Q1 2022 Xenon Pharmaceuticals Inc Earnings Call

Okay.

Operator: Good day. Thank you for standing by. And welcome to today's Xenon Pharmaceuticals first quarter results call for 2020. At this time, all participants are in a listen-only mode.

Good day, Thank you for standing by and welcome to the Xenon Pharmaceuticals.

Operator: After the speaker's presentation, there will be a question-and-answer session. To ask a question during that session, you will need to press star 1 on your telephone keypad. If you require any further assistance, please press star 0.

He calls she reports first quarter results call 2022.

At this time all participants are in a listen only mode.

The speaker's presentation, there will be a question and answer session to ask a question.

Question in children that session, you will need to press star one on your telephone keypad. If you require any further assistance. Please press star zero. Thank you Ali.

Operator: Thank you. I would now like to hand the conference over to your speaker today, Ms. Sherry Aulin, Chief Financial Officer of Xenon Pharmaceuticals. The floor is yours.

I'd like to hand, the conference over to your Speaker today, Ms Sherry Allen Chief Financial Officer of Pharmaceuticals.

Yours.

Sherry Aulin: Thank you. Good afternoon, everyone. Thank you for joining us on our call and webcast to discuss Xenon's first quarter 2022 financial and operating results. Joining me are Ian Mortimer, Xenon's president and chief executive officer, Dr. Chris Kenney, Xenon's chief medical officer, and Dr. Chris Bonsackern, Xenon's chief commercial officer. Please be advised that during this call, we will make a number of statements that are forward looking, including statements regarding our and our collaborators development plans, anticipated regulatory interactions and submissions, anticipated results and timelines, the potential efficacy, safety profile, addressable market and commercial potential of our proprietary and partner product candidates, the efficacy of our clinical trial designs and anticipated enrollment, the potential receipt of milestone payments and royalties from our collaborators, our expectation of having sufficient cash to fund operations into at least 2024, and the timing of potential release of future clinical data.

Thank you good afternoon, everyone. Thank you for joining us on our call and webcast to discuss <unk> first quarter 2022 financial and operating results. Joining me are Ian Mortimer, <unk>, President and Chief Executive Officer, Dr. Chris Kenny Xenon, Chief Medical Officer, and Dr. Chris One sector in V. NAND is cheap.

Marshall Officer, please be advised that during this call we will make a number of statements that are forward looking including statements regarding our and our collaborators development.

Anticipated regulatory interactions and submissions anticipated results and timelines the potential efficacy safety profile addressable market and commercial potential of our proprietary and partnered product candidates.

I can see if our clinical trial designs and anticipated enrollment the potential receipt of milestone payments and royalties from our collaborators our expectation of having sufficient cash to fund operations into at least 2024 and the timing of potential release of future clinical data forward looking statements are subject to numerous raw.

Risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected on today's call. We undertake no obligation to publicly update any forward looking statement today's press release summarizing <unk> first quarter 2022 financial result.

Sherry Aulin: 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 STC filings. Our results may differ materially from those projected on today's call. We undertake no obligation to publicly update any forward-looking statement.

<unk> and the accompanying quarterly report on Form 10-Q will be made available under the investors section of our website at www Dot Dash pharma dot com and filed with the SEC and on SEDAR now I'd like to turn the call over to Ian.

Sherry Aulin: Today's press release summarizing Xenon's first quarter 2022 financial results and the accompanying quarterly report on Form 10-Q will be made available under the investor section of our website at www.xenon-pharma.com and filed with the SEC and on CDAR. Now, I'd like to turn the call over to Ian. Thanks, Sherry. Good afternoon, everyone.

Thanks, Sherry good afternoon, everyone. Thanks for joining our call today I will provide a high level update on our proprietary pipeline programs and then I'll turn the call over to Chris Kenny.

Ian Mortimer: Thanks for joining our call. Today, I will provide a high-level update on our proprietary pipeline programs, and then I'll turn the call over to Chris Kenney, who will provide additional color around the new developments and next steps within our XCN 1101 program, including the newly initiated XCN 1101 Phase 2 clinical trial in major depressive disorder, or MDD. Sherry will conclude our call by providing an update on our partner programs and briefly summarizing our financial results and anticipated key milestone events ahead. Chris von Seggern is also on the call to provide his perspective during the Q&A session.

Who will provide additional color around the new developments and next steps within our exon 11, or one program, including the newly initiated <unk> 11 O. One phase II clinical trial in major depressive disorder or M. D. D. Sherry will conclude our call by providing an update on our partnered programs and briefly summarizing our financial results and anticipated key mile.

Stone events ahead, Chris One segment is also on the call to provide his perspective during the Q&A session.

Ian Mortimer: Within our own proprietary pipeline, we continue to support our ongoing XCN496 Phase 3 EPIC Pediatric Clinical Trial, which is a randomized, double-blind, placebo-controlled, parallel group clinical trial evaluating the efficacy, safety, and tolerability of XCN496 in approximately 40 pediatric patients aged 1 month to less than 6 years who have KCNQ2-DEE. Based on published physician case studies with azogabine and its KV7 mechanism of action, we believe that XCN496 has the potential to address an important unmet medical need.

Within our own proprietary pipeline, we continue to support our ongoing <unk> phase III epic pediatric clinical trial, which is a randomized double blind placebo controlled parallel group clinical trial evaluating the efficacy safety and Tolerability of <unk> and approximately 40 pediatric patients aged one month.

And six years with Casey on Q2 D E based.

Based on published physician case studies with <unk> and its kv <unk> mechanism of action, we believe that <unk> hundred 96 has the potential to address an important unmet medical need we continue to receive encouraging feedback from clinicians caregivers and patient advocates on our <unk> hundred 96 program, including most recently at the pediatric <unk>.

Ian Mortimer: We continue to receive encouraging feedback from clinicians, caregivers, and patient advocates on our XCN496 program, including most recently at the Pediatric Academic Societies Conference in Denver. There is significant interest in the opportunity to provide precision medicine which has the potential to positively impact the lives of these young patients. We continue to build momentum with new sites and jurisdictions coming on board, and we expect to complete the XTN-496 EPIC Phase III clinical trial in 2023.

Academic societies conference in Denver, There is significant interest in the opportunity to provide a precision medicine, which has the potential to positively impact. The lives of these young patients. We continue to build momentum with new sites and jurisdictions coming on board and we expect to complete the CN for 96 epic Phase III clinical trial in 2023.

Right.

Ian Mortimer: Turning now to our XCN 1101 program, we have made significant progress advancing XCN 1101 into a broad clinical development program for both epilepsy and depression. Building on our top-line Phase IIb X-Tol results in adult focal epilepsy from last fall, we continue to accrue compelling evidence from various subgroup analyses of the X-Tol data and interim safety and efficacy data from the ongoing X-Tol Open Label Extension Study, or OLE.

Turning now to our accident at 11 O. One program, we have made significant progress advancing <unk> hundred 11 O one into a broad clinical development program in both epilepsy and depression.

Building on our top line phase <unk> results in adult focal epilepsy from last fall, we continue to accrue compelling evidence from various subgroup analyses of the actual data and in term safety and efficacy data from the ongoing <unk> open label extension study or OLED. Most recently at <unk> 2020.

Ian Mortimer: Most recently, at ASCENT 2022, the annual meeting hosted by the American Society for Experimental Neurotherapeutics, we presented additional data showing that XEN1101 has demonstrated substantial efficacy in a difficult-to-treat patient population with even more impressive efficacy in subgroup analyses of patients with less severe disease. Later this year, we expect to be in a position to share additional XEN1101 X-Tol data, both from additional subgroup analyses, including a time course to efficacy analysis, as well as data from the ongoing X-Tol Open-Label Extension.

To the annual meeting hosted by the American Society for experimental Neuro Therapeutics, we presented additional data showing that <unk> 11 O. One has demonstrated substantial efficacy in a difficult to treat patient population was even more impressive efficacy and subgroup analysis of patients with less severe disease.

Later this year, we expect to be in a position to share additional <unk> 11 O. One X tole data both from additional subgroup analyses, including the time course of efficacy analysis as well as data from the ongoing X Tole O L. A.

Ian Mortimer: As we analyze additional XEN11-01 data, our confidence continues to grow based on robust, compelling, and consistent data across seizure reduction endpoints and subgroups and in the OLE, indicating that XEN11-01 could play a key role in treating adult patients with focal epilepsy. We are excited to be able to share additional data highlighting the already impressive profile of XCN 1101. In addition to its robust efficacy, the tolerability profile of XCN1101 is consistent with an active CNS drug, and its AE profile is in line with other anti-seizure medications.

As we analyze a dish.

Alexia at 11 O. One data our confidence continues to grow based on robust compelling and consistent data across seizure reduction end points and sub groups and in the OLED, indicating that <unk> 11 O. One could play a key role in treating adult patients with focal epilepsy.

We are excited to be able to share additional data augmenting the already impressive profile of vaccine at 11 O. One.

In addition to its robust efficacy the tolerability profile of <unk> at 11 O. One is consistent with an active CNS drug and its AE profile is in line with other anti seizure medications.

Ian Mortimer: XEN11-01 also presents other differentiating attributes, including its only-in-class potassium channel mechanism and a dosing regimen of one pill once a day with no titration required. Our team is excited to continue to advance this program, and it's made considerable progress over the last quarter.

At 11 O. One also presents other differentiating attributes, including its only in class potassium channel mechanism and a dosing regimen of one pill once a day with no titration required.

Our team is excited to continue to advance this program and has made considerable progress over the last quarter. We have finalized the proposed trial designs for our two phase III clinical trials, along with completing the <unk> vendor selection our end of phase two meeting with the U S. FDA taking place this quarter also marks an important milestone.

Ian Mortimer: We have finalized the proposed trial designs for our two Phase 3 clinical trials, along with completing CRO vendor selection. Our End of Phase 2 meeting with the U.S. FDA, taking place this quarter, also marks an important milestone. We look forward to providing an update from this important regulatory interaction after we receive written FDA minutes. In addition, we anticipate providing further details around the potential expansion into another epilepsy-related indication in the coming months.

We look forward to providing an update from this important regulatory interaction. After we receive written FDA minutes. In addition, we anticipate providing further details around the potential expansion into another epilepsy related indications in the coming months.

Ian Mortimer: We have also made great progress in our work examining indications outside of epilepsy. We are excited that our Xenon-sponsored Phase 2 clinical trial, which we are calling XNOVA, is now underway to assess if XEN11-01 improves depressive symptoms in patients with MDD and anhedonia. In addition, the investigator-led Phase 2 MDD study with our collaborators at Mount Sinai continues to progress. So, in summary, this has been an incredibly exciting time at Xenon, with a number of mid- and late-stage clinical trials ongoing and more on the horizon.

We have also made great progress in our work examining indications outside of epilepsy. We are excited that our xenon sponsored phase II clinical trial, which we're calling ex Nova is now underway to assess if ex CN 11 O. One improves depressive symptoms in patients with Mds and Antonio in addition, the <unk>.

Investigator led phase two Mds study with our collaborators at Mount Sinai continues to progress. So in summary. This is an incredibly exciting time I'd seen on with a number of mid and late stage clinical trials ongoing and more on the horizon.

Ian Mortimer: On behalf of the entire team, we look forward to keeping you posted on our progress. So I'll pause here and ask Chris Kenney to provide some more details on XNOVA and other developments within our clinical programs.

The entire team we look forward to keeping you posted on our progress so I'll pause here and ask Chris Kenny to provide some more details on X Nov and other developments within our clinical programs.

Yeah.

Thanks, a lot and we've made a lot of progress driving forward multiple ongoing clinical trials and planning for etsy on a loved one O one phase III initiation.

Chris Kenney: Thanks a lot. We've made a lot of progress driving forward multiple ongoing clinical trials and planning for Xeon 1101 Phase 3 initiation. Let me start by providing further details about the Xenon Lead Xeon 1101MG.

Let me start by providing further details about the xenon led X you know an 11 O. One M D D trial.

Chris Kenney: As a background, we've built a strong scientific rationale to support our exploration of XCN 1101, as a treatment for symptoms of depression and anhedonia. Published preclinical studies suggested increased activity of KCNQ-type potassium channels reverses depressive phenotypes following chronic social stress. We conducted our own preclinical work with XEN 1101, including data published at the 2021 Ascent Conference, that demonstrated a potential benefit of XCN 11-01 in mood... Further, the efficacious doses in plasma concentrations from the rodent depression, anhedonia, and epilepsy-related

As background, we've built a strong scientific rationale to support our exploration of vaccine at 11 O. One.

As a treatment for symptoms of depression and Antonio.

Published preclinical studies suggest that increased activity.

Casey on Q type potassium channels versus depressive phenotypes following chronic social defeat stress, we conducted our own preclinical work with exon 11 O one including data published at the 2021 is sent conference.

Demonstrating the potential benefit of exon 11 O one in mood disorders further.

The efficacious doses in plasma concentrations from the rodent depression and had the ONEOK and epilepsy related Mes studies overlap.

Chris Kenney: Suggesting that the exposure concentrations of XeN-1101 in epilepsy patients may also provide appropriate drug exposure to have a beneficial impact on mood. In addition, a paper published in the American Journal of Psychiatry outlines statistically significant clinical results generated from a randomized placebo-controlled clinical trial that explored the targeting of KCNQ channels as a treatment for MDD and anhedonia using Zaga. The results from our own XTOL Phase 2B Epilepsy Clinical Trial showed an efficacy signal in focal-onset seizures at all doses, including the low dose of 10 milligrams, which had excellent tolerability.

Suggesting that the exposure concentrations of Etsy at 11 O. One in epilepsy patients may also provide appropriate drug exposure to have a beneficial impact on mood.

In addition, a paper published in the American Journal of Psychiatry outlines statistically significant clinical results generated from our randomized placebo controlled clinical trial that explored the targeting of case here in Q channels as a treatment for M. D D.

And using his argument.

The results from our own X tole phase two b epilepsy clinical trial showed an efficacy signal and focal onset seizures with all doses.

Including the low dose of 10 milligrams, which had an excellent tolerability profile.

Chris Kenney: So, you will see within our MDT trial design, we intend to further study the 10 milligram dose alongside the 20 milligram. XNOVA will enroll approximately 150 subjects who will be randomized on a one-to-one-to-one basis into three trials. 10mg, 20mg, The primary objective is to assess the efficacy of 10mg and 20mg doses of XEN11-01 Comparative Placebo on Improvement in Depressive Disorders in Subjects Diagnosed with Moderate to Severe M.D. using the Montgomery Asperg Depression Rating Scale or MODRIS change.

So you will see within our MTT trial design, we intend to further study the 10 milligram dose alongside the 20 milligram dose.

Ex Nova will enroll approximately 150 subjects, who will be randomized on a one to one to one basis into three treatment arms 10.

10 milligrams 20 milligrams and placebo.

The primary objective is to assess the efficacy of 10 milligrams and 20 milligram doses of vaccine at 11 O one compared to placebo on improvement of depressive symptoms in subjects diagnosed with moderate to severe M. D D. Using the Montgomery Asbury depression rating scale or modest change through week six.

Secondary endpoints include improvement of anhedonia as assessed by the Snake Hamilton pleasure scale or shops through week, six as well as improvement of anxiety using the Beck anxiety inventory scale.

Chris Kenney: Secondary endpoints include improvement of anhedonia as assessed by the Snape Hamilton Pleasure Scale, or SHAP, as well as improvement of anxiety using the Beck Anxiety... We anticipate top-line results from the ex-NOVA study in 20. At the same time, our collaborators at the Icahn School of Medicine at Mount Sinai are conducting an investigator-led clinical trial examining XEN1101 in approximately 60 subjects with. Their primary objective Fung Shiu, Secondary measures will look at the effect of XEN-1101 compared to placebo on depression and anhedonia using the Madras and Schaff skills.

We anticipate top line results from the Nova study in 2023.

In parallel our collaborators at the Icahn School of Medicine at Mount Sinai are conducting an investigator led clinical trial examining axion 11 O. One in approximately 60 subjects with M D D.

Their primary objective is to look at the effect of exiting an 11 O. One on the brain reward circuit as measured by the change in bilateral ventral striatum activity using functional MRI.

Secondary measures will look at the effect of exon 11 O one compared to placebo on depression, an anecdote here using the module and shop skills respectively.

Chris Kenney: We believe there is a strong medical need for new therapies and modalities to treat depression. And importantly, depression commonly exists as a comorbidity with epilepsy. Our belief is bolstered by the market research we conducted to better understand the treatment landscape and unmet medical need for MDD. Physicians indicated the need for new treatments with alternative mechanisms of action for patients inadequately managed with SSRIs and SSIs.

We believe there's a strong medical need for new therapies, and modalities to treat depression, and importantly depression, commonly exists as a co morbidity in epilepsy patients are.

Our belief is bolstered by the market research, we conducted to better understand the treatment landscape and unmet medical need in M. D D.

Physicians indicated the need for new treatments with alternative mechanisms of action for patients inadequate you'd manage with Ssris and S N arise.

Sherry Aulin: We believe the KB7 mechanism may offer a compelling clinical alternative for these patients in the future. And I'm looking forward to keeping you up to date on our progress as we further explore the use of Xeon 1101 as a treatment for MDD. In summary, and as Ian noted, in addition to MDD, we're excited to move forward with our Phase 3 plans for Xeon 1101 and Focalon. Our end of Phase 2 meeting with FDA allows us to obtain agreement on our Phase 3 program and the overall data package needed for NDA filing.

We believe the kv seven mechanism may offer a compelling clinical alternative for these patients in the future.

And I'm looking forward to keeping you up to date on our progress as we further explore the use of exiting at 11 O. One as a treatment for M. D D.

In summary, and as Ian noted in addition to the M. D D. Whereas excited to move forward with our phase III plans for exon 11 O one in focal onset seizures.

Our end of phase two meeting with FDA allows us to obtain agreement on our phase III program and the overall data package needed for NDA filing.

Sherry Aulin: After incorporating this feedback, we intend to engage European regulators through scientific advice to obtain agreement on XEN 1101 Phase III. Our indication expansion efforts also continue, and I look forward to updating these plans in the coming months as well. I would like to now turn it over to Sherry to summarize our partnered programs, our financial position, and briefly recap upcoming milestones. Thanks, Chris.

After incorporating this feedback we intend to engage European regulators through scientific advice to obtain agreement on the Axion 11 O one phase III program.

Our indication expansion efforts also continue and I look forward to updating these plans in the coming months as well.

I would like to now turn it over to Sherry to summarize our partnered programs, our financial position and briefly recap upcoming milestones Sherry.

Sherry Aulin: Before I make a few comments on our Q1 financials, I'm pleased to report progress on our partner programs with NeuroCurrent Biosciences and Tessera Biosciences. Of note, we received a milestone payment from NeuroCurrent in connection with successfully reaching a collaborative milestone within the quarter. Both collaborators have clinical studies underway. Tessera is conducting a Phase 1b proof-of-concept trial that's evaluating the safety and tolerability of PCRX301 administered as a single dose in patients undergoing bunionectomy.

Thanks, Chris before I make a few comments on our Q1 financials I'm pleased to report progress from our partnered programs with Neurocrine Biosciences Antisera Biosciences of note. We received a milestone payment from Neurocrine biosciences in connection with successfully reaching a collaborative milestone within the quarter.

Both collaborate our collaborators have clinical studies underway.

Sierra is conducting a phase <unk> proof of concept trial that is evaluating the safety and Tolerability of P. C. R X 301 administered as a single dose in patients undergoing bunionectomy and Neurocrine now has two separate phase two clinical trials underway evaluating N V. I 90, 1352 and adult patients.

Sherry Aulin: And NeuroCurrent now has two separate Phase 2 clinical trials underway evaluating NBI-921352 in adult patients with focal onset seizures and pediatric patients with SCN8A-related epilepsy. And NeuroCurrent is guided to expect to have data from the focal epilepsy study in 2023. We look forward to keeping you updated as these partner programs reach important milestones. Next, I'll briefly touch on the highlights from this quarter's financial statements. Please refer to our news release and 10-Q report filed today for more detailed information on Xenon's financial statements. Cash and cash equivalents and marketable securities as of March 31, 2022 were $537.9 million, compared to $551.8 million as of December 31, 2021.

Couple onset seizures in pediatric patients with SG&A related epilepsy, and Neurocrine has guided that they expect to have data from the focal epilepsy study in 2023, we look forward to keeping you updated as these partners programs reach important milestones.

Next I'll briefly touch on the highlights from this quarters financial statements. Please refer to our news release and 10-Q report filed today for more detailed information in front of the nonfinancial statements cash.

Cash and cash equivalents in marketable securities as of March 31, 2022 were $537 9 million.

Compared to $551 8 million as of December 31, 2021 based.

Sherry Aulin: Based on current assumptions, which include fully supporting the planned XCN 1101 clinical development program, XCN 496, and preclinical and discovery programs, we anticipate having sufficient cash to fund operations into at least 2024, excluding any revenue generated from existing partnerships or potential new partnering arrangements. Looking ahead, there are a number of key objectives and milestone opportunities within the Xenon pipeline. So, following our end of phase 2 meeting in the second quarter and receipt of final FDA minutes, we anticipate being in a position to share our final Phase 3 plans for Exeon 11-01.

Based on current assumptions, which include fully supporting the planned <unk> 11 O one clinical development program.

<unk> and preclinical and discovery programs, we anticipate having sufficient cash to fund operations into at least 2024 exclusive excluding any revenue generated from existing partnerships or potential new partnering arrangements.

Looking ahead, there are a number of key objectives and milestone opportunities with them in the non pipeline.

Following our end of phase two meeting in the second quarter and receipt of final FDA minutes, we anticipate being in a position to share our final phase III plans vaccine 11 O one.

Sherry Aulin: In parallel, we'll continue to evaluate and plan for an Exxon 1101 program and another epilepsy indication and expect to be in a position to outline our plans in the coming months, will provide continued support for both XNOVA and the ongoing investigator-led study examining XCN11-01 and MDD. And with the ongoing advancement of our EPIC Phase 3 clinical trial in pediatric patients with KCNQ2-DEE, our team is striving towards study completion in 2023. In summary, we intend to continue to build on the positive momentum and excitement generated since the release of our top-line Phase 2b EXFL results last fall.

In parallel we will continue to evaluate and plan for an <unk> 11 O. One program and another epilepsy indication and expect to be in a position to outline our plan in the coming months.

We will provide continued support for both <unk> and the ongoing investigator led study examining <unk> 11 O. One M D D and.

And with the ongoing advancement of our epic phase III clinical trial in pediatric patients with Casey on Q2 D. E. Our team is driving towards study completion in 2023 and.

In summary, we intend to continue to build on the positive momentum and excitement generated since the release of our topline phase to be excellent results last fall, we're grateful for the support of our shareholders and Ian and I have had the pleasure of conducting in person meetings at recent conferences with some of you on the call.

Sherry Aulin: We're grateful for the ongoing support of our shareholders, and Ian and I have had the pleasure of conducting in-person meetings at recent conferences with some of you on the call. With a strong balance sheet and prudent management of capital, we believe Xenon is well-positioned to support our business objectives across our proprietary programs, and we look forward to reporting our progress in the coming quarters.

With a strong balance sheet and prudent management of capital. We believes the non is well positioned to support our business objectives across our proprietary programs and we look forward to reporting our progress in the coming quarters.

Operator: I'll now ask the operator to open the line for any questions. As a reminder, to ask a question, you will need to press star 1 on your telephone keypad. Again, that is star 1 on your telephone keypad.

I'll ask the operator to open the line for any questions.

As a reminder to ask a question you will need to Paas star one on your telephone keypad.

Again that is star one on your telephone keypad to withdraw your question. Please press the pound key.

Also really limit participants to one question and one follow up only.

Operator: To withdraw your question, please press the pound key. Also, we limit participants to one question and one follow-up only. Your first question comes from the line of Andrew Chai from Jeffreys. Your line is now open.

Your first question comes from the line of Andrew Tsai from Jefferies. Your line is now open.

Andrew Chai: Okay, very good. Thanks, and good afternoon. Thank you for taking my questions. My first one is at 1101.

Okay very good thanks, and good afternoon, and thank you for taking my questions. My first one is on 11 O. On you know clearly the base case for you guys for your Phase III program is to do two studies, regardless, although you will see if the FDA is willing to consider external as a pivotal study. So my question is are there precedents.

Ian Mortimer: You know, clearly, the base case for you guys for your Phase III program is to do two studies regardless, although you will see if the FDA is willing to consider XTOL as a pivotal study. So my question is, are there precedents out there where the FDA kind of explicitly told the sponsor, yeah, we'll consider your Phase II as a pivotal study? You know, in other words, can we expect that level of detailed confirmation from that?

[noise] out there where the F D. A kind of explicitly told the sponsor yeah, well consider your phase two as a pivotal study Ah yeah. So in another words can we expect that level of detailed confirmation from the FDA.

Yeah.

Ian Mortimer: Thanks, Andrew, for the question. I'm happy to address it. You know, we've been really consistent with our, our, messaging and communication with investors.

Thanks, Andrew for the question I'm happy to address that.

So.

Ian Mortimer: We believe the EXTOL data is very robust, and we're going to ask the FDA as part of the end of phase two meeting whether EXTOL can be one of the two registration studies. Regardless, we've been clear that we're going to run two phase, two phase three clinical trials regardless of the outcome you asked about. So, I and I are going to try to get clarity and, obviously, you know, what we can receive in terms of clarity from the FDA once we're in receipt of the minutes. Then we'll be in a position to communicate that publicly.

You know, our we've been really consistent with our messaging and communication with investors.

We believe the external data were very robust and we're going to ask the FDA as part of the end of phase two meeting on whether <unk> can be one of the two registration studies.

Guard less we've been clear that we're going to run two phase two phase III clinical trials, regardless of the outcome.

You asked about so we are going to try to get clarity and obviously you know what we can receive in terms of clarity from the FDA. Once we're in the receipt of minutes, then we'll be in a position to communicate that publicly.

Ian Mortimer: In terms of precedent, obviously, we don't have the opportunity to read regulatory minutes from other companies, but we have seen other companies and disclosure that is consistent with being able to communicate on whether their phase two study has been a registration study or has been seen as a registration study from an efficacy point of view. Obviously, when we think about the broader clinical development of any program and the NDA, it's a much broader package than just looking at efficacy results. Thank you.

In terms of precedent, obviously, we don't have the opportunity to read our regulatory minutes from other companies, but we have seen other companies and disclosure that is consistent with being able to communicate on whether their phase II study has been a registration or has been seen as a registration study from an efficacy point of view.

Obviously, when we think about the broader clinical development of any program and the NDA. Its a much broader package than just looking at efficacy results.

Chris Kenney: And my follow-up question is on the MDD program that you started up. Can you kind of talk about the powering assumptions, whether both doses need to work for the study to succeed, and how have you tailored your MDD study to succeed in terms of the trial design? Any differences here for the Ex Nova study versus Isogatin's prior placebo-controlled study, for instance? Thank you, guys. Sure, Chris Kenny, do you want to walk through both the kind of our company-sponsored design and some of the things that we're doing a little bit differently as well as the powering question?

Makes sense and my thank you and my follow up is on on the M. D. D program that you've started up can you kind of talk about the powering assumptions, whether both doses need to work for the study to succeed and how have you tailored your M. D. D study to succeed in terms of the <unk>.

While design any differences here for the next Nova study versus Zagunis. Prior placebo controlled study for instance, thank you guys again.

Sure Chris Kenny do you want to walk through both kind of the our company sponsored design and some of the things that were.

Doing a little bit differently as well as the powering question.

Chris Kenney: Yeah, sure, happy to do so, Ian. So, I think the first thing, you know, just to kind of take a step back. You have zogabine, you have a drug that demonstrated improvement in focal onset seizures. And now we've done the same with a similar mechanism using Exxon 1101.

Yes, sure happy to do so and so I mean, I think the first thing.

Just to kind of take a step back I mean do you have with US arguably you have a drug.

The demonstrated improvement and focal onset seizures and now we've done the same with a similar mechanism using exon 11 O one.

Chris Kenney: And when we think about the differences in potencies, and we think about that, you know, there's a significant difference there, but we think that there's overlap in terms of the doses that we use and the doses that they use that were effective in FOS. And same thing with MDD, that we're currently using doses that were quite similar, take into account differences in potency with what is an Aug Small Proof of Concept Study that was paused. [inaudible] It was alluded to earlier.

And when we think about the differences in the potencies and we think about that.

There's a significant difference there, but we think that there's overlap in terms of the doses that we use and the doses that they use that was effective in F O S.

And same thing with M. D D that we're currently using doses.

Quite similar when you take into account differences in potency with with what is arguably used in the small proof of concept study that was positive and an M. D. D that was alluded to earlier.

Chris Kenney: And the difference there is that they were able to demonstrate statistical significance in a study with about half the number of patients. So in the context of that, you know, we think that there's, there's a reasonable. Chance that if Xenon 1101 is effective in MDD, we'll see it. Ian, do you want me to go further in terms of that, or do you want me to leave it there and then go back to the study? Yeah, why don't we go?

And the difference there is that they were able to demonstrate statistical significance and.

Study with about half the number of patients per treatment arm. So in the context of that you know we think that there's there's a reasonable.

Chance that if Exxon at 11 O. One is effective in M. D D that will see it.

You know I mean, you can't do it.

I'm going to go further in terms of that or do you want me to leave it there and then go back to it.

Study design.

Chris Kenney: Yeah, let's go through a little bit of the study design. And obviously, there are always questions around trying to manage the placebo rate, so we can talk a little bit about that. And then we can get specific, more specific on the powering calculations. And I'm happy to walk through those as well.

Yeah, why don't we go yes.

Let's go through a little bit of the study design and obviously, there's always questions around trying to manage the placebo rates. So we can talk a little bit about that and then we can get specific more specific on the on the powering calculations and I'm happy to talk through those as well. So you know in terms of like planning for success with this study to say a few different things I mean first.

Chris Kenney: So, you know, in terms of, like, planning for success with this study, you say a few different things. I mean, first of all, you're very careful to keep the number of sites. Unknown Attendee, Dr. David Hoagy, Unknown Attendee, Unknown Attendee, Unknown Attendee, Obviously you need to pick a good CRO and so we went through a rigorous process to choose that, um... you know we're doing thing we're working with uh... ct and i to complete route eligibility review of patients so that want to play to turn and that particular patient is eligible for the study that patient is better reviewed and uh... uh... remote for Eligibility based upon everything that the site has provided and an independent assessment of for the confirmation of the...

Of all seem very careful to keep the number of sites.

Limited and to make sure that the quality of the sites is as good as it can possibly be can sometimes see differences in terms of placebo effect in different regions and what we can tell you is that the sites that have been chosen are all U S based.

Obviously, you need to pick a good C O ROE and so we went through a rigorous process to choose that.

You know, we're doing we're working with a C T and I to complete.

Eligibility review of patients so that once a site determines the particular patient is eligible for the study.

That patient has been reviewed and a remotely for eligibility based upon everything that the site has provided an independent assessment of the confirmation of the.

Chris Kenney: Diagnosis of MDD and then also an assessment of the extent. That group, which is composed of psychiatrists and psychologists from Mass General, will also be involved with training the Raiders. Surveillance Over a Period So I think we're doing a lot of different things that we're doing in hopes of planning for success with that trial and then, you know, obviously having it, having the number of patients per arm twice, twofold higher. The Park that was positive with the Zogby should help.

The diagnosis of M. D D. And then also an assessment of the extent of the M. D D.

That group, which is composed of psychiatrists and psychologists from from mass General will also be involved with training the Raiders and then keeping an eye on them surveillance over a period of time. So I think we're so there's a lot of different things that we're doing in hopes of planning for success with that trial and then you know obviously having it.

Having the number of patients per arm twice.

Higher than the the pocket was positive with it it's all giving should help with that as well.

Yeah.

Thanks, Chris.

Let's go operator, if we can go to the next to the next question.

Chris Kenney: Thanks, Chris. Let's go, operator, if we can go to the next question. Your next question comes from the line of Paul Matteis from Estifo. Your line is now open.

Your next question comes from the line of Paul.

From Stifel. Your line is now open.

Paul Matteis: Hey, thanks so much for taking my questions. I had a couple, if you don't mind. On XTN-1101 and epilepsy, as it relates to FDA and EMA feedback, is it your expectation that the EMA will prefer responder analysis as the registrational endpoint, whereas the FDA may prefer median seizure reduction and any other discrepancies that you may anticipate? And then on the additional seizure indication, I was just curious, you know, again, I don't want to speculate on what you might pursue, but if you're going to do generalized seizures or something like that, can you just sort of point to, you know, what other seizure populations out there are there that would materially change the way this drug is used in the right way?

Hey, Thanks, so much for taking my questions I had.

A couple if you don't mind onto an accident at 11 O wanted in epilepsy.

As it relates to the FDA and EMA feedback is your expectation that EMEA will prefer a responder analysis as the registrational endpoint, whereas the FDA may prefer immediate eager reduction and any other discrepancies that you that you may anticipate.

And then on the additional feature indication I was just curious you know again I don't want to speculate on what you might pursue but if you're gonna do generalized seizures or something like that you know can you just sort of point to.

What other seizure populations out there are there that would materially change the way. This drug is used in the real world I guess asked another way if you have a label for focal seizures.

Paul Matteis: I guess ask another way, if you have a label for focal seizures, do you need a broader indication to really kind of broaden the prescribing within the refractory population? And then, just lastly, in MDD, I was just curious how you're handling concomitant antidepressant use or prior antidepressant use in treatment refractory patients. Thanks so much.

Do you need a broader indication to really kind of broaden the prescribing within the refractory population and then just lastly, an M. D. D. I was just curious how you're handling concomitant anti depressant user or prior anti depressant treatment refractory there. Thanks, so much.

Ian Mortimer: Okay, great. Thanks, Paul. Why don't I? I'll tackle it, Chris. Maybe I'll tackle the first one.

Okay, great. Thanks, Paul why don't I, I'll tell Chris maybe I'll tackle the first one and then Chris.

Chris one sector and why don't you talk a little bit about the market opportunity in other seizure disorders outside of focal and how we think about you know kind of a market. There and then and then Chris Kenny when you can get to the continent question on M. D. D. So your first question Paul was just around <unk>.

The regulators in the U S versus Europe , yes.

Ian Mortimer: And then, Chris von Seggern, why don't you talk a little bit about the market opportunity and other seizure disorders outside of focal and how we think about, you know, kind of the market there. And then, and then Chris Kenney, we can get to the ConMed question on MDD. So your first question, Paul, was just around regulators in the US versus Europe.

You you described it well that our European and U S. Regulators FDA, we expect will focus on MPC that was the primary endpoint and the X Tole study and would be the primary endpoint in the phase III program.

And European regulators will focus on the responder analysis or the <unk> and that's the key that was the first secondary endpoint and ex tool and we can we can do that analysis.

Look at that under the statistical analysis plan and obviously given the robustness of the data was 11 O. One is you just see massive consistency between those two endpoints, regardless of which one you do we see we see very strong statistical significance, which is to be expected with a very active drug.

Ian Mortimer: Yes, I think you described it well that European or US regulators, FDA, we expect will focus on MPC. That was the primary endpoint in the XTOL study and would be the primary endpoint in the phase three program. And European regulators will focus on the responder analysis or the RR50. And, and that's the key, that was the first secondary endpoint in XTOL.

Based on those two statistical analysis.

So Chris one second.

The kind of expanding the market opportunity outside of football.

Ian Mortimer: And we can do that analysis and look at that under the statistical analysis plan. And obviously, given the robustness of the data with 1101, as you just see massive consistency between those two endpoints, regardless of which one you do, we see, we see very strong statistical significance, which is to be expected with a very active drug, based on those two statistical analyses. So, Chris von Seggern, what kind of expanding the market opportunity outside of focal is it?

Yeah, absolutely so.

As we said previously focal onset it's the biggest component of the <unk>.

<unk> see opportunity representing approximately 60% of the patients who are who are treated in managed but that leaves a fairly sizable segment of the marketplace that has either what we would generally consider a generalized form of epilepsy or a mixed etiology within that bucket that side of the equation is much more fragmented.

With different conditions contributing to the.

Chris von Seggern: Yeah, absolutely. As we said previously, focal onset is the biggest component of the epilepsy opportunity, representing approximately 60% of the patients who are treated and managed. But that leaves a fairly sizable segment of the marketplace that has either what we would generally consider a generalized form of epilepsy or meteorology within that bucket. That side of the equation is much more fragmented, with different conditions contributing to the different manifestations that would fall into a broader generalized bucket. But they are broadly treated similarly, although not the same.

The the different manifestations that would fall into a broader generalized bucket, but they are broadly treated similarly, although not the same.

And there are products that have indications that sit on either side of the F O last versus the the primary generalized marketplace. As a result, we do think expansion of the clinical label as is important for two reasons first having clinical data in unique patient populations that will be important given that not all products are broad spectrum.

Chris von Seggern: And there are products that have indications that sit on either side of the FOS versus the primary generalized marketplace. As a result, we do think expansion of the clinical label is, is important for two reasons. First, having clinical data in unique patient populations will be important, given that not all products are broad spectrum. And we want to be able to be in a position where we can have data specifically supporting use in adjacent patient population, as well as that we do believe this is a promotionally sensitive market. And being able to communicate that data through commercial and medical means will be important in order to establish positioning for a product.

And we want to be able to be in a position, where we can have data specifically supporting use in an adjacent patient population as well as that we do believe this is a promotional sensitive market and being able to communicate that data through commercial and medical needs will be important in order to establish positioning for our product.

Chris von Seggern: Even in light of having a potential broad spectrum outcome. So, both of those reasons necessitate exploration of at least generating data and pursuing labeling. Should the data be positive, it is something we feel quite strongly about. Thanks, Chris.

Even in light of having a potential broad spectrum outcome. So both of those reasons necessitate exploration of it.

At least generating data in pursuing labeling should the data be positive is something we feel quite strongly about.

Chris Kenney: Chris Kenney on the MDD ConMed question. Yeah, Paul, so with regard to the medication, patients entering the study will not be allowed to take antidepressants. And in terms of eligibility, it's okay to have failed one antidepressant in the current... Press of the episode, but no more. [inaudible] and then any failure of greater than three antidepressants. All right. Thank you all very much. Your next question comes from the line of Brian Abrahams from RBC Capital Markets. Please go ahead. Hi, good afternoon.

Thanks, Chris Chris Kenny on the MDT Con Med question.

Yeah, Hey, Paul So with regard to the medication. So patients entering the study will not be allowed to be taking an anti depressant.

And in terms of eligibility, it's okay to have filled one anti depression in the current depressive episode, but no more than one.

And then any any failure of greater than three anti depressants at any point in time will be exclusionary as well.

Alright, Thank you all very much.

Thanks, Paul.

Your next question comes from the line of Brian Abrahams from RBC capital markets. Please go ahead.

Hi, good afternoon. Thanks for taking my questions. It sounds like you mentioned your confidence is continuing to grow on an 11 O. One.

Brian Abrahams: Thanks for taking my questions. It sounds like you mentioned your confidence is continuing to grow on 1101 as the data continue to evolve. So I'm actually curious if you could talk maybe a little bit more about the emerging data. I know the specifics around the open label extension update are going to be presented later this year, but maybe if you could just remind us how far along patients are at this point on dosing and maybe qualitatively what you're seeing out of that that helps shape your confidence.

As the data continue to evolve so I'm actually curious if you could talk maybe a little bit more about the emerging data I know the specifics around the open label extension update is it going to be presented later this year, but maybe if you could just remind us how far along patients are at this point on dosing and maybe qualitatively.

What what youre seeing out of that that that helps shape your confidence.

Brian Abrahams: And then secondarily, you did mention we were going to see updated cuts from extol later this year, and I'm just curious if you could maybe talk broadly about how some of those analyses, such as the time to efficacy, could further help differentiate 1101's profile. Thanks. Thanks, Brian.

And then secondarily you did mentioned, but we're gonna see updated cuts from X. Tole later this year and I'm. Just curious if you could maybe talk broadly about how some of those analyses such as the the time to to efficacy.

Could further help differentiate <unk>.

I don't want to profile. Thanks.

Ian Mortimer: Chris, I'll make a few comments and then I'll pass it over to you on maybe some, a little bit of color on the open label extension, and I don't know if we, Chris, I don't know if we know off the top of our head, just kind of, I know we have patients that are out quite some exposure now, but maybe we can just give a little bit of information, if you have it at On the other hand, yeah, Brian, I think, you know, one of the things that's really strong about the data set overall is regardless of how we cut the data, it's remarkably consistent and very intuitive.

Thanks, Bryan Chris I'll make a few comments and then I'll pass it over to you on maybe some a little bit of color on the open label extension.

And I don't know if we Chris I don't know if we know if you don't have to.

Top of your head just kind of I know, we have patients that are out quite some exposure now, but maybe we can just get a little bit of information.

If it's if you have it at your fingertips on how many patients we're seeing kind of a.

<unk> to 24 months.

On the yes, Brian I think you know one of the things that's really strong about the data set overall is regardless of how we cut the data it's remarkably consistent and very intuitive you know a lot of the subgroup analyses in patients with less severe disease. The data looks even more impressive which is what you would expect but it's nice to see that consistency.

Ian Mortimer: You know, a lot of these subgroup analyses in patients with less severe disease, the data looks even more impressive, which is what you would expect, but it's nice to see that consistency. We're interested in this time course to efficacy because of the no titration. So, although this is a novel mechanism, and we would say, you know, likely the best in category efficacy that we've seen so far, we are continuing to look at other ways where we could differentiate against what are a number of other anti-seizure medicines that are available.

I'm more interested in this time of course to efficacy because of the no titration. So although this is a novel mechanism in and we would say you know likely best in category efficacy that we've seen so far.

Continuing to look at other ways, where we can differentiate.

Against what are a number of other anti seizure medicines that are available. So what we've been doing is we've been looking at cuts of the data on efficacy at this was an eight week study. So on a weekly basis and we can start to look at where efficacy shows up and again without the drug being titrated. The hypothesis is that theres an opportunity to see that earlier than you may see.

Ian Mortimer: So, what we've been doing is we've been looking at cuts of the data on efficacy at, you know, this was an eight-week study. So, on a weekly basis, and we can start to look at where efficacy shows up, and again, without the drug being titrated, the hypothesis is that there's an opportunity to see that earlier than you may see at some of the other drugs.

Some of the other drugs. So that's something that we're interested in among other things and then I'll pass it to Chris maybe just to give a bit of color on OLED, because we're just starting to dig into some of that data we had focused on lease.

Ian Mortimer: So, that's something that we're interested in, among other things. And then I'll pass it to Chris, maybe just to give a bit of color on OLE because we're just starting to dig into some of that data. We focused on the OLE safety data initially as part of preparation for our end of Phase 2 meeting, but now we're starting to think about the efficacy cuts that we would like to share later this year as well. Chris?

Safety data initially.

As part of preparation of the friend or our end of phase two meeting, but now we're starting to think about the efficacy cuts that we would like to share later this year as well Chris.

Chris Kenney: Yeah, sure. Yeah, I mean, I think that the main point is that as we look into the data, the double-blind data, regardless of how we cut it, the signal persists. And so that's part of the story.

Yeah sure Yeah, I mean, I think that's the main point is that as we look into the data.

The double blind data, regardless of how we cut at the signal persists.

And so that's part of the story in terms of being reassured the other part.

Chris Kenney: Reassured. The other part, you know, will be communicated clearly in the second half of this year regarding interrogating the open label data, and we're just getting our hands around it. You know, it's a moving target, right, because it's an ongoing study, and every day patients have one more day of exposure. But, and the other thing is that, you know, the number -- not all patients have finished up the first year because they wrapped up in the summer last year. The last patients who enrolled wrapped up in the summer.

We'll be messaged clearly in the second half of this year regarding interrogating the open label data and where we're just getting our hands around it its a moving target right because it's an ongoing study in everyday patients have one more day of exposure, but.

The other thing is is that you know the number not all patients have finished up the first year because they they wrapped up in the summer of last year, the last patients who enrolled wrapped up in the summer, but roughly speaking we're closing in on having a couple of hundred patients.

Chris Kenney: But roughly speaking, we're closing in on having a couple hundred patients, up to a year and then about. So it's a fairly robust data. And we're taking a look at that data and obviously having it vetted by key opinion leaders who are respected, and then being sure that we go out with.., and a balanced story about what... Great. Thanks, Chris.

Up to a year and then about 50 over two years, so it's a fairly robust dataset.

We're taking a look at that data and obviously, having an embedded by by key opinion leaders, who are respected and and then being sure that we grew up with them.

Balanced story about what we're seeing.

Great. Thanks, Chris.

Yeah.

Operator: Again, if you would like to ask a question, please press star 1 on your telephone keypad. Your next question comes from the line of Mark Goodman from SVB Security. Your line is now open. Hey, thanks for taking my question. It's really on the line for Mark.

Again, if you would like to ask a question. Please press star one on your telephone keypad.

Your next question comes from the line of Martin did move from SBB.

Your line is now open.

Operator: Just a quick follow-up question for the Ex Nova study for 11.01. Can you provide more color on the powering of the study? Like, what are your expectations for the magnitude of effect in measures for both placebo and 1101.

Hey, Thanks for taking my question is really on a like for Mark just said.

Quick follow up question for ex Nova study, where you live in a one kemper.

More color on the powering the study like what are your expectations for the magnitude of effect you can imagine this for both placebo and 11 to one.

unknown: And secondly, given the enrollment criteria, it seems like we are targeting monotherapy instead of adjunctive use. Maybe we can provide more color here on the clinical setting for 11.01. Thanks. Do you want me to do the driving, or do you want to do the driving and the monotherapy? I'm happy to start it off, and maybe you can add color to it afterwards.

And then secondly, given the enrollment criteria. It seems like we are targeting a monotherapy instead of adjunctive use maybe can't provide more color here on the clinical study for Illinois.

Yeah.

Yeah.

Yes sure Joe.

To do the Repowering or do you want to do the powering in the monotherapy.

I'm happy to make it started off and then maybe you can add color to it afterwards or so so I sort of alluded to the fact that we're gonna have about twice the number of patients that were in the saga being.

Chris Kenney: So I sort of alluded to the fact that we're going to have about twice the number of patients that were in ISAGI. Unknown Attendee, Dr. David Cohn, Dr. David Cohn, Dr. David Cohn, Dr. David Cohn, Dr. David Cohn, that there would be about a five point separation between active and placebo and that that would give us a power to detect a So that's the powering. And then in terms of monotherapy, Yeah, I mean, you have it right.

A concept study so from like a Cohen's D perspective, you guys you were shooting for an effect size around 0.5, but in terms of the separation between active and placebo, where the powering assumptions assume that there would be about a five point separation between active and placebo.

That would give us an 80% power to detect a change for each one of the doses compared to placebo.

So that's the powering and then in terms of the the mono therapy.

Yeah, you have it right. So these patients will not be on an additional anti depressant and so we're looking for a signal in patients who are not being treated with another anti depressant at the same time.

Chris Kenney: So these patients will not be on an additional antidepressant. And so we're looking for a signal in patients who are not. Got it. That's very helpful. Thank you. Again, that is Star 1 to ask a question. Your next question comes from the line of Yatin Asunidja from Guggenheim. Please go ahead. Yeah, so Ian, do you want me to go? Yeah, why don't you start? And I'm happy to add in.

Got it that's very helpful. Thank you.

Again that is star one to ask a question.

Your next question comes from the line of <unk> <unk> from Guggenheim.

Go ahead.

Hey, guys. Just a couple of question for me on the MTBE side can you just talk about the dose selection there.

Using a 10 milligram dose.

Just curious.

How did you come up with a lower dose.

And then did you mention.

The effect size that youre looking at a point in time.

Can you just talk about.

At that 0.5, Cohen's D side, and five points out opinion, having assumption.

Yeah. So you want me to go.

Yeah, why don't you start and I'm happy to add it.

Chris Kenney: Yes, so the, you know, the 10 milligram dose in the focal onset seizure, Study, Demonstrated F tolerability and a safety signal that made it difficult to extinguish the 10 milligram dose. For more information, visit www.fema.gov, Evidence of Efficacy. And so we want to take that forward into MDD and see if, and then as far as the powering, I think it's probably better to just focus on, you know, this is an MDD study. We're expecting a fairly pronounced placebo effect, as has been the case historically, despite, you know, efforts to keep it minimal. The separation between active and placebo we're assuming is five, a standard deviation that's about And that's, you know, a little bit less than what was seen with the Zaga.

Yes. So the you know the 10 milligram dose and the focal onset seizure study demonstrated efficacy and Tolerability and safety signal that was made it difficult to extinguish the 10 milligram group from placebo, so really good tolerability and evidence of efficacy and so.

We want we want to take that forward into M. D D and see if the same would be true with an M. D. D and then as far as the powering I think it's probably better to just focus on you know this is an M. D. D study, we're expecting a fairly pronounced placebo effect as has been the case historically despite efforts to keep it in there.

And then the separation between active and placebo were assuming as five points and our standard deviation, that's about two fold higher than that.

And that's you know a little bit less than what was seen with the zagha beam proof of concept study completed in two sites.

Operator: Proof of Concept Study Completed on Tuesday. Thank you, everyone, for having me here today. So, yeah, it's still early days, the Mount Sinai study started in Q4 of last year, and we're not giving specific guidance on it. I will mention just because it's publicly available on clinicaltrials.gov, they say that it's going to be early 24 when that study completes. So our expectation has always been that our company-sponsored study, although it has started after the IST, will read out before the IST because we expect data from our study in 2020 straight. Next question is from the line of David Hoang from SMBC; please go ahead. Hi, thanks for taking the questions. So I had one and then a follow-up appointment.

Gonna be going to more sites, so that that signal.

Some less robust as.

As we do that.

So that's the powering background.

Got it.

Do you have any clarity on when you might.

The data from our investigator initiated study.

So yes, it's still early days.

The Mount Sinai study started in Q4 of last year.

And we're not giving specific guidance on it I will mention just because it's probably available on clinical trials dot Gov. They say that it is going to be early 'twenty for when that study completes.

So our expectation has always been that our company sponsored study. Although has started after the S. T will readout before the ISG because we expect data from our study in 2023.

Thank you.

Next question is from the line of David <unk> from.

F N B C.

Go ahead.

David Hoang: So first, in terms of 1101 in MDD, if we think about how it might be positioned and adopted in the real world setting, you know, do you think about the low hanging fruit as epilepsy patients with comorbid MDD? Or is this really more of something for the broad, you know, all-comer MDD population that could be conceivably used in anyone who had maybe failed an SSRI? Chris von Seggern, do you want to talk about the opportunity? Yeah, no, absolutely not.

Hi, Thanks for taking the questions. So I had one and then a follow up so first in terms of 11 O. One in MTBE, if we think about how it might be positioned and adopted in the real world setting.

Do you think about the low hanging fruit as epilepsy patients with co morbid mbd or is this really more of something for the broad all comer population that could be conceivably used in any one who had maybe failed an SSRI.

Chris One thing I can do you want to talk about the opportunity.

Chris von Seggern: So first, let's start with MDD. That indication, while it does have numerous available agents, as you've mentioned, an overwhelming number of patients will be treated with an FSRI or SNRI. But many of those patients will fail first or second-line therapy.

Yeah, no absolutely. So first let's start with M D D.

That indication while it does have numerous available agents as you've mentioned.

An overwhelming number of patients will be treated with an SSRI or SNRI.

But many of those patients will fail first or second line therapy, and just like in the Fos space. There is a sizable percentage of patients that require an alternative mechanism and the situations predominantly mono therapy to address their depression symptoms.

Chris von Seggern: And just like in the FOS space, there is a sizable percentage of patients that require an alternative mechanism, in this situation, predominantly mammotherapy, to address their depression. Unknown Attendee, Dr. Brian Abrahams, Timothy Lugo, Brian Skorney, Joseph John, Laura Chico, Your second question, though, relates to the fact that within the FOS patient population, there is a sizable percentage of patients that have It's one of the most common comorbidities within the epilepsy space, and there certainly is the opportunity to differentiate with appropriate data in that segment of the patient population where you can imagine that you can be a go-to agent with compelling antidepressant effects as well as best-in-class efficacy, as we've seen with XCN11.

And we do believe that there is an opportunity for novel for in Asia with a novel mechanism of action that has.

A good safety tolerability profile to fit in nicely. Despite the competitive dynamic that sits in that space.

Your second question now relates to the fact that within the <unk> patient population. There was a sizable percentage of patients that have co morbid depression. That's one of the most common comorbidities within the epilepsy space and there certainly is the opportunity to differentiate with appropriate data.

That segment of the patient population, where you can imagine that you could be a go to Aegean with compelling anti depressant effect as well as best in class efficacy as we've seen with actually an 11 O. One.

Chris von Seggern: That's helpful. Thanks. And then just quickly, if I may, in terms of the IST study, which we'll read out after your company-sponsored study, are there any key learnings that you expect to glean from that study that may not be apparent in the company-sponsored study? I don't think so.

That's helpful. Thanks, and then just quickly if I may in terms of the the I S. T study, which will read out. After your company sponsored study are there any key learnings that you expect to glean from that study that may not be apparent in the the company sponsored study.

Yeah.

Ian Mortimer: I mean, Chris mentioned in his prepared remarks, and if you look at the Azogabine publication from a year ago from the study, so it's the same group out of Mount Sinai and Baylor that ran the Azogabine study that was published last year, and then they're the same ones running the RIST or the IST with 1101. They're interested in a functional endpoint, a functional MRI at primary because they're interested based on some of the preclinical data and where the expression is, the increased expression of KV73 in the brain, and so that's going to be an endpoint that we're not replicating, so that'll be new information from their study, but then when they get into their secondary endpoints in terms of the clinical scales of depression and anhedonia, that will be consistent with our studies.

I don't think so I mean, Chris mentioned.

His prepared remarks.

If you look at the lithography in publication from a year ago from the study and so it's the same group.

Out of Mount Sinai and Baylor that ran the geography in the study.

It was published last year and then there are the same ones running the R. I S. T. R are the ISC west with 11 O. One they are interested in a functional endpoint and functional MRI at primary because theyre interested based upon some of the preclinical data and where the expression is.

The increased expression of <unk> seven three in the brain and so that's going to be an endpoint that they were not replicating so that'll be new information from their study, but then when they get into their secondary endpoints in terms of the clinical scales of depression, an antidote.

That will be consistent with our studies, so I'm not sure that we learn a whole lot David from from their study that would be a read through in terms of our future development.

Ian Mortimer: So I'm not sure that we can learn a lot, David, from their study that would be a read-through in terms of our future development. Okay, thanks a lot. I appreciate it. Again, to ask a question, please press star 1 on your telephone keypad. You have your next question coming from the line of Laura Chico from Wedbush. Please go ahead. Hey, good afternoon, and thank you for taking the questions. I just have two.

Okay. Thanks, a lot I appreciate it.

Again to ask a question. Please press star one on your telephone keypad.

You have your next question comes from the line of Laura Chico from Wedbush. Please go ahead.

Laura Chico: One, we saw a recent report looking at correlation of seizure frequency and quality of life in D patients. Interestingly, there's better correlation between quality of life and days of uninterrupted due to seizures. When you're looking at the recent 1101 data, I'm wondering if there's a similar type of relationship that exists in the focal epilepsy setting, so not necessarily seizure freedom days, but days that were uninterrupted due to seizures.

Hey, good afternoon, and thank you for taking the question I just have two one we.

We saw a recent report looking at correlation of seizure frequency and quality of life and D patients.

Interestingly, there's been a correlation between quality of life and days of uninterrupted.

Due to seizures.

When you're looking at the recent 11 O. One data I'm wondering if there's a similar type of relationship that exists in the focal epilepsy setting so not necessarily.

As your freedom days, but they the uninterrupted due to seizures.

Chris Kenney: And then, secondarily, I guess with respect to the study in MDD, the XNOVA trial, could you just elaborate a little bit more fully in terms of how you're going to be assessing patients remotely, kind of what steps you're taking to kind of control the placebo response? Thank you. Chris Kenney, can you address both of those?

And then secondarily I guess with respect to the the study.

In N V D. The Nova trial could you just elaborate a little bit more fully in terms of how youre going to be assessing patients remotely kind of what what steps you're taking to kind of control placebo response. Thank you.

Chris Kenny into earlier, both of those can you address.

Chris Kenney: Well, I don't know if I can address the placebo response any better than I already did. So, I'll just go through it again quickly. It basically has to do with choosing good sites, U.S.-focused, making sure that the sites were trained properly by CT&I, ensuring that we choose a good CRO, assessing the eligibility criteria for entrance into this study using a different scale than is being used to assess the primary endpoints, so specifically Hamdi versus Madras, and then using this group of CT&I, who are Mass General Attendings in Psychology or And then keep using those same folks to train the sites and to surveil them over a period of time to ensure that there isn't anything aberrant going on with the data.

Well I don't know if I can address the placebo response any better than that I already did so.

Chris Kenney: So I don't think I can add anything more. And what was the other one? I apologize. Unknown Speaker It was just a question. Oh, go ahead, Lon.

So I'll just go through it again quickly.

Basically it has to do with choosing good sites U S focused making sure that the sites were trained properly by sea TNI, ensuring that we choose a good cero assessing the eligibility criteria for entrance into this study using a different skills and it's being used to assess the primary endpoint, so specifically Ham D.

Versus modules and then using this group of C. TNI, who are mass general.

Attendings in psychology, or psychiatry, performing this remote assessment of patient eligibility, ensuring that the Ham D score.

Appropriate for it.

Recruitment into the study.

And then keeping using those same folks to train to sites and to surveil them over a period of time to ensure.

But there isn't anything bearing going on with the with the data. So I don't think I can add anything more to that.

And what was the other one I apologize.

No I'm sorry.

Go ahead Mike.

Chris Kenney: Unknown Speaker Oh, I remember it was seizure free. So we've taken a look at seizure freedom; some of that has been released previously and in press releases. We've also looked at seizure-free days; that data hasn't been released, although it sort of shows what you might expect it would show. We haven't tried to correlate that. Seizure Freedom or Seizure Free Days with Quality of Life.

I remember it was the seizure free yes, so we've taken a look at seizure freedom.

Some of that has been released previously in press releases. We've also looked at seizure free days that data hasn't been released although it sort of shows what you might expect it would show we haven't tried to correlate that.

Seizure freedom or seizure free days with quality of life.

Chris Kenney: Okay, and if I could maybe sneak in a quick one, I'm sorry if I missed this on 1101 and the MDD study, have you disclosed any kind of expectations around a screening failure rate? Thanks very much. We have, yeah, we have not.

Okay, and if I could maybe sneak in a quick one I'm sorry, if I missed this on 11 to one and the M. D. D study have you disclosed kind of expectation around screening failure rate. Thanks very much.

We have yes, we have not.

Ian Mortimer: Oh, sorry, I just answered that last question operator. So no, Laura, we haven't. We haven't given any guidance on where we expect the screen failure rate to be. That's something that I think we can track over time and then give more information on.

Oh, sorry, I just answer that last question operator.

Laura we haven't we.

We haven't.

Given any guidance on where we expect the screen failure rate may maybe that's something that I think we can track over time, and then give more information on.

Sherry Aulin: Okay, thank you. That ends our question and answer session. I'll turn the call back over to Sherry Aulin for closing remarks. Thank you everyone for joining our call and webcast to discuss our first quarter 22 results. Operator, you may now end the call. Ladies and gentlemen, that concludes this conference call. Thank you all for participating. You may now disconnect. BF-WATCH TV 2021

Okay. Thank you that ends our question and answer session I'll turn the call back over to Sherry Buck.

Closing remarks.

Thank you everyone for joining our call and webcast to discuss our first quarter of 'twenty. Two results. Operator, you may now on the call.

Ladies and gentlemen that concludes today's conference call. Thank you all for participating you may now disconnect.

[music].

Okay.

Okay.

Okay.

[music].

Okay.

Yeah.

Yes.

[music].