult focal epilepsy space, we believe XEN 1101 has a product profile that could be meaningfully differentiated from other anti-seizure medications.

Great. Thanks, so much.

Statistical questions from me, if you don't mind.

Thanks for all the color.

For the primary analysis for the linear regression analysis can you speak a little bit qualitatively to some of the scenarios. There I guess, if the test dose.

Sub clinical or having no effect versus placebo.

Mess up the powering at the highest dose looks good and then second I was wondering if you could comment on the powering specifically as it relates to our pair wise comparison for 25 versus placebo. Thanks, so much.

Ian C. Mortimer: I'll now ask Sherry to recap our financial position. Thanks, Ian. Today, I will focus on some highlights

Thanks, Paul I can I can take both of those.

Sherry Aulin: Thank you for joining us for this week's Financial Statements and I would refer you to our news release and 10-Q report for further details.

So.

What we know about anti NGF electric drugs is generally for.

There are other drugs that we've looked at including <unk>. They have a dose response and so overall, that's our expectation going and we can take advantage of that and as you call. It kind of Theres linear trend tester monotonic dose response, where we can take advantage of including all of the patients in the analysis.

Sherry Aulin: Marketable securities, as of June 30, 2021, were $260,000.

Sherry Aulin: $160.5 million, compared to $177 million as of December 2020.

But that said if the lower doses are not as you say.

They are sub therapeutic from a clinical perspective, we can still show statistical significance. So as long as one dose is better than placebo.

Sherry Aulin: December 31, 2020. Based on current assumptions, which include fully supporting the XTN 1101 XTOL trial and company-sponsored MDD proof-of-concept study, The XCN 496 Epic Trial, and the XCN 007 Investigator-Led Proof of Concept Study, as well as funding our preclinical and discovery activities, we anticipate having sufficient cash to fund operations into 2023, excluding any revenue generated from existing partnerships or potential new We plan to revisit our cash runway guidance post-Exel data with increased visibility on our spend in 2022 and beyond.

The the analysis holds and works to show a positive P value of <unk> <unk> five so we still feel comfortable that it's the right analyses and physical analysis to do and we can still show the differentiation between the high dose and placebo.

Your second question is a good one as a reminder, in Simon went through this in his remarks, because we have a two to one to one to two randomization that means we have more subjects in the high dose group and placebo and Thats really where the power of the study is coming from and although I don't have the numbers directly directly in front of me if we look at the same and.

<unk> on a pair wise comparison for MPC, we will have more than 80% power to detect that separation for 25 milligrams and placebo.

Great. Thank you.

Your next question is from Marc Goodman from <unk> Leerink. Your line is open.

Yes.

Give us a sense of how to think about the 50% responder analysis kind of how you're expecting it and maybe what some of the competition is at that level. Just so we have a sense of.

Sherry Aulin: We expect to have more clarity on partnership milestone revenue in the coming months as well. Bolstered by our strong balance sheet, we continue to have a lot of flexibility as we manage our business and continue to advance our product candidates. As of June 30, 2021, there were 41,117,568 common shares, 1,081,081 pre-funded warrants, and 1,016,000 Series 1 Preferred Shares outstanding. I would refer you to today's press release and our 10-Q filing for other specifics.

When the data comes out.

Thoughts about it.

Second of all the epic study could you just give us a sense of.

Where you are now you mentioned that.

But youre Intuit patient enrollment continues but are we are we talking about getting data next year or is this probably 2023.

Okay great.

Women do you want me I'm happy to handle.

My perspective on the epic study.

And then maybe both of US can give our perspective on the 50% responder analysis.

Thanks, Paul So why don't I start with with Opex.

So mark our goal for this year given.

We were really getting the study up and running.

During COVID-19.

To get a critical mass of sites up and running and we continue to work with our collaborators at <unk> as well as academic centers, where we are where the many of these children with fees developmental and epileptic encephalopathy or now being genotype and an opportunity for us to identify patients to enter into the study.

Ian C. Mortimer: Thank you all for joining us today, and I look forward to hearing your specific details from this quarter's financial statements. At this point, I'll turn the call back to Ian, who will summarize the key milestone events we're anticipating for the remainder of this year.

So this year is about getting sites up and running and additional countries. So we started in the U S and getting our IND approved and getting.

Ian C. Mortimer: Thanks, Sherry. As we look ahead, our key corporate objectives include, importantly, within our XEN11-01 Phase IIb XTOL clinical trial, we anticipate top-line data in late September to mid-October. The continued advancement of our EPIC Phase III clinical trial in pediatric patients with KCNQ2-DEE. A development decision and results from a larger patient cohort by year-end from the investigator-led XCN007 proof-of-concept study in absence seizures. Continued support from our partner programs with Neurocrine Biosciences, including the anticipated initiation of two Phase II clinical trials with MBI-921352 in 2021.

Working with sites in the U S. And then we've already expanded outside of the U S.

In terms of so we said give us till the end of this year. When we have a critical mass of sites and we see where we are for patient enrollment before we give guidance to topline data and we'll be able to give you.

Some some better information and guidance towards the end of this year in terms of kind of where we are directionally.

I don't expect topline data in the next six to 12 months, where it is outside of that is really going to be on how aggressively we can get sites and patients into the study over the next number of quarters. So in our Q3 results in November would be a great time for us to give you an update there.

Simon I don't know if you want to talk about trying to responder analysis and I'm happy to provide my perspective as well.

Yeah, Mark Thanks.

Obviously these vary a little bit from study to study.

But generally.

<unk> with its argument at least in.

Ian C. Mortimer: Results from FLEXION's FX301 Phase I-B clinical trial are anticipated in late 2021, and we anticipate the initiation of an investigator-led, phase two proof of concept study, as well as ongoing planning for a company-sponsored clinical trial examining XEN1101 in major depressants. We are incredibly proud of the breadth and depth of our neurology pipeline and equally excited about our upcoming release of top-line data from our XEN11-01 Phase IIb XTOL clinical trial. I'll now ask the operator to open the line for questions.

Pooled analysis in terms of the 50% responder was generally in that kind of 35, 40% range.

Haven't really set thresholds I don't know what.

What specific to expect.

And of course, as we've said many times before I mean look obviously, we have to have a certain degree of efficacy in the study.

That has to be competitive.

The added benefits of this drug I think are extremely important.

In terms of.

In terms of.

Ease of use characteristics and some of it seems that Chris mentioned, but generally I think if you look at drugs in this space.

Operator: Thank you, sir. Ladies and gentlemen, if you have a question at this time, please press the star and then the number one key on your touchtone telephone.

The impacts and others the previous experience with <unk>.

<unk> been with you have in an adjuvant therapy monotherapy, but current therapy plus added agent.

Operator: Then press the number one key on your touchtone telephone.

Operator: We ask that you limit yourself to one question and one follow-up.

You generally in and around that.

Operator: Your first question is from Paul Matteis from Stifel. Your line is open.

In terms of the 50% responder rate in and around that 35% to 40%.

Ian C. Mortimer: Great, thanks so much. I have two statistical questions for you, if you don't mind, and thanks again for all the color. For the primary analysis, for the linear regression analysis, can you speak a little bit qualitatively about some of the scenarios there? I guess if the 10th dose ends up being subclinical or having no effect versus placebo, does that mess up the powering if the highest dose looks good? And second, I was wondering if you could comment on the powering specifically as it relates to a pairwise comparison of 25 mg versus placebo. Thanks so much. Thanks, Paul. I can take both of those.

Of the of the cohorts at generally placebos seen it around.

High teens to low twenties.

Yeah, and the only thanks, Simon and the only thing that I would add is at least when we've analyzed all of the ASM in adult focal epilepsy is theres remarkable consistency so drugs that in the U S. We look at the MPC and in Europe from a regulated regulator point of view they are looking at the responder analysis.

But one of the things that's really nice about epilepsy as we generally see good consistency in concordance across efficacy endpoints, but we also see that across studies as well a drug that works in phase two generally works in phase III and you have that consistency within a range of efficacy across studies.

Thanks.

Ian C. Mortimer: So, you know, what we know about anti-epileptic drugs is, generally, for other drugs that we've looked at, including azogabine, they have a dose response. And so, overall, that's our expectation going in, and we can take advantage of that in, as you call it, kind of this linear trend test or monotonic dose response, where we can take advantage of including all of the patients in the analysis. But that said, if the lower doses are not, as you say, they're sub-therapeutic from a clinical perspective, we can still show statistical significance. So as long as one dose is better than placebo, the analysis holds and works to show a positive P value of.05.

Your next question is from Andrew <unk> from Jefferies. Your line is open.

Okay. Thanks. Good afternoon first question is.

As investors think about what you could show on safety, obviously CNS related side effects.

Naturally we expected, but based on our phase one can you talk about if you think vision muscular skeletal cardiovascular aes could happen and if they were to happen would that be totally totally fine to you because of the big picture thinking is we should be putting 11 O onto overall safety profile in context with what the.

Other existing drugs show so.

Ian C. Mortimer: So we still feel comfortable that it's the right statistical analysis to do. I think your second question is a good one. As a reminder, and Simon went through this in his remarks, because we have a 2 to 1 to 1 to 2 randomization, that means we have more subjects in the high-dose group and in placebo, and that's really where the power of the study is coming from. And although I don't have the numbers directly in front of me, if we look at the same analysis on a pairwise comparison for MPC, we will have more than 80% power to detect that separation for 25 mg. Great, thank you. Your next question is from Mark Goodman from SVD Lyrinc.

Basically my question is why do you think is relevant for the street to kind of focus on and the safety aspect of the topline release. Thanks.

Sure Simon do you want to take a first crack at diamond market why.

Why don't you and all of that okay. It sounds good.

Yes, Andrew I mean, you've touched upon.

The CNS adverse events, which we will see.

Drugs that get into the CNS.

And and have a dampening of electric electrical activity and have an impact on efficacy and on seizures youre going to see some CNS adverse events things like dizziness, and somnolence fatigue, headache, and even things like blurred vision. So we expect to see we expect to see that and likely in a dose we our anticipation going in.

Would be on a dose dependent manner as well and so we always think about this really in the totality of the data. So we need to see kind of where we are in terms of the overall AE profile and where we are from an efficacy point of view you did mentioned some other adverse events that would be outside of outside of CNS, obviously, we would be.

Ian C. Mortimer: Your line is open. Yes, can you give us a sense of what to think about the 50% responder analysis, kind of how you're expecting it and maybe what some of the competition is at that level, just so we have a sense of when the data comes out, you know, thoughts about it. And second of all, the EPIC study, can you just give us a sense of where you are? I know you mentioned that, you know, you're into it, patient enrollment continues, but are we talking about getting data next year, or is this probably 2023? Thanks. Okay, great. Simon, do you want me?

At those and seeing at what rate they are in whether it's anything concerning.

As a reminder, I think we've discussed this previously we havent seen although there are potassium channels that are expressed in the heart, we haven't seen any cardiac issues.

To date and through phase one.

And we haven't had any concern with any of the other adverse events. We did mention in our remarks earlier, just given the history with those auger being we will be looking at at urinary adverse events and we'll also be looking at pigmentation and we'll be doing we're doing high exams, both at baseline and throw out so all of.

Ian C. Mortimer: I'm happy to handle, give my perspective on the EPIC study. And then maybe both of us can give our perspective on the 50% responder analysis. Okay, yeah.

Those were tracking and we will be able to give information when we're in a topline data.

Great as a follow up second question is can you just remind us what drives your confidence placebo response will in fact be in line or better than what you've modeled I guess.

Ian C. Mortimer: So why don't I start with EPIC? So Mark, you know, our goal for this year, given that we were really getting the study up and running during COVID, was to get a critical mass of sites up and running. You know, we continue to work with our collaborators at Invitae, as well as academic centers where we are, where many of these children with these developmental and epileptic encephalopathies are now being genotyped, and this provides an opportunity for us to identify patients to enter into the study.

In what ways are you trying to control for a.

Placebo response thanks.

Thanks, Andrew So on placebo, obviously, we've as we said in our remarks, we've modeled a 20% reduction, which we think is kind of more contemporary.

Placebo rate that we've seen in studies obviously.

Placebo rate will be an actual rate and audited and so what we're really looking for is the separation between active and placebo and ensuring that we believe that the efficacy for the active drug as clinically medically relevant. So we're really looking for that for that separation.

Ian C. Mortimer: So this year is about getting sites up and running and additional countries. So we started in the U.S. and got our IND approved and started working with sites in the U.S., and then we've already expanded outside of the U.S.

Ian C. Mortimer: So we said give us till the end of this year when we have a critical mass of sites and we see where we are for patient enrollment. Before we give guidance on top-line data, we will be able to give you some better information and guidance towards the end of this year. In terms of kind of where we are directionally, I don't expect top-line data in the next 6 to 12 months. Where it is outside of that is really going to be on how aggressively we can get sites and patients into the study over the next number of quarters.

In terms of managing placebo rates or at least doing what we can for the study there has been a few things one obviously the quality of sites that we go to the jurisdictions. We go to when we analyzed we recognize the placebo rates have gone up in certain non western jurisdictions. So we've been saying, we don't have any clinical trial sites.

In those jurisdictions, where historically have seen higher placebo rates.

We also know our.

Or there is a hypothesis that using an electronic diary for seizure capture has an opportunity to at least ensure that the patient is filling in their diary on a more regular basis and when they are in if they have missing data points. We can follow up on that almost through the CRO and the study coordinators essentially real time.

Ian C. Mortimer: So our Q3 results in November would be a great time for us to give you an update there. Simon, I don't know if you want to talk about this 50% responder analysis, and I'm happy to provide my perspective as well, you know, but generally, what was seeded with this argument, at least in pooled analyses in terms of the 50% responder was, you know, generally in that kind of 35, 40% range. So I don't, you know; we haven't really set a threshold. I don't know what, you know, what specifically to expect.

Whereas with a paper diary, you have less a lot less control there so.

So I think we're doing what we can to to ensure.

We can manage the placebo rate as best we can but I also think that the size of the study and the powering gives us some confidence there.

Very good. Thank you wishing you guys all of that on the topline data. Thanks Andrew.

Ian C. Mortimer: And of course, you know, as we've said many times before, I mean, look, obviously, we have to have a certain degree of efficacy in the study that has to be competitive. But the added benefits of this drug, I think, are extremely important, you know, in terms of, you know, ease of use characteristics and some of the things that Chris mentioned. But generally, I think if you look at drugs in the space, like Limpat and others, and the previous experience with azogabine, where you have in an adjuvant therapy, not monotherapy, but current therapy plus added agent, you're generally in and around that 50% responder rate, in and around that 35% to low 40% of the cohort. Generally, placebo is seen at around high teens to low 20s. Yeah, thanks, Simon.

Your next question is from Yadkin Finito from Guggenheim Partners. Your line is open.

Oh, Hey, guys. Thank you for taking my question one.

One clarification question.

Regarding the powering for the dose response, it's about 88% to 90% power, but sort of across payer right. Its about 80% for the 25 milligram dose confirming that yes.

Yes, so you're asking the question the answer I gave earlier I don't have the powering right in front of me right now I said it would it would be if you do the same analysis paralyzed versus the monotonic dose response, I said that the paralyzed with 25 milligrams would have more than 80% power I don't know the specific number off the top of my head I can I can.

Follow up post call, but theres good power for the 25 milligram arm for that separation with placebo also okay. Very good. Thank you and then do you also plan to look forward two sided P bad news or not.

Ian C. Mortimer: The only thing that I would add is, at least when we've analyzed all of the ASMs in adult focal epilepsy, there's remarkable consistency. So, drugs that, you know, in the U.S., we look at the MPC, and in Europe, from a regulator point of view, they're looking at the responder analysis. But one of the things that's really nice about epilepsy is we generally see good consistency and concordance across efficacy endpoints, but we also see that across studies as well. A drug that works in phase two generally works in phase three, and you have that consistency within a range of efficacy across studies.

That's more of like a post hoc analysis prepare wise.

So the the first analysis under the statistical analysis plan as we've talked about is the monotonic dose response.

That is done on.

On a on a one sided point O five.

And then when we if that is positive and we go to the pairwise analysis, we're still finalizing the SAP that'll be submitted to the FDA in the near term, but the current thinking is then we would we would move to a one sided plano two five because you've now hit your primary statistical analysis.

Operator: Your next question is from Andrew Chai from Jeffries. Your line is open.

And then you would move to the point out 254 for the subsequent analyses starting with <unk> 25 milligrams MPC and responder analysis, and then moving to the other doses I didn't mention this earlier, but I think it's worth noting is that because we have a two to one to one to two randomization.

Operator: Okay, thanks. Good afternoon.

Operator: First question is, you know, as investors think about what 1101 could show on safety, obviously, CNS-related side effects are naturally expected, but, based on phase one, can you talk about whether you think vision, musculoskeletal, cardiovascular, and other AEs could happen, and if they were to happen, would that be totally fine to you? Because the big picture thinking is, you know, we should be putting 1101's overall safety profile in context with what the other existing drugs show. So, basically, my question is, you know, what do you think is relevant for the street to kind of focus on in the safety aspect of this top-line release? Thanks.

We have really good power in the 25 milligram arm, but obviously, we have we have much less power and 20 milligrams and 10 milligrams really based on the sample size in those two arms.

Got it very helpful.

Can you also talk about.

Your expectation is this trial could this be one of the pivotal trials.

Actually in the U S. Given that the endpoint that you are going to be doing in a follow up study in the future and just talk about your expectations.

Ian C. Mortimer: Sure. Simon, do you want to take a first crack at that, and I'm happy to add to it? Ian, why don't you? I'll add.

Yes.

Good question, we got we got quite a bit right now.

So that would be a discussion that we would have with the FDA at an end of phase II meeting.

Ian C. Mortimer: Okay, sounds good. Yeah, Andrew, I mean, you've touched upon the CNS adverse events, which we will see. You know, drugs that get into the CNS and have a dampening of electrical activity and have an impact on efficacy and on seizures, you're going to see some CNS adverse events, things like dizziness, insomnolence, fatigue, headache, and even things like blurred vision. So, we expect to see that, and likely in a dose, you know; our anticipation going in would be in a dose-dependent manner as well.

I mean, obviously, the stronger and the more robust signal I think the better our arguments are in that discussion with the agency we have had regulatory input.

If we have a robust a robust signal.

Value in.

In terms of our discussions with the FDA I think we have a shot at it on whether we need to whether this can be one of the two registration studies are a confirmatory study with one more phase III.

The input we've had is that from in Europe will require two additional studies. So it is likely that we're going to be running two more studies. The real question is will we need to have one of those complete for an NDA filing and then and then there may be a stagger for the second study that will be required in Europe.

Ian C. Mortimer: And so, you know, we always think about this really in the totality of the data. So, we need to see kind of where we are in terms of the overall AE profile and where we are from an efficacy point of view. You mentioned some other adverse events that would be outside of CNS. Obviously, we would be looking at those and seeing at what rate they are and whether it's anything concerning.

Got it one more question and I, probably know how you feel about this and what else do us. So one question that we have recently begun and from investors regarding the protein binding properties of <unk> hundred one which might be a little bit different than it's ever been can you just help us understand if there are any implications of that and what they might be.

Ian C. Mortimer: As a reminder, I think we've discussed this previously. We haven't seen, although there are potassium channels that are expressed in the heart, we haven't seen any cardiac issues to date and through Phase I, and we haven't had any concern with any of the other adverse events.

Sure Yes.

Yes, we've had some questions recently I mean every drug has different protein binding and quite frankly every drug.

As a whole bunch of different pharmaceutical properties and when we're designing a drug pre clinically in our discovery group, we're tracking a number of different attributes of the drug.

Kind of across the board when we not and are looking at not just target engagement and Tolerability, but also how we may predict what the metabolic fate may be in the PK and other things. So every drug is a little bit different we do know that 1100, one has a higher protein binding.

Ian C. Mortimer: We did mention in our remarks earlier, just given the history with azogabine, we will be looking at urinary adverse events, and we'll also be looking at pigmentation, and we're doing skin exams both at baseline and throughout. So, all of those we're tracking, and we'll be able to give information when we get to top-line data.

Then as AGA being.

But we also know that.

That likely provides better PK for the drug as we have higher.

Protein binding and and it's metabolized.

Ian C. Mortimer: As a follow-up, the second question is, can you just remind us what drives your confidence? You know, the placebo response will, in fact, be in line or better than what you've modeled, I guess. In what ways are you trying to control for the placebo response? Thanks, Andrew.

More and more slowly than in comparison to <unk>.

Obviously, we feel super comfortable with all of the data that we've generated and so I think focusing on protein binding is just one piece of information and not something that we pay.

Particularly a lot of attention to is a single data point.

Ian C. Mortimer: So, on placebo, obviously, we've, as we said in our remarks, modeled a 20% reduction, which we think is kind of a contemporary placebo rate that we've seen in studies. Obviously, the placebo rate will be an actual rate, and so what we're really looking for is the separation between active and placebo and ensuring that we believe that the efficacy of the active drug is clinically and medically relevant. So, we're really looking for that separation.

We're getting drug to target, we have very robust activity in pre clinically in a number of different in vivo models. Obviously, we're seeing a very robust effect in the Tms PD assay in healthy volunteers in humans, we're seeing an AE profile, that's consistent with drug getting into the CNS. So overall.

The profile and the attributes the pharmaceutical properties of $11. One we think are very very good.

Very good. Thank you so much good luck. Thank you.

Your next question is from Tim Lugo from William Blair. Your line is open.

Ian C. Mortimer: In terms of managing placebo rates, or at least doing what we can for the study, there were a few things. One, obviously, is the quality of sites that we go to and the jurisdictions we go to. When we analyze, we recognize that placebo rates have gone up in certain non-Western jurisdictions, so we've been saying, you know, we don't have any clinical trial sites in those jurisdictions where we have historically seen higher placebo rates. We also know, or there is a hypothesis, that using an electronic diary for seizure capture has an opportunity to at least ensure that the patient is filling in their diary on a more regular basis, and if they have missing data points, we can follow up on that almost through the CRO and the study coordinators in essentially real time, whereas with a paper diary, you have a lot less control there.

Thanks for taking my question can you comment on the baseline characteristics that you know of as of now are the background is across all arms relatively well balanced.

And can you also maybe talk about how much that's total influenced the company led MTB study maybe how many doses you are looking at in that study.

Sure.

I will yes, I can go through the baseline characteristics or at least give you a little bit of.

More more detail there and then Simon do you want to talk a little bit about how were thinking at least today on the MDT study sure.

So in terms of the baseline characteristics.

A reminder.

<unk> are on background therapy, they need to be on stable background drugs there'll be on 1% to three <unk>.

Antiseizure medicines coming in but that needs to be stable as they come into screening and into baseline then they go through a baseline period, where they need to have a minimum of four seizures on a monthly basis and they can't have any three week period of seizure freedom and.

And so we have an eight week baseline we look at the total number of seizures. They sell it in via electronic diary on how many seizures. They have during that time period, and then we normalize it to a 28 day number and it has to be more than four.

Ian C. Mortimer: So I think we're doing what we can to ensure that we can manage the placebo rate as best we can, but I also think that the size of the study and the powering give us some confidence.

When we've looked at the literature and what we expect from this study is the mediums are going to be obviously higher than that and the medians for the baseline characteristics coming in will be kind of high single digits to low double digits. So think kind of upwards of 10 or just above 10 in terms of the median monthly seizures coming into the study before.

Ian C. Mortimer: Very good. Thank you. Wishing you guys all the best on the top line data. Thanks, Andrew. Your next question is from Yatin Sunidjo from Guggenheim Partners. Your line is open.

Operator: Hey, guys. Thank you for taking my question. One clarification question regarding the powering. So for the dose response, it's about 88 to 90 percent power, but for the first pair-wise, it's about 80 percent for the 25 milligram dose. Just confirming that.

Sure before randomization.

In terms of what ASM is there on I mean, there'll be on a variety of different.

Antiseizure medicines.

Haven't gone.

I haven't gone and kind of looked at the blinded data.

But we expect again that.

We will see a lot of the drugs, obviously that are highly prescribed.

Ian C. Mortimer: No, I – yeah, so, yeah, and the question – the answer I gave earlier is I don't have the powering right in front of me right now. I said it would be – if you do the same analysis pair-wise versus the monotonic dose response, I said that the pair-wise analysis with 25 milligrams would have more than 80 percent power. I don't know the specific number off the top of my head.

Would be the types of drugs that these patients will be on coming into the study.

So maybe I'll pass it to Simon on the MDT and then Tim If you had any more detailed questions on baseline we can come back to that.

Thanks, Tim.

I guess the MDT study, obviously will be a completely distinct design.

Ian C. Mortimer: I can follow up post-call. But there's good power for the 25 milligram arm for that separation with placebo. Okay, very good. Thank you.

And.

In a very different patient population.

I think probably with.

It'll be most helpful and ultimately.

Ian C. Mortimer: And then, do you also plan to look for two-sided p-values, or is that more like a post hoc analysis? [inaudible] So the first analysis under the statistical analysis plan, as we've talked about, is the monotonic dose response. That is done on a one-sided 0.05. And then when we, if that is positive, and we go to the pairwise analysis, we're still finalizing the SAP that'll be submitted to the SBA in the near term, but the current thinking is then we would move to a one-sided 0.025 because you've now hit your primary statistical analysis, and then you would move to the 0.025 for the subsequent analyses, starting with

Setting dose for a sponsored study will be waiting to see what the effect size is at different doses.

What the Tolerability looks like from the study at different doses. So while we're making very good progress on the sponsored study design.

We will wait until we've really got that input.

Topline data to finalize key elements of the AMD trial in terms of the sponsored studies. So I think that's probably going to be with.

It will have its greatest effect other than that so I think we will.

Employee a pretty standard.

<unk> designed to just to make sure that there is an ability to.

Ian C. Mortimer: MPC and responder analysis, and then moving to the other doses. I didn't mention this earlier, but it's worth noting that because we have a 2 to 1 to 1 to 2 randomization, we have really good power in the 25 milligram arm, but obviously, we have much less power in 20 milligrams and 10 milligrams, really based on the sample size in those. Got it, very helpful. Then, can you also talk about your expectations?

How to benchmark this against other agents.

In this controlled study so.

I hope that answers your question.

Sure that's fine I understand the BD is.

Kind of a work in progress.

Going back to the Baselines remind me a thought that there was in the preclinical data, suggesting suggestion of synergistic responses depending on the asm's.

Can you just kind of refresh us on that.

Operator: https://www.youtube.com

Yes, so we've done a.

Battery of vivo Pharmacology studies, where we've looked at the combination.

Operator: [inaudible] It's a good question. We get it quite a bit right now.

Ian C. Mortimer: So that would be a discussion that we would have with the FDA at an end-of-phase 2 meeting. I mean, obviously, the stronger and the more robust the signal, I think the better our arguments are in that discussion with the agency. We have had regulatory input that if we have a robust signal and p-value in terms of our discussions with the FDA, I think we have a shot at it. Whether this can be one of the two registration studies or a confirmatory study with one more phase 3.

11 O one with other than what we would consider a highly prescribed or are well used ASM with different mechanisms. So we've looked at combinations.

<unk> of <unk> hundred one as the only potassium channel modulator being combined with a sodium channel blocker or are in our in <unk> drug like <unk>.

And in all circumstances, when you combine 1100, one with another drug you get.

It looks like.

At least additive efficacy.

So when you dose.

Kind of sub therapeutically for both and then you add them together you get a very very robust.

Ian C. Mortimer: The input we've had is that in Europe, we'll require two additional studies. So it's likely that we're going to be running two more studies. The real question is, will we need one of those complete for an NDA filing, and then there may be a stagger for the second study that would be required in Europe. One more question, and I probably know how you feel about this, Ian, but I'll still ask.

Signal and that cant and Thats not explained by changes in plasma concentrations of the drug. So it's not like we're having one drug at least in these preclinical models is having a DDI effect and changing the concentration of the other drug either way to 11 on one or the drug that we combined it with we.

We havent done actually to run a study that that elucidate synergy are quite large studies some of the effects to look very very robust and look like they may be better than additive, but we haven't defined those preclinical experiments to show a synergy per se, but there were no drugs I think maybe this is more of a.

Ian C. Mortimer: So I think one question that we have recently gotten from investors is regarding the protein-binding properties of 1101, which might be a little bit different than azethamine. Can you just help us understand if there are any implications of that and what they might be? Sure. Yeah, we've had some questions recently.

Point, there were no drugs, regardless of mechanism that didn't have this beneficial effect when combining them with 1100 one.

Okay, great to hear thanks.

Your next question is from David Wong from NBC. Your line is open.

Ian C. Mortimer: I mean, every drug has different protein binding. And quite frankly, every drug has a whole bunch of different pharmaceutical properties. And when we're designing a drug preclinically in our discovery group, we're tracking a number of different attributes of a drug kind of across the board when we are looking not just at target engagement and tolerability but also how we may predict what the metabolic fate may be, and the PK and other things.

Hey, Thanks for taking the question.

So I was just refreshing myself with the slides on your R&D day, and I am just looking at the.

The current therapeutic landscape.

I get where <unk> fits in.

Or where do you think it fits in.

Other branded products in third line plus so the.

The Opry I understand well, but I also see <unk> and <unk> here I'm, a little less familiar with the profile of those agents. So.

I guess my question is what gives you confidence that you'd be able to differentiate against these other branded products.

Ian C. Mortimer: So every drug is a little bit different. We do know that 1101 has higher protein binding than azogabine. But we also know that that likely provides better PK for the drug as we have higher protein binding and it's metabolized more slowly than in comparison to azogabine.

Yes, Thanks, David It's a good question I'll pass it to Chris. He is he can give his perspective and Chris maybe we can talk not just today and specifically, but we should think forward about the time and $111 one would be launched and what the branded market would look like at that point.

Absolutely. It's a great question when we look at the marketplace. There clearly products that are used early in lines of therapy and leverage our asset Tam and Lamotrigine are commonly used as first line but.

Ian C. Mortimer: Obviously, we're seeing a very robust effect in the TMS PD assay in healthy volunteers and humans. And we're seeing an AE profile that's consistent with the drug getting into the CNS. So overall, the profile and the attributes, the pharmaceutic properties of 1101, we think are very, very, very good. Thank you so much, Ian. Good luck with the results. Thank you. Your next question is from Tim Lugo from William Blair. Your line is open.

The majority of patients actually pass through what that is what what would be a first or a second line agent and then end up into this broader paradigm that requires additional ASM to manage the seizure burden and.

The key component within this.

Consideration is that clinicians are looking for alternative mechanisms in order to add to the backbone of therapy to provide additional seizure benefit. So when you think about <unk> is the second generation of <unk> in patients, who do well with that product, but have mood related issues tend to move on to <unk>.

Ian C. Mortimer: Thanks for taking the question. Can you comment on the baseline characteristics that you know of as of now? Are the background ASMs across all arms relatively well-balanced? And can you also maybe talk about how much X-Toll will influence the company-led MDD study and maybe how many doses you're looking at in that study?

As an example, because they want to keep the same mechanism of action <unk> has a different mechanism of action and often is added.

As part of the management profile to try and get patients under control, we feel that exon 11 O one fits in nicely in this.

Ian C. Mortimer: Sure. I will, yeah, I can go through the baseline characteristics or at least give you a little bit of more detail there, and then Simon, do you want to talk a little bit about how we're thinking at least today about the MDD study? Sure.

Future paradigm, where clinicians are looking for additional medicines to add onto that backbone in order to provide.

Greater seizure control for the patients and typically what theyre looking for easy to use products that offer alternative mechanisms of action because if you've not responded to one mechanism of vaccine or you're maintaining therapy on a different mechanism of action rather than switching the ideal approach is to go to a different product and that's one of the.

Ian C. Mortimer: So in terms of the baseline characteristics, a reminder, patients are on background therapy. They need to be on stable background drugs. They'll be on one to three anti-seizure medicines coming in, but that needs to be stable as they come into screening and into baseline. Then they go through a baseline period where they need to have a minimum of four seizures on a monthly basis, and they can't have any three-week periods of seizure freedom.

The real key components in this marketplace and.

An important consideration.

You had mentioned is this landscape will evolve then Pat is commonly used in this marketplace. Today. It is one of the leading branded even in the marketplace is that product loses exclusivity.

Ian C. Mortimer: And so we have an eight-week baseline. We look at the total number of seizures. They fill it in via electronic diary on how many seizures they have during that time period, and then we normalize it to a 28-day number, and it has to be more than four.

Likely we will continue to be used quite widely but it doesn't provide sufficient benefit that all patients will end up being seizure free. So we imagine that actually opens up a space for another branded even as patients continue to require additional anti seizure medications.

Ian C. Mortimer: When we've looked at the literature and what we expect from this study is the medians going to be obviously higher than that, and the medians for the baseline characteristics coming in will be kind of high single digits to low double digits. So think about it, you know, kind of upwards of ten or just above ten in terms of the median monthly seizures coming into the study before before randomization. In terms of what ASMs they're on, I mean they will be on a variety of different anti-seizure medicines.

Great. Thanks, so much that's really helpful.

And then just just a follow up.

With the with the new.

New IP that you are pursuing can you just talk a little bit about with the current I guess prior occurring at.

What your assumptions are there in terms of length of exclusivity and then how much of an expansion that would give you.

Thanks, David.

No.

Ian C. Mortimer: We haven't gone, or I haven't gone and kind of looked at the blinded data, but we expect again that, you know, we'll see a lot of the drugs that are obviously highly prescribed would be the types of drugs that these patients will be on coming into the study. So maybe I'll pass it to Simon on the MDD, and then Tim, if you have any more detailed questions on baseline, we can come back. Yeah, thanks, Jim. I mean...

As a reminder, we brought 11 one in from another company, we Werent the company that did the original composition of matter of filings that took place.

In the late two thousands and so with media and hatch Waxman under the original IP that we had acquired with the asset and it took us into probably kind of the early maybe up to kind of the mid <unk> and so when we bought the.

The molecule and we wanted to continue to build out the IP estate, we've been doing that over the last number of years.

And we've just had as we mentioned today.

A really nice notice of allowance on some claims that.

Simon N. Pimstone: I guess the MDD study obviously will be a completely distinct design and a very different patient population. I think probably where it'll be most helpful in ultimately setting the doses for our sponsored study will be waiting to see what the effect size is at different doses and what the tolerability looks like from the study at different doses. So while we're making very good progress on the sponsored study design, we will wait until we've really got that important top-line data to finalize key elements of the MDD trial in terms of the sponsored study.

We kind of think about them as polymorph claims.

Look at different crystal forms of the drug.

Which which we now have the allowance of claims and so it's really administratively.

We'll get the passion patent issued which would take us out to 2040, and then behind that as we've talked about often with investors. We filed additional intellectual property around other methods of manufacturing and methods of use and also around the food effect, which was something that was not predicted before.

We got into humans and something that was.

Was identified in phase one and we've also filed on that so we're continuing to layer on intellectual property that pushes out that exclusivity exclusivity quite materially.

Simon N. Pimstone: So I think that's probably going to be where it will have its greatest effect. Other than that, I think we will employ a pretty standard MDD design just to make sure that there is the ability to benchmark this against other agents in this controlled study. I hope that answers your question.

Got it thanks for taking the question.

Your next question is from Serge Belanger from Needham <unk> Company. Your line is open.

Hey, good afternoon.

First question is related to the open label study.

Ian C. Mortimer: Sure, that's fine. I understand MDD is kind of a work in progress. And I guess going back to the baselines, remind me, I thought that there was, in the preclinical data, a suggestion of synergistic responses depending on the ASMs. Can you just kind of refresh us on that?

External.

Just curious if you have any updates on the rollover rate if it has changed and I think during the investor Webinar last month.

You mentioned that it had been extended from 12 months to three years.

Ian C. Mortimer: Yeah, so we've done a battery of in vivo pharmacology studies where we looked at the combination of 1101 with other what we consider highly prescribed or well-used ASMs with different mechanisms. So we looked at 1101 as the only potassium channel modulator being combined with a sodium channel blocker or an SV2A drug like levofloxacin. And in all circumstances, when you combine 1101 with another drug, you get what looks like at least additive efficacy.

I'm, just curious about the thinking behind that.

And secondly.

I'm jumping ahead here, but assuming we get positive excellent results over the next 60 ish days.

When you think about the.

Phase III trial, either a single one or two.

Expect to have just one dose or you will still be evaluating multiple doses in the next phase III Charles Thanks.

Thanks, Serge So we haven't given specific numbers on OLED rollover. We have said is that for those patients that get to the end of the double blind portion we have a very high rollover rate much higher than we had predicted are expected going into the study.

Ian C. Mortimer: And so when you dose kind of sub-therapeutically for both and then you add them together, you get a very, very robust signal that's not explained by changes in plasma concentrations of the drug. So it's not like we're having one drug, at least in these preclinical models, that is having a DDI effect and changing the concentration of the other drug either way to 1101 or the drug that we combined it with. We haven't actually done to run a study that elucidates synergy are quite large studies.

And that's been consistent throughout the study.

Earlier this year, we had patients that were coming up against I think it was towards the end of last year. Early this year patients that were coming up to the 12 months. So they've been on drug for the entire open label extension and we were getting requests to extend it and so we made a decision to extend it from 12 months to three years as you mentioned.

And I think one of the reasons, we've done that obviously, we want to continue to generate long term data.

Both from an efficacy point of view, where we can have a bit of an indication of how patients are doing in terms of longer term exposure, but also from the safety and Tolerability and we still got questions around pigmentations given the liability with <unk> that we don't believe has any.

Ian C. Mortimer: Some of the effects look very, very robust and look like they may be better than additive, but we haven't designed those preclinical experiments to show synergy per se. But there were no drugs, regardless of mechanism, that didn't have this beneficial effect when combined with 1101.

Extrapolation to $11, one, but I think the more data that we can collect there and continue to share publicly both with the medical community and with Wall Street is important so that was the thinking behind the extension of the OE.

In terms of phase III and trial design the phase III studies would look very similar to the study in terms of the endpoints.

Operator: Okay, great to hear. Thanks.

Operator: Your next question is from David Wong from SMBC. Your line is open.

In terms of the number of doses I think it's too early to.

Operator: Hey, thanks for taking the questions. So I was just refreshing myself with slides from your R&D day. And I'm just looking at the Current Therapeutic Landscape. I understand where 1101 fits in, or where you think it fits in, but I do see a few other branded products in third-line plots. So, I think Exopri, I understand well, but I also see Aptium and Briviac here. I'm a little less familiar with the profile of those agents, so, you know, my question is, what gives you confidence that you'd be able to differentiate against these other branded products?

To say today until we unblinded ex tall.

Generally we see companies take more than one dose into <unk>.

Phase III, so I think that would be the working hypothesis based on what we know today and generally theres more than one dose on label when you look at some antiseizure medicines.

Thank you.

Your next question is from Antonio <unk> from Bloomberg Your line is open.

Hi, Thanks for taking my question so I just.

One regarding actual.

I know that theyre not formal outcome measures, but just wondering.

Electronic diary, if you're also recording seizure.

<unk> are seizure duration.

Christopher E. Von Seggern: Yeah, thanks, David. It's a good question. I'll pass it to Chris. He can give his perspective. And Chris, maybe we can talk not just today and specifically, but we should think forward about the time and when 1101 would be launched and what the branded market would look like at that point. Absolutely.

Hi.

So Simon.

Simon I don't know if you.

These details a little bit better than me. So I know, we're collecting the types of seizures. So focal seizures can can manifest themselves differently. They can either have awareness or not they can have a motor component or not so we're definitely collecting the type of focal seizure that the patient.

Christopher E. Von Seggern: Absolutely, and it's a great question. When we look at the marketplace, there are clearly products that are used early in lines of therapy, and levofiracetam and limotrigine are commonly used as first line, but the majority of patients actually pass through what would be a first or second line agent and then end up in this broader paradigm that requires additional ASMs to manage the seizure burden. And the key component in this consideration is that clinicians are looking for alternative mechanisms in order to add to the backbone of therapy to provide additional seizure benefit.

Just having but I don't believe we're collecting data because I think it might be challenging for the patient to estimate exactly how long an individual seizure as so I don't think we are asking that question as part of the electronic diary assignment I don't know if <unk> had otherwise I'm happy to follow up.

I think we should follow I don't think we should follow up I'm not sits in on those challenges I know, it's an important.

Measure just from at least a patient perspective can you give a perspective as well.

Christopher E. Von Seggern: So when you think about Breviac, Breviac is a second generation of levofetiracetam, and patients who do well with that product but have mood-related issues tend to move on to Breviac as an example because they want to keep the same mechanism of action. Aptium is a different mechanism of action and is often added as part of the management profile to try and get patients under control. We feel that Exeon 1101 fits in nicely in this future paradigm where clinicians are looking for additional medicines to add to the backbone in order to provide greater seizure control for patients.

Actually interesting that China, it's not often even reported in randomized clinical studies. So I think there are many measures.

Relevant that probably a notch.

<unk> reported on that probably should and I think seizure frequency obviously is key.

Severity and duration of seizures or.

I mean I think.

The point being made is given the subjectivity around this.

Actually quite hard to.

Christopher E. Von Seggern: And typically, what they're looking for are easy-to-use products that offer alternative mechanisms of action because if you've not responded to one mechanism of action or you're maintaining therapy on a different mechanism of action rather than switching, the ideal approach is to go to a different product. And that's one of the real key components of this marketplace. An important consideration, as Ian mentioned, is that this landscape will evolve.

To measure I mean, typically patients do not time.

Seizures, they'll tell you because either seasonal or not but they were one time.

Yeah Okay.

That's the challenge measuring it becomes very very tough.

I am showing no further questions at this time I would now like to turn the conference back to Jodi rates.

Thank you on behalf of Athena and leadership team, we look forward to updating you on our progress over the coming months operator, we will now end the call.

Christopher E. Von Seggern: VinPad is commonly used in this marketplace today. It is one of the leading branded agents in the marketplace. As that product loses exclusivity, it likely will continue to be used quite widely, but it doesn't provide sufficient benefit that all patients will end up being seizure free. So we imagine that that actually opens up a space for another branded agent as patients continue to require additional anti-seizure medication.

Ladies and gentlemen. This concludes today's conference. Thank you for your participation have a wonderful day you may all disconnect.

Okay.

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Operator: Right. Thanks so much.

Ian C. Mortimer: That's really helpful. Then just to follow up, with the new IT that you're pursuing, can you just talk a little bit about, you know, with the current, I guess, prior or current IT, what the assumptions are there in terms of, you know, length of exclusivity, and then with new IP, how much of an extension do you anticipate that would give you? Thanks, David.

Ian C. Mortimer: So, just as a reminder, we brought 1101 in from another company. We weren't the company that did the original composition of matter filings that took place kind of in the late 2000s. And so, with Median Hatch Waxman, you know, under the original IP that we had acquired with the asset, it took us into probably kind of the early, maybe up to kind of the mid-2030s. And so, when we brought the molecule in, we wanted to continue to build out the IP estate.

Ian C. Mortimer: We've been doing that over the last number of years, and we've just had, as we mentioned today, a really nice notice of allowance on some claims that, you know, we kind of think about them as polymorph claims. And also around the food effect, which was something that was not predicted before we got into humans and something that was identified in phase one. And we've also worked on that. So, we're continuing to layer on intellectual property that pushes out that exclusivity quite materially. Thanks.

Operator: Hi, good afternoon. My first question is related to the open label study post-Axol. Just curious if you have any updates on the rollover rate, if it has changed. And I think during the investor webinar last month, you mentioned that it had been extended from 12 months to three years. Just curious about the thinking behind that.

Ian C. Mortimer: And secondly, I'm jumping ahead here, but assuming we get positive expo results over the next 60-ish days, when you think about the... phase 3 trial, either a single one or two, do you expect to have just one dose, or will you still be evaluating multiple doses in the next phase 3 trials? Thanks, Serge.

Ian C. Mortimer: So we haven't given any kind of specific numbers on OLE rollover. What we have said is that for those patients that get to the end of the double blind portion, we have a very high rollover rate, much higher than we had predicted or expected going into the study, and that's been consistent throughout the study. Earlier this year, we had patients that were coming up against, I think it was towards the end of last year or early this year, patients that were coming up to 12 months, so they'd been on the drug for the entire open label extension, and we were getting requests to extend it, and so we made a decision to extend it from 12 months to 3 years, as you mentioned. And I think sharing publicly, both with the medical community and with Wall Street, is So that was the thinking behind the extension of the OLE.

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Operator: Phase 3 studies would look very similar to this study in terms of the endpoints and the number of doses. I think it's too early to say today until we unblind the extol. Generally, we see companies take more than one dose into Phase 3, so I think that would be the working hypothesis based on what we know today. And generally, there's more than one dose on the label when you look at anti-seizure medications.

Operator: Your next question is from Antonia Borovina from Bloomberton. Your line is open. Hi, hello, thanks for taking my question. So I just have one regarding XTOL. I know that they're not formal outcome measures, but just wondering, in the electronic diary, if you're also recording seizure severity or seizure duration?

Operator: Thank you for joining us today. Have a great day!

Ian C. Mortimer: I – so we're – Simon, I don't know if you know these details a little bit better than me, but I know we're collecting the types of seizures. So focal seizures can manifest themselves differently. They can either have awareness or not. They can have a motor component or not.

Simon N. Pimstone: So we're definitely collecting the type of focal seizure that the patient is having. But I don't believe we're collecting data, because I think it might be challenging for the patient to estimate exactly how long an individual seizure is. So I don't think we're asking that question as part of the electronic diary. Simon, I don't know off the top of your head.

Simon N. Pimstone: Otherwise, I'm happy to follow-up. Yeah, I think we should follow-up. But I'm not certain.

Operator: I know there are challenges, but I know it's an important measure just from at least a patient perspective and a caregiver perspective as well. Actually, interestingly, Antonio, it's not often even reported in randomized clinical studies. I think there are many measures that are relevant that are probably not generally reported on that probably should be. And I think seizure frequency obviously is key, but severity and duration of seizures are important. I mean, you know, I think the point Ian made is given the subjectivity around this.

Operator: Actually, quite hard to measure. I mean, typically, patients do not find their seizures. They'll tell you if they have a seizure or not, but they won't time it. So that's the challenge. Measuring it becomes very, very tough.

Operator: I'm showing no further questions at this time. I would now like to turn the conference back to Jody Ray.

Operator: Operator, we will now end the call. Ladies and gentlemen, this concludes today's conference.

Operator: Ladies and gentlemen, this concludes today's conference. Thank you for your participation. Have a wonderful day. You may all disconnect.

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