Q4 2021 Xenon Pharmaceuticals Inc Earnings Call

March 1, 2022

Thank you for standing by.

Operator: Thank you for standing by and welcome to Xenon Pharmaceuticals 2021 Eurien. At this time, all participants are now disconnected; you will need to press star 1. The advice at today's conference is being recorded. If you require, I will now like to Thank you to your host, Sherry Aulin, Chief Financial Officer of Xenon Pharmaceuticals. Good afternoon.

And welcome to <unk> Pharmaceuticals, 2021 year end financial results call.

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. During this session you will need to press star one on your telephone.

Today's conference is being recorded.

You required any further assistance. Please press star Zero I would now like to hand, the conference over to your host Sharon Allen Chief Financial Officer of seen on Pharmaceuticals. Please go ahead.

Good afternoon. Thank you for joining us on our call and webcast to discuss <unk> year end 2021 financial and operating results joining me here and Martin <unk>, President and Chief Executive Officer, Dr. Chris Kenny <unk>, Chief Medical Officer, and Dr. Chris <unk>, our Chief commercial officer.

Sherry Aulin: Thank you for joining us on our call and webcast to discuss Xenon's year-end 2021 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 von Seggern, 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 research and clinical development plans and timelines, and results of operations.

Please be advised that during this call we will make a number of statements that are forward looking including statements regarding the research and clinical development plans and timelines and results of operations.

Sherry Aulin: The timing of and results from clinical trials and pre-clinical development activities of our proprietary and partnered product candidates. The potential efficacy, safety profile, future development plans, addressable market, regulatory success, and commercial potential of our proprietary and partnered product candidates.

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

Candidates, the anticipated timing of IND or IND equivalent submissions submissions and the initiation of future clinical trials for our proprietary products and those related to other partnered candidates the efficacy of our clinical trial designs, our ability to successfully develop our proprietary development.

Sherry Aulin: The anticipated timing of IND or IND-equivalent submissions and the initiation of future clinical trials for our proprietary products and those related to other partnered candidates. The efficacy of our clinical trial design, our ability to successfully develop our proprietary development programs, the timing and results of our and our collaborators' interactions with regulators, the timing and anticipated enrollment in our clinical trials, the potential receipt of milestone payments and 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.

Graham the timing and results of our and our collaborators interactions with regulators the timing and anticipated in 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 2002.

For and the timing of potential publication 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 todays.

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.

Paul we undertake no obligation to publicly update any forward looking statements.

Sherry Aulin: Today's press release summarizing Xenon's year-end 2021 financial results and the accompanying annual report on Form 10-K will be made available under the investor section of our website at www.xenon-pharma.com and filed with the SEC and on CDART. Now, I'd like to turn the call over to Ian. Thanks, Sherry. Good afternoon, everyone.

Today's press release summarizing xenon with year end 2021 financial results.

The accompanying annual report on Form 10-K will be made available under the investors section of our website at www dot the noncash pharma dot com and filed with the SEC and on SEDAR now I'd like to turn the call over to Ian.

Ian Mortimer: Thanks for joining our call. Today, I'll provide a high-level update on our partnered and proprietary programs, and then I'll turn the call over to Chris Kenney, who will provide additional color around our plans for XCN 1101 moving forward. Sherry will conclude our call by briefly summarizing our financial results and anticipated key milestone events ahead.

Thanks, Jerry good afternoon, everyone. Thanks for joining our call.

Today I'll provide a high level update on our partnered and proprietary programs and then I'll turn the call over to Chris Kenny who will provide additional color around our plans for <unk> hundred one moving forward <unk> will conclude our call by briefly summarizing our financial results and anticipated key milestone events ahead Christiane vigor and is also on the call to provide his perspective during Q&A.

Overall, when we look back on 2021, we are proud of the significant progress we made across our proprietary drug development pipeline and partner programs, including the transformational event of the positive readout of strong efficacy data from our <unk>, one phase <unk> clinical trial, we enter.

Ian Mortimer: Chris von Seggern is also on the call to provide his perspective during Q&A. Overall, when we look back on 2021, we are proud of the significant progress we made across our proprietary drug development pipeline and partner programs, including the transformational event of the positive readout of strong efficacy data from our XCN 1101 Phase IIb XTOL clinical trial. We enter 2022 with incredible momentum, with multiple mid to late stage clinical programs and important milestone opportunities throughout the year, which we'll discuss today.

<unk> 2022, with incredible momentum with multiple mid to late stage clinical programs and important milestone opportunities throughout the year, which we'll discuss today.

Ian Mortimer: I'll start by briefly touching on our partner program. In November, Pacira Biosciences completed its acquisition of Flexion Therapeutics, along with the rights to develop and commercialize Xen 402 and NAB 1.7 inhibitors. XTN-402 has been formulated for extended release from a thermosensitive hydrogel and is now known as PCRX-301.

I will start by briefly touching on our partnered programs in November <unk> Biosciences completed its acquisition of flexion therapeutics, along with the rights to develop and commercialize <unk> zero, two and NAV one seven inhibitor.

<unk> zero two has been formulated for extended release from a thermosensitive hydrogel and is now known as <unk> 301, CRE has indicated that they expect data in the second quarter of this year from our phase <unk> proof of concept trial that is evaluating the safety and Tolerability of PCR <unk> III <unk>.

Ian Mortimer: PCR has indicated that they expect data in the second quarter of this year from a Phase 1b proof-of-concept trial that is evaluating the safety and tolerability of PCRX-301 administered as a single dose in patients undergoing bunionectomy. In addition, I'm pleased to report that our partner programs with NuroKern Biosciences also continue to advance through development. In January, we received a $15 million regulatory milestone under our Collaborate, and Neurocrin now has two separate Phase II clinical trials underway evaluating MBI-921352 in adult patients with focal onset seizures and pediatric patients with SCN8A-related epilepsy.

One administered as a single dose in patients undergoing bunionectomy.

In addition, I am pleased to report that our partner programs with Neurocrine Biosciences also continue to advance through development.

In January we received a $15 million regulatory milestone under our collaborations and Neurocrine now has two separate phase II clinical trials underway evaluating <unk> nine to 1352 in adult patients with focal onset seizures and pediatric patients with <unk> related epilepsy.

Ian Mortimer: We look forward to keeping you updated as these partner programs reach important milestones. Meanwhile, within our proprietary pipeline, we continue to enroll patients in our pediatric XCN496 Phase 3 EPIC clinical trial. This Phase 3 randomized double-blind placebo-controlled parallel group global multicenter clinical trial is evaluating the efficacy, safety, and tolerability of XCN496 in approximately 40 pediatric patients aged 1 month to less than 6 years with KCNQ2

We look forward to keeping you updated as these partner programs reach important milestones.

Within our proprietary pipeline, we continue to enroll patients in our pediatric <unk> 496 phase III epic clinical trial.

This phase III randomized double blind placebo controlled parallel group global Multicenter clinical trial is evaluating the efficacy safety and Tolerability of <unk> hundred 96, and approximately 40 pediatric patients aged one months to less than six years with KFC in Q2.

Based on published physician case studies with <unk> and its cave seven mechanism of action. We believe that <unk> hundred 96 has the potential to address an important unmet medical need for these young patients.

Ian Mortimer: Based on published physician case studies with azogabine and its KV7 mechanism of action, we believe that Xen 496 has the potential to address an important unmet medical need for these young patients. As the EPIC trial continues to expand through the onboarding of new sites and new geographical jurisdictions, our clinical team is anticipating study completion in the first half of 2023. We also continue to make meaningful progress within our XTN 1101 program and have spent considerable time since our X-Tool top-line data in October 2021, analyzing and presenting additional subgroup analyses, building out a robust PK-PD model, evaluating interim safety data in the X-Tool Open Label Extension Study, and completing our planning for our Phase III program.

As the epic trial continues to expand through the Onboarding of new sites and new geographical jurisdictions. Our clinical team is anticipating the study completion in the first half of 2023.

We also continue to make meaningful progress within our <unk> one program and have spent considerable time from our X tole topline data in October 2021, analyzing and presenting additional subgroup analyses building out a robust PK PD model evaluating in terms of safety data in the <unk> open label.

<unk> study and completing our planning for our phase III program.

Ian Mortimer: This is all in preparation for our anticipated end of Phase 2 meeting with FDA in Q2 of this year and expected initiation of our Phase 3 program in the second half of the year. Before passing the call to Chris, we have had some questions recently from investors on the Biohaven-Knopf preclinical KV deal. We haven't discussed the XEN 1101 preclinical data in some time, but we're happy to provide our perspective as these questions have come up.

This is all in preparation for our anticipated end of phase II meeting with FDA in Q2 of this year and expected initiation of our phase III program in the second half of the year.

Before passing the call to Chris we have had some questions recently from investors on the bio Haven cannot preclinical AAV deal. We haven't discussed the <unk> hundred 11 O. One preclinical data in some time, but we're happy to provide our perspective as these questions have come up.

Ian Mortimer: The first question we've received is the activity of XeN-1101 on GABA-A. XeN-1101 has no activity on GABA-A at 10 micromolar. These experiments on XeN-1101 have been conducted at established CRO labs and are also included in our regulatory filings supporting our clinical study.

The first question. We've received is the activity of 11 <unk> hundred one on Gaba a next Gen 1100, one has no activity on Gaba a at 10 micro molar. These experiments on <unk> 11 O. One has been conducted at established CRO Labs and are also included in our regulatory filings supporting our clinical studies and just to put us into <unk>.

<unk> 10 micro molar is approximately 50 fold higher than the concentrations. We reached clinically. So we have no reason to believe that <unk> hundred 11, and no. One has any Gaba activity in human contributed to either the efficacy or the tolerability of <unk> hundred one.

Ian Mortimer: 10 micromolar is approximately 50-fold higher than the concentrations we reach clinically, so we have no reason to believe that XCN1101 has any GABA activity in a human contributing to either the efficacy or the tolerability of XCN1101. The second question we've received is around in vivo pharmacology and therapeutic index. Comparison across experiments is always challenging, and the data presented on their KB compound, BVH7000, is in a different preclinical species and with different toxological measures than the data they showed for XTN1101 or azogabate.

The second question. We've received is around in vivo pharmacology and therapeutic index comparison across experiments are always challenging and the data presented on their kv compound.

<unk> hundred 7000 is in a different preclinical species and with different influx of logical measures. Then the data they showed for <unk> hundred $11, one or <unk>, we've chosen to use a much broader number of preclinical efficacy models and we focused on data generated in the mouse Mes model as the EC 50 is a mismatch.

Ian Mortimer: We have chosen to use a much broader number of preclinical efficacy models, and we focused on data generated in the mouse MES model, as the EC50s in this model predict well the concentrations required to see efficacy in human clinical trials. And this is now being validated with both the Zagreb and XCN11. The BVH7000 efficacy data presented is in the RAT MES model. RATs are known to show efficacy in this model at significantly lower concentrations for the KV mechanism than the mouse. We see roughly a four-fold leftward shift in our EC50s in the RAT MES model for the KB method. So, at the end of the day, data generated using different preclinical species and different experimental endpoints cannot be compared.

Model predicts well the concentration required to see efficacy in human clinical trials and this has now been validated with both <unk> and <unk> hundred one.

The BVA 7000 efficacy data presented as in the Rat Mes model routes are known to show efficacy in this model at significantly lower concentrations for the kv mechanism in the mouse, we see roughly a four fold leftward shift in our <unk> and the Mes model for the kv mechanism so bottom line.

<unk> data generated using different preclinical species and different experimental endpoints cannot be compared.

Ian Mortimer: But now moving back to our XCN 1101 clinical program, in summary, we have considerable data supporting the role that XCN 1101 could play in treating adult patients with focal epilepsy. The X-toll clinical results demonstrated substantial efficacy in a difficult-to-treat patient population, with even more impressive efficacy in some subgroup analyses of patients with less severe disease, a tolerability profile consistent with an active CNS drug, and additional clearly differentiating attributes, including an only-in-class mechanism dosing of one pill once a day with no titration required.

Now moving back to our <unk> hundred one clinical program in summary, we have considerable data supporting the role that <unk> could play in treating adult patients with focal epilepsy. The X tole clinical results demonstrated substantial efficacy in a difficult to treat patient population was even more impressive efficacy in some.

Subgroup analysis of patients with less severe disease tolerability profile consistent with an active CNS drug <unk>.

Additional clearly differentiating attributes, including an only in class mechanism dosing of one pill once a day with no titration required feedback.

Ian Mortimer: Feedback from KOLs and from our proprietary market research supports our belief that XTN1101 has the potential to significantly improve the current standard of care for patients with residual seizure burden and, if approved, would represent a meaningful advancement in the therapeutic armamentarium for this disease. On that note, I'd like to turn the call over to Chris Kenney, who can provide an update on where we are with our Phase III plans for XTN1101 and also on our other Phase II proof-of-concept studies running in parallel. Chris?

Feedback from Kols and from our proprietary market research supports our belief that <unk> hundred one has the potential to significantly improve the current standard of care for patients with residual seizure burden and if approved would represent a meaningful advancement in the therapeutic armamentarium for this disease.

On that note I'd like to turn the call over to Chris Kenny who can provide an update on where we are with our phase III plans for <unk> hundred 1100, one and also on our other phase II proof of concept studies running in parallel Chris.

Chris Kenney: Thanks Ian, I appreciate it. In our last call, which included our American Epilepsy Society presentations, we outlined additional encouraging data generated from our deep dive into the X-toll data. As we continue to complete additional data analysis, our confidence grows in the high potential we anticipate for XEN 1101 to address important unmet needs. Tomorrow, Dr. Jacqueline French will present an encore presentation of the Phase 2b EXTOL data at the ASCENT 2022 Annual Meeting hosted by the American Society for Experimental Neurotherapeutics. We also have a second presentation in a poster format summarizing several sub-analyses addressing the impact of disease severity that suggest efficacy may be more robust in patients with less severe disease burden.

Yes, Thanks again I appreciate it.

Last call with you.

Our American epilepsy Society presentations, we outlined additional encouraging data generated from our deep dive into the X tole data as we continue to complete additional data analysis, our confidence grows in the high potential we envision for.

11 O one to address important unmet needs.

Tomorrow, Dr. Jacqueline French will present, an encore presentation of the phase <unk> data at the <unk> 2022 annual meeting hosted by the American Society for experimental therapy Neuro Therapeutics. We also have a second presentation in a poster format summarizing several sub.

She's addressing the impact of disease severity.

Suggest efficacy may be more robust in patients with less severe disease burden.

Chris Kenney: I encourage you to access these posters on the Xenon website following this event. Given its robust efficacy, along with an AE profile in line with other anti-seizure medications, we're excited to move forward with our Phase III plans for Axion 1101. We remain on track to conduct an end-of-Phase II meeting with FDA during the second quarter of this year. This meeting represents a key milestone for our XEN 1101 program.

I encourage you to access these posters on the xenon website. Following this event.

Given its robust efficacy along with an AE profile in line with other anti seizure medications. We're excited to move forward with our phase III plans for <unk> hundred one.

We remain on track to conduct an end of phase II meeting with the FDA during the second quarter of this year.

This meeting represents a key milestone for <unk> hundred one program the.

Chris Kenney: The objectives for this meeting are to obtain agreement on our Phase 3 program and the overall data package needed for NDA financing. We will also discuss with FDAD the opportunity for X Seoul to be considered a pivotal trial. We anticipate that our future development plans include two phase 3 trials in adult focal epilepsy with the first of these phase 3 trials in the second half of the year.

The objectives for this meeting are to obtain agreement on a phase III program and the overall data package needed for NDA filing.

We will also discuss with the FDA the opportunity for ex told to be considered a pivotal trial.

We anticipate that our future development plans include two phase III trials in adult focal epilepsy with the first of these phase III trials in the second half of the year.

Chris Kenney: After the end of the Phase 2 meeting, we intend to engage European regulators through scientific advice to obtain their agreement on the Axiom 1101 Phase 3 program. In addition to focal epilepsy, we're evaluating other epilepsy indications and expect to outline our plans in the coming... Preclinical and clinical evidence exists around the KV7 mechanism that supports a strong scientific rationale for developing XCN-1101 in major depressive disorder, or We continue to support our collaboration with the School of Medicine at Mount Simon. Patient enrollment is underway in their investigator-sponsored Phase II, proof-of-concept, placebo-controlled clinical trial of XEN1101 in approximately 60 patients for the treatment of major depressive disorder and anhedonia.

After the end of phase II meeting, we intend to engage European regulators through scientific advice to obtain their agreement on the <unk> hundred one phase III program.

In addition to focal epilepsy, we're evaluating other Apple FC indications and expect to outline our plans in the coming months.

Preclinical and clinical evidence exists around the cave seven mechanism that supports a strong scientific rationale for developing <unk> 11 O. One in major depressive disorder or <unk>, we continue to support our collaboration with the school of medicine at Mount Sinai patient enrollment is underway with their investigator.

Our phase two proof of concept placebo controlled clinical trial of <unk> hundred one in approximately 60 patients for the treatment of major depressive disorder and in Indonesia.

Chris Kenney: In addition, an Investigational New Drug, or IND, application has been submitted to FDA to support our plans for a larger Xenon-sponsored clinical study in MDD with XCN 1101, which is expected to be initiated in the first half. We look forward to providing the finalized trial design once the IND has been cleared and the study initiated. Overall, we've made tremendous progress on our XCN 1101 program, and we look forward to initiating the Phase II MDD trial in the near term, followed by our Phase III program in focal epilepsy, which is our target for the second half.

In addition, an investigational new drug or IND application has been submitted to FDA to support our plans for larger xenon sponsored clinical study in MTBE with <unk> 11, O one which is expected to be initiated in the first half of this year.

We look forward to providing the finalized trial design once the IND has been cleared and the study initiated.

Overall, we've made tremendous progress on our <unk>, one program and we look forward to initiating the phase two <unk> trial in the near term followed by a phase III program in focal epilepsy.

<unk> for the second half of this year.

Sherry Aulin: I'd now like to ask Sherry to summarize our financial position and briefly recap our upcoming milestone. Sherry. Thanks, Chris. I'm excited to see the immense amount of momentum in our business as we continue to prudently manage Xenon's operations. As noted on our last quarterly call, I believe Xenon is well capitalized to support our business objectives, the advancement of our clinical development programs, as well as our preclinical and discovery programs. I'll briefly touch on the highlights from this year's financial statements. Cash and cash equivalents and marketable securities as of December 31, 2021 were $551.8 million compared to $177 million as of December 31, 2020.

I'd now like to ask Sheri to summarize our financial position and briefly recap our upcoming milestones Sherry.

Thanks, Chris I'm excited to see the immense amount of momentum in our business as we continue to prudently manage the non US operations as noted on our last quarterly call I believes the non is well capitalized to support our business objectives. The advancement of our clinical development programs as well as our preclinical and discovery program.

I'll briefly touch on the highlights from this year's financial statements cash.

Cash and cash equivalents and marketable securities as of December 31, 2021, or $551 8 million compared to $177 million as of December 31, 2020 Subsys.

Sherry Aulin: Subsequent to year-end, we achieved a $15 million regulatory milestone under our collaboration with Neurocrin Biosciences. Based on current assumptions, which include fully supporting the planned XEN 1101 and XEN 496 clinical development programs, as well as 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. I'd refer you to our news release and 10K report filed today for further details on our financial statements.

Subsequent to year end, we achieved $15 million regulatory milestone under our collaboration with Neurocrine Biosciences.

Based on current assumptions, which include fully supporting the planned <unk>, one and <unk> six clinical development programs as well as 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.

I would refer you to our news release and 10-K report filed today for further details from our financial statements.

Sherry Aulin: Looking ahead, there are a number of key objectives and milestone opportunities in our pipeline. As noted by Chris, we anticipate conducting an end-of-phase 2 meeting with the FDA in the second quarter of 2022 to support the initiation of our Phase 3 development program for XCN 1101 expected in the second half of the year. Post our end-of-phase 2 meeting and receipt of the final FDA minutes, we anticipate being in a position to share our final Phase 3 plans for XCN 1101.

Looking ahead, there are a number of key objectives and milestone opportunities in our pipeline as noted by Chris We anticipate conducting and then just phase two meeting with the FDA in the second quarter of 2022 to support the initiation of our phase III development program for <unk> hundred one expected in the second half of the year posted vendor.

Post our end of phase two meeting and receipt of final FDA minutes, we anticipate being in a position to share our final phase III plans for <unk> hundred one.

Sherry Aulin: In parallel, we'll continue to evaluate and plan for an XEN 1101 program in another epilepsy indication and expect to be in a position to outline our plans in the coming months. We will provide continued support for the ongoing investigator-led study examining XCN 1101 and MDD and expect to initiate our own company-sponsored MDD clinical study in the near term with our IND recently filed. With the ongoing advancement of our EPIC Phase III clinical trial in pediatric patients with KCNQ2-DEE, our team is striving towards study completion in the first half of 2020.

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

I'll provide continued support for the ongoing investigator led study examining <unk> and MTBE and expect to initiate our own company sponsored MVD clinical study in the near term with our <unk> recently filed.

With the ongoing advancement of our epic phase III clinical trial in pediatric patients with Casey in Q2 day. Our team is driving towards study completion in the first half of 2023.

Operator: Finally, we look forward to providing updates on any key milestones reached within our partnered programs with Neurocrin and Pacira Biosciences. In conclusion, I echo Ian's comment that 2021 proved to be a transformative year for Xenon, and on behalf of the entire team, we're energized and driven to continue this momentum. We look forward to keeping you up to date on our progress with multiple Phase 2 and Phase 3 clinical trials anticipated this year, and in particular, our advancements in our Xeon 1101 program.

Finally, we look forward to providing updates on any key milestones reached within our partnered programs with Neurocrine and <unk> Biosciences and.

In conclusion, I Echo <unk> comment that 2021 proved to be a transformative year for xenon and on behalf of the entire team are energized and driven to continue this momentum.

We look forward to keeping you up to date on our progress with multiple phase II and phase III clinical trials anticipated this year and in particular, our advancements in our <unk> program.

Operator: I'll now ask the operator to open the line for any questions. And to ask a question, you will... press 1 on your telephone. To withdraw the question, press the pound or, Stand by while we compile the results.

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

Thank you.

To ask a question you will need to press star one on your telephone to withdraw your question press the pound key.

Please standby, while we compile the Q&A roster.

Our first question comes from Paul Matteis with Stifel.

Unknown Attendee: The first questions come from Paul Mattei. Hey, thanks for taking our question. This is Alex. I'm for Paul.

Hey, Thanks for taking our question. This is Alex on for Paul.

Unknown Attendee: I was just hoping you could provide maybe a little bit more detail on sort of the hooks to patentability for your new patents for 1101 related to food effects and polymorph. Maybe walk through some of the key features there and maybe some precedent related to preventing infringement from these patents. Thanks.

Just hoping you could provide maybe a little bit more detail on sort of the hooks to patent ability for your new patents for 11, one related to food effect and polymorph, maybe walk through some of the key features there and maybe some precedent related to.

Preventing infringement.

These patents.

Unknown Attendee: So, yeah, as you mentioned, we've talked about this on previous calls. We had some good success on the patent front in 2021, and we had US issued patents and claims on both the food effect and polymorphs, the two that you referenced. So on the food effect, this was something that wasn't anticipated early in development, but Xenon 1101 clearly does have a food effect. It's multi-fold on cement.

Thanks, Alex.

Happy to answer that question. So yes, as you mentioned.

We've had we've talked about this on previous calls we've.

We've had some good success on the patent front in 2021, and we had.

<unk> issued patents and claims on both food effect and polymorphous, but two that you referenced so on the food effect. This was something that wasn't anticipated early in development.

But <unk> hundred 11%, one clearly does have a food effect its multi fold on C. Max and AUC and so it was something that we had filed and now all of the efficacy data that we've generated for 11 O won to date. So the X Tole study was taken.

The drug the one pill once a day was taken in the evening and proximity with the evening meal and so we expect that that to be continued development as we move forward and that would be something on label and now we've got IP covering that.

Unknown Attendee: And now we've got IP covering it. And then on the polymorph side, so over the last number of years, we've done extensive polymorph screening to elucidate the number of polymorphs of the drug and to file on that, and that covers, obviously, the form that's in development and will be approved. And so we now have issued claims covering the compositional polymorph as well for XTN-1101. So these two sets of new intellectual property that have been granted over the past number of months, it was in the summer and fall of 2021, would take the exclusivity for XTN-1101 out to 2039-2040, absent any extensions of term from that point forward. Great, thanks. Hi, thanks. This is Leonid on for Brian.

And then on the polymorph side.

The.

Over the last number of years, we've done extensive polymorph screening.

To elucidate the number of polymorph of the drug and to file on that and that covers obviously the form that that's in development and will be approved and so we now have issued claims covering the compositional polymorph is well frac sand 1100 ones. So these two sets of kind of new intellectual property.

That have been granted over the past.

A number of months it was in the summer and fall of 2021 would take the exclusivity for <unk> hundred 11, <unk> out to 2039 to 2040 absent any extensions of term from that point.

Great. Thanks.

Okay.

Our next question comes from Brian Abrahams with RBC capital markets.

Alright. Thanks, this is lean it on for Brian .

Unknown Attendee: I know you guys get a lot of questions on which doses you're going to take forward, so I'd actually like to stay with that for just a minute. And I guess my question is, would you consider taking a dose that you haven't explicitly tested in phase two forward, but one that's intermediate, such as the 15 milligram dose? It sounds like you've got some of that exposure mapping work in hand now, so I'm kind of curious, what are the final considerations that you're sort of working through before you decide on committing a dose, and when you meet with the FDA, Thanks. Thanks, Leo. Good question.

I know you guys get a lot of questions on which doses youre going to take forward. So I'd actually like to stay with that for just a minute.

I guess my question is would you consider taking a dose that you haven't explicitly tested in the phase II forward, but one thats intermediate which is the 15 milligram dose and it sounds like you've got some of that exposure mapping work in hand, now so I'm kind of curious what are the final considerations that youre working through before you decide on committing a dose.

With the FDA are you going to have the two doses that you are thinking of that meeting are you sort of going to shape that based on their feedback as well. Thanks.

Ian Mortimer: Chris Kenney, maybe I'll make a couple of high-level comments, and then you can dig in a little bit deeper. Obviously, we haven't yet publicly talked about the doses that we anticipate taking forward, but as you mentioned, we have done a lot of work, including some detailed PK-PD modeling. The expectation is to take two doses into Phase 3, so the Phase 3 studies would have two active doses and placebo. But I'll let Chris go into greater detail as he kind of thinks about the dose range.

Thanks, Leah good question, Chris maybe I'll make a couple of high level comments and then you can dig in a little bit deeper obviously, we haven't yet publicly talked about the doses that we anticipate taking forward, but as you mentioned, we have done a lot of work.

Including some some detailed PK PD modeling the expectation is to take two doses into phase III. So the phase III studies would have two active doses and placebo.

But I'll, let Chris go into greater detail as he kind of thinks about the dose range.

Ian Mortimer: Obviously, we studied three doses in the Phase 2 program, but Chris and his team have done a lot of work on thinking about dose selection for Phase 3. Yeah, thanks, Ian. I mean, the bottom line is that we're going to, you know, come out publicly with exactly what the plan is once it's been vetted by FDA. We have a very good idea what we want to do, but we just want to go through that step before, you know, bringing it out to the public.

Obviously, we studied three doses in the phase II program, but Chris and his team have done a lot of work I'm thinking on dose selection for phase III.

Yeah. Thanks, Ian I mean, the bottom line is that we're going to come out publicly with exactly what the plan is once it's been vetted by FDA.

Have a very good idea of where we want to do but we just wanted to go to that step before bringing it out to the public.

Chris Kenney: I mean, if you take a look at the Phase 2 data, you could make an argument that really anything between 10 milligrams and 25 milligrams could be brought forward into Phase 3. You know, if you take a look at the factors that we'll weigh in on that, Ian in his presentation talked about PK PD modeling, obviously that's part of the picture, and then also, you know, a heavier weight is being put on sort of safety and efficacy from the actual phase two data, so as I've said before, I think we're in a pretty good situation where any of those doses Page PAGE Operator, yes sir. The next question is from Andrew Tsai. Okay, thanks, and good afternoon.

I mean, if you take a look at the phase two data you could make an argument that really anything between 10 milligrams and 25 milligrams could be brought forward into phase III.

<unk>.

If you take a look at the I mean in terms of the factors that will weigh in on that.

Good.

And in his presentation talked about PK PD modeling, obviously, that's part of the picture and then also.

The heavier weight is being put on sort of safety and efficacy from the actual phase two data so.

As I've said before I mean I think.

We're in a pretty good we're in a luxury situation where any of those doses.

Could be brought forward into phase III or anything between 10 and 25 milligrams. So we will be.

The enthusiasm, but we're going to be happy to go.

Go public with everything once it's been vetted by the agency.

Operator, if we can go to the next question.

Yes, Sir our next question is from Andrew Tsai with Jefferies.

Okay, Thanks, and good afternoon.

Unknown Attendee: So, you know, obviously, you're meeting with the FDA in Q2, and you've kind of outlined your kind of base case scenario as it relates to, you know, the Phase 3, you know, next steps, but I'm curious at this, you know, upcoming FDA meeting, do you guys have an upside scenario in terms of the outcome, if there's one, or even a downside scenario, anything that you can share? Thanks. Thanks, Andrew. Yeah, I'll provide some comments. And Chris and Kenny, you should provide your perspective as well.

Obviously, you are meeting with the FDA in Q2, and you've kind of outlined your kind of base case.

Scenario as it relates to the phase III.

Next steps that I'm curious in this upcoming FDA meeting do you guys have an upside scenario in terms of the outcome. If there is one or even in a downside scenario anything that you can share. Thanks.

Thanks, Andrew Yeah, I'll provide some comments Chris.

Chris Kenny you should provide your perspective as well.

Ian Mortimer: I think, you know, we've talked often with investors about there being a lot of things that we need to discuss with the FDA and make sure that we're aligned, but I don't think there's any kind of big binary questions that we're going in with. Chris talked about in his prepared remarks that we think we have good arguments that X-Tool may be considered a pivotal study, so we'll have that conversation, but our base case is that we're running two phase three clinical trials regardless.

We've talked often with investors that there's a lot of things that we need to have a discussion with the FDA and make sure that we're we're aligned but I don't think theres any kind of big binary questions that we're going in with Chris.

Chris talked about in his prepared remarks that we think we have good arguments that extra or may be considered a pivotal studies that will have that conversation, but our base cases that we're running two phase III clinical trials, regardless, so although lots to talk about I'm not sure. We really go into it Andrew or thinking about kind of a base case or an upside case.

Ian Mortimer: So, although there is lots to talk about, I'm not sure we really go into it, Andrew, thinking about, you know, kind of a base case or an upside case. We're really planning for the phase three program that we think is appropriate for the drug and what's going to be required to get the drug approved and what the NDA package will look like. Chris, do you want to add to that? Yeah, I think that what Ian said just now is a reflection that, you know, we have no intention of cutting any corners; we want to develop the drug properly so that it has a really good chance of being approved within, you know, as quickly as possible. So I don't think that there's anything that's particularly challenging about that interaction.

We are really planning for the phase III program that we think are appropriate.

For the drug and what's going to be required to get the drug approved and what the NDA package will look like Chris don't have stuff.

Yes, I mean, I think that what <unk> said, just now is it a reflection that we have no intention of cutting any corners, we wanted to develop the drug properly so that it has.

Chris Kenney: We do, you know; getting extol to be considered pivotal will provide some optionality. So I guess if I were to pick an upside, I would choose that. But either way, we're going to be doing two additional studies. Thanks. And a follow-up on the MDD program, depression program that's, you know, that you filed an IND, it's more of a kind of high-level question is just that, you know, Zaga being the predecessor drug, approved for epilepsy, it has shown benefits, signals, and, you know, an open label as well as a placebo-controlled study for MDD, and now that we know from XTOL that Chris, do you want to answer that?

A really good chance of being approved within.

As quickly as possible so.

Don't think that there is anything that is particularly challenging both interaction we do getting X told to be considered pivotal will provide some optionality. So I guess, if I were to pick an upside I would choose that but either way, we're going to be doing two additional studies.

Thanks.

And a follow up on the MDT program Depression program.

You filed an IND.

It's more of a kind of a high level question is just that zagha being the predecessor drug proof of epilepsy has shown benefits signals in an open label as well as placebo controlled study for <unk> and now that we know from extra on that 1100, one is indeed more potent and more efficacious.

And Apple FC as it could.

Sure.

Could that be the same case and MDT exactly.

Thanks.

Chris do you want answer that.

Chris Kenney: Yeah, sure. I mean, I don't, I mean, we're obviously enthusiastic about Speaker 1 because we have an investigator-initiated ongoing and even larger sponsor- initiated trial, and enthusiasm comes in terms of the meeting, some kind of mechanism of MDD, and in particular, it may relate to patients who have mood dysfunction. You know, you look at the data; you have preclinical data that suggests that the drugs should be active in depressive models. And then you have the azogging story and the bridges you already pointed out between efficacy and MDD and Faust, and then our focal onset seizure data. So I think that the chance of success might be better than the typical Pock, but who knows? You never know until the end of the day.

Yes sure.

I mean, we're obviously enthusiastic about.

This path because we have an investigator initiated study ongoing and then even the larger sponsor initiated trial.

The enthusiasm comes in terms of the mechanism being interesting.

<unk> in and of itself and then in particular as it may relate to patients with epilepsy, who have moved dysfunction.

You look at the data you have preclinical data that suggests that the.

Drove should be active in depressive models.

And then you have the you saw a good news story in the bridge as you already pointed out between.

Efficacy in MTBE and fast and then <unk>.

Onset seizure data, so I think that the.

The chance of success might be better than the typical path, but who knows you never know until youre at the end of the day.

Thanks Andrea.

Thank you. Our next question comes from Marc Goodman with SBB Leerink.

Hi, Thanks. This is another one for mark.

Unknown Attendee: Just a couple quick ones from us today. You mentioned previously that you're expecting a more formal cut of the XTOL open label extension data sometime before your end of Phase 2 meeting with the FDA. Could we still expect to see that data sometime in the next few months? And then secondly, just wondering if the BioHaven announcement has caused you to rethink or revisit any part of your development plan for Xenon 1101. Thanks. Yeah, thanks for the questions.

Just a couple of quick ones from us today.

<unk> previously that you are expecting a more formal of the X tole.

The open label extension data sometime before your.

<unk> phase II and the phase two meeting with the FDA could we expect to see that data sometime in the next few months, though.

And then secondly, just wondering if the bio Haven announcement cause you to rethink or revisit any part of your development plan for 11, one thanks.

Ian Mortimer: On the ex-toll open-label data, yeah, we have looked at some of that data as it relates, as you mentioned, to the end of Phase 2 meeting. That's really focused on the safety aspects of that data, and we haven't done any analyses of efficacy, but that's kind of on our list of things that we will continue to get at. So no current plans, meaning we haven't submitted an abstract to any medical or scientific meetings in terms of providing any of the ex-toll OLE data.

Yes, thanks for the questions.

On the.

On the X Tole open label data, yes, we have looked at some of that data as it relates to as you mentioned to the end of phase two meeting Thats really focused on the safety aspects of that data and we haven't done any analyses of efficacy, but that's kind of on our list of things that we will continue to.

To get at so no current plans, meaning we haven't submitted an abstract to any medical or scientific meetings in terms of.

Providing any of the extra OLED data, but I do think that that'll be something that will absolutely submit and sure at the appropriate meeting in the future. So we can look forward to that.

Ian Mortimer: But I do think that that'll be something that we absolutely submit and share at the appropriate meeting in the future. So we can look forward to that. On the BioHaven announcement, we had a couple of comments earlier just because we received a number of questions on Friday and over the weekend and yesterday. But no, it doesn't change anything in terms of our plans.

On the bio Haven announcement, we had a couple of comments earlier just because.

We have received.

Number of questions on Friday, and over the weekend and yesterday, but no. It doesn't change anything in terms of our plans, we're very comfortable and the profile of 11 O. One and obviously we're significantly ahead. There is no other cave modulator activator and development and clinical studies right now so none.

Ian Mortimer: We're very comfortable with the profile of 1101, and obviously we're significantly ahead. There is no other KV modulator activator in development for clinical studies right now. So nothing's changed on our side, and our focus is to move 1101 into the Phase 3 program and generate data in MDD as well. Thanks. Hey guys, two quick ones for me.

Things changed on our side and our focus to move 1100, one into the phase III program and generate data in <unk> as well.

Thanks.

Our next question comes from <unk> <unk> with Guggenheim Partners. Please go ahead.

Hey, guys two quick one for me.

Unknown Attendee: Did you speak about the size of the phase three studies? Apologize if I missed it. And also, what would be the time point of an endpoint?

Did you speak about the size.

Of the phase three studies.

Unknown Attendee: Will it be 8 weeks or 12 weeks? I have a follow-up. Sure Chris, do you want to answer those two quick ones? Yeah, sure. I mean, we haven't gone, you know, public with the details, but the spirit of our phase three studies will be as follows. XTOL worked, you know; the data was robust. The other exception, in terms of a change, has to do, outside of going from three doses to two, the other exception is that the duration of the double-blind period will be 12 weeks, as you've pointed out, for both phase III studies. Got it.

I apologize if I missed it and also what would be the time point dolphin endpoint. It will be eight week and 12 week I have a follow up.

Unknown Attendee: And are you waiting for EMA feedback, given that the Europeans require a little bit of a different endpoint before you initiate the studies? Ian, I'm not sure what's public about that, so I think maybe you should field that. Yeah, so often, as we know, European regulators are focusing on the responder analysis. So, you know, we, again, haven't gone through all the detailed Phase 3 protocol synopsis, but we will be looking at MPC and RR50 as we did in X-TOL, so we'll have all of that data.

Sure Chris do you want to answer those two quick ones.

Yes sure.

We haven't gone public with the details, but the spirit of our phase three studies will be.

As follows external work.

The data was robust.

There was a nice separation between active and placebo so if.

If it's working there is no need to fix it so as we go forward into phase III.

We're going to only bring forward two doses <unk> already said that so that will be one difference, but in terms of the general size of the study.

A number of sites et cetera to try to keep it as similar don't want to deviate from the plan that already worked.

The other exception in terms of a change has to do outside of going from three doses to two the other exception is that the.

The duration of the double blind period will be 12 weeks as you've pointed out for both phase III studies.

And are you waiting for EMA feedback given that the European to class a little bit of a different endpoint.

<unk> initiated the studies.

I'm not sure if everyone Eric.

Eric on that.

So I think maybe you should feel that.

Yes so.

Often as we know European regulators or are focusing on the responder analysis. So.

Again, we haven't gone through all the details.

Phase III protocol synopsis, but we will be looking at MPC and our 50 as we did in X tole. So we will have all of that data.

Unknown Attendee: I wouldn't say yet that the scientific advice is gating to getting the Phase 3 trial up and running, but it'll follow, you know, with not a lot of time after the end of the Phase 2 meeting, and then the Phase 3 program, as we said, we'd like to be up and running and initiate the Phase 3 trial within the second half of the month. Okay, just one final question for me.

I wouldn't say that the scientific advice is.

Is gating to getting the phase III trial up and running but it'll follow.

With not a lot of time after the end of phase two meeting and then the phase III program as we said, we'd like to be up and running and initiated the phase III trial within the second half of the year.

Ian Mortimer: So, assuming you initiate these studies in the second half, is XTOL a good proxy of the timeline within which you can complete these studies? Maybe just tell us, you know, how long it might take for you to run these studies. Yeah, I think XTOL is probably a reasonable proxy.

Okay. Just final question from me.

So assuming you initiate these studies in the second half.

Is that still a good proxy of.

The timeline within which you can complete the study maybe just tell us how long it might take for you to run these studies.

Yes, I think Exxon is probably a reasonable proxy.

Ian Mortimer: You know, a couple of things that people may want to take into consideration as they think about the timeline are, so from a sizing point of view, as we've talked about, there's probably not a big difference between the phase three trial and XTOL as we compare them. And Chris has mentioned both in terms of the size and number of sites as well. You know, obviously, the challenge we had for, for those that have followed the company for some time, is that we did have a COVID impact on recruiting and screening patients during XTOL.

A couple of things that people may want it to take into consideration as they think about the timeline.

So from a sizing point of view as we've talked about there's probably not a big difference between the phase III trial and ex told as we compare that <unk> mentioned, both in terms of the size, but a number of sites as well.

Obviously the challenge we had for <unk> for those that have followed the company for some time.

We did have.

Ian Mortimer: And obviously, you know, we can't predict the future. But, But it definitely is the second part of the study of XTOL recruited much better than those months in 2020, early on in the pandemic. And obviously, we now have clinical efficacy. So we have an opportunity to talk to the investigators about that. But, but, but, yeah, and overall, it's probably not a bad proxy because it is a similar-sized study. To the XTOL trial Very good

Covid impact on recruiting and screening of patients during next toll and obviously.

We can't predict the future, but but definitely the second part of the study of ex told recruited much better than than those months in 2020 early on in the pandemic and obviously, we now have clinical efficacy. So we have an opportunity to talk to investigators about that but.

But yes overall, it's probably not a bad proxy because it is a similar size study.

To the X tole trial.

Ian Mortimer: Thanks, Ian. Thank you. Thank you. Your next question comes from Tim Lugo. Hey, this is Lachlan on behalf of Tim.

Very good thanks Ian.

Thank you.

Thanks. Your next question comes from Tim Lugo with William Blair.

Unknown Attendee: Thanks for taking the questions. So we had a couple questions just about somnolence and XTOL. Can you maybe just remind us sort of what you saw there and what is, I guess, typical or standard with other anti-seizure medications? And then on the partnered programs with NeuroCurrent, are you able to provide any more sort of granularity on when in 2023 that data might come or how enrollment is going?

Hey, this is lachlan on for Tim Thanks for taking the questions.

Had a couple questions just about some loans in X tole. So can you maybe just remind us sort of what you saw there and what is I.

I guess typical standard with.

Other antiseizure medications and then on the partnered programs with Neurocrine.

To provide any sort of granularity on when in 2023 that <unk> might come more.

Enrollment is going.

Ian Mortimer: I'll answer, Chris, the question on the partner program on Neurocrin, and then you want to address the question on somnolence. So on the partner programs, yeah, we're really, Lachlan, we're really guided by the guidance that Neurocrin provides. They are, just to be, just to be clear, I know we've talked about this previously; they are running the program and paying for the program, and are in control of it.

Thanks, a lot Glenn I'll answer Chris I'll answer the question on the partner on Neurocrine and then you want to address the question on <unk>.

So on the on the partnered programs, Yes, we're really Laughlin, we really guided by the guidance that Neurocrine provides they are just to be just to be clear I know we've talked about it previously they are running the program and paying for the program and are in control of it.

Two phase II trials are up and running the only one they've given guidance on as the adult focal epilepsy study that they expect to have data in 2023, they havent narrowed the guidance more than just during the calendar year, but those that study is up and running and recruiting and and then in the pediatric epilepsy that is also running and recruit.

Ian Mortimer: And then in pediatric epilepsy, that is also running and recruiting, but they haven't given guidance on when they would expect top-line data. So, as they, as they narrow that guidance going forward, then we can update you there. Chris, I'll pass it to you on somnolence. Yeah, I was trying to look up the exact number because I don't want to misquote it.

But they haven't given guidance on when they would expect top line data so as they as they narrow the guidance going forward. Then then we can update you there Chris.

Let's see on some nodes.

Yes, I was I was trying to look up the exact number because I don't want to misquote it but the more common adverse event was with dizziness and I just don't want to quote the number was somnolence there was a little bit of an imbalance in terms of active versus placebo.

Chris Kenney: But I mean, the more common adverse event was dizziness, and I just don't want to quote what the number was for somnolence. There was a little bit of an imbalance in terms of active versus placebo. I believe it was hovering, you know, under 10%. And there was a bit of a dose response, as there was with dizziness. In terms of, you know, its comparison to other ASMs, we thought that it was very much in line with other anti-seizure medications. Yeah, and Chris, I was just looking at the AE tables as well. And yeah, somnolence actually was, was about 15%. So it was less, quite a bit less than dizziness.

I believe it was hovering under 10%.

And there was a bit of a dose response as there was with dizziness in terms of its comparison to other asm's. We thought that it was very much in line with other anti seizure medications.

Yeah, and Chris I'm, just I was just looking at the AE tables as well and.

Chris Kenney: And actually, we thought about that same level of somnolence in the high dose group of 25 milligrams at approximately 15%. Thanks, and your next question. Hey, thanks for taking the question. So I just had, you know, maybe a little bit of a kind of big picture question.

Yes somnolence.

Overall was.

It was about 15% so it was less quite a bit less in dizziness and.

Actually we saw about that same level of somnolence and the high dose script 25 milligrams at approximately 15%.

Got it thanks.

And your next question comes from David <unk> with NBC.

Hey, Thanks for taking the question.

Unknown Attendee: The, you know, the focal epilepsy landscape may change a bit near term. I think UCB's VIMPAT may lose exclusivity and go generic. And so 1101, there's still a bit of time before it potentially comes to market. But just given, you know, given that landscape and that shift, how are you thinking about down the line potentially positioning for the, you know, the best commercial launch out of the gates?

I just had maybe a little bit of a kind of a big picture question.

The focal epilepsy landscape it may change a bit near.

Near term I think UCB Vimpat may lose exclusivity and go generic and so 11 one.

A bit of time before it potentially comes to market, but just given given that landscape and that shift how are you thinking about down the line potentially positioning for the.

The best commercial launch out of the gates.

Okay.

I think David I think yes, it's a really important question on how <unk> could fit into the focal epilepsy landscape crystalline staggering.

Unknown Attendee: Thanks, David. I think that's a really important question about how 11.01 could fit into the focal epilepsy landscape. Chris von Seggern, can you jump in and provide your perspective? Yeah, absolutely. So VIMPAT's expected to lose exclusivity later this month, and correspondingly, we anticipate that product will move up in lines of therapy based on being one of multiple products that would be used in a generic environment before moving on to branded agents. It does leave behind a massive hole to fill with commercial space.

Can you jump in and provide your perspective.

Chris von Seggern: And when you think about the other available branded agents, none have nearly the reach that VIMPAT does from a commercial standpoint. And when we think about the profile of Axion 1101, it has a combination of safety and efficacy attributes that will make it very competitive for the add-on agent of choice within that first branded market, which is predominantly where VIMPAT stands today. So we view the loss of exclusivity of VIMPAT as one that will shift the nature of the standard of care for early lines of treatment but actually create significant opportunity from commercial products downstream, which is likely where we'll be. Okay, thanks so much.

Absolutely. So the impact is expected to lose exclusivity later this month and correspondingly, we anticipate that product will move up and lines of therapy based on being one of multiple products that will be used in the generic environment before moving onto branded agents. It does leave behind a massive.

To fill from a commercial space and when you think about the other available branded agents.

<unk> have nearly the reach that impact does from a commercial standpoint, and when we think about the profile of <unk> hundred one it has a combination of safety and efficacy attributes that will make it very competitive for the add on agent of choice within that first branded market, which is predominantly web.

And Pat stands today, so we view the loss of exclusivity of impact as one that will shift the nature of the standard of care early lines of treatment, but actually create significant opportunity from commercial products downstream, which is likely where it will be used.

Okay. Thanks, so much.

Thanks, Thanks, David.

Unknown Attendee: The next question comes from Antonia Corovina. Hello, thanks for taking my question. Most of mine have been asked already.

Next question comes from Antonio <unk> with.

Barton.

Hello.

Unknown Attendee: So maybe just a follow-up to the earlier commentary, can you maybe speak to how XCN 1101 would fit in the treatment landscape, given its profile in the KV7 mechanism in MDD? And then, just briefly, on your discovery programs, when can we expect you to announce some additional programs? And do you plan to stick to epilepsies, or would you focus on neurology more broadly?

Thanks for taking my question most of mine have been asked already so maybe just.

A follow up to the earlier commentary can you maybe speak to how <unk> would fit in the treatment landscape.

Given its profile in the cave seven mechanism.

<unk>.

And then just briefly on <unk>.

Youre discovery program when can we expect you to announce some additional programs.

Do you plan to stick to epilepsy or would you focus on neurology more broadly.

Ian Mortimer: Thanks, Antonia. I'll address the discovery one, and then Chris von Seggern, if you want to provide your perspective on the MDD market and the need, and where a drug with a profile like 1101 could fit. I know it's early days, but we can probably provide some high-level commentary. On the discovery portfolio, as many of you know, we have a very active drug discovery group and a number of targets that we're interested in.

Thanks Antonio.

I'll address the discovery, one and then Chris Fund segment, if you want to provide your perspective on the MVD market.

And the need and where a drug with a profile like 11 O. One could fit I know, it's early days, but we can probably provide some high level commentary on.

The discovery portfolio.

As many of you know we have a very active drug discovery group.

And a number of targets that we're interested in Antonio I would say broadly we're interested in neurology, we have had a focus on epilepsy.

Ian Mortimer: Antonia, I would say broadly we're interested in neurology, and we have had a focus on epilepsy. Some of you may have seen our data that we've presented at meetings on a target called NAV1.1, where we're looking at activators of that target that could be used in epilepsy indications such as Dravet syndrome, and we have some very interesting preclinical data there. Obviously, we have a large KB backup effort now where we have backup molecules that, over the next couple of years, will go into clinical development and could give We have different ideas on how to interrogate the target as we move forward, so we have a big effort there.

Some of you will have seen our data that we presented at meetings on a target called NAV, one one where we're looking at activators, but that target that can be used in epilepsy indications such as drive a syndrome and we have some very interesting preclinical data there and obviously, we have a large kv backup FERC.

Now, where we have backup molecules that over the next couple of years will go into clinical development that could either give us a lot of options in the clinic.

Either from an LCM point of view, we're looking at different therapeutic indications as well and we have different ideas on how to interrogate.

<unk> the target as we move forward. So we have a big effort there and then Theres a number of other targets that we like and we're working on that we just haven't talked about publicly yet. So I would say we have brought over efforts pretty clinically and you'll see a number of molecules transition from our discovery portfolio into the clinic over the next few years.

Ian Mortimer: Then there's a number of other targets that we like and we're working on that we just haven't talked about publicly yet. I would say we have broad efforts in preclinical, and you'll see a number of molecules transition from our discovery portfolio into the clinic over the next few years. Chris, on MDD?

Chris on MDT.

Chris von Seggern: Yeah, absolutely. So the MDD marketplace is as complex, if not more complex than the epilepsy space, but it has some similarities in terms of the treatment paradigm. There are entrenched standard of care products that are used early in lines of therapy, SSRIs, and SNRIs, that address a portion of the patient population but leave a sizable percentage of patients who require additional efficacy, either in an add-on, adjunctive environment, or as downstream monotherapy treatment. We anticipate the profile of XEN 1101 to be quite competitive in later lines of therapy, where patients often turn to products that have alternative mechanisms of action with equivalent or comparable efficacy profiles.

Yes, absolutely so the FTB marketplaces as complex if not more complex in the epilepsy space, but has some similarities in terms of the treatment paradigm. There are entrenched standard of care products that are used early in lines of therapy SSRI or SNRI.

Dressed a portion of the patient population, but leave.

Sizable percentage of patients who require additional efficacy either in an add on adjunctive environment or as downstream monotherapy treatment.

<unk> bin the profile for <unk> 11, and want to be quite competitive in later lines of therapy, where patients often turn to products that have alternative mechanisms of action with.

Equivalent or comparable efficacy profiles.

What you are looking for is a mechanism.

Mystic approach, it's either complimentary to the Ssris SRM mris or something that is an alternative for patients who require additional efficacy or have safety or tolerability.

Chris von Seggern: And what you're looking for is a mechanistic approach that's either complementary to SSRIs and SNRIs or something that is an alternative for patients who require additional efficacy or have safety or tolerability issues with earlier lines of therapy. patient population, and one that is going to be increasingly competitive as additional products move forward.

Issues with the earlier lines of therapy that is.

<unk> patient population and one that is going to be increasingly competitive as additional products move forward.

Thanks for the clarification.

Unknown Attendee: Thanks for the clarification. And with that, we end the Q&A session for today. I will turn the call over to Sherry Aulin for the final closing remarks. On behalf of the Xenon team, thank you everyone for joining us on our 2021 financial results conference call. Ad-Ladies and Jen, [music] [inaudible].

Thank you and with that we can.

Q&A session for today.

Turn the call back to Sherry all in for final remarks.

On behalf of the xenon team. Thank you everyone for joining us on our 2021 financial results Conference call.

And with that ladies and gentlemen, we conclude today's program. Thank you for your participation and you may now disconnect.

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[music].

Thank you for standing by and welcome to <unk> seen them Pharmaceuticals 2021 here in financial results call. 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 during the session you will need to.

Operator: .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. [inaudible].

Press Star one on your telephone D.

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

Now like to hand, the conference over to your host Jerry Allen Chief Financial Officer I've seen on Pharmaceuticals. Please go ahead.

Good afternoon. Thank you for joining us on our call and webcast to discuss the non as year end 2021 financial and operating results. Joining me are in more to learn as the President and Chief Executive Officer, Dr. Chris Kenny <unk>, Chief Medical Officer, and Dr. Crisp on staggering.

Operator: ......

These commercial officers.

Be advised that during this call we will make a number of statements that are forward looking including statements regarding their research and clinical development plans and timelines and result of operations.

The timing of and results from clinical trials and preclinical development activities of our proprietary and partnered product candidates.

The potential efficacy safety profile future development plans addressable market regulatory success and commercial potential of our proprietary and partnered product candidates the anticipated timing of R&D or IND equivalent submissions submissions and the initiation of future clinical trials.

For our proprietary products and that was related to other 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 tie.

<unk> 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 publication 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 publicly update any forward looking statement.

Today's press release, summarizing xenon yearend 2021 financial results.

And the accompanying annual report on Form 10-K will be made available under the investors section of our website at www Dot xenon gas pharma dot com and filed with the SEC and on SEDAR now I'd like to turn the call over to Ian.

Operator: Ingrid Ibarra, Dina Ramadane, Sanjay Matthew, Madhumita Yennawar, Xenon Pharmaceuticals Inc Ingrid Ibarra, Dina Ramadane, Sanjay Matthew, Madhumita Yennawar, Xenon Pharmaceuticals Inc Ingrid Ibarra, Dina Ramadane, Sanjay Matthew, Madhumita Yennawar, Xenon Pharmaceuticals Inc Ingrid Ibarra, Dina Ramadane, Sanjay Matthew, Madhumita Yennawar, Xenon Pharmaceuticals Inc Ingrid Ibarra, Dina Ramadane, Sanjay Matthew, Madhumita Yennawar, Xenon Pharmaceuticals Inc Ingrid Ibarra, Dina Ramadane, Sanjay Matthew, Madhumita Yennawar, Xenon Pharmaceuticals Inc Ingrid Ibarra, Dina Ramadane, Sanjay Matthew, Madhumita Yennawar, Xenon Pharmaceuticals Inc Ingrid Ibarra, Dina Ramadane, Sanjay Matthew, Madhumita Yennawar, Xenon Pharmaceuticals Inc Ingrid Ibarra, Dina Ramadane, Sanjay Matthew, Madhumita Yennawar, Xenon Pharmaceuticals Inc Ingrid Ibarra, Dina Ramadane, Sanjay Matthew, Madhumita Yennawar, Xenon Pharmaceuticals Inc, [inaudible] [music] Thank you for standing by and welcome to Xenon Pharmaceuticals. 2021 Year End, At this time, all participants are now disconnected. You will need to press star 1.

Thanks, Jerry good afternoon, everyone. Thanks for joining our call.

Today I'll provide a high level update on our partnered and proprietary programs and then I'll turn the call over to Chris Kenny who will provide additional color around our plans for <unk> hundred one moving forward Sheri will conclude our call by briefly summarizing our financial results and anticipated key milestone events ahead, Chris one zircon is also on the call to provide his perspective during the Q&A.

Overall, when we look back on 2021, we are proud of the significant progress we made across our proprietary drug development pipeline and partner programs, including the transformational event of the positive readout, a strong efficacy data from our <unk> one phase two B X tole clinical trial, we entered.

2022, with incredible momentum with multiple mid to late stage clinical programs and important milestone opportunities throughout the year, which we'll discuss today.

Operator: The advice for today's conference is being recorded. If you require it, I would now like to thank you to your host, Sherry Aulin, Chief Financial Officer of Xenon Pharmaceuticals. Good afternoon.

I'll start by briefly touching on our partnered programs in November <unk> Biosciences completed its acquisition of flexion therapeutics, along with the rights to develop and commercialize <unk> zero, two and NAV one seven inhibitor.

Sherry Aulin: The timing of and results from clinical trials and preclinical development activities of our proprietary and partnered product candidates, the potential efficacy, safety profile, future development plans, addressable market, regulatory success, and commercial potential of our proprietary and partnered product candidates, the anticipated timing of IND or IND equivalent submissions, submissions and the initiation of future clinical trials for our proprietary products and those related to other partnered candidates, the efficacy of our clinical trial designs, our ability to successfully develop our proprietary development programs, the timing and results of our and our collaborators' interactions with regulators, the timing and anticipated enrollment in our clinical trials, the potential receipt of milestone payments and 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. 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 statements.

<unk> has been formulated for extended release from a thermo sensitive hydrogel and is now known as <unk> 301, CRE has indicated that they expect data in the second quarter of this year from our phase <unk> proof of concept trial that is evaluating the safety and Tolerability of PCR X three zero.

One administered as a single dose in patients undergoing bunionectomy.

In addition, I am pleased to report that our partner programs with Neurocrine Biosciences also continued to advance through development.

In January we received a $15 million regulatory milestone under our collaboration and Neurocrine now has two separate phase II clinical trials underway evaluating <unk> nine to 1352 in adult patients with focal onset seizures in pediatric patients with <unk> related epilepsy.

We look forward to keeping you updated as these partner programs reach important milestones.

Within our proprietary pipeline, we continue to enroll patients in our pediatric <unk> 496 phase III epic clinical trials.

Yes.

As the epic trial continues to expand through the Onboarding of new sites and new geographical jurisdictions. Our clinical team is anticipating the study completion in the first half of 2023.

We also continue to make meaningful progress within our <unk> one program and have spent considerable time from our ex told topline data in October 2021, analyzing and presenting additional subgroup analyses building out a robust PK PD model evaluating interim safety data in the <unk> open label extent.

<unk> study and completing our planning for our phase III program.

This is all in preparation for our anticipated end of phase two meeting with FDA in Q2 of this year and expected initiation of our phase III program in the second half of the year.

Before passing the call to Chris we have had some questions recently from investors on the bio Haven cannot preclinical kv deal. We haven't discussed the <unk> 11 O. One preclinical data in some time, but we're happy to provide our perspective of these questions have come up.

The first question. We've received is the activity of <unk> hundred one on Gaba a <unk> hundred 1100, one has no activity on Gaba a at 10 micro molar. These experiments on <unk> 11 O. One have been conducted at established CRO Labs and are also included in our regulatory filings supporting our clinical studies and just to put us into <unk>.

<unk> 10 micro molar is approximately 50 fold higher than the concentrations. We reached clinically. So we have no reason to believe that <unk> hundred 11, no. One has any gaba activity in a human contributing to either the efficacy or the tolerability of <unk> hundred one.

The second question. We've received is around in vivo pharmacology and therapeutic index comparison across experiments are always challenging and the data presented on their kv compound.

The age 7000 is in a different preclinical species and with different flex a logical measures then the data they showed for <unk> hundred 11, O one or as AGA beam, we have chosen to use a much broader number of preclinical efficacy models and we focused on data generated in the mouse Mes model as the EC <unk> in this <unk>.

Model predicts well the concentration required to see efficacy in human clinical trials and this is now being validated with both <unk> and <unk> hundred 11, <unk> hundred one.

<unk> data generated using different preclinical species and different experimental endpoints cannot be compared.

Now moving back to our <unk> hundred 11, <unk> hundred one clinical program in summary, we have considerable data supporting the role that <unk> 11 O. One could play in treating adult patients with focal epilepsy. The X tole clinical results demonstrated substantial efficacy in a difficult to treat patient population was even more impressive efficacy in some.

Subgroup analysis of patients with less severe disease, a tolerability profile consistent with an active CNS drugs.

Additional clearly differentiating attributes, including an only in class mechanism dosing of one pill once a day with no titration required feedback.

On that note I'd like to turn the call over to Chris Kenny who can provide an update on where we are with our phase III plans for <unk> hundred 11, <unk> hundred one and also on our other phase II proof of concept studies running in parallel Chris.

Yes, Thanks again I appreciate it.

Last call would you be.

Eric epilepsy.

Presentations, we outlined additional encouraging data generated from our deep dive into the X tole data as we continue to complete additional data analysis, our confidence grows in the high potential we envision for <unk> 11 O one to address important unmet needs.

Tomorrow, Dr. Jacqueline French will present, an encore presentation of the phase <unk> data at the <unk> 2022 annual meeting hosted by the American Society for experimental Neuro Therapeutics.

We also have a second presentation in a poster format summarizing several sub analyses addressing the impact of disease severity.

Efficacy may be more robust in patients with less severe disease burden.

I encourage you to access these posters on the xenon website. Following this event.

Given its robust efficacy along with an AE profile in line with other anti seizure medications.

Excited to move forward with our phase III plans for <unk> hundred one we.

We remain on track to conduct an end of phase II meeting with the FDA during the second quarter of this year.

This meeting represents a key milestone for <unk> 11 O one program the.

The objectives for this meeting are to obtain agreement on a phase III program and the overall data package needed for NDA filing.

We will also discuss with FDA the opportunity for ex told to be considered a pivotal trial.

We anticipate that our future development plans include two phase III trials in adult focal epilepsy with the first of these phase III trials in the second half of the year.

After the end of phase II meeting, we intend to engage European regulators through scientific advice to obtain their agreement on the <unk> 11 of one phase III program.

In addition to focal epilepsy, we're evaluating other Apple FC indications and expect to outline our plans in the coming months.

<unk> phase two proof of concept placebo controlled clinical trial of <unk> hundred one in approximately 60 patients for the treatment of major depressive disorder and anhedonia.

In addition, an investigational new drug or IND application has been submitted to FDA to support our plans for a larger xenon sponsored clinical study and Mgd with exon 11 O one which is expected to be initiated in the first half of this year.

We look forward to providing the finalized trial design once the IND has been cleared and the study initiated.

Overall, we've made tremendous progress on our <unk> 11 O. One program and we look forward to initiating the phase two <unk> trial in the near term followed by a phase III program in focal epilepsy targeted for the second half of this year.

I'd now like to ask Sheri to summarize our financial position and briefly recap our upcoming milestones Sherry.

Thanks, Chris I'm excited to see the immense amount of momentum in our business as we continue to prudently manage the operations as noted on our last quarterly call I believe beyond well capitalized to support our business objectives, the advancement of our clinical development programs as well as our preclinical and discovery program.

I'll briefly touch on the highlights from this year's financial statements.

Cash and cash equivalents and marketable securities as of December 31, 2021, or $551 8 million compared to $177 million as of December 31, 2020 subsea.

Ian Mortimer: PCR has indicated that they expect data in the second quarter of this year from a Phase 1b proof of concept trial that is evaluating the safety and tolerability of PCRX-301 administered as a single dose in patients undergoing bunionectomy. In addition, I'm pleased to report that our partner programs with NuroKern Biosciences also continue to advance through development. In January, we received a $15 million regulatory milestone under our collaboration.

Subsequent to year end, we achieved a $15 million regulatory milestone under our collaboration with Neurocrine Biosciences.

Based on current assumptions, which include fully supporting the planned <unk>, one and <unk> 496 clinical development programs as well as preclinical and discovery program, we anticipate having sufficient cash to fund operations into at least 2024, excluding any revenue generated from existing partnerships.

Or potential new partnering arrangements.

I would refer you to our news release and 10-K report filed today for further details from our financial statements.

Looking ahead, there are a number of key objectives and milestone opportunities in our pipeline as noted by Chris We anticipate conducting an end of phase two meeting with the FDA in the second quarter of 2022 to support the initiation of our phase III development program for <unk> hundred one expected in the second half of the year posted vendor.

Post our end of phase two meeting and receipt of final FDA minutes, we anticipate being in a position to share our final phase III plans for <unk> hundred one.

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

Well provide continued support for the ongoing investigator led study examining <unk> 11 O one mbd and expect to initiate our own company sponsored MVD clinical study in the near term with our <unk> recently filed.

Ian Mortimer: And Neurocrin now has two separate Phase II clinical trials underway evaluating MBI-921352 in adult patients with focal onset seizures and pediatric patients with SCN8A-related epilepsy. We look forward to keeping you updated as these partner programs reach important milestones. Within our proprietary pipeline, we continue to enroll patients in our pediatric XCN496 Phase 3 EPIC clinical trial. This Phase 3 randomized, double-blind, placebo-controlled, parallel-group, global multicenter clinical trial is evaluating the efficacy, safety, and tolerability of XCN496 in approximately 40 pediatric patients aged 1 month to less than 6 years who have KCNQ2DEE.

With the ongoing advancement of our epic phase III clinical trial in pediatric patients with Casey in Q2 day. Our team is driving towards study completion in the first half of 2023.

Ian Mortimer: Based on published physician case studies with azogavine and its KV7 mechanism of action, we believe that Xen 496 has the potential to address an important unmet medical need for these young patients. As the EPIC trial continues to expand through the onboarding of new sites and new geographical jurisdictions, our clinical team is anticipating study completion in the first half of 2023. We also continue to make meaningful progress within our XTN 1101 program and have spent considerable time since our X-Tool top-line data in October 2021, analyzing and presenting additional subgroup analyses, building out a robust PK-PD model, evaluating interim safety data in the X-Tool Open Label Extension Study, and completing our planning for our Phase III program.

Finally, we look forward to providing updates on any key milestones reached within our partnered programs with Neurocrine Antisera Biosciences.

In conclusion, I Echo <unk> comment that 2021 proved to be a transformative year for xenon and on behalf of the entire team are energized and driven to continue this momentum we look forward to keeping you up to date on our progress with multiple phase II and phase III clinical trials anticipated this year and in particular our advanced.

Ian Mortimer: This is all in preparation for our anticipated end of Phase 2 meeting with FDA in Q2 of this year and expected initiation of our Phase 3 program in the second half of the year. Before passing the call to Chris, we have had some questions recently from investors on the Biohaven-Kanop preclinical KV deal. We haven't discussed the XEN 1101 preclinical data in some time, but we're happy to provide our perspective as these questions have come up.

<unk> and our <unk> hundred one program.

Ian Mortimer: The first question we've received is the activity of XEN11-01 on GABA-A. XEN11-01 has no activity on GABA-A at 10 micromolar. These experiments on XEN11-01 have been conducted at established CRO labs and are also included in our regulatory filings supporting our clinical studies.

Ill now ask the operator to open the line for any questions.

Thank you.

To ask a question you will need to press star one on your telephone to withdraw your question press the pound or hash key.

Ian Mortimer: We have chosen to use a much broader number of preclinical efficacy models, and we focused on data generated in the mouse MES model, as the EC50s in this model predict well the concentrations required to see efficacy in human clinical trials, and this is now being validated with both Zagabin and XeN11. The BVH7000 efficacy data presented is in the rat MES model. RATs are known to show efficacy in this model at significantly lower concentrations for the KV mechanism than the mouse. Therefore, we see roughly a four-fold leftward shift in our EC50s in the RAT MES model for the KB method.

Please standby, while we compile the Q&A roster.

Our first question comes from Paul Matteis with Stifel.

Ian Mortimer: So, bottom line, data generated using different preclinical species and different experimental endpoints cannot be compared. But now moving back to our XTN 1101 clinical program, in summary, we have considerable data supporting the role that XTN 1101 could play in treating adult patients with focal epilepsy. The X-toll clinical results demonstrated substantial efficacy in a difficult-to-treat patient population, with even more impressive efficacy in some subgroup analyses of patients with less severe disease, a tolerability profile consistent with an active CNS drug, and additional clearly differentiating attributes, including an only-in-class mechanism dosing of one pill once a day with no titration required.

Hey, Thanks for taking our question is Alex on for Paul.

Ian Mortimer: Feedback from KOLs and from our proprietary market research supports our belief that XTN11-01 has the potential to significantly improve the current standard of care for patients with residual seizure burden and, if approved, would represent a meaningful advancement in the therapeutic armamentarium for this disease. On that note, I'd like to turn the call over to Chris Kenney, who can provide an update on where we are with our Phase III plans for XTN11-01 and also on our other Phase II proof-of-concept studies running in parallel. Chris?

Was just hoping you could provide maybe a little bit more detail.

On sort of the hooks to patent ability for your new patents for 11, one related to food effect and polymorph, maybe walk through some of the key features there and maybe some precedent related too.

Preventing infringement.

These patents.

Chris Kenney: Thanks, Ian. I appreciate it. In our last call, which included our American Epilepsy Society presentations, we outlined additional encouraging data generated from our deep dive into the X-Toll data. As we continue to complete additional data analysis, our confidence grows in the high potential we anticipate for XEN 1101 to address important unmet needs. Tomorrow, Dr. Jacqueline French will present an encore presentation of the Phase IIb XTOL data at the ASCENT 2022 Annual Meeting hosted by We also have a second presentation in a poster format summarizing several sub-analyses addressing the impact of disease severity that suggest efficacy may be more robust in patients with less severe disease burden.

Thanks, Alex.

Chris Kenney: I encourage you to access these posters on the Xenon website following this event. Given its robust efficacy, along with an AE profile in line with other anti-seizure medications, we're excited to move forward with our Phase III plans for Axion 1101. We remain on track to conduct an end of Phase 2 meeting with the FDA during the second quarter of this year. This meeting represents a key milestone for our XEN 1101

Chris Kenney: The objectives for this meeting are to obtain agreement on our Phase 3 program and the overall data package needed for NDA financing. We will also discuss with the FDA the opportunity for XTOL to be considered a pivotal trial. We anticipate that our future development plans include two phase 3 trials in adult focal epilepsy, with the first of these phase 3 trials in the second half of the year. After the end of the phase 2 meeting, we intend to engage European regulators through scientific advice to obtain their agreement on the Axiom 1101 Phase 3 program.

Happy to answer that question. So yes, as you mentioned.

Chris Kenney: In addition to focal epilepsy, we're evaluating other epilepsy indications and expect to outline our plans in the coming... Preclinical and clinical evidence exists around the KV7 mechanism that supports a strong scientific rationale for developing XeN-1101 in major depressive disorder, or MD. We continue to support our collaboration with the School of Medicine at Mount Simon. Patient enrollment is underway in their investigator-sponsored Phase II, proof-of-concept, placebo-controlled clinical trial of XEN1101 in approximately 60 patients for the treatment of major depressive disorder and anhedonia.

Sherry Aulin: I'm excited to see the immense amount of momentum in our business as we continue to prudently manage Xenon's operations. As noted on our last quarterly call, I believe Xenon is well capitalized to support our business objectives, the advancement of our clinical development programs, as well as our preclinical and discovery programs. I'll briefly touch on the highlights from this year's financial statements. Cash and cash equivalents and marketable securities as of December 31, 2021 were $551.8 million compared to $177 million as of December 31, 2020.

We've had we've talked about this on previous calls we've.

Sherry Aulin: Looking ahead, there are a number of key objectives and milestone opportunities in our pipeline. As noted by Chris, we anticipate conducting an end-of-Phase 2 meeting with the FDA in the second quarter of 2022 to support the initiation of our Phase 3 development program for XCN 1101 expected in the second half of the year. Post our end-of-Phase 2 meeting and receipt of the final FDA minutes, we anticipate being in a position to share our final Phase 3 plans for XCN 1101.

Sherry Aulin: In parallel, we'll continue to evaluate and plan for an Xeon 1101 program and another epilepsy indication and expect to be in a position to outline our plans in the coming months. We will provide continued support for the ongoing investigator-led study examining XCN 1101 and MDD and expect to initiate our own company-sponsored MDD clinical study in the near term with our IND recently filed. With the ongoing advancement of our EPIC Phase III clinical trial in pediatric patients with KCNQ2-DEE, our team is striving towards study completion in the first half of 2020.

Sherry Aulin: Finally, we look forward to providing updates on any key milestones reached within our partnered programs with Neurocrin and Pacira Biosciences. In conclusion, I echo Ian's comment that 2021 proved to be a transformative year for Xenon, and on behalf of the entire team, we're energized and driven to continue this momentum. We look forward to keeping you up to date on our progress with multiple Phase 2 and Phase 3 clinical trials anticipated this year, and in particular, our advancements in our Xeon 1101 program.

We've had some good success on the patent front in 2021, and we had.

Sherry Aulin: I'll now ask the operator to open the line for any questions. And to ask a question, you will press 1 on your telephone. To withdraw the question, press the pound or, Stand by while we compile the results.

S issued patents and claims on both food effect and poly amongst the two that you referenced so on the food effect. This was something that wasn't anticipated early in development, but <unk> 11 O. One clearly it does have a food effect, it's multifold on C. Max and AUC and so it was something that we had filed and now all of the.

Operator: The first question comes from Paul Matteis. Hey, thanks for taking our question. This is Alex. I'm for Paul.

Efficacy data that we've generated for 1100 won to date. So the X Tole study was taken.

The drug, but one pill once a day was taken in the evening and proximity with the evening meal and so we expect that that to be continued development as we move forward and that would be something on label and now we've got IP covering that.

Unknown Attendee: So yeah, as you mentioned, and we've had, we've talked about this on previous calls, we've had some good success on the patent front in 2021, and we had U.S. issued patents and claims on both Food Effect and Polymorph, the two that you referenced. So on the Food Effect, this was something that wasn't anticipated early in development, but XEN1101 clearly does have a food effect. It's multifold on CMAX and AUC, and so it was something that we had filed, and now all of the efficacy data that we've generated for 1101 to date, so the X-Toll study was taken, the drug, the one pill once a day was taken in the evening in proximity with the evening meal, and so we expect that that to be continued development as we move forward, and that would be something on label, and now we've got IP covering that.

And then on the polymorph side.

So the.

Over the last number of years, we've done extensive polymorph screening.

To elucidate the number of polymorph of the drug and to file on that and that covers obviously the form that that's in development and will be approved and so we now have issued claims covering the compositional polymorph as well for <unk> hundred 11, <unk> hundred one. So these two sets of kind of new intellectual property.

Unknown Attendee: And then on the polymorph side, so over the last number of years, we've done extensive polymorph screening to elucidate the number of polymorphs of the drug and file on that, and that covers, obviously, the form that's in development and will be approved. And so we now have issued claims covering the compositional polymorphs as well for XTN-1101.

That have been granted over the past.

A number of months it was in the summer and fall of 2021 would take the exclusivity for <unk> hundred 1100, one out to 2039 to 2040 absent any extensions of term from that point.

Great. Thanks.

Unknown Attendee: So these two sets of kind of new intellectual property that have been granted over the past number of months, it was in the summer and fall of 2021, would take the exclusivity for XTN-1101 out to 2039-2040, absent any extensions of term from that point forward. Great, thanks. Hi, thanks. This is Leonid on behalf of Brian.

Our next question comes from Brian Abrahams with RBC capital markets.

Hi, Thanks, This is lean it on for Brian .

Unknown Attendee: I know you guys get a lot of questions on which doses you're going to take forward, so I'd actually like to stay with that for just a minute. And I guess my question is, would you consider taking a dose that you haven't explicitly tested in phase two forward, but one that's intermediate, which is the 15 milligram dose? It sounds like you've got some of that exposure mapping work in hand now, so I'm kind of curious, what are the final considerations that you're sort of working through before you decide on committing a dose, and when you meet with the FDA, Thanks, Leo. That's a good question.

I know you guys got a lot of questions on which doses youre going to take forward. So I'd actually like to stay with that for just a minute.

And I guess my.

My question is would you consider taking a dose that you haven't explicitly tested in the phase II forward, but one thats intermediate which is the 15 milligram dose and it sounds like you've got some of that exposure mapping work in hand, now so I'm kind of curious what are the final considerations that you're sort of working through before you decide on committing a dose and when you meet with the FDA are you going.

Have the two doses that you're thinking of that meeting are you sort of going to shape that based on their feedback as well. Thanks.

Ian Mortimer: Chris Kenney, maybe I'll make a couple of high-level comments, and then you can dig in a little bit deeper. Obviously, we haven't yet publicly talked about the doses that we anticipate taking forward, but as you mentioned, we have done a lot of work, including some detailed PK-PD modeling. The expectation is to take two doses into Phase 3, so the Phase 3 studies would have two active doses and placebo, but I'll let Chris go into greater detail as he kind of thinks about the dose range.

Including some some detailed PK PD modeling the expectation is to take two doses into phase three so the phase III studies would have two active doses and placebo.

But I'll, let Chris go into greater detail as he kind of thinks about the dose range.

Obviously, we studied three doses in the phase II program, but Chris and his team have done a lot of work on thinking on dose selection for phase III.

Yeah. Thanks, Ian I mean, the bottom line is that we're going to come out publicly with exactly what the plan is once it's been vetted by FDA.

Have a very good idea of where we want to do but we just wanted to go to that step before bringing it out to the public.

I mean, if you take a look at the phase two data you could make an argument that really anything between 10 milligrams and 25 milligrams could be brought forward into phase III.

<unk>.

If you take a look at the I mean in terms of the factors that will weigh in on that.

Yes.

And in his presentation talked about PK PD modeling, obviously, that's part of the picture and then also.

Chris Kenney: And then also, you know, the heavier weight is being put on sort of safety and efficacy from the actual phase two data. So, as I've said before, I mean, I think, you know, we're in a pretty good, we're in a luxury situation where any of those doses. Page PAGE of NUMPAGES www.verbalink.com Page PAGE of NUMPAGES, H-H-H-H-H-H-H-H-H-H-H, Operator, if we can go to the next question.

The heavier weight is being put on sort of safety and efficacy from the actual phase two data so.

As I've said before I mean, I think we're in a pretty good we're in a luxury situation where any of those doses.

Could be brought forward into phase III anything between 10, and 25 milligrams, so where we'll be.

Great. The enthusiasm, we're going to be happy to go public with everything once it's been vetted by the by the agency.

Okay.

Yes.

Operator, if we can go to the next question, Yes, Sir and our next question is from Andrew Tsai with Jefferies.

Operator: Operator, yes, sir. And our next question is from Andrew Tsai. Okay, thanks, and good afternoon. Obviously, you're meeting with the FDA in Q2, and you've kind of outlined your kind of base case scenario as it relates to, you know, the phase three, you know, next steps, but I'm curious at this, you know, upcoming FDA meeting, do you guys have an upside scenario in terms of the outcome, if there's one, or even a downside scenario, anything that you Thanks. Thanks, Andrew. Yeah, I'll provide some comments. And Chris, and Kenny, you should provide your perspectives as well.

Yeah.

Okay, Thanks, and good afternoon.

Obviously, you are meeting with the FDA in Q2, and you've kind of outlined your kind of base case scenario as it relates to the phase III.

Next steps that I'm curious in this upcoming FDA meeting do you guys have an upside scenario in terms of the outcome. If there is one or even in a downside scenario or anything that you can share. Thanks.

Thanks, Andrew Yeah, I'll provide some comments.

And Chris Kenny you should provide your perspective as well.

Ian Mortimer: I think, you know, we've talked often with investors about a lot of things that we need to have a discussion with the FDA and make sure that we're aligned, but I don't think there's any kind of big binary questions that we're going in with. Chris talked about in his prepared remarks that we think we have good arguments that X-Tool may be considered a pivotal study, so we'll have that conversation. But our base case is that we're running two phase three clinical trials regardless.

We've talked often with investors that there's a lot of things that we need to have a discussion with the FDA and make sure that where we're aligned but I don't think theres any kind of big binary questions that we're going in with.

Chris talked about in his prepared remarks that we think we have good arguments that extra or may be considered a pivotal studies that will have that conversation, but our base cases that we're running two phase III clinical trials, regardless, so although lots to talk about it I am not sure. We really go into it Andrew or thinking about kind of a base case or an upside case.

Ian Mortimer: So although there is lots to talk about, I'm not sure we really go into it, Andrew, thinking about, you know, kind of a base case or an upside case. We're really planning for the phase three program that we think is appropriate for the drug and what's going to be required to get the drug approved and what the NDA package will look like. Chris, do you want to add to that?

We are really planning for the phase III program that we think are appropriate for.

For the drug and what's going to be required to get the drug approved and what the NDA package will look like.

Go ahead.

Yeah, I mean, I think that what <unk> said, just now is a reflection that we have no intention of cutting any corners, we wanted to develop the drug properly so that it has.

Chris Kenney: Yeah, I mean, I think that what Ian said just now is a reflection that, you know, we have no intention of cutting any corners; we want to develop the drug properly so that it has a really good chance of being approved within, you know, as quickly as possible. So I don't think that there's anything that's particularly challenging about that interaction. We do, you know, getting extol to be considered pivotal will provide some optionality. So I guess if I were to pick an upside, I would choose that.

A really good chance of being approved.

As quickly as possible so.

I don't think that there's anything that's particularly challenging about the interaction you redo getting X told to be considered pivotal will provide some optionality. So I guess, if I were to pick an upside I would choose that but either way, we're going to be doing two additional studies.

Thanks.

Chris Kenney: But either way, we're going to be doing two additional studies. Thanks. And a follow-up on the MDD program, depression program that's, you know, that you filed in the IND, it's more of a kind of a high-level question is just that, you know, Zaga being the predecessor drug, you know, approved for epilepsy, it has shown benefits, signals, and, you know, an open label as well as placebo-controlled study for MDD, and now that we know, you know, from XTOL that, you know, 1101 is indeed more potent and more efficacious in epilepsy, you know, is it shouldn't that, you know, could that be the same case in MDD? Chris, do you want to answer that?

And a follow up on the MDT program Depression program.

File the IND.

It's more of a kind of a high level question is just that zagha being the predecessor drug approved for epilepsy.

Benefits signals.

The open label as well as placebo controlled study for <unk> and now that we know from X 12, 11% one is indeed more potent and more efficacious.

And Apple FC.

Sure.

That would be the same case.

<unk> basically.

Thanks.

Chris do you want answer that.

Chris Kenney: Yeah, sure. I mean, I don't, I mean, we're obviously enthusiastic about this path because we have an investigator-initiated study ongoing and then even a larger sponsor-initiated trial. The enthusiasm comes in terms of the mechanism being interesting and MDD in and of itself, and then in particular as it may relate to patients with epilepsy who have mood dysfunction. You know, you look at the data; you have preclinical data that suggests that the drug should be active in depressive models.

Yes sure.

I don't I mean, we.

We are obviously enthusiastic about.

This path because we have an investigator initiated study ongoing and then even a larger sponsor initiated trial.

The enthusiasm comes in terms of the mechanism being interesting and.

<unk> in and of itself and then in particular as it may relate to patients with epilepsy, who have moved dysfunction.

You look at the data you have preclinical data that suggests that the.

Drugs should be active in depressive models.

Chris Kenney: And then you have the Azagabim story and the bridges you've already pointed out between efficacy in MDD and FOS and then our focal onset seizure data. So I think that, you know, the chance of success might be better than the typical POC, but, you know, who knows? You never know until you're at the end of the day.

And then you have the you saw a good news story in the bridges you already pointed out between.

Efficacy in MTBE and fast and then focal onset seizure data so.

I think that you know the.

The chance of success might be better than the typical path, but you know who knows you never know until youre at the end of the day.

Thanks Andrea.

Unknown Attendee: Thanks so much. Hi, thanks. This is Madhuwan for Mark.

Thank you. Our next question comes from Marc Goodman with SBB Leerink.

Hi, Thanks. This is another one for mark.

Unknown Attendee: Just a couple quick ones from us today. You mentioned previously that you're expecting a more formal cut of the XTOL open label extension data sometime before your end of Phase 2 meeting with the FDA. Could we expect to see that data sometime in the next few months? And then secondly, just wondering if the BioHaven announcement caused you to rethink or revisit any part of your development plan for Xenon-1101. Thanks.

Just a couple of quick ones from us today.

<unk> previously that you are expecting a more formal of the X tole.

<unk> open label extension data sometime before your phase.

<unk> phase II and the safety meeting with the FDA and could we expect to see that data sometime in the next few months, though.

And then secondly, just wondering if the bio Haven announcement caused you to rethink or revisit any part of your development plan for as you know of anyone.

Ian Mortimer: Yeah, thanks for the questions. On the ex-toll open-label data, yeah, we have looked at some of that data as it relates, as you mentioned, to the end of Phase 2, meaning that's really focused on the safety aspects of that data, and we haven't done any analyses of efficacy, but that's kind of on our list of things that we will continue to get at. So, no current plans, meaning we haven't submitted an abstract to any medical or scientific meetings in terms of providing any of the ex-toll OLE data, but I do think that that'll be something that we absolutely submit and share at the appropriate meeting in the future, so we can look forward to that.

Yes, thanks for the questions.

On the.

To get at so no current plans, meaning we haven't submitted an abstract to any medical or scientific meetings in terms of.

Providing any of the extra OLED data, but I do think that that'll be something that will absolutely submit and sure at the appropriate meeting in the future. So we can look forward to that.

Ian Mortimer: On the BioHaven announcement, we had a couple of comments earlier just because we'd received a number of questions on Friday and over the weekend and yesterday, but no, it doesn't change anything in terms of our plans. We're very comfortable with the profile of 1101, and obviously, we're significantly ahead.

On the bio Haven announcement, we had a couple of comments earlier just because.

We've received.

Modulator activator and development and clinical studies right now so nothing has changed on our side and our focus to move 11 O one into the phase III program and generate data in Mds as well.

Ian Mortimer: There is no other KV modulator activator in development in clinical studies right now. So, nothing's changed on our side, and our focus is to move 1101 into the Phase 3 program and generate data in MDD as well. Thanks. Hey guys, two quick ones for me.

Thanks.

Our next question comes from <unk> <unk> with Guggenheim Partners. Please go ahead.

Hey, guys two quick one for me.

Unknown Attendee: Did you speak about the size of the phase three studies? Apologize if I missed it. And also, what would be the time point of an endpoint?

Could you speak about the size.

Of the phase three studies.

Chris Kenney: Will it be 8 weeks or 12 weeks? I have a follow-up. Sure Chris, do you want to answer those two quick ones? Yeah, sure. I mean, we haven't gone, you know, public with the details, but the spirit of our phase three studies will be as follows. XTOL worked, you know; the data was robust. There was a nice separation between active and placebo. So if it's working, there's no need to fix it.

I apologize if I missed it and also what would be the time point dolphin endpoint. It will be eight week and 12 week I have a follow up.

Sure Chris do you want to answer those two quick ones.

Yes sure.

We haven't gone public with the details, but the spirit of our phase III studies will be as follows external work.

The data was robust there was a nice separation between active and placebo. So if.

If it's working there is no need to fix it so as we go forward into phase III.

Chris Kenney: So, you know, as we go forward into phase three, we're going to only bring forward two doses. Ian's already said that. So that will be one difference. But in terms of the general size of the study, and the number of sites, etc., try to keep it as similar as possible.

We're going to only bring forward two doses <unk> already said that so that will be one difference, but in terms of the general size of the study.

Chris Kenney: You don't want to deviate from the plan that has already worked. The other exception, in terms of a change, has to do, outside of going from three doses to two, the other exception is that the duration of the double-blind period will be 12 weeks, as you've pointed out, for both Phase III studies.

A number of sites etcetera try to keep it as similar don't want to deviate from the plan that already worked.

The other exception in terms of a change has to do outside of going from three doses to two the other exception is that.

The duration of the double blind period will be 12 weeks as you've pointed out for both phase III studies.

Unknown Attendee: And are you waiting for EMA feedback, given that the Europeans require a little bit of a different endpoint before you initiate the studies? Ian, I'm not sure if you want to panic about that, so I think maybe you should feel that. Yeah, so often, as we know, European regulators are focusing on the responder analysis. So, you know, we, again, haven't gone through all the detailed phase three protocol synopsis, but we will be looking at MPC and RR50 as we did in XTOL, so we'll have all of that data.

Got it and are you waiting for EMA feedback given that the European the class a little bit of a different endpoint.

Before you initiate the studies.

Yes.

I'm not sure if everyone Eric.

Eric on that so I think maybe you should feel that.

Yes so.

Often as we know European regulators or are focusing on the responder analysis. So.

Again, we haven't gone through all the details.

Phase III protocol synopsis, but we will be looking at MPC and <unk> as we did in <unk>. So we'll have all of that data.

Unknown Attendee: I wouldn't say yet that the scientific advice is gating to getting the phase three trial up and running, but it'll follow, you know, with not a lot of time after the end of the phase two meeting. And then the phase three program, as we said, we'd like to be up and running and initiate the phase three trial within the second half of the year. Okay, just one final question for me.

I wouldn't say, yes that the scientific advice is.

Is gating to getting the phase III trial up and running but it will follow.

Unknown Attendee: So, assuming you initiate these studies in the second half, is XTOL a good proxy of the timeline within which you can complete these studies? Maybe just tell us, you know, how long it might take for you to run these studies. Yeah, I think EXTOL is probably a reasonable proxy.

Okay. Just final question for me.

So assuming you initiate these studies in the second half or.

Is that still a good proxy of.

The timeline within which you can complete the study maybe just tell us how long it might take for you to run these studies.

Yes, I think Exxon is probably a reasonable proxy.

Ian Mortimer: You know, a couple of things that people may want to take into consideration as they think about the timeline are, so from a sizing point of view, as we've talked about, there's probably not a big difference between the phase three trial and EXTOL as we compare them, and Chris has mentioned both in terms of the size and number of sites as well. You know, obviously, the challenge we had for those that have followed the company for some time is that COVID had an impact on recruiting and screening patients during EXTOL, and obviously, you know, we can't predict the future, but definitely, the second part of the study of EXTOL recruited much better than those months in 2020 early on in the pandemic.

A couple of things that people may want to take into consideration as they think about the timeline.

So from a sizing point of view as we've talked about there's probably not a big difference between the phase III trial and ex told as we compare that and Chris has mentioned both in terms of the size, but number of sites as well.

Obviously the challenge we had for <unk> for those that have followed the company for some time.

We did have.

Covid impact on recruiting and screening of patients during next toll and obviously.

We can't predict the future, but but definitely the second part of the study of <unk> recruited much better than than those months in 2020 early on in the pandemic and obviously, we now have clinical efficacy. So we have an opportunity to talk to investigators about that but.

But yes overall, it's probably not a bad proxy because it is a similar size study.

To the X tole trial.

Ian Mortimer: Thanks, Ian. Thank you. Thank you. Your next question comes from Tim Lugo. Hey, this is Lachlan on behalf of Tim.

Very good thanks Ian.

Thank you.

Thanks. Your next question comes from Tim Lugo with William Blair.

Unknown Attendee: Thanks for taking the questions. We had a couple questions just about somnolence and extol. So can you maybe just remind us sort of what you saw there and what is, I guess, typical or standard with other anti-seizure medications? And then on the partnered programs with NeuroCurrent, are you able to provide any more sort of granularity on when in 2023 that data might come or how enrollment is going? Thanks, Lachlan.

Hey, this is lachlan on for Tim Thanks for taking the questions.

Had a couple questions just about cell phones and X tole. So can you maybe just remind us sort of what you saw there and what is I.

I guess typical standard with.

Other antiseizure medications and then on the partnered programs with Neurocrine.

To provide any sort of granularity on when in 2023 that thought in mind might.

Tom.

Enrollment is going.

Yes.

Ian Mortimer: I'll answer, Chris, the question on the partner program with Neurocrin, and then you want to address the question on somnolence. Sure. So on the partner programs, yeah, we're really, Lachlan, we're really guided by the guidance that Neurocrin provides. They are, just to be clear, I know we've talked about it previously, they are running the program and paying for the program, and are in control of it

Thanks, a lot Glenn I'll answer Chris I'll answer the question on the partner on Neurocrine and then you want to address the question on <unk>.

So on the on the partner program, Yeah, We're really Laughlin, we really guided by the guidance that Neurocrine provides they are just to be just to be clear I know we've talked about previously they are running the program and paying for the program and are in control of it too.

Ian Mortimer: Two phase two trials are up and running. The only one they've given guidance on is the adult focal epilepsy study that they expect to have data on in 2023. They haven't narrowed the guidance more than just during the calendar year, but that study is up and running and recruiting. And then in pediatric epilepsy, that is also running and recruiting, but they haven't given guidance on when they would expect top-line data. So as they narrow that guidance going forward, then we can update you there. Chris, I'll pass it to you on somnolence.

But they haven't given guidance on when they would expect topline data so as they as they narrow the guidance going forward then we can update you there.

Yes.

T on some nodes.

Yes, I was I was trying to look up the exact number because I don't want to misquote it but the more common adverse event was with dizziness and I just don't want to quote with the number was somnolence there was a little bit of an imbalance in terms of active versus placebo.

Chris Kenney: Yeah, I was trying to look up the exact number because I don't want to misquote it. But I mean, the more common adverse event was dizziness, and I just don't want to quote what the number was for somnolence.

Chris Kenney: There was a little bit of an imbalance in terms of active versus placebo. I believe it was hovering, you know, under 10%, and there was a bit of a dose response, as there was with dizziness. In terms of, you know, its comparison to other ASMs, we thought that it was very much in line with other anti-seizure medications. Yeah, and Chris, I'm just, I was just looking at the AE tables as well. And yeah, somnolence actually was overall about 15%. So it was less, quite a bit less than dizziness.

I believe it was hovering under 10%.

And there was a bit of a dose response as there was with dizziness in terms of its comparison to other asm's. We thought that it was very much in line with other anti seizure medications.

Yeah, and Chris I'm, just I was just looking at the AE tables, as well and somnolence.

Somnolence.

Actually as overall was.

Was about 15% so it was less quite a bit less in dizziness and.

Actually we saw about that same level of somnolence in the high dose group of 25 milligrams at approximately 15%.

Got it thanks.

And your next question comes from David <unk> with MDC.

Hey, Thanks for taking the question.

Chris Kenney: And actually, we saw about that same level of somnolence in the high dose group of 25 milligrams at approximately 15%. Thanks, and your next. Hey, thanks for taking the question. So I just had, you know, maybe a little bit of a kind of big picture question. The, you know, the focal epilepsy landscape may change a bit near term. I think, UCB, and VIMPAT may lose exclusivity and go generic.

I just had maybe a little bit of a kind of a big picture question.

The focal epilepsy landscape it may change a bit.

Near term I think UCB and Pat May lose exclusivity and go generic and so 11 one.

A bit of time before it potentially comes to market, but just given given that landscape and that shift how are you thinking about down the line potentially positioning for the.

The best commercial launch out of the gates.

Chris Kenney: And so 1101, you know, there's still a bit of time before it potentially comes to market. But just given that landscape and that shift, how are you thinking about positioning yourself down the line for the, you know, the best commercial launch out of the gates? Thanks, David.

Yeah.

I think David I think that's yes, it's a really important question on how <unk> could fit into the focal epilepsy landscape crystalline staggering.

Unknown Attendee: I think that's a really important question about how 11.01 could fit into the focal epilepsy landscape. Chris von Seggern, can you jump in and provide your perspective? Yeah, absolutely.

Can you jump in and provide you a perspective.

Chris von Seggern: So, VIMPAT's expected to lose exclusivity later this month, and correspondingly, we anticipate that product will move up in lines of therapy based on being one of multiple products that would be used in a generic environment before moving on to branded agents. But it does leave behind a massive hole to fill in the commercial space.

Absolutely. So then that's expected to lose exclusivity later this month and correspondingly, we anticipate that product will move up and lines of therapy based on being one of multiple products that will be used in the generic environment before moving onto branded agents. It does leave behind a massive <unk>.

All to fill from a commercial space and when you think about the other available branded agents.

<unk> have nearly the reach that impact does from a commercial standpoint, and when we think about the profile of <unk> hundred one it has a combination of safety and efficacy attributes.

Chris von Seggern: And when you think about the other available branded agents, none have nearly the reach that VIMPAT does from a commercial standpoint. And when we think about the profile of Axion 1101, it has a combination of safety and efficacy attributes that will make it very competitive for the add-on agent of choice within that first branded market, which is predominantly where VIMPAT stands today. So, we view the loss of exclusivity of VIMPAT as one that will shift the nature of the standard of care for early lines of treatment but actually create significant opportunity from commercial products downstream, which is likely where we'll be. Okay, thanks so much.

Make it very competitive for the add on agent of choice within that first branded market, which is predominantly web and Pat stands today. So we view the loss of exclusivity of impact as one that will shift the nature of the standard of care early lines of treatment, but actually create significant.

Opportunity from commercial products downstream, which is likely where it will be used.

Okay. Thanks, so much.

Thanks, Thanks, David.

Unknown Attendee: The next question comes from Antonia Colovina. Hello, thanks for taking my question. Most of mine have been asked already.

Next question comes from Antonio <unk> with.

Barton.

Hello.

Thanks for taking my question most of mine have been asked already so maybe just.

A follow up to the earlier commentary can you maybe speak to how <unk> would fit in the treatment landscape.

Given its profile and the <unk> mechanism and M D D.

And then just briefly on <unk>.

Our discovery programs when can we expect you to announce some additional programs.

Do you plan to stick to epilepsy or would you focus on neurology more broadly.

Ian Mortimer: I'll address the discovery one, and then Chris von Seggern, if you want to provide your perspective on the MDD market and the need and where a drug with a profile like 1101 could fit. I know it's early days, but we can probably provide some high-level commentary. On the discovery portfolio, as many of you know, we have a very active drug discovery group and a number of targets that we're interested in. Antonia, I would say broadly that we're interested in neurology.

Thanks Antonio.

I'll address the discovery, one and then Chris Fund segment, if you want to provide your perspective on the MVD market.

And the need and where a drug with a profile like 1100, one could fit I know, it's early days, but we can probably provide some high level commentary on.

On the discovery portfolio.

As many of you know we have a very active drug discovery group.

And a number of targets that we're interested in and Tony and I would say broadly we're interested in neurology, we have had a focus on epilepsy.

Ian Mortimer: We have had a focus on epilepsy. Some of you will have seen our data that we've presented at meetings on a target called NAV1.1, where we're looking at activators of that target that could be used in epilepsy indications such as Dravet syndrome. We have some very interesting preclinical data there. Obviously, we have a large KB backup effort now where we have backup molecules that, over the next couple of years, will go into clinical development and could give us a lot of options in the clinic, either from an LCM point of view or looking at different therapeutic indications as well.

Some of you will have seen our data that we've presented at meetings on a target called NAV, one one where we're looking at activators, but that target that can be used in epilepsy indications such as drive a syndrome and we have some very interesting preclinical data there and obviously, we have a large kv backup FERC.

Now, where we have backup molecules that over the next couple of years will go into clinical development that could either give us a lot of options in the clinic.

Either from an LCM point of view are looking at different therapeutic indications as well and we have different ideas on how to interrogate the targets as we move forward. So we have a big effort there and then Theres a number of other targets that we like and we're working on that we just haven't talked about publicly yet so I would say we have brought over efforts pretty clinically.

Ian Mortimer: We have different ideas on how to interrogate the target as we move forward, so we have a big effort there. Then there's a number of other targets that we like and we're working on that we just haven't talked about publicly yet. I would say we have broad efforts preclinical, and you'll see a number of molecules transition from our discovery portfolio into the clinic over the next few years. Chris, on MDD? Yeah, absolutely.

And you'll see a number of molecules transition from our discovery portfolio into the clinic over the next few years Chris.

Chris on MDT.

Chris von Seggern: So the MDD marketplace is as complex, if not more complex than the epilepsy space, but it has some similarities in terms of the treatment paradigm. There are entrenched standard of care products that are used early in lines of therapy, SSRIs, and SNRIs, that address a portion of the patient population but leave a sizable percentage of patients who require additional efficacy, either in an add-on, adjunctive environment, or We anticipate the profile of XEN 1101 to be quite competitive in later lines of therapy, where patients often turn to products that have alternative mechanisms of action with equivalent or comparable efficacy profiles.

Yeah, absolutely so the FTB marketplaces as complex if not more complex in the epilepsy space, but has some similarities in terms of the treatment paradigm. There are entrenched standard of care products that are used early in lines of therapy SSRI SNRI did address a portion of the patient population, but leave.

<unk>.

Sizable percentage of patients who require additional efficacy either in an add on adjunctive environment or as downstream monotherapy treatment. We envision the profile for excellent 11, I want to be quite competitive in later lines of therapy, where patients often turn to products that have.

Alternative mechanisms of action with.

Equivalent or comparable efficacy profiles and what youre looking for is a mechanism mechanistic approaches either complimentary to the ssris SRM mris or something that is an alternative for patients who require additional efficacy or have safety or tolerability.

Issues with the earlier lines of therapy that is <unk>.

LOL patient population.

One that is going to be increasingly competitive as additional products move forward.

Thanks for the clarification.

Unknown Attendee: Thanks for the clarification. And with that, we end the Q&A session for today. I will turn the call over to Sherry Aulin for the final question. On behalf of the Xenon team, thank you everyone for joining us on our 2021 financial results conference call. Adelaide, Sinjay

Thank you and with that.

Q&A session for today.

I'll turn the call back to Sheri.

Our final remarks.

On behalf of the xenon team. Thank you everyone for joining us on our 2021 financial results Conference call.

And with that ladies and gentlemen, we conclude today's program. Thank you for your participation and you may now disconnect.

Unknown Attendee: So you're the end of the day. You're the end of the day. Thanks so much. Hi, thanks. This is Madhuwan for Mark.

Unknown Attendee: And so it was something that we had filed, and now all of the efficacy data that we've generated for 1101 to date. So the X-Full Study was taken, the drug, the one pill once a day was taken in the evening in proximity to the evening meal. And so we expect that to be a continued development as we move forward. And that would be something on label.

Ian Mortimer: And obviously, we now have clinical efficacy, so we have an opportunity to talk to investigators about that, but yeah, and overall, it's probably not a bad proxy because it had a similar size study to the EXTOL trial. Very good.

Q4 2021 Xenon Pharmaceuticals Inc Earnings Call

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