Q3 2021 Xenon Pharmaceuticals Inc Earnings Call

Operator: Good day, and thank you for standing by. Welcome to the third quarter 2021 Zenon Pharmaceuticals Incorporated earnings conference call.

Good day, and thank you for standing by and welcome to the third quarter 'twenty to 'twenty, One xenon Pharmaceuticals incorporated earnings conference call.

Operator: At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session to ask questions. You'll need to press Star 1 on your telephone. Please be advised of today's conference as being. If you require any further assistance, please press Star zero. I would now like to hand the conference over to your first speaker for today, Ms. Sherry Allen, the chief financial officer of Zanath Pharmaceuticals. Please go ahead.

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

After the speaker's presentation, there will be a question and answer session to ask a question you will need to press star one.

We'll keep at.

Please be advised that today's conference is being recorded if you require any further assistance. Please press star zero.

I would now like to hand, the conference over to your first speaker for today, Ms. Sherry Allen, our Chief Financial Officer of Xenon Pharmaceuticals. Please go ahead.

Sherry Aulin: Thank you. Good afternoon, everyone.

Thank you good afternoon, everyone. Thank you for joining us on our call and webcast to discuss our third quarter 2021 financial and operating results. Joining me are Ian Mortimer <unk>, President and Chief Executive Officer, Dr. Chris Kenny <unk>, Chief Medical Officer, and Dr. Christopher <unk>.

Sherry Aulin: Thank you for joining us on our call and webcast to discuss our third quarter 2021 financial and operating results. Joining me are Ian Mortimer, Zinon's President and Chief Executive Officer, Dr. Chris Kenny, Zonon's Chief Medical Officer, and Dr. Chris von Segerne, the non-chief commercial officer. Today, Ian will provide a corporate update on our proprietary programs and then turn the call over to Chris Kenney, who will provide a summary of the XTOL data and our XEN111 plans moving forward. Chris von Segern will then provide context regarding the adult focal epilepsy market based on market research with leading KOLs and treating physicians.

Chief commercial officer.

Ian will provide a corporate update on our proprietary programs and then turn the call over to Chris Kenny who.

We will provide a summary of the actual data and our <unk> one plans moving forward, Chris <unk> will then provide context regarding the.

Adult focal epilepsy market based on market research with leading Kols and treating physicians lastly, I will summarize our high level financial results and milestones from birth, both proprietary and partnered programs for the months ahead before opening up the call to your questions. Please be advised that during this call we will make a number.

Statements that are forward looking including statements regarding the research and clinical development plans and timelines and results of operations the timing of and results from clinical trials and preclinical development activities of our proprietary and partnered product candidates the potential efficacy safety profile future development plans.

Sherry Aulin: Lastly, I will summarize our high-level financial results and milestones from both proprietary and partnered programs for the months ahead before opening up the call to your questions. The anticipated timing of I&D or I&D equivalent submissions and the initiation of future clinical trials for our proprietary products and those related to our partnered candidates. The efficacy of our clinical trial designs, our ability to successfully develop our proprietary development programs, the timing and results of our and our collaborators' interactions with regulators, the timing and anticipated enrollment in our clinical trials, the potential receipt of milestone payments involved, royalties from our collaborators, our expectation of having sufficient cash to fund operations into at least 2024, and the timing of potential publication or presentation of future clinical data.

<unk> 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 partnered candidates the efficacy of our clinical trial designs, our ability to successfully develop our proprietary development programs the timing and results of <unk>.

Our and our collaborators interactions with regulators the timing and anticipated enrollment in our clinical trials the potential receipt of milestone payments and royalties from our collaborators our expectation of having sufficient cash to fund operations into at least 2024 and the timing of potential public.

<unk> or presentation of future clinical data forward looking statements are subject to numerous risks and uncertainties many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected on today's call. We undertake no obligation to.

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 SEC filings. Our results may differ materially from those projected on today's call. We undertake no obligation to publicly update any forward-looking statement. Today's press release summarizing Xenon's third quarter 2021 financial results and the accompanying quarterly report on Form 10Q will be made available under the investor section of our website at www.zenon-farma and filed with the SEC and on CEDAR. Now, I would like to turn the call over to Ian.

Publicly update any forward looking statement today's press release summarizing <unk> third 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 the noncash <unk> dot com.

And filed with the SEC and on SEDAR now I would like to turn the call over to Ian.

Ian C. Mortimer: Thanks, Sherry, and good afternoon, and thanks for joining us today. Xenon marked an incredibly important milestone last month when we announced the positive top-line results from our Phase 2B XTol clinical trial. Exxian 1101 demonstrated impressive efficacy in difficult-to-treat adult patients with focal epilepsy. With its differentiated potassium channel mechanism of action, strong efficacy data, and ease-of-use attributes, including once-a-day evening dosing and no titration, we believe XN1101 could play an important role in treating adult focal epilepsy. These data exceeded our expectations with consistent, dose-dependent, and statistically significant efficacy across the key primary and secondary seizure reduction energies.

Thanks, Sherry and good afternoon, and thanks for joining us today.

Mark is an incredibly important milestone last month, when we announced the positive topline results from our phase two B X tole clinical trial.

<unk> hundred 11 O one demonstrated impressive efficacy and difficult to treat adult patients with focal epilepsy.

With its differentiated potassium channel mechanism of action strong efficacy data and ease of use attributes, including once a day evening dosing and no titration, we believe <unk> 11 O. One could play an important role in treating adult focal epilepsy. These data have exceeded our expectations with consistent dose dependent.

And statistically significant efficacy across the key primary and secondary seizure reduction endpoints.

Ian C. Mortimer: With these positive data in hand, we conducted a detailed analysis of our product pipeline, including the evaluation of additional indications for XN1101. Moving forward, we intend to sharply focus our efforts on the finalization of clinical development plans for XN1101, including a planned end of phase two meeting with FDA anticipated in the second quarter of 2022, and the initiation of our phase three program in adult focal epilepsy anticipated in the second half of 2020.

With these positive data in hand, we conducted a detailed analysis of our product pipeline, including the evaluation of additional indications for <unk> hundred 11 O. One.

Moving forward, we intend to sharply focus our efforts on the Finalization of clinical development plans for <unk> hundred one, including a planned end of phase II meeting with FDA anticipated in the second quarter of 2022, and the initiation of our phase III program in adult focal epilepsy anticipated in the second half of 2022.

Yes.

We look forward to providing more details on the final <unk> hundred 1100, one clinical development plan in the first half of 2022, including the final design of our Phase III program and our plans to evaluate other epilepsy indications as well as supporting phase II development in major depressive disorder or <unk>.

Ian C. Mortimer: We look forward to providing more details on the final XN1101 clinical development plan in the first half of 2022, including the final design of our Phase 3 program and our plans to evaluate other epilepsy indications, as well as supporting Phase 2 development in major depressive disorder or MD. In addition to XN111, our XEN 496 EPIC phase three trial continues to enroll patients with KCNQ2 developmental and epileptic encephalopathy, Further, this portfolio focus on XN1101 and XN 496 has helped shape our decision on our XEN 007 program.

In addition to <unk> 11, O one or <unk> 49, six epic phase III trial continues to enroll patients with Casey on Q2, developmental and epileptic encephalopathy or Casey on Q2 D.

Further this portfolio focus on <unk> hundred one and <unk> 496 has helped shape our decision around our <unk> seven program.

To date, a total of eight subjects have been enrolled and an investigator led phase II proof of concept study examining the potential clinical efficacy safety and Tolerability of <unk> seven as a treatment in patients diagnosed with treatment resistant absence seizures, including childhood and juvenile absence epilepsy.

As disclosed previously we believe <unk> seven is demonstrating efficacy in these patients with absence seizures. However, given the focus and resources required to advance <unk> hundred 11 O. One and <unk> 496, we do not intend to allocate any resources to company sponsored <unk> 007 development activities.

In 2022.

So looking forward you will see that our company objectives and activities are centered around our cave seven potassium channel programs and advancing our proprietary neurology pipeline.

Ian C. Mortimer: To date, a total of eight subjects have been enrolled in an investigator-led phase two proof of concept study examining the potential clinical efficacy, safety, and tolerability of XN007 as a treatment in patients diagnosed with treatment-resistant absinence seizures, including childhood and juvenile absinence epilepsy. As disclosed previously, we believe XEN 007 is demonstrating efficacy in these patients with absent seizures. However, given the focus and resources required to advance XN1101 and XN 496, we do not intend to allocate any resources to company-sponsored XEN 007 development activities in 2022.

In addition to our clinical advancements we are also focused over the past few years on expanding our intellectual property portfolio for <unk> hundred 11 in one and we have made excellent progress on this front over the past few months two new U S patents were issued to Zane on the first contained claims related to four distinct crystal informs of SDN and <unk>.

Oh, one drug substance, including the farm that we intend to use in our phase III development and for commercialization along with methods for their preparation the second patent relates to the methods of enhancing the bioavailability of <unk> 11 O. One by administration with food and this is consistent with the dosing of our <unk> 11 O one in our clinical studies.

Absent any extensions of patent term. These U S patents are expected to expire in 2039, and $20 40, respectively, providing us with an extensive runway protecting <unk> 11 O one.

Turning now to our other kv potassium channel program <unk> 496, new sites. Some jurisdictions continue to come online to support our epic study, which is a phase III randomized double blind placebo controlled parallel group multicenter clinical trial evaluating the efficacy safety and Tolerability of <unk>.

Ian C. Mortimer: So looking forward, you will see that our company objectives and activities are centered around our KV7 potassium channel programs and advancing our proprietary neurology pipeline. In addition to our clinical advancements, we have also focused over the past few years on expanding our intellectual property portfolio for XN1101, and we have made excellent progress. In the past few months, two new U.S. patents were issued to Xenon. The first contained claims related to four distinct crystalline forms of XTN1101 drug substance, including the form that we intend to use in our Phase 3 development and for commercialization, along with methods for their preparation.

<unk> hundred 96, and approximately 40 pediatric patients aged one month to less than six years with Casey on Q2 D. E based on its cave seven mechanism of action as well as published physician case studies, we believe that actually on 49 six has the potential to address an important unmet medical need.

For these patients we anticipate that the epic study will be completed in the first half of 2023, and we look forward to keeping you updated on its progress.

Before turning the call over to Chris Kenny I want to remind everyone that we're planning a significant presence at Aes 2021. This is the annual meeting of the American Epilepsy Society held in December we look forward to presenting additional external data at this event, including sub analyses of the responder analysis as well as more detailed safety data and <unk>.

Late breaking poster presented by Dr. Jackie French as well as during our sponsored scientific symposium.

Ian C. Mortimer: The second patent relates to methods of enhancing the bioavailability of XN1101 by administration with food. And this is consistent with the dosing of XN1101 in our clinical study. Absent any extensions of patent terms, these U.S. patents are expected to expire in 2039 and 2040, respectively, providing us with an extensive runway to protect XN1101. Turning now to our other KV potassium channel program, XEM 496, new sites and jurisdictions continue to come online to support our epic study, which is a phase three randomized, double-blind, placebo-controlled parallel group multi-center clinical trial evaluating the efficacy, safety, and tolerability of XN 496 in approximately 40 pediatric patients aged one month to less than six years with KCNQ2DE. Based on its KVV,

Activities at Aes 2021 include scientific posters related to <unk> 11, O one, including the late breaking X tole poster as well as 496 and seen on other earlier stage preclinical work, we will be participating in a joint industry scientific exhibit relating to rare genetically defined epilepsy, and we will also be.

Sponsoring a scientific symposium featuring a panel discussion with key opinion leaders in adult focal epilepsy space to just to discuss <unk> 11 O. One kv mechanism for those of you who are unable to join US in Chicago. This year, we expect to host a conference call and webcast to discuss our presentations at Aes specifically.

<unk> on the new analyses within our ex told data.

We will circulate details in our news release closer to the event and we look forward to connecting with you either in person or virtually so with those invitations extended I'd now like to turn the call over to Chris Kenny and Chris will touch upon some of the highlights from the X tole data and our Hexion 11 O one plans moving forward.

Thanks Ian.

Today I'm going to hit on some of the highlights of the X tole data. So I encourage listeners to also review the October 4th news release or you can listen to our webinar from that date as we went into considerable detail around the X tole topline results.

As a reminder, Expo was designed as a randomized double blind placebo controlled.

They used to be study to evaluate the clinical efficacy safety and Tolerability of exon 11 O. One.

[noise] administered once daily adjunctive treatment.

Ian C. Mortimer: mechanism of action, as well as published physician case studies, we believe that XN 496 has the potential to address an important unmet medical need for these patients. We anticipate that the epic study will be completed in the first half of 2023, and we look forward to keeping you updated on its progress. Before turning the call over to Chris Kenney, I want to remind everyone that we're planning a significant presence at AES 2021.

In adult patients with focal epilepsy.

Yes.

The study results include a total of 325 randomized and treated subjects in the safety population of 323 subjects in the modified intent to treat population for the efficacy analysis.

Of the 285 subjects, who completed the double blind period 96, 5% entered the open label extension to evaluate the long term safety Tolerability and effectiveness.

See on 11 to one.

This high rollover rate.

It provides important insight into the comfort of clinicians and their patients with the overall benefit and Tolerability profile of the vaccine at 11 O. One.

Ian C. Mortimer: This is the annual meeting of the American Epilepsy Society held in December. We look forward to presenting additional extol data at this event, including sub-analyses of the responder analysis, as well as more detailed safety data, in a late-breaking poster presented by Dr. Jackie French, as well as during our sponsored scientific symposium. Activities at AES 2021 include scientific posters related to XN1101, including the late-breaking extol poster, as well as 496 and Xenon's other earlier stage preclinical work.

The trial met its primary endpoint with Exxon at 11 O one demonstrating a statistically significant dose dependent reduction from baseline and monthly focal seizure frequency when compared to placebo.

Monotonic dose response with a P value of less than 0.001.

Key secondary efficacy measures included a pair wise comparison as each active dose to placebo and the proportion of patients who receive who achieved a 50%.

Or greater reduction in monthly focal seizure frequency from baseline.

Median percent reduction in monthly focal seizure frequency was 52, 8% in the 25 milligram group.

46, 4% in the 20 milligram group and 33, 2% in the 10 milligram group compared to 18, 2% in the placebo group.

Ian C. Mortimer: We will be participating in a joint industry scientific exhibit relating to rare genetically defined epilepsies, and we will also be sponsoring a scientific symposium featuring a panel discussion with key opinion leaders in the adult focal epilepsy space to discuss XN1101 and the KV mechanism. For those of you who are unable to join us in Chicago this year, we expect to host a conference call and webcasts to discuss our presentations at AES, specifically focused on the new analyses within our XTOL data.

These data suggest the clinically meaningful dose response relationship for <unk> 11 O one.

The treatment of focal seizures in adult patients.

We believe these data are even more impressive when we take into consideration the history of these patients in terms of their exposure to previous anti seizure medications.

And the concomitant anti seizure medications while on study.

In this context excellent at 11 O one demonstrated a statistically significant reduction from baseline in.

Monthly focal seizure frequency compared to placebo.

Ian C. Mortimer: We will circulate details in a news release closer to the event, and we look forward to connecting with you either in person or virtually. So with those invitations extended, I'd now like to turn the call over to Chris Kenny, and Chris will touch upon some of the highlights from the XTOL data and our XN11-01 plans moving forward. Thanks, Ian.

For all three exiting out of 11 O one doses and pairwise comparisons between each dose and placebo with two sided P values of P less than 0.001 for 25 milligrams versus placebo.

That's 1.001 for 20 milligrams versus placebo and up.

P value of 0.035 or 10 milligrams versus placebo.

Efficacy data strongly suggest that <unk> 11 O. One is highly active in the central nervous system.

Christopher John Kenney: Today I'm going to hit on some of the highlights of the X-Toll data, so I encourage listeners to also review the October 4th news release, or you can listen to our webinar from that date as we went into considerable detail around the X-Tol top-line results. As a reminder, Expo was designed as a randomized, double-blind, placebo-controlled ASTB study to evaluate the clinical efficacy, safety, and tolerability of XN1101, administered as once daily adjunctive treatment in adult patients with focal epilepsy.

Actually at 11 O. One was generally well tolerated in the study with adverse events consistent with other commonly utilized anti seizure medications.

There were no pigmentary abnormalities reported during the double blind study ore during the open label extension today.

With 70 subjects now treated more than 12 months.

The most common treatment emergent at.

Across all exon 11 O one dose groups were dizziness, somnolence fatigue, and headache, the treatment emergent adverse event rates were consistent with other anti seizure medications and at rates that were expected.

Overall, the safety and Tolerability profile of vaccine at 11 O. One is in line with other anti seizure medication and what would be expected given the axion 11 O. One appears highly active in the central nervous system.

Christopher John Kenney: The study results include a total of 325 randomized and treated subjects in the safety population and 323 subjects in the modified intent-to-treat population for efficacy. Of the 285 subjects who completed the double-blind period, 96.5% entered the open-label extension to evaluate the long-term safety, tolerability, and effectiveness of XN1101. This high rollover rate provides important insight into the comfort of clinicians and their patients with the overall benefit and tolerability profile of XN11. The trial met its primary endpoint with XN1101, demonstrating a statistically significant dose-dependent reduction from baseline and monthly focal seizure frequency when compared to placebo, a monotonic dose response with a p-value of less than 0.001.

To summarize.

The X full results demonstrate impressive efficacy vaccine on 11 O. One for adult patients with focal epilepsy, including those with seizures that are deep and difficult to treat when compared to other clinical trials.

In addition, we believe physicians and patients could benefit from exiting at 11 O ones other important attribute.

Such as once a day.

Sure.

Given exiting on 11 of one's unique potassium channel mechanism of action and the strength of these data we believe exiting at 11 O. One can play a very important role in treating focal epilepsy in the future.

Since announcing the topline data we have focused on building out our phase III development plans, we anticipate having an end of phase two meeting with FDA in the second quarter of 2022 to support the initiation of a phase III clinical program in adult patients with focal epilepsy anticipated in the second half of the year. In addition, the X tole.

Open label extension, which has been extended to three years is expected to continue to generate important long term data for exiting and 11 O. One.

As you noted we're also expanding the development of vaccine at 11 O one to M. D D major depressive.

The disorder, we have a strong scientific rationale based on promising preclinical data as well as clinical results from both an open label study and a randomized placebo controlled clinical trial that explore the targeting of Casey in Q2 channels as a treatment for M. D D. Using a zogby an earlier generation KD seven potassium channel.

Christopher John Kenney: Key secondary efficacy measures included a pairwise comparison of each active dose to placebo and the proportion of patients who achieved a 50% or greater reduction in monthly focal seizure frequency from base Median percent reduction in monthly focal seizure frequency was 52.8% in the 25 milligram group, 46.4% in the 20 milligram group, and 33.2% in the 10 milligram group compared to 18.2% in the placebo, These data suggests a clinically meaningful dose response relationship for XN 1101 in the adjunctive treatment of focal seizures and adult, We believe these data are even more impressive when we take into consideration the history of these patients in terms of their exposure to previous anti-seizure medication, and the concomitant antiseasure medications while on study. In this context, XN111 demonstrated a statistically significant reduction from baseline, in monthly focal seizure frequency compared to placebo, for all three Exxian 1101 doses in pairwise comparisons between each dose and placebo with two-sided P values of P less than .001 for 25 milligrams versus placebo, P of less than .001 for 20 milligrams versus placebo, and a P value of .035 for 10 milligrams versus placebo.

That's no longer commercially available.

We're collaborating with the school of Medicine at Mount Sinai to conduct an investigator sponsored phase two proof of concept randomized placebo controlled clinical trial of the Axion 11 O. One for the treatment of major depressive disorder.

Patient screening and randomization currently underway.

Approximately 60 patients with M. D D will be randomized in a one to one fashion to accident at 11 O one or placebo with subjects, taking 20 milligrams once a day of either exiting at 11 O one or placebo over the course of eight weeks.

The primary objective is to investigate the effect of exiting at 11 O. One on brain measures of reward using functional magnetic resonance imaging seconds.

Secondary endpoints include clinical measures of depression and Anhedonia. In addition, we're planning a larger company sponsored clinical study in major depressive disorder with Exxon at 11 O one which is expected to be initiated in the first half of 2022.

Now a few months ago I joined based in part on the promise of maturing neurology pipeline and I couldn't be more excited that the X tole results exceeded our expectations.

Which allowed us to accelerate our phase III development program for <unk> hundred 11 O one.

You noted we're committed and focused on advancing the accident at 11 O. One as we believe it could benefit a large number of patients suffering with adult focal epilepsy with that I'd like to turn the call to Chris Upon Fagan, who will share some market research insights shaping our current plans for exiting around 11 O one Chris turning to you.

Christopher John Kenney: These efficacy data strongly suggest that XN1101 is highly active in the central nervous system. Exce at 1101 was generally well tolerated in a study with adverse events consistent with other commonly utilized anti-seizure medication. There were no pigmentary abnormalities reported during the double-blind study or during the open label extension today, with 70 subjects now treated for more than 12. The most common treatment emergent adverse events across all XN-110 dose groups were dizziness, somnolence, fatigue, and headache. The treatment emergent adverse events were consistent with other antiseasur medications and at rates that were expected.

Chris.

Briefly by way of background prior to the external top line readout, we conducted primary market research in a blinded fashion with 50 clinicians ranging from academic epileptic allergists to high volume prescribing neurologists in epilepsy <unk> across the U S.

This earlier market research underscored the enduring unmet need that remains despite the availability of numerous anti seizure medications for the treatment of adult F O S.

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

The results of our prior market research suggests that there's the potential profile of <unk> 11 O. One was compelling given an anticipated efficacy profile.

Time was in line with current standard of care.

We modeled a 35% reduction in the 25 milligram treatment group, a comparable safety tolerability profile of the existing ASM, along with differentiated use abuse attributes such as QD dosing and no titration.

Christopher John Kenney: Overall, the safety and tolerability profile of XN1101 is in line with other anti-seizure medication and what would be expected, given XN1101 appears highly active in the central nervous system. To summarize, the X-Tol results demonstrate impressive efficacy of Axian 1101 for adult patients with focal epilepsy, including those with seizures that are deemed difficult to treat when compared to other clinical trials. In addition, we believe physicians and patients could benefit from XN1101's other important properties, such as once a day. Given XN1101's unique potassium channel mechanism of action and the strength of these data, we believe XN1101 could play a very important role in treating focal epileps. Since announcing the top-line data, we have focused on building out our phase three development plans.

Then following the <unk> results, we surveyed 148 prescribing epileptic allergist neurologists in the U S to understand their perspectives on the anticipated <unk> 11 O one product profile based on the external data.

The survey sampled followed.

Following the <unk> results had prescribing behavior is consistent with the broader U S market and surveyed physicians noted that the efficacy and safety are the most important factors contributing to the treatment decisions for ASM.

Overall, the profile of exon 11, one was very well regarded and both neurologists and uplift colleges viewed the efficacy and Tolerability of Axion 11 O. One as potential differentiators in particular differential efficacy was cited as a driver of use for <unk> 11 O one across all lines of therapy.

Beyond efficacy QD dosing no titration and the novel mechanism mechanism of action reviewed favorably to hire highly favorable compared to current <unk> and.

In light of the strong efficacy the overall product profile physicians indicated comparable utilization of vaccine 11 and want to vimpat competing for the first branded opportunity for patients with residual seizure burden.

Given the substantial efficacy demonstrated in the <unk> results combined with all we have learned from our market research. We believe the profile of <unk> and 11 O. One has the potential to significantly improve the standard of care for patients with residual seizure burden and if approved would represent a meaningful advancement in the therapeutic armamentarium for this disease.

Christopher John Kenney: We anticipate having an end of phase two meeting with FDA in the second quarter of 2022 to support the initiation of a phase three clinical program and adult patients with focal epilepsy, anticipated in the second half. In addition, the X-Tol open-label extension, which has been extended to three years, is expected to continue to generate important long-term data for XN11. As Ian noted, we're also expanding the development of XN1101 to MD2, which is major depressive disorder.

I'd now like to turn the call over to Sherry, who will provide some financial highlights and a summary of our important milestones ahead.

Sherry.

Today I will 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 September 32021 were $249 6 million compared to $177 million as of December 31, 2020.

Sequentially the quarter, we raised additional net proceeds of approximately $324 3 million net of underwriting discounts and commissions that before offering expenses and a public offering.

Christopher John Kenney: We have a strong scientific rationale based on promising preclinical data, as well as clinical results from both an open label study and a randomized placebo control clinical trial that explored the targeting of KCNQ2 channels as a treatment for MDD using a Zogabine, an earlier generation KV7 potassium channel opener that's no longer commercially available. We're collaborating with the School of Medicine at Mount Sinite to conduct an investigator-sponsored phase two proof of concept randomized placebo control clinical trial of XN111 for the treatment of major depressive disorder, with patient screening and randomization currently under, Approximately 60 patients with MDD will be randomized in a one-to-one fashion to XN1101 or placebo, with subjects taking 20 milligrams once a day of either XN1101 or placebo over the course of eight weeks.

Dan noted following the actual data, we thoroughly analyzed our product portfolio and revisited our cash runway guidance focusing on our most important programs.

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

Our SDN <unk> FX phase III clinical trial, and our preclinical and discovery programs, we anticipate having sufficient cash to fund operations into at least 2024, excluding any revenue generated from existing partnerships or potential new partnering arrangements.

Guided by our focus on our proprietary <unk> potassium channel programs. We believe we are in a strong position to execute against our corporate goals.

Refer you to today's press release, and our 10-Q filing for other specific details from this quarter's financial statements I'll give you a quick update on our partnered programs before reviewing upcoming milestones from our proprietary pipeline.

<unk> partners Neurocrine inflection has made important progress this year.

Neurocrine collaboration there are now Q ongoing phase two clinical trials with MDI <unk>, including one study in adolescent patients, aged 12 years and older with <unk> developmental and epileptic encephalopathy.

The second study has recently been initiated in adult patients with focal onset seizures were excited for these studies to test our hypotheses are selective <unk> six inhibitors inhibition and the impact on seizures and both the genetic gain of function patients as well as the broader population of focal epilepsy.

Christopher John Kenney: The primary objective is to investigate the effect of XN1101 on brain measures of reward using functional magnetic resonance. Secondary endpoints include clinical measures of depression in Anhedonia. In addition, we're planning a larger company-sponsored clinical study of major depressive disorder with XN1101, which is expected to be initiated in the first half of 2020. Now, a few months ago, I joined Xenon based on the promise of Xenon's maturing neurology pipeline, and I couldn't be more excited that the X Toll results exceeded our expectations, which allowed us to accelerate our Phase 3 development program for XN11.

Turning to our partners at flexion following the decision to expand the study with an additional cohort selection and anticipate data in the first quarter of 2020 Q from our phase <unk> proof of concept trial evaluating the safety and Tolerability and FX 301 in patients undergoing Bunionectomy and addition.

Looking ahead key objectives and milestone opportunities in our proprietary pipeline, including our activities at Aes 2021, and the release of additional phase <unk> data within a scientific poster presentation at a scientific symposium.

<unk> and <unk> meeting with the FDA in the second quarter of 2022 to help guide our phase III development program for <unk>, one which will be initiated in the second half of 2022.

Christopher John Kenney: As Ian noted, we're committed and focused on advancing XN1101, as we believe it could benefit a large number of patients suffering with adult focal epilepsy. With that, I'd like to turn the call over to Chris von Sager, who will share some market research insights shaping our current plans for XNN11. Chris, I turn it to you.

<unk> support for the ongoing investigator led study examining <unk> and MTBE Andy.

And the initiation of a larger company sponsored <unk> clinical study in the first half of 2020, Q continued evaluation of other epilepsy indications well suited for the future development of <unk> and the ongoing advancement of our epic phase III clinical trial in pediatric patients with <unk> two dee.

With estimated completion in the first half of 2023 on behalf of the entire executive team. We are proud of the hard work that led us to this exciting point in <unk> history. As we look ahead to 2022, we have multiple ongoing phase two and three clinical trials underway from both our partnered and proprietary programs.

Christopher E. Von Seggern: Chris Briefly, by way of background, prior to the XTOL top line readout, we conducted primary market research in a blinded fashion with 50 clinicians ranging from academic epileptologists to high volume prescribing neurologists and epileptologists across the U.S. This earlier market research underscored the enduring unmet need that remains despite the availability of numerous anti-seizure medications for the treatment of adult FOS. Physicians emphasize that high clinical unmet need exists, particularly among patients who are not well controlled despite being treated with multiple drugs in a polypharmacy approach.

Im excited to keep you updated on our progress as we continue to advance <unk> and the rest of our neurology focused pipeline.

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

Thank you Sherry.

Remind me to our audio attendance.

You would like to register a question. Please press star followed by the number one on your telephone. If your question has been answered then you would like to withdraw your registration. Please press the pound key.

Also please limit yourselves to one question at a time and then reenter the queue.

One moment please for the first question.

Sherry Aulin: The results of our prior market research suggested that the potential profile of XN1101 was compelling, given an anticipated efficacy profile that at the time was in line with the current standard of care. We modeled a 35% reduction in the 25 milligram treatment group, a comparable safety tolerability profile to existing ASMs, along with differentiated use of use attributes such as QD dosing and no titration. Then, following the X-PIL results, we surveyed 148 prescribing epileptologists and neurologists in the U.S. to understand their perspectives on the anticipated XN-1101 product profile based on the X-PIL data.

And our first question is from Paul Maritz.

Stifel. Your line is now open.

Hey, Thanks for taking our question. This is Alex on for Paul a couple of 11 O. One and then one on Douglas evidence that's alright.

I guess moving forward with 11 O one.

Is your expectation that you would only run one phase III study or are you planning on running too how are you thinking about that.

And then I'll ask a couple of follow ups, if that's okay.

Sounds good Alex I'll pass it to Chris Kenny just to talk about.

Kind of what our proposal will be in front of FDA and the phase III program in focal epilepsy.

Yeah sure. Thanks, Yes, it was.

Gonna be going out next year with more details about this but we're of the opinion that simply conducting one more randomized controlled trial will probably not be sufficient to have a large enough safety database at the NDA submission.

Increase our chance of success. So we're planning on doing you know more than that and the details of which will be forthcoming.

Sherry Aulin: The surveyed sample followed, following the extol results, had prescribing behaviors consistent with the broader U.S. market, and surveyed physicians noted that efficacy and safety were the most important factors contributing to the treatment decisions for ASM. Overall, the profile of XN111 was very well regarded, and both neurologists and epileptologists viewed the efficacy and tolerability of XN1101 as potential differentiators. In particular, differential efficacy was cited as a driver of use for XN1101 across all lines of therapy.

Can imagine I mean, these are pretty straightforward in terms of their design and so what you're seeing you'll see a repeat of what was already done to a large extent and then something beyond that to return.

Thanks, Alex.

Sorry, Yes I was.

Just kind of maybe how does that feel free to jump in on <unk>.

We believe strongly in the strength of the external data. So we will be making our arguments in front of the FDA that this is one of two registration studies, which is I think maybe a bit of a nuance on your question, but as Chris mentioned expect the phase III program overall will be broader than just one phase III trial.

Yes, It makes sense and then one more on 11, 1% for Douglas Elliman, but I guess is there anything gating through your own phase II <unk> study out of bounds are nice steady or are you planning to.

Sherry Aulin: Beyond efficacy, QD dosing, no titration, and the novel mechanism of action reviewed favorably to highly favorable compared to current ASM. In light of the strong efficacy in the overall product profile, physicians indicated comparable utilization of XN1101 to Vimpat, competing for the first branded opportunity for patients with residual seizure burden. Given the substantial efficacy demonstrated in the XTol results, combined with all we have learned from our market research, we believe the profile of XN1101 has the potential to significantly improve the standard of care for patients with residual seizure burden and, if approved, would represent a meaningful advancement in the therapeutic armamentarium for this disease. I'd now like to turn the call over to Sherry, who will provide some financial highlights and Terry?

Start that before you might see any more data out of that.

Chris do you want to just go through our thought process on our own company sponsored MDT.

Sure I mean, the quick answer to your question is that there is nothing gating.

D M D D trial at Mount Sinai, just began screening and randomization and we're gonna be doing the same.

Shortly so we're not waiting for any data during this year.

Makes sense.

And then quickly on <unk> I guess has your view of the of the molecule changed over the last quarter or so I mean, any any more color that you can give on sort of the prioritization of 11 O 1496 next year. Thanks.

No not at all it's really about prioritization as you can imagine a lot of the focus on the <unk>. One program, we talked about what the phase III trials will look like but we're gearing to moving as quickly as we can to get this drug filed and approved and so there's a massive amount of work.

Both in talks as well as Clinton farm other clinical trials will need to run and all of the CMC work and it's those are the competing resources to put those resources on other programs and so to us.

<unk> is ongoing and the 11 of the broad 11 of one development program is the most important objective, but we're focused on.

Sherry Aulin: Thanks, Chris. Today I will focus on some highlights from this quarter's financial statements and would refer you to our news release and 10Q report for further details. Cash and cash equivalents and marketable securities as of September 30, 2021 were $249.6 million compared to $177 million as of December 31, 2020. Subsequent to the quarter, we raised additional net proceeds of approximately $324.3 million, net of underwriting discounts and commissions but before offering expenses and a public offering.

So it's really a focus on prioritization effort there rather than anything specific around 007, we believe the drug is active we've seen that and we've talked about that publicly.

And obviously the investigator led study has gone slowly and I think a lot of that was due to COVID-19 impacts that we've seen across clinical development, but we absolutely believe that we are seeing drug activity. If reserves are seven right now we just need to focus our efforts on 11 to 190 <unk>.

Makes sense. Thanks, so much.

A reminder, again to limit yourselves to one question and one follow up.

Next we have Andrew <unk> from Jefferies. Your line is open.

Sherry Aulin: As Ian noted, following the X-Fold data, we thoroughly analyzed our product portfolio and revisited our cash runway guidance, focusing on our most important programs. Based on current assumptions, which include fully supporting the planned XN111 clinical development program, our XN 496 EPEC phase three clinical trial, and our preclinical and discovery programs, we anticipate having sufficient cash to fund operations into at least 2024, excluding any revenue generated from existing partnerships Guided by our focus on our proprietary KV7 potassium channel programs, we believe we are in a strong position to execute on our corporate goals. I would refer you to today's press release and our 10Q filing for other specific details on this quarter's financial statements.

Okay.

Data in terms of PK and other things from the study.

I had mentioned in my prepared remarks that will break down the responder analysis. So to answer your question very specifically, yes, you'll see seizure freedom data and also kind of those bins of those that responded more than more than 50% more than 75% and other bins as well there's some additional subgroup.

Because the analysis that we're interested in that were running right. Now also so you'll probably see some more efficacy data and subgroups as well as more detailed.

Tables and overall safety.

I think my overall comment and I'll pass it to Chris to add is.

Sherry Aulin: I'll give you a quick update on our partner programs before reviewing upcoming milestones from our proprietary pipeline. Our two key partners, Neurocrin Inflection, have made important progress this year. Under our Neurokrin collaboration, there are now two ongoing phase two clinical trials with NBI 921352, including one study in adolescent patients age 12 years and older with SCN8A developmental and epileptic encephalopathy, and a second study has recently been initiated in adult patients with focal onset seizures.

Nothing changes our view here I think it's always great to do additional analyses and have additional information presented.

In scientific forms in a medical meetings, but nothing's changed in terms of our overall view.

Top line efficacy in terms of the dose dependency in the efficacy.

And what we would expect to see on the safety side Nothing's changed our views as we get deeper into the data.

Yes.

Anything to add.

Oh, Okay. We just started I just got a note that Chris Kenny just lost connection so will carry on Andrew or do you want to do you want to go on your second question.

Hey, Thanks, Yes. Thank you for the details my second one is actually.

I would love to your latest thinking and you're kind of appetite around partnerships, where 11 O. One.

Sherry Aulin: We are excited for these studies to test our hypotheses of selective nav 1.6 inhibitors, inhibition, and the impact on seizures in both the genetic gain of function patients, as well as the broader population of focal epilepsy.

I'm curious if you are keen on licensing out U S rights or is it X U S. You're interested in and then.

A corollary to.

That is just as I think about Y-you development and.

Operator: Turning to our partners at Flection, following the decision to expand the study with an additional cohort, Flection anticipates data in the first quarter of 2022 from a Phase 1B proof-of-concept trial evaluating the safety and tolerability of FX301 in patients undergoing bunionectomy. In addition, looking ahead, key objectives and milestone opportunities in our proprietary pipeline include our activities at AES 2021 and the release of a test, additional phase 2B exfold data in a scientific poster presentation and at a scientific symposium, and conducting an end of phase two meeting with the FDA in the second quarter of 2022 to help guide our phase three development program for XN1101, which will be initiated in the second half of 2022.

And tying that with your upcoming FDA meeting.

I don't know I mean could there be us an idea of where you run one phase III, one phase III Global and then together that's how you can file.

And Indiana.

Down the road at the same time, I guess, maybe talk about those two dynamics. Thanks.

Yeah.

A fair bit there so I'll get a couple of comments and maybe Chris one second and you can.

Talk a little bit about some of our thinking on the commercial side also so.

So Andrew we don't give guidance on partnering and when we when we may be in partnering discussions or not but we are in terms of our strategic objectives. Our goal is to launch 11 O. One just like to watch for 96 and the U S market ourselves we have focused our comments today on an end of phase two meeting and getting feedback from.

FDA, but we will be doing the same thing with European regulators, we will be going through the process to receive scientific advice.

And and I think as we get through those meetings. We can answer one of your questions more directly which is what are you going to be the requirements.

For the NDA in the in the filing in the U S versus the requirements in Europe.

So we will be able to get into more of those details in 2022, but that's our overall thinking an overall strategy, Chris one SEC or maybe you can comment a little bit as we think about U S commercialization in our forward integration.

Operator: Continued support for the ongoing investigator-led study examining XN111 in MDD and the initiation of a larger company-sponsored MDD clinical study in the first half of 2022; continued evaluation of other epilepsy indications well suited to the future development of XN1101, and the ongoing advancement of our Epic Phase 3 clinical trial in pediatric patients with KCNQ2 DEE, with estimated completion in the first half of 2023. On behalf of the entire executive team, we are proud of the hard work that led us to this exciting point in Xenon's history.

Yeah happy to you. So when we think about the the fos opportunity on a global basis. The U S represent the lion's share of the commercial opportunity predominantly.

Predominantly driven by the differential pricing that one can achieve in the U S market. It's our belief that we have the capacity to bring this product to the market in the US built on the backbone of the commercial infrastructure that will first have with <unk> and 496, and it's our intention to be able to build and execute within the U S market the European.

Operator: As we look ahead to 2022, we have multiple ongoing phase two and three clinical trials underway from both our partnered and proprietary programs. I'm excited to keep you updated on our progress as we continue to advance XN1101 and the rest of our neurology-focused pipeline. I'll now ask the operator to open the line for any questions.

Market is a much more challenging one but also a very meeting meaningful commercial opportunity in its own right for fos products and that's an area, where we still have work to do to think through the best commercialization strategy to optimize the opportunity in that market as well.

Thanks for all the color congrats on all the progress thanks.

Operator: Thank you, Sherry. As a reminder for our audio attendance, if you would like to register a question, please press Star Files by the number one on your telephone. If your question has been answered, then you would like to withdraw your registration. Please press the Pounder. Also, please limit yourselves to one question at a time, then re-answer the following: One moment, please, for the first question. And our first question is from Paul Maddoz from Stiefel. Your line is now open.

Thanks, Andrew.

Before we proceed I'd like to ask these because for as to how is your audio is everything fine and you hear the question is perfectly.

The audio is good on on our side, we did drop one of one of our speakers got disconnected, Chris Kenny So if you can.

Reconnect him I think he was trying to dial back in but we can continue on with the Q&A.

Thank you for confirming.

Our next question is from Mark Goodman SBB looming your line is open.

Mark are you there.

Mark.

Withdraw the question Nexus, Brian Abraham some RBC capital markets. Your line is open.

Alex: Hey, thanks for taking our question. This is Alex on behalf of Paul.

Hey, guys. Thanks, so much for taking my questions.

Alex: A couple on 1101 and then one on 007 if that's all right. I guess moving forward with 1101, you know, is your expectation that you would only run one phase three study, or are you planning on running two? How are you thinking about that? And then I'll ask you to have a follow-up.

911 O one <unk>.

Curious if you've done any additional PK PD and safety analyses.

Since the topline X told data and maybe where that steering you with respect to potential phase III dosing as well as dosing for the MTBE study and then had a quick follow up.

Sure, Brian I'll I'll take that because I think.

Ian C. Mortimer: Sounds good, Alex. I'll pass it to Chris Kenny just to talk about what our proposal will be in front of FDA.

Oh actually correct, Kenny or your back online now.

Okay did you hear the question maybe you can if you heard the question maybe you can address kind of the <unk> I know a lot of that stuff still coming in and then you are thinking around dose selection for phase three an empty day.

Christopher John Kenney: Yeah, sure, thanks, Ian. We're certainly going to be going out next year with more details about this, but we're of the opinion that simply conducting one more randomized control trial will probably not be sufficient to have a large enough safety database at the time of the NDA submission to increase our chance of success. So we're planning on doing, you know, more than that, and the details of which will be forthcoming.

Yeah sure. So so obviously you know the information that we already have is suggestive.

Of which doses, we could bring into phase three we're we're in a very fortunate situation, where I think you could make an argument that you could bring any or all of those three doses forward and we're just trying to figure out which doser doses would be best PK P. D is certainly a part of that we're in the process of having that information come in right.

Right now regarding the safety. We are also spending a lotta time evaluating all the safety data and much of that will be presented at a E S and a more granular format than what you saw it in the press release. So we're we're bringing in all the information and next year, we're going to be more forthcoming about exactly which groups.

Christopher John Kenney: You can imagine. These are pretty straightforward in terms of their design, and so what you're seeing is a repeat of what was already done to a large extent and then something beyond that to return.

Ian C. Mortimer: Thanks, Alex, and I guess, sorry. Yeah, I was just going to maybe add to that before you jump in on 007. You know, look, we believe strongly in the strengths of the ex-tull data, so we will be, you know, making our arguments in front of the FDA that this is one of two registration studies, which is, I think, maybe, a bit of a nuance on your question, but as Chris mentioned, expect that the phase three program overall will be broader than just one phase three trial.

Reduces we're bringing into phase three.

Got it and then maybe just a quick follow up if I could maybe alluded to.

Broadening out the 11 O one program epilepsy program given the strength of the data just curious if you could expand a little bit on some of the possible. Other epilepsy indications you might consider and might this also include going down in age to a pediatric population. Thanks.

Alex: Yeah, makes sense. And then one more 1101 before 007. But I guess is there anything gating for your own phase 2 MBD study out of the Bouncini study, or are you planning to start that before you might see any more data from that?

Yeah, Brian good questions all.

I'll start and then Chris kind of if you want to join as well.

We're.

We did we did a webinar on 11 O one and in the summer where one of our Kols talked a lot about the preclinical data and I think what's fascinating about the cave mechanism.

And 11 O. One is just it's broad spectrum activity and and so that gives us a lot of confidence combined with the actual data to go into other epilepsy indications. In addition to adults vocal we're doing that evaluation right now they are other large epilepsy markets to give you a bit of an idea.

Christopher John Kenney: Chris, do you want to just go through our thought process on our own company-sponsored MDDC? Sure.

Christopher John Kenney: Sure, I mean, the quick answer to your question is that there is an engaging The MDD trial at Mount Sinai just began screening and randomization, and we're going to be doing it shortly, so we're not waiting for any data that makes sense. And then quickly on 007: I guess, has your view of the molecule changed over the last quarter or so? I mean, any more color that you can give on sort of the prioritization of 1101 and 496 next year? Thanks.

And then specifically around pediatrics, that's another part of our planning again I think many of you will know kind of what the extrapolation guidance is from FDA in terms of expanding the label anti into younger patients with focal epilepsy, and that's something we're working through right now and we will be submitting.

Definitely our formal pediatric plans to both FDA and European regulators Chris.

Christina anything to add kind of on your thought on expansion.

Yeah, I mean, it's a similar answer to what I said about doses I mean, we have the luxury of broad spectrum activity in preclinical models in conjunction with really robust clinical data and vocal onset seizures. So we're we're looking at all potential avenues, you can be sure will be.

Ian C. Mortimer: No, not at all. It's really about prioritization, as you can imagine, a lot of the focus on the 1101 program, we talk about what the phase three trials will look like, but we're gearing up to move as quickly as we can to get this drug filed and approved. And so there's a massive amount of work, both in talks as well as Clin Farm, other clinical trials will need to be run, and all of the CMC work.

Sort of specifying what our plans are again next year.

Great. Thanks, Chris Thanks, Ian very helpful.

Next we have Laura Chico from Wedbush Securities Your lines now open.

Hi, This is Sam on for Laura Chico. Thanks.

Thanks for taking the question.

I'm wondering if you can tell me what.

What the communication around the.

The one on one open label extension study.

Ian C. Mortimer: And it's, it's, those are competing resources to put those resources on other programs. And so to us, you know, 496 is ongoing, and the 11th of the broad 1101 development program is the most important objective that we're focused on. So it's really a focus on prioritization and effort there rather than anything specific around 007. We believe the drug is active. We've seen that. We've talked about that publicly before. And obviously, the investigator-led study has gone slowly, and I think a lot of that was due to COVID-immet, as we've seen across clinical development. But we absolutely believe that we're seeing drug activity for 007. Right now, we just need to focus our efforts on 1101 and 496.

So.

Thinking about additional updates from that study.

Thanks, Sam that's a that's a good question as as we had mentioned in our remarks.

It is very common to have 12 month oled's, but we did extend for external are open label extension to three years to generate some of that longer term safety data.

We're not gonna have any cuts of the OLED data. So maybe I can just be clear on kind of a near term and then I expect that we will have some updates from the early in 2022, we haven't quite quite mapped out exactly where that is but we will be wanting to share some of that data with FDA at the end of phase two meeting, but exactly where.

That fits in the medical meetings schedule, we haven't mapped out yet, but I would expect that we'll see we'll be disclosing some additional open label extension data during 2022.

Thank you. Thank you.

Next we have Mark Goodman from SVP living with your line is open.

Sorry about that I'm not sure what happened, but can you just talk a little bit about uhm upcoming.

A meeting with F D. A that you're planning on having what are your goals what are the side of the.

Question that you feel like you need to get the answer there. Thanks.

Alex: That makes sense. Thanks so much.

Chris Joannou address.

Sure one of 'em, Ian already alluded to so as you take a look at the X told data, it's really quite robust right and if you take a look at the size of that study and the convincing nature of the efficacy data, we think that there's a reasonable chance that we considering it as a pivotal trial. We just don't know what's after you agree.

Operator: Reminder again to limit yourselves to one question and one follow-up. Next, we have Andrew Chai from Jeffries.

Andrew Chai: Okay, great, thanks for taking my questions. Good afternoon.

Andrew Chai: So my first one is on AES when you present the full data set. You know, you did mention responder analysis, which is more safety. I mean, I guess my question is, could you share more? And if so, what would you encourage us to focus on as it relates to kind of understanding 1101's competitive profile? And I also want to ask, you know, could we see seizure freedom data for it or even kinetics around efficacy?

He's with that position or not so that'll be an important topic and then the rest of it is you know sort of the the typical stuff that you would expect so we're planning on doing at least we're gonna do at least one more randomized controlled trial and folklore that seizure and so.

We want to run the study design by them for that although it's pretty pretty basic from study to study so not expecting any sort of surprises there we've already talked about no considering other areas of epilepsy. Besides vocal onset seizures. So we're gonna want to go through.

Andrew Chai: Just maybe talk a little bit more about that. That would be helpful and have a follow up. Thanks.

Ian C. Mortimer: Sure, Chris, maybe I'll give a couple of comments on AES and then you jump in as you're close to the details. So, you know, I know you suggested, Andrew, kind of the full data set; the full data set would come in a publication later, but there's definitely going to be more information at AES than in our top line press release. And we're still receiving, you know, additional data in terms of P.K. and other things from the study. You know, we, I had mentioned in my prepared remarks that we'll break.

All the implications of that in terms of making sure that they're on board with this study design and what implications there would be from a label perspective.

And then of course, there's toxicology, making sure that you're gonna be coming to the N b, a with everything that they're gonna need to be able to support the clinical program from the talks perspective, and then of course, the clinical pharmacology. So we have a.

Clinical pharmacology plan with several NDA, enabling.

Studies, and we want to make sure that they're that they think that what we're doing is sufficient.

Ian C. Mortimer: down the responder analysis. So to answer your question very specifically, yes, you'll see seizure freedom data and also kind of those bins of those that responded more than more than 50% more than 75% and other bins as well. There's some additional subgroup efficacy analysis that we're interested in that we're running right now also. So you'll probably see some more efficacy data in subgroups as well as more detailed AE tables and overall safety.

And just so I'm clear your plan is to do probably two studies.

But that's not necessarily because you feel like you need to study do you really think I mean, obviously they will confirm it that you feel extols the pivotal you'll need one more pivotal. The reason you do two studies does not for efficacy that's really more for just enough safety data is that correct.

The the primary driver there is that if you if you take a look at the other anti seizure medications and in terms of what they brought to the table at the time of approval, they're they're fairly robust safety database. So we don't think that just doing another randomized control trial and epilepsy, we think that.

Ian C. Mortimer: You know, my overall comment, and then I'll pass it to Chris to add, is that nothing changes our view here. You know, I think it's always great to do additional analyses and have additional information presented in scientific forms and at medical meetings. But nothing's changed in terms of our overall view. The top line efficacy, you know, in terms of the dose dependency and the efficacy and what we would expect to see on the safety side. Nothing's changed in our views as we get deeper into the data.

There would be certain amount of regulatory risk, though that it would be a very thin NDA. So we're planning on doing more and what we're trying to figure out is you know what exactly that means and so does that.

What other areas and epilepsy would reconsider et cetera.

Thanks.

Alright next we have <unk> <unk>.

From the Guggenheim Your line is now open.

Thanks. This is Eddie on for you out and I. Appreciate you guys, taking my question. So.

Operator: Chris, anything to add? Oh, okay, sorry, I just got a note that Chris, Kenny just lost the connection. So we'll carry on, Andrew. Do you want to go on your...

So thanks for the IP update can you remind us when the competition a matter of pattern and polymorph patents expire and do you have any additional patents pending that could extend protection beyond 2040, and then when do you think we could see some MDT data from either the investigator or company generated studies.

Andrew Chai: on your second question. Hey, thanks.

Andrew Chai: Yeah, thank you for the details. My second one is actually, I would love your latest thinking and your kind of appetite around partnerships for 1101. I'm curious if you're keen on licensing out US rights, or is it XUS you're interested in? And then, a corollary to that, as I think about EU development and tying that to your upcoming FDA meeting, I don't know. I mean, could there be a scenario where you run one phase three U.S., one phase three global, and then together, that's how you can file both Maybe we can talk about those two dynamics. Thanks.

Are there any post hoc analyses from the <unk> study to support the MDT indication. Thanks.

Thanks.

So.

Thanks for the question on IP I think we've done.

An excellent job really identifying other ways to extend exclusivity and and obviously some of the work we've done over the last couple of years is now coming to fruition with some of these patents being issued.

So the.

I think many many people on the call know the based composition of matter when we acquired the drug.

With medium hatch Waxman took us into the twenties thirties, but we wanted to extend that and and obviously we've had a strategy that so far has been successful focus on the food effect as well as on polymorph and.

And the Polymorph is polymorph SAR compositions in terms of the polymorph pattern that has now been issued that gets us out to 22039 2040 absent any patent term extension there.

Ian C. Mortimer: Yeah, I mean, there's a fair bit there. So I'll give a couple of comments, and maybe Chris Wonsegian, you can talk a little bit about some of our thinking on the commercial side also. So, Andrew, we don't give guidance on partnering and when we may be in partnering discussions or not, but we are, in terms of our strategic objectives, our goal is to launch 1101, just like we launched 496 in the U.S. market ourselves.

There we do have other other ideas that we are working on but nothing yet that would take us past that timeframe, we're really focusing on that timeframe.

In terms of your MTBE question.

We haven't guided on this.

We believe although the Sinai study is up and running meaning that they are screening and they've randomized patients. So that's that's a really nice progress in the last quarter in our study will start later, but we expect our study would probably go more quickly because it'll be out multiple centers rather than just too.

Ian C. Mortimer: We have focused our comments today on an end-of-phase two meeting and getting feedback from FDA, but we will be doing the same thing with European regulators. We will be going through the process to receive scientific advice. And I think as we get through those meetings, we can answer one of your questions more directly, which is what are going to be the requirements for the NDA and the filing in the U.S. versus the requirements in Europe.

And and when we've looked at other companies that have run kind of these phase II proof of concept study as they've Austin had data in a reasonable period of time. So if we can get the study up and running which is our expectation in the first half of next year I think we could see MTBE data in 2023.

I appreciate it thanks for the color.

Yeah. There was also a questionnaire about whether X Colgate is needed to inform those studying for me the major driver for the M. D D trials as the preclinical data.

Then the clinical <unk>.

Ian C. Mortimer: And so we'll be able to get into more of those details in 2022. But that's our overall thinking and overall strategy. Chris von Seeger, maybe you can comment a little bit as we think about U.S. commercialization and our forward integration.

Clinical data with 11 O one and on the clinical data with a dog thing. So we don't necessarily need X told her to to inform what we wanted to.

Next we have a team logo from William Blair. Your line is now open.

Hey, guys. This lock on for Tim Thanks for taking my questions.

So on the topic of the empty day trials I realize it's alien investigator initiated studies generally enrolled pretty slowly but is there anything you can say about the enrollment progressive trends.

Christopher E. Von Seggern: Yeah, Ian; happy to. So when we think about the FOS opportunity on a global basis, the U.S. represents the lion's share of the commercial opportunity, predominantly driven by the differential pricing that one can achieve in the U.S. market. It's our belief that we have the capacity to bring this product to the market in the U.S., built on the backbone of the commercial infrastructure that we will first have with XEN 496. And it's our intention to be able to build and execute within the U.S. market.

And that study and then on the company sponsored one.

Have you made progress on the design for that in terms of dosing. It's been mentioned earlier that you're going to allow concomitant therapies.

Any sort of high level.

Criteria like that that you have to fill out of them.

[noise] Sherlock on I'll give a couple of comments and then creston cannot as well.

We don't give guidance on any of our studies in terms of where we are with enrollment, but I will give the caveat that the.

The investigator study is just up and running now so it's very very early days for that but they have randomized.

Which is great.

And in terms of our study we've.

We've given a little bit of color previously I think one of the things that we.

Christopher E. Von Seggern: The European market is a much more challenging one, but also a very meaningful commercial opportunity in its own right for FOS products. And that's an area where we still have work to do to think through the best commercialization strategy to optimize the opportunity in that market as well.

I've kind of paused on although we're making good progress is is just tried to know incorporate are thinking with the external data. So that's really around kind of a final dose selection for our company sponsored study.

In terms of the endpoints, we will not have a functional mris plan, which is the primary endpoint in the in the ISP was Sinai will be focused on clinical endpoints of depression in Indonesia and it is currently being designed as as a mono therapy study.

Andrew Chai: Thanks for all the color. Congratulations on all the progress.

Operator: Before we proceed, I'd like to ask the speakers first: how is your audio? Is everything fine? Can you hear the questions perfectly?

Chris any any additional color and yes I came.

Operator: The audio is good on our side. We did drop one of our speakers got disconnected, Chris Kenney, so if you can reconnect him, I think he was trying to dial back in, but we can continue on with the Q&A. Thank you for confirming this. Sorry, Ian.

You're covered.

The.

Okay great.

Next we have David.

S N B C. Your line is now open.

It looks like David.

Operator: Thank you for confirming. Our next question is from Mark Goodman, SBB Living. Your line is open. Mark, are you there? Mark with Jordan. Next is Brian Abrahamson, RBC Capital Markets. Your line is open.

The question. Our last question is for the surgery, the lender from Needham and company. Your line is now.

Hi, Thanks for squeezing me in a couple of questions first one O. Seven you still plan to report results from the ongoing investigators study and is that a a program you could eventually partner.

Brian Abrahams: Hey, guys, thanks so much for taking my questions. I'm sort of curious if you've done any additional PKPD and safety analyses since the top-line X-Tol data and maybe where that's steering you with respect to potential phase three doses, as well as doses for the MDD study, and then had a quick follow-up.

And then secondly regarding the flexion collaboration just curious if there's any changes in the economics of that collaboration would be expected.

Ian C. Mortimer: Sure, Brian, I'll take that because I think, oh, actually Chris Kenny, are you back online now? Okay, did you hear the question? Maybe you can, if you've heard the question, maybe you can address kind of the PK, and PD. I know a lot of that stuff is still coming in, and then you're thinking around dose selection for phase 3 and MD.

Change in control of that company. Thank you.

Thanks search.

I'll answer the second one first so no changes to any of the economics as flexion is going through through their transactions. So.

The new company would just step into into their shoes in terms of the economics too xenon So no change there.

Terms of 007.

So the ISP is continuing and will really be driven by the investigator.

Christopher John Kenney: Yeah, sure. So obviously, the information that we already have is suggestive of which doses we could bring into phase three. We're in a very fortunate situation where I think you could make an argument that you could bring any or all of those three doses forward, and we're just trying to figure out which dose or doses would be best. PKPD is certainly a part of that.

In terms of her plans to to publish data are present data at medical meetings. So I do expect at some point, we will see more data from that there are seven studying as I had answered in one of the questions earlier.

We believe that the drug is active based on what we've seen this is an open label study and and so in terms of what our strategic Optionality for that asset I still think we have some really today's decision and communication and what we've been focused on internally and are planning is is is the work that.

Christopher John Kenney: We're in the process of having that information come in right now. Regarding safety, we are also spending a lot of time evaluating everything. The safety data and much of that will be presented at AES in a more granular format than what you saw in the press release. So we're bringing in all the information, and next year we're going to be more forthcoming about exactly which dose or doses we're bringing into phase three.

That is coming for 11 O, one and 496 and the focus on that but.

But we absolutely feel that 007 is is an active drug and will continue to support the investigator as she finishes off her study.

And there are no further questions that concludes the Q&A session I will now turn the call back to Sherry Allen for closing remarks.

Brian Abrahams: Got it. And then maybe just a quick follow-up, if I could. You've maybe alluded to broadening out the 1101

I just wanted to say thank you everyone for joining us today and operator, you will now end the call.

And this concludes today's conference call. Thank you all for your participation enjoy the rest of your day keep safe and you may now disconnect.

Brian Abrahams: Epilepsy Program, given the

Brian Abrahams: strength of the data. Just curious if you could expand a little bit on some of the possible

Yeah.

Brian Abrahams: of the possible other epilepsy indications you might consider, and might this also include going down an age to a pediatric population? Thanks.

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Ian C. Mortimer: Yeah, Brian, good questions. I'll start, and then Chris Kenny, if you want to join as well.

Ian C. Mortimer: You know, we did a webinar on 1101 in the summer where one of our KOLs talked a lot about the preclinical data. And I think what's fascinating about the KV mechanism and 1101 is just its broad spectrum activity. And so that gives us a lot of confidence combined with the XTOL data to go into other epilepsy indications in addition to adult focal. We're doing that evaluation right now.

Ian C. Mortimer: They are other large epilepsy markets to give you a bit of an idea. And then specifically around pediatrics, that's another part of our planning. Again, I think many of you will know kind of what the extrapolation guidance is from FDA in terms of expanding the label into younger patients with focal epilepsy. And that's something we're working through right now, and we'll definitely be submitting our formal pediatric plans to both FDA and European regulators. Chris, Kenny, anything to add kind of on your thoughts on expansion?

Christopher John Kenney: Yeah, I mean, it's a similar answer to what I said about doses. We have the luxury of broad-spectrum activity and preclinical models in conjunction with really robust clinical data and focal onset seizures. So we're looking at all potential avenues, you can be sure. We'll be, you know, sort of specifying what our plans are again.

Operator: Great, thanks, Chris, thanks Ian, very helpful. Next we have Laura Chico from Wedbridge. Your line is now.

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Sam: Hi, this is Sam on behalf of Laura Chico. Thanks for taking the question.

Ian C. Mortimer: I'm wondering if you can tell me what the communication around the 101 open label extension study is like. Curious about how you're thinking about additional updates from that study. Thanks, Sam. That's a good question.

Ian C. Mortimer: As we mentioned in our remarks, you know, it's very common to have 12-month OLEs, but we extended for XTOL, our open label extension, to three years to generate some of that longer-term safety data. We're not going to have any cuts of the OLE data at AES, so maybe I can just be clear on kind of the near term. And then I expect that we will have some updates from the OLE in 2022.

Ian C. Mortimer: We haven't quite mapped out exactly where that is, but we will be wanting to share some of that data with FDA at the end of the Phase 2 meeting. But exactly where that fits in the medical meeting schedule, we haven't mapped out yet. But I would expect that we'll be disclosing some additional open label extension data during 2022.

Operator: That makes sense. Thank you. Next, we have Mark Goodman from SVP Lering. Your line is open.

Marc Harold Goodman: Sorry about that, not sure what happened, but can you just talk a little bit about the upcoming meeting with FDA that you're planning on having, and what are your goals, and what are kind of the key questions that you feel like you need to get answered there? Chris, do you want to address that?

Christopher John Kenney: Sure. I mean, one of them Ian already alluded to, so as you take a look at the X-told data, it's really quite robust, right? And if you take a look at the size of that study and the convincing nature of the efficacy data, we think that, you know, there's a reasonable chance that we're considering it as a pivotal trial. We just don't know if FDA agrees with that position or not.

Christopher John Kenney: So that'll be an important topic. And then the rest of it is, you know, sort of the typical stuff that you would expect. So we're planning on doing, you know, at least one more randomized controlled trial in focalont seizure. And so we want to run the study design by them for that, although it's pretty basic from study to study. So I am not expecting any sort of surprises there.

Christopher John Kenney: We've already talked about considering other areas of epilepsy besides focal onset seizures. So we're going to want to go through all the implications of that in terms of making sure. that they're on board with the study design and what implications there would be from a label perspective. And then, of course, there's toxicology, making sure that you're going to be coming to the NDA with everything that they're going to need to be able to support the clinical program from the talks perspective. And then, of course, clinical pharmacology. So we have a clinical pharmacology plan with several NDA-enabling studies, and we want to make sure that they think that what we're doing is sufficient.

Marc Harold Goodman: And just so I'm clear, your plan is to do probably two studies. But that's not necessarily because you feel like you need two studies. You really think, and I mean, obviously they'll confirm it, but you feel X total is a pivotal. You only need one more pivotal. The reason you do two studies is not for efficacy. It's really more for just enough safety data. Is that correct? The primary driver there

Christopher John Kenney: The primary driver there is that, you know, if you take a look at the other anti-seizure medications in terms of what they brought to the table at the time of approval, you know, they had fairly robust safety databases. So we don't think that just doing another randomized control trial in epilepsy, there would be, you know, a certain amount of regulatory risk there, that it would be a very thin NDA. So we're planning on doing more, and what we're trying to figure out is, you know, what exactly that means. and so does that. What other areas and epilepsy would we consider, et cetera?

Operator: All right, next we have Yotin Seneha from Guggenheim. Your line is now.

Eddie: Thanks, this is Eddie Onfriott, and I appreciate you guys taking the question. So, thanks for the IP update.

Ian C. Mortimer: Can you remind us when the Composition of Matter Patent and Polymorph patents expire? And do you have any additional patents pending that could extend protection beyond 2040? And then when do you think we could see some MDD data from either the investigator- or company-generated studies? Are there any post hoc analyses from the XTOL study to support the MDD indication?

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Ian C. Mortimer: Thanks, Eddie. So, yeah, I mean, thanks for the question on IP. I think we've done an excellent job, you know, really identifying other ways to extend exclusivity, and obviously some of the work we've done over the last couple of years is now coming to fruition with some of these patents being issued. So I think many people on the call know the base composition of matter when we acquired the drug with median hatch waxman took us into the 2030s, but we wanted to extend that.

Ian C. Mortimer: And obviously, we've had a strategy that so far has been successful, focused on the food effect as well as on polymorph. And polymorphs are compositions in terms of the polymorph patent that's now being issued that gets us out there.

Ian C. Mortimer: you know, 2039, 2040, absent any patent term extension there. There We do have other ideas that we are working on, but nothing yet that would take us past that time frame. We're really focusing on that time frame. In terms of your MDD question, we haven't guided you on this. We believe that although the Sinai study is up and running, meaning that they are screening and they've randomized patients, so that's really nice progress in the last quarter.

Ian C. Mortimer: And our study will start later, but we expect our study would probably go more quickly because it'll be at multiple centers rather than just two. And when we've looked at other companies that have run kind of these phase two proof of concept studies, they've often had data in a reasonable period of time. So if we can get the study up and running, which is our expectation in the first half of next year, I think we could see MDD data in 2023.

Ian C. Mortimer: Thank you. There was also a question.

Ian C. Mortimer: There was also a question there about whether XTol data is needed to inform those studies. I mean, the major driver for the MDD trials is the preclinical data and then the clinical data, the preclinical data with 1101 and then the clinical data with Zogabine, so we don't necessarily need XTol data to inform what we want to do.

Operator: Next, we have Team Luggo from William Blair. Your line is now open.

Lockwood: Hey guys, this is Lockwood on for Tim. Thanks for taking the questions. So on the topic of the MDD trials, you know, I realize it's early in the investigator-initiated studies generally enrolled pretty slowly, but is there anything you can say about the enrollment progress or trends there that you're seeing in that study? And then on the company-sponsored one, have you made progress on the design for that in terms of, you know, I know dosing has been mentioned earlier, are you going to allow concomit Level criteria like that that you've decided on.

Ian C. Mortimer: Sure, Lachlan, I'll give a couple of comments and then Chris can add as well. You know, we don't give guidance on any of our studies in terms of where we are with enrollment, but I will give the caveat that the investigator study is just up and running now, so it's very, very early days for that, but they have randomized, which is great. And in terms of our study, you know, we've given a little bit of color previously. I think one of the things that we...

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Ian C. Mortimer: I've kind of paused on, although we're making good progress, is just trying to now incorporate our thinking with the XTOL data. So that's really around kind of the final dose selection for our company-sponsored study. In terms of the endpoints, we will not have a functional MRI end point, which is the primary endpoint in the IST with Sinai. Instead, we'll be focused on the clinical endpoints of depression in anadonia, and it's currently being designed as a monotherapy study. Chris, any additional color in your thinking? You covered that.

Christopher John Kenney: I think you covered it in you. Nothing to ask. Okay, great.

Operator: Next, we have David Juan from SMBC. Your line is now open, publica your David Oiddoch question. Our last question is from Serge Belander, from Needham and Company. Yolonne is now open.

Serge D. Belanger: Hi, thanks for squeezing me in. A couple of questions. First one on 007: do you still plan to report results from the ongoing investigator study? And is that a program you could eventually part with?

Serge D. Belanger: And then, secondly, regarding the Flection Collaboration,

Serge D. Belanger: Just curious if there are any changes in the economics of that collaboration with the expected change in control of that company. Thank you.

Ian C. Mortimer: Thanks, Serge. I'll answer the second one first.

Ian C. Mortimer: So there are no changes to any of the economics as Flection goes through their transactions. So the new company would just step into their shoes in terms of the economics to ZNon, so there is no change there. In terms of 007, so the IST is continuing and will really be driven by the investigator in terms of her plan to publish data or present data at medical meetings. So I do expect at some point, we will see more data from that 007 study.

Ian C. Mortimer: And as I had answered in one of the questions earlier, you know, we believe that the drug is active based on what we've seen. This is an open-label study. And so in terms of our strategic optionality for that asset, I still think we have some, really today's decision in communication and what we've been focused on internally in our planning is the work that is coming for 1101 and 496 and the focus on that. But we absolutely feel that 007 is an active drug, and we'll continue to support the investigator as she finishes off her stage.

Operator: And there are no further questions, and that concludes the Q&A session. I will now turn a call back to Chevroar Allen in the closing room.

Sherry Aulin: I just wanted to say thank you to everyone for joining us today, and operator, we will now end the call.

Operator: And this concludes today's conference call. Thank you all for your participation. Enjoy the rest of your day, stay safe, and you may now disconnect.

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