Q2 2023 Xenon Pharmaceuticals Inc Earnings Call
[music].
Good afternoon, ladies and gentlemen, and thank you for standing by.
Welcome to the Xenon Pharmaceuticals report second quarter 2023 results conference 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.
I will now turn the call over to Sherri Holeman, Chief Financial Officer.
Good afternoon. Thank you for joining us on our call and webcast to discuss the second quarter 2023 financial and operating results. Joining me are Ian Mortimer <unk>, President and Chief Executive Officer, Dr. Chris Kenny Xenon as Chief Medical Officer, and Dr. Crisp on staggering chief commercial.
The officer.
Ian will open today's call with a summary of our proprietary pipeline programs and Chris Kenny will provide an overview of our ongoing Exeunt 11 O one clinical program.
I will summarize our financial results progress within our partnered programs and our anticipated company milestone events crisp on Sanger and will be available during our Q&A session to address questions about our commercialization strategies. Please.
Please be advised that during this call we will make a number of statements that are forward looking including statements regarding the timing of and potential results from clinical trials the potential efficacy safety profile future development plans.
The bull market regulatory success and commercial potential of our and our partners' product candidates.
Because of our clinical trial designs, our ability to successfully develop and achieve milestones in our accident at 11 O one and other developmental development programs, the timing and results of our interactions with regulators our ability to successfully develop and obtain regulatory approval a vaccine 11 O one and our other product.
Candidates anticipated enrollment in our clinical trials and the timing thereof.
And our expectation that we will have sufficient cash to fund operations into 2026 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.
Our results may differ materially from those projected on today's call. We undertake no obligation to publicly update any forward looking statements. Today's press release summarizing xenon second quarter financial results and the accompanying annual report on Form 10-Q will be made available under the investment investors section of our website at www.
W. Dot xenon dashed pharma dot com and filed with the SEC and on SEDAR now I'd like to turn the call over to it yet.
Thanks, Jerry good afternoon, everyone. Thanks for joining us on our call today.
We are excited about the continued progress across all aspects of our business during the past quarter.
To begin I am pleased to announce that patient enrollment is now complete and our <unk> hundred one phase two ex Nova study in major depressive disorder, or <unk> and we expect the last patient to be randomized in the very near term.
Based on the completion of screening we estimate that more than a 160 patients will be randomized and just as a reminder, the original trial design was to randomize 150 patients or 50 patients per arm of 10 milligrams of <unk> 11, O 120 milligrams of <unk> or placebo added.
Additionally, we have now further narrowed our Q4 guidance and look forward to announcing ex know the top line data in late November to mid December .
In advance of these results, we intend to host a webinar with key opinion leaders to review the MDT landscape, including findings from our own market research.
Also discussed the mechanistic rationale supporting kv modulation as a treatment for M. D and review the key elements of our ex Nova clinical trial, we are targeting mid September for this webinar and we will issue a webcast advisory notice confirming our speakers and additional access details to ensure that you can all virtually attend and participate.
We also continue to advance our broad channel 11 O one phase III epilepsy program and strengthen our leadership position in the <unk> field was <unk> 11 O one representing the only potassium channel opener in late stage clinical development with important derisking clinical data generated from our <unk> phase III clinical trial, all phase III.
Clinical trials are actively recruiting patients, including ex told two and X tole three in patients with focal onset seizures were asked a lot.
And exact in patients with primary generalized tonic clonic seizures or PG Tcs.
As noted on our last call. We continue to maintain a high degree of confidence in our ability to execute on our <unk> hundred one phase III epilepsy clinical development plans, we have the advantage of being able to draw upon our experience with our <unk> phase <unk> study, which was similar in size and design to both ex told you <unk> three and <unk>.
Tableau has strong relationships with key investigators who are already familiar with <unk> know what.
We expect to provide guidance later this year regarding our estimated timing of study completions.
In addition to our ongoing phase III epilepsy program in adults. We also continue to execute on our strategy for the pediatric development plan for <unk> hundred one based in part on feedback from FDA.
Our team is conducting ongoing work on a pediatric formulation of <unk> hundred one for younger patients in.
In addition, the Fda's PK extrapolation role for focal onset seizures allows us to move into cohorts are progressively younger patients with focal onset seizures was X. Gen 11 O. One in an open label setting over time. Finally also driven by feedback from FDA. We are in the process of expanding the exact phase III clinical trial to include patients as young.
His 12 years of age.
Before I pass the call to Chris Kenny I'd like to extend a warm welcome to Dr. Gillian Cannon and Mr. Mr. Justin Gover, the two newest appointments to our board of directors that were announced yesterday brief.
Briefly Julien brings a vast knowledge of commercializing novel medicines, and leading successful neuroscience franchises at large pharmaceutical companies she's been involved in the commercial efforts of some of the most important epilepsy and depression drugs over the past decade.
And many of you will be familiar with Justin as the founding CEO of GW pharma, Justin and his team led the development and commercial launch of that the dialogues and the eventual sale of GW to jazz Pharmaceuticals in 2021 for $7 2 billion.
Justin has a deep understanding of what it takes to build companies like xenon and he's passionate about the epilepsy space. We're.
We're looking forward to leveraging the experience of both Julian and Justin as we continue our efforts on the late stage clinical development of <unk> hundred one prepare for commercialization.
And progress towards achieving our strategic objective of building a leading fully integrated neurology company I would now like to turn the call over to Chris Kenny who will give additional details on the progress made across our clinical programs and provide a look ahead at some of the upcoming medical meetings, where the xenon team will have a strong presence Chris will also discuss the.
Of the additional <unk> 11 O. One X Tole open label data that is focused on quality of life measures, which has to be presented at the upcoming international epilepsy Congress in September so Chris over to you.
Thanks, a lot Ian building upon <unk> comments, beginning first with our <unk> program and MDT I'm looking forward to co hosting a webinar in mid September alongside key opinion leaders in the major depressive disorder space.
We intend to focus our discussion on the potential for the <unk> mechanism to treat MDT.
<unk> outlined the importance of the rationale and trial design of our phase two <unk> study.
Importantly.
These topline data will help guide our future plans.
<unk> <unk> hundred one and MDT you will recall that our initial decision to examine <unk> 11 O. One and Mgd was based on encouraging published clinical results with <unk> as well as promising preclinical data with <unk> at 11 O. One we were further interested in gathering additional data given that day.
The common comorbidity within the epilepsy patient population.
With patient enrollment now complete the.
The last few patients are expected to be randomized.
In the very near term, which will then be followed by a six week treatment period, a four week follow up visit and then database lock and data analysis. Given these steps we're looking forward to a top line data readout for <unk> in late November to mid December of this year.
Turning to our phase III epilepsy programs as a brief reminder of the ongoing clinical trials within our robust phase III program are ex told too.
And X tole III clinical trials are running in parallel with each study targeting enrollment of approximately 360 subjects with focal onset seizures, who.
Who will be randomized one to one to one for once daily dosing of either 15 or 25 milligrams of exiting at 11 O one or placebo.
Mary efficacy endpoint is the median percent change or MPC and monthly seizure frequency from an eight week baseline to the 12 week double blind period with <unk> hundred one.
<unk> to placebo.
Our phase III exact clinical trials expected to enroll approximately 160 subjects with primary generalized tonic clonic seizures.
Subjects will be randomized one to one for once daily dosing of either 25 milligrams of <unk> 11, O one or placebo. The primary efficacy endpoint is the MPC and monthly PGE Tcs frequency from an eight week baseline to the 12 week double blind period of exiting an $11 one compared to placebo.
No.
We believe we have a strong development rationale for <unk> based on the JV seven mechanism in the photo sensitivity proof of concept model a generalized epilepsy.
<unk> data in multiple preclinical epilepsy models.
And the phase two B X tole clinical data as it looked at seizure subtypes, including those focal seizures that progressed to bilateral generalized seizures.
Our unique parallel development approach in both focal onset seizures and primary generalized tonic clonic seizures allows us to set the foundation for potentially broader use of <unk>, one and two of the most common forms of epilepsy should it be approved as Ian mentioned our team is excited to showcase.
This excellent 11 O one at medical conferences later this year, including our presence at the upcoming 35 International Epilepsy Congress in Dublin in September where we have the opportunity to highlight new quality of life data from the ongoing <unk> Open label extension study. We're excited to present these new data that focus on the <unk>.
Quality 31, subscales of seizure worry social functioning and medication effects.
Our analysis of these quality of life domains is important and can potentially provide us with insights around how drug tolerability better seizure control and improved seizure freedom rates positively affect patients quality of life.
Looking at the further ahead at Aes 2023 in Orlando. This year, we expect to provide longer term OLED data from external supporting the long term use of the exon 11 O one as well as important seizure freedom data. We're excited to continue to raise the profile of <unk> 11 O one with physician.
<unk> and the medical community and look forward to keeping you updated on our progress I will now turn the call over to Sherri, who will give us a brief update on our partnered program with Neurocrine before summarizing our first quarter financial results and upcoming milestones Sherri.
Thanks, Chris.
Beginning with our partnered programs our collaborators at Neurocrine are conducting two separate phase II clinical trials evaluating <unk> 91, three <unk>. One study is focused on adult patients with focal onset seizures. Any other study is examining the use of MDI 90, 1352 in pediatric patients.
With SG&A related epilepsy.
Neurocrine has now completed patient enrollment in its adult focal study and we look forward to results in the fourth quarter of this year.
I'll now touch on some highlights from the financial statements and would refer you to our news release and 10-Q report for further details cash.
Cash and cash equivalents in marketable securities were $652 2 million as of June 32023, compared to $728 8 million as of December 31, 2022 based on current operating plans, including the completion of the excellent <unk> 11 O one phase III epilepsy.
<unk> studies, we anticipate having sufficient cash to fund operations into 2026.
Before concluding our prepared remarks, I'll briefly summarize some of our goals and milestone events ahead, including as Ian mentioned, a data rich period for Athene on between now and the end of the year.
Firstly, we look forward to two important clinical data readouts in the near term our top line results are anticipated in late November to mid December from our ex Nova clinical trial and M. D. D. We also expect another data readout in the fourth quarter of this year.
From the adult focal onset study conducted by our partner Neurocrine in September we're looking forward to hosting a webinar focused on axiom.
N and M D D.
We're excited to present additional Exeunt 11 O. One X Tole open label extension clinical data with a focus on quality of life data at IEC in September and longer term OLED data, including rates of seizure reduction in seizure freedom at Aes in December importantly, we continue to make progress on it.
Advancing our <unk> hundred one phase III program, including our ex told to an ex told three clinical trials and fos and our exact clinical trial N. P. G. Tcs with the intention of providing guidance on study completion later this year in closing I'd like to Echo and warm welcome to our newest board members.
Who will bring additional world class leadership to being on I believe this is an incredibly exciting time at the company and our team is motivated to execute on our ambitious plans driven by the hope that we can improve the lives of patients living with epilepsy, we look forward to reporting on our progress in the months ahead.
Now ask the operator to open the line for any questions.
It is now time for the Q&A session. The floor is now open for questions to ask a question at this time.
<unk> Press Star one on your telephone keypad, if at any point you would like to withdraw from the queue. Please press star one again.
We would like to ask that you. Please limit yourself to one question.
For any additional questions. Please rejoin the queue.
I will now take a moment to compile our roster.
Our first question comes from Tessa Romero with Jpmorgan Chase.
Okay.
Hi, good afternoon, guys. Thanks, so much for taking our question.
No.
Bigger picture have you landed on what level of detail you think you might provide in your topline release for ex Nova.
And Relatedly.
Thank you previously confirm that there will be P values on your key secondary endpoint of the shops and the Bay just curious.
And have you disclosed any details on the statistical assumptions on these two scales.
Thanks, so much.
Thanks, Tom.
So I'll start off and provide a little bit of detail and then Chris Kenny.
I think that's maybe a good opportunity and just to remind people of the statistical analysis used obviously driven by the primary endpoint on my address.
But in terms of level of detail in our disclosure, we said a couple of things.
Historically test.
One is I think you can look at our X tole data in epilepsy is a bit of a guide. So you should expect in the topline press release from US obviously, the key efficacy endpoints, which includes not just the primary endpoint, but it is as you referred to some key secondary endpoints overall, we'll have some discussion just around the AE profile and Tolerability in this.
Patient population as well and then we're committed to talking about the next steps in terms of the development of vaccine <unk> hundred one as.
As we mentioned in both the press release and in the prepared remarks, we do have this webinar coming up that we're planning for in mid September that will be another opportunity for us just to refine a little bit better.
For everyone in terms of the information that will be provided at top line, but thats a bit of a guide.
Maybe we can just talk about the statistical analysis on the primary endpoint.
Yes, just I mean, I think if you take a look at the X Tole topline press release from a couple of years ago. I think you will get a pretty good idea.
The program is the study rather is obviously focused on depression and so the endpoints will focus on depression depressive symptoms.
As far as the powering of this study goes.
We focused on powering it for the for the primary endpoint, which is the modules and this study is powered to achieve a four point separation between active and placebo.
Okay, great. Thanks, Thanks for taking our questions.
Sure. Thank you.
Sure.
Our next question comes from Paul <unk> with stifle.
Hey, thanks, so much and congrats on all the progress.
As it relates to the phase III studies in epilepsy, just what specifically.
Do you want to learn between now and later this year Ian before you feel comfortable guiding I mean asked another way, where do you kind of want to be out with the study in terms of sites open and enrollment to have kind of that full visibility and then just quickly on the Neurocrine partnered one six program just curious kind of how <unk> is thinking about the.
Criteria that you would want to see clinically in order to exercise your option there.
To be able to augment your economics ultimately thank you.
Thanks, Paul so.
Yeah, I'll comment on kind of the phase III epilepsy guidance and.
And Sherri.
And I can talk about the Neurocrine. Both what is the opt in I think we can just remind people what the opt in background is and then.
The information that we are required to make that decision. So in terms of the phase III epilepsy program. It's probably helpful. Maybe just review a little bit of history. So the <unk>. Two study was first up and running and that was really right at the end of last year.
And then that was followed by the exact study.
Few months later and then a few months after that in terms of X tole three so we've been kind of rolling getting all of these studies up and running.
The first jurisdiction for all of the studies is being has been the U S. So we've had U S sites up and running and then over time, we've been bringing other jurisdictions online and just as a reminder, if we go back to the export program, which we're trying to mirror as best we can especially in the ex told two clinical trial, 60% of the patient enrolled.
And X Tole came from Europe , and 40% came from the U S. So I would say whats the information that we're continuing to generate while we're continuing to get sites up and running and jurisdictions.
Some of those come on line over time as everybody is aware.
And then we're monitoring so site initiation, we're monitoring the patients that are being screened what our screen failure rate is and then what our overall kind of randomization and it's all of that information that we are bringing together that gives us confidence in providing guidance to study completion and and I think.
We've been really consistent in saying that later this year, we'll be in a position I guess that guidance.
On the move.
Moving to the Neurocrine question, maybe you can walk through kind of what the opt in rights are and what that means just as a reminder for everyone and then I'm happy also to provide some comments on what we may want to see before moving forward with that often so as a reminder for the lead compound we have co fund option.
And we would be able to trigger that co fund option. Once we have certain pieces of information and importantly that includes an approved phase III protocol as well as a complete phase III budget from Neurocrine at that stage, we can make a decision to potentially opt in to co fund the phase III program and that would give us an additional five.
<unk> step up in the royalty just for as a reminder, that program the royalty rates under that program are tiered and the low to mid teens and so at the highest and if we do co fund phase III, we would be eligible for up to 20%.
And then in terms of what to build on what Sharon said I mean, obviously the budget is important the benefit that we have sitting here at xenon as we have a tremendous amount of experience in running global.
Epilepsy studies in phase two and now in phase III. So I think we have a good handle on.
Really what the budget implications would be but we have the opportunity to see the complete data set I think one outstanding question is after this phase II study and we see the data from Neurocrine and focal onset seizures in Q4 of this year what are the next steps in the program and so today we.
Don't know whether the next steps would be to go directly into a phase III study or would be additional work prior to that so we're not sure of the timing that will need to make the opt in decision, but obviously, we'd want to see the data to be able to do that.
The benefit in epilepsy, and we've talked about this previously is just the consistency we see between the studies. So we see this with other anti seizure medicines.
And obviously, our expectation was <unk> 11 O. One is that drugs that work in phase two do have this consistency and data when they go into phase III clinical trials and across different kind of fall.
Studies, and so I think we have the benefit of if we see data that we believe are supportive of our opt in that Theres a high probability of consistency.
Alright, Thank you very much.
Our next question.
It comes from Brian Abrams with RBC capital markets.
Okay.
Hi, there. Thanks for taking my question and congrats on the continued progress and welcome to the two new board members.
Question on the Mds study.
I'm curious the latest on what you guys are looking for from a safety standpoint.
To potentially move ahead in M. D D. As a discrete indication is there a bar for CNS side effects, among regulators or physicians and any changes to where that bar may be given some of the recent regulatory developments in the MDT space over the last week.
Thanks, Brian I think.
Be helpful here is Chris.
I'll make a couple of comments, maybe on regulatory obviously theres been a lot of conversations with xenon and publicly around.
Updates on the MDT space. Most recently, so I'm happy to provide a little bit of commentary there and then Chris Kenny Let's why don't you walk through the safety data, we know to date from X to all because that's the information that we have now on an unblinded basis.
From the X Tole study as well as open label extension and thank you first of all on <unk>.
Done, let's walk through our market research, where we've looked at that adverse event profile.
And at least testing that from from a research point of view with physicians in the Mds space.
Kind of our overall comment I think just on on recency and what's been going on publicly because I don't think it changes anything Brian in the near term for US I mean, we're in phase III in depression right now as.
As we've talked about we finished patient enrollment in the <unk> study, we need to get to those topline data we need to look at the efficacy.
As well as the overall safety and Tolerability profile and.
And as we said we would give guidance on next steps in the program at that time and if the next steps are to move into a late stage clinical development program, we would engage with regulators at that time and I think we would that would be very informative.
Premature to say anymore than that right now.
Chris Kenny over to you and maybe just to talk about the AE profile overall on what we know on 11 O. One and then over to Chris One second.
Right. So I mean first of all in terms of what we would expect with the depression I mean, it remains to be seen how the drug will be tolerated in that population relative to.
Two to the epilepsy population, we obviously during the conduct of the trial, we keep an eye on the data very closely it's being assessed in a blinded fashion and so there are limitations to what you can.
It really glean from that but what we can say is that it's behaving very much on par with what would be expected with pooled data from from external and so.
What I mean by that is that we learned from X tole were a few different things one that the 10 milligram dose again I want to be clear what I'm allowed to say, it's about X 12, we don't know what it will be for ex Nova but with ex told in focal onset seizures. The safety profile of 10 milligrams was hard to distinguish from placebo.
And many of them if not all instances and then going up to the 20 milligram dose there was an increase.
Adverse events, such as dizziness, and somnolence, and fatigue and to a lesser extent.
So it remains to be seen how.
The major depressive disorder population will will tolerate the drugs they are not on concomitant medications.
And obviously they're different.
<unk> patient, so we will see but so far the blinded data.
You would expect from a study with placebo 10, and 20 milligrams is behaving as we would expect will flip the card later this year and we'll see what it shows.
Got it thank you so much.
Yes.
Build for a moment from a from a market research perspective, as Ian mentioned, we've conducted.
Market research to better understand the potential path forward for <unk> one.
In major depressive disorder, and given what Chris just mentioned about the AE profile.
We've leveraged the data coming from ex tool to understand the range of receptivity from a physician perspective with the data we have again in an epilepsy population and what we've heard is quite consistently enthusiasm around the profile of <unk> given the potential range of adverse events. If they are consistent without epilepsy population.
And part of this is anchored on the novel mechanism of action of the product potential to differentiate from other therapeutic options available in the lack of important adverse events that exist in the <unk> space.
Such as sexual dysfunction.
So there is receptivity in light of the AE profile that has been tested in the past and that's an important component to note.
That's really helpful. Thank you.
Okay.
Alright.
Next question comes from Andrew Tsai with Jefferies.
Okay. Thanks.
Appreciate all the updates good afternoon. So.
As we think about the next steps for <unk>, and MDT that which will be shared in conjunction with your topline data I think you said one option could be to introduce a new ion channel. So can you give us a flavor on the characteristics of these compounds you have pre clinically how much better efficacy better safety.
And C and so forth and if you were to introduce a new compound would there be a way to expedite its clinical path as it relates to January phase two proof of concept data. Thank you.
Thanks, Andrew.
And just to remind people.
We have said historically that.
We believe we have different options in that.
After the <unk> data are available we have done a lot of work both in terms of looking at future clinical development as well as having commercial input.
Our options are to do continued development in major depressive disorder as a primary indication we've talked about that we've also talked about continuing to differentiate actually at 11 O. One in the epilepsy space. We know that depression is the most common comorbidities are generating data on mood is important in Appalachia and then Andrew.
You've referred to potential chemistry, our molecule differentiation as we think about different therapeutic areas.
Our back our backup molecules are molecules behind <unk> hundred one that target.
That same channel modulation are still preclinical so they havent yet moved into clinical development. So there is a time gap and there would be the required studies to do both pretty clinically as well as in early clinical development before we could get those into efficacy studies. So there are a number of steps that we need to do.
How we compare.
We feel strongly about our leadership position.
And ion channel drug development and drug discovery, we have multiple chemistries that we've looked at and are looking at in terms of targeting potassium channels. When we look at <unk> 11 O. One there's nothing obvious that we need to solve for if we look at the current attributes of the drug it's clearly a QD drug.
Which has a long half life, which is really probably benefiting for any potential missed doses. Obviously, we have a compelling efficacy profile when we compare it on a placebo adjusted basis to other anti seizure medicines. We obviously have a novel mechanism no titration associated with <unk> 11 O. One so there is no.
Obvious thing that we're trying to solve for it is really about chemistry differentiation and every molecule is going to look a little bit different both on potency as well as on.
A different profile overall, so we're not too hung up on any one characteristic pre clinically more just having camera chemical diversification that we would move forward into clinical development.
Thanks very much.
Alright. Our next question comes from Jason Burberry from Bank of America.
Hi, Good afternoon. This is dana on for Jason Congrats on the quarter and thank you so much for taking our question.
Just wondering if you see any read across from the recent seeds TRL as it pertains to the broader leniency of the FDA Neuro Division with Billy Dan's departure, and whats your continued confidence that ex tool to be will be counted as a pivotal trial. Thank you so much.
Thanks Dana.
Happy to start Chris Kenny.
I think you provide your let's provide your perspective as well.
Yes, just as a reminder, I mean, we've had your question is specifically even though.
The CRM that you're referring to is an MTBE what read across that may have into a different division, which is neurology.
For our epilepsy program, obviously, where we are today as we've had an end of phase two meeting and we've communicated to the agency or plan to run a broad phase III development plan, which includes two phase III clinical trials and focal onset seizures and a study in parallel a single study in primary generalized tonic clonic seizures.
But our plan to file.
What's gating to file is X tole too so using X tole.
As one of the studies using <unk> two as the second study and we believe we have good and constructive dialogue and conversation with the agency at the outer end of phase two meeting and they understand our plan. Ultimately these are always review issues.
And the agency looking at the totality of the data that's being generated.
But as we sit today.
Confident in terms of the development plan, which we've which we've laid out Chris anything to add.
Well, so I fully acknowledge that.
People rotate in and out of organizations like the FDA that there can be.
Difference in some of our view there is no doubt about that.
When things are crystal clear, there's probably less fluctuation from one individual to another and so if you take a look at the X Tole study and you take a look at the FDA guidance in terms of what it is what it takes to be considered an adequate well controlled study.
The study that appears to check all those boxes.
To <unk> point, we won't know until its a review issue, but our plan hasn't changed which is to rollout ex told two data.
I'm, assuming those results are positive combine them with X tool and that should be sufficient information for what FDA requires for.
Granted summary of efficacy so that our position hasn't changed.
Thank you so much.
Thank you.
Alright. Our next question comes from Paul Choi with Goldman Sachs.
Hi, good afternoon, and congratulations on the progress.
I have two questions on ex Nova My first is can you maybe comment on what a placebo response risk mitigation.
You've undertaken here.
Clinical trials Gov hasn't been updated in over a year, but I assume you've added additional sites to the six that are currently listed there so.
The center experience recruiting for patient competing with other.
Trials or studies.
What youre doing there if you could maybe comment on that that would be great.
Second.
If both the 10 and 20 Meg.
Doses showed statistically significant results can you maybe comment on scenario on how youre thinking of approaching the FDA for <unk>.
For for your Registrational study with regard to a minimum.
Cassius dose versus.
For the 10 versus the 20 millimeter 20 milligram doses. Thank you very much.
Okay.
Thanks, Paul.
So I can yes.
Tackle the second question, Chris in that if you want to if you can walk through I know we've done it on previous calls, but I think it is.
Irrelevant question. So thanks, Paul on just the risk mitigation strategies around managing placebo in depression studies, and how that relates to our ex Nova study.
On the second question, Paul I think it's just a bit premature until we see the data I mean as a reminder, just as a data point on on X Tole study looked at 10.
2020 five milligrams and then after we unblinded all three doses were statistically significant.
A little more noise in the data at the 10 milligram dose.
But a clear dose response, among those three doses and when we did our detailed PK PD modeling.
We went forward to the agency that we thought the two best doses to test in phase III, where 15 milligrams and 25 milligrams and we didn't get any push back from the agency on our phase III clinical trial design as it relates to dose selection. So I think we need to lean dissimilar.
The amount of information from ex Nova in order to go forward.
Really think about appropriate dose selection for phase III, if that's the plan and Mds, so but stay tuned on that one Chris do you want to walk through the placebo risk mitigation work.
Sure. So there are several things that has been done to try to minimize the placebo effect in ex Nova first as a reminder, all of the sites that are conducting this study are based in the U S.
And so there's been some evidence that that's one way to decrease the placebo effect.
We're limiting the total number of sites there is theres more than six that youre seeing on clinical trials Gov. I don't think we would have been able to get to the number of patients that we did with such a limited number of sites, but we also wanted to keep that number limited to minimize the potential noise as you would increase the number of sites significantly.
The sites that were chosen were chosen because of their experience.
In terms of the.
The principal investigator and of course, the coordinator and the staff.
Crow itself.
Plays a critical role in the conduct of these studies and so they were chosen for a number of reasons, but obviously expertise and in major depressive disorder was the major driver there.
The other thing Thats been learned as you really kind of want to limit the number of assessments that these patients undergo and so the protocol is very.
Very much focused on what's most important.
With no sort of.
Additional endpoints included so you want the patients to be in the clinic shorter period of time to get the proper clinical assessments, but not overdo. It and then and then have them.
Exits and hopefully avoid.
People effect there.
We're also using CNI group mass general to evaluate these patients. So you have sort of an independent assessment using the safer criteria just before randomization and so that obviously in some cases leads to screen failure because of an appropriate patient selection up to that point. So it's nice to have that sort of external validation.
The patient is appropriate.
And then we're monitoring blinded data.
As well to make sure that.
Nothing unexpected is happening either at a patient level or.
Site level or of course.
Steady level for that matter.
Okay.
One of the ways, we know that we're not.
And reaching a population of patients who had insufficient depressive symptoms at baseline.
We're doing quite a bit and.
Hopefully it will be effective.
Okay.
Okay. Thank you for all that color.
Thanks, Paul.
Okay.
Yeah.
Our next question.
TD Cowen.
Hey, guys. Good afternoon, and thanks for taking our questions I guess, maybe a little more detail on the progress in the pediatric formulation would be nice specifically what interactions have occurred with the regulatory agencies.
What's left in order to begin to open label PK Extrapolation study and then I guess, maybe looking a little more long term out how are you thinking about incorporating the pediatric population into your overall regulatory filing strategy.
Both the focal and generalized epilepsy should those programs will be successful.
Thanks.
Alright, thanks for the question so.
As we've stated not only we focus most of our comments on FDA, but we've had we've had appropriate regulatory interaction both in the U S and in Europe on our pediatric development plans. So we believe we've got.
<unk> on the pediatric plans, which are required so these take place over multiple years.
Some of the early work we're doing on.
On the formulation development side I'll come back to in a second and then adjusting the protocol is exactly to go down to 12 years of age so to get into 12 years of age and above we will continue to use the adult's formulation of the capsule in that population as we get into younger population, obviously, we looked at our pediatric formulation develop.
So we're doing that work internally right now.
And Thats ongoing and will continue for us to get the appropriate formulation and have the appropriate stability.
Before we can get into a much younger patients, we're going to need to do juvenile tox work, as well, which which hasnt been completed yet. So you can imagine there's a number of <unk>.
<unk> that happen.
Over over a number of years. So initially we will get into these patients.
In primary generalized down to age 12, we'll also then do some open label work as we mentioned using the PK extrapolation rule for those first cohorts of patients that will use the adult's formulation and then over time, we'll step down into the younger patients, but the pediatric development plan is a multi year plan, it's not game.
Adding to any of our adult work and not getting to an NDA filing.
But we do have agreement from regulators on what the expectations are on the overall timeline for pediatric development.
Great. Thank you that's super helpful.
Our next question comes from Danielle Brill from Raymond James.
Hi, guys. Good afternoon. Thanks for the question I have one on the quality of life benefit and your IEC abstract.
The quality subscale scores observed in the overall group clinically meaningful or was it just the seizure free group demonstrated clinically relevant improvement and how new findings like these compare to other anti epileptic drugs like X Capri. Thank you.
So Danielle I think I think it's best to wait just a few weeks from now when we have the IEC.
Presentation, we've got two podium presentations and posters that AUC. So we'll wait for the data.
As you mentioned and we mentioned in our prepared remarks, there are some.
Subscales of.
The quality is 31 used in epilepsy, including things like seizure worry and social functioning and medication effects. We're looking at those both in the overall open label population as.
As well as in the seizure free population, we're looking at both sets of data. So we will be able to provide the entire data set.
And in the presentation.
That's being drafted but it's premature until that's being presented to go through the data on today's call Chris anything anything to add overall on the quality of Lifelock.
Meet me in Dublin, and we will go over everything.
Fair enough. Thanks, Danielle Thank you.
Okay.
Yeah.
Alright.
Our next question comes from Marc Goodman from Leerink partners.
Hey, good afternoon, ludy underlying for Mark Thanks.
Thanks for taking my question. So Ford at Sonoma trial, you're already completed study enrollment and patients will be treated for six weeks can maybe provide more color on the timeline, how do you get to later.
Late November to mid December for data Readouts, and secondly, what ongoing investigator sponsored phase II study amongst ni Hao importantly that study regarding your decision to move forward.
<unk>.
Okay. Thanks Rudy.
Yes happy to address these questions. So as we mentioned the last patients have been enrolled and ex Nova and what you heard in our prepared remarks is that the various last few patients are being randomized in the near term. So you can think about kind of the last randomization is happening.
In mid August and then as we've talked about a six week treatment. So that gets us to the end of September then there is a four week follow up which gets us kind of end of October into early November and then we have the steps of.
Cleaning and locking unblinded data analysis, and then release and so when we kind of add all that up together, our best estimate of topline data right now as we've mentioned is end of November to mid December So thats, how all those timelines come together.
In terms of the Mount Sinai study. So yeah. As a reminder, there is a parallel depression study ongoing with <unk> hundred 11, I'll want it's in ISG being run by two medical centers at Mount Sinai and Baylor.
Our expectation is that study is not going to read out this year and so it will read out after ex Nova in terms of our next steps and in terms of <unk> hundred one development, we're really focused on the ex Nova study. So we believe we will have all the information we require to make our decision at the end of this year, whether it be ex Nova data are available.
We won't be waiting and specifically for the Sinai readout.
Got it that's super helpful. Thanks.
Thank you.
Our next question comes from Laura Chico with Wedbush Securities.
Hey, good afternoon, and thanks very much for taking the question I wanted to ask about epilepsy enrollment trends in clinical trials. This is more of a high level question, but.
Obviously, there was some disruption during COVID-19.
That's kind of gone away, but could you just talk about enrollment dynamics generally in the epilepsy space has it gotten better has it gotten.
More challenging I guess I'm kind of curious if the introduction of newer therapies in the market has made it a little bit more challenging to recruit patients any thoughts there thanks very much.
Sure, Yes, I'm happy to provide commentary and Chris if there's anything to add on your side in terms of what we're seeing out in the field from our clinical operations focused on any any color there.
We've been pretty consistent in our comments that based on our experience we have confidence in our ability to execute and I don't think anything is going to hit us.
We the challenges we had during Covid right, we ran X tole kind of pre COVID-19.
In 2019 into early 2020, we have the study up and running.
Then we had a really significant impact of the early days of Covid about a quarter or two where we <unk> enrollment completely fell.
<unk> fell off a class and we werent screening any patients. We are really just trying to maintain the patients in the study.
And then we kind of almost have to pick the study back up again in the fall of 'twenty and into 2020, one and then our external data were available in the fall of 2021. So I don't think were going to see any types of headwinds that we've had to seeing that we've seen historically. So I think we're we feel comfortable and confident that we can adjust anything that.
That comes our way.
Chris anything specific in terms of Lauren's question around new drugs available and if theres any feedback from from sites, our investigators on any impact that.
Yes sure.
Few thoughts I mean first of all.
You have a new drug relatively new drug like <unk> and patient comes into the clinic is in need of something.
Going to be and.
An option to either mobile in a clinical trial like like we have ongoing or to choose <unk>.
<unk> ends up getting chosen and it works out and they are not going to be.
Eligible for the clinical trial, if it doesn't it's going to take a little bit of time to figure that out, especially considering how long it takes to titrate Sunoco Nate So I would say that it has had some impact I would say just to build on what Ian said I mean, you think about what was pulled off.
The achieved during COVID-19 with the X Tole study the environment certainly isn't as.
And much turmoil as it was two three years ago.
If you take a look at.
Dr. Jackie French has an interesting article out just this month about increasing challenges in trial recruitment one of the things she points out what is that over time.
Sorry at the site level they recruited fewer participants.
At the site as you look over decades.
But if you take a look at the article like the number that they are expecting per site, which is about five is fairly consistent with.
What we saw in X tole. So I don't think anything has changed considerably in that from that perspective since the X Tole study was completed.
No.
As a consequence of Covid there are less people, it's hard to find workers and so I do think that there are some challenges with.
With sites being able to find the appropriate number of people and to have the.
The support staff will say that you know.
The sites that we that we have up and running are performing really well.
Thank you.
Thanks, Laura.
Yeah.
Our next question comes from Mohit Bansal with.
Wells Fargo.
Great. Thanks for taking my question and I can give you a little more idea for <unk>, we would be happy to wholesale MDT, though not at a conference in September .
For the same discipline.
So the question is.
When we talk to Xbox they say that having like the other elements just more than efficacy, which could be important for epilepsy drug like <unk>.
Broad therapeutic window DDA adult driving direction.
He's of use things like that so when you when you look at Xenial that one alone versus some of the successful versus IMAX.
Unsuccessful, let let's suggest out there.
Do you how do you rate a rank.
Zane Lowe <unk> compared to these trends that have been out there before thank you.
Okay.
Thanks Mohit.
We would add other ones to your left as well including novel mechanism.
Ease of use can talk can can can look at things like titration and monitoring and can have an impact from a DDA perspective, but first of all on <unk>, we've done a lot of work here.
Why don't you walk through some of the market research in terms of prescribing decisions overall efficacy tolerability, but also some of these other attributes that we've.
We've had really positive feedback from physicians on.
And first and foremost I think we would agree that the.
<unk> successfully if high seizure medication in this space goes beyond efficacy, but what we hear from market research first and foremost is that physicians are excited about the efficacy that's been demonstrated coming out of <unk> and its been highlighted as potentially best in category from an efficacy standpoint for Matt from a seizure reduction but the real.
<unk> value attributes that shine for 11 O. One in the context of very compelling efficacy are those ease of use attributes that sit beneath and we've highlighted a number of them, but physicians do latch on to the fact that the product doesn't require titration.
It has a long half life that potentially can confer the ability to missed doses.
The lack of DDI is something that is very frequently pointed out because of the frequency of.
Use of multiple medications to manage these patients there are number of acts reviews that really do shrout shine and your unique but the novel mechanism itself because of that polypharmacy environment is one of them and they're very excited about the <unk> mechanism.
Working in concert potentially with other products that are commonly used in the space as we've continued to evolve our market research though.
There are components that are emerging from our story, both with respect to the the rapidity of onset that emerge as because of the lack of titration and the ability for us to demonstrate efficacy potentially as soon as one week as well as the compelling open label efficacy that has emerged.
What is closer to a real world population in that open label extension for Max Tor. The totality of evidence is really compelling and we hear that very consistently from our market research. When you look now in transition to successful or less successful products in the space. Those that are most successful do you have efficacy that is competitive and.
Other ease of use attributes that aligned with some of the value attributes that <unk> has and it's because of that component that we feel quite strongly and what we hear from our research is supportive that <unk>. If approved is going to be a very meaningful player in that space.
Thank you.
Thank you thanks, Chris.
Alright. The next question comes from Charles Duncan with Cantor Fitzgerald.
Hi, This is <unk> Kim on for Charles Thank you for taking our questions can you provide any color on the phenotype of the MDT patients enrolled in the study and how it does represent a heterogeneous patient population.
Thank you.
So as the question on the type of Mds patient looking at the as the question around just the baseline patient characteristics and demographics.
Yes.
Okay.
Chris do you want to go through just the entry criteria and obviously monitoring the types of patients that are coming in.
Okay.
Yes sure so.
So one of the things I mentioned in terms of keeping an eye on the study is too.
Keep an eye on the plane to data.
And that's not only to keep an eye on the safety and efficacy data, but also to keep track of the population of patients.
<unk> four and so the.
As you look at gender.
Age.
Disease severity and so forth, that's all sort of very much in keeping with what we would predict based upon other moderate to severe.
MDT populations.
Particularly with regard to sort of the cutoff, it's being used for the module is translating into a moderate to severe population do you have the specifics.
Aspect.
Inclusion criteria that you want to understand better.
I understand that you also have.
On the enrollment criteria for IHOP ton while small.
A lot of places.
Patients report that other arm.
Characteristics I E.
With the leading software colson.
We're focused on as well.
Right right. So I think that the most important thing.
I will get to the shops in a moment, but I would say that the most important thing is really the cutoff and really the definition of moderate to severe depression being at 20% or greater on the Ham D 17.
So thats one thing also you have to make sure that the duration of the current episode is of sufficient duration.
And then there is a cut off on the.
On the shops, as well, which is the scale that's assessing plan for <unk> and what we found in general is that by the time patient have the degree of depression that.
To get them in the study based upon the Hamilton cut off that just about everybody has that same degree of Antonio as well.
I think those are probably the most important criteria in terms of getting into this study.
Thank you for all the color this is helpful.
Thank you.
Thank you.
And for our last question comes from Tim Lugo from William Blair.
Thanks for squeezing me in.
And I'd love to hear an update on your views on commercialization, obviously ex Nova is going to be.
Major variable in the value of the company, but is it going to influence your thinking around.
<unk> ability to commercialize.
Epilepsy.
You've obviously added some board experience and commercialization, but also in transactions online and just curious how we.
We use a view.
Ex Nova influencing.
Ability to take it alone into the epilepsy market.
Yeah. Thanks, Tim So yeah, I'll provide maybe higher level comments, and then Chris one sag.
And provide more detailed commentary as he is thinking about the commercial plans in both indications maybe starting with epilepsy, but we've done a fair bit of work on depression as well.
In terms of the overall strategy of the organization, we've been consistent for some period of time. Our goal is to build a fully integrated neurology company. We do drug discovery, we have deep development capabilities and we want to forward integrate in house have commercial.
Commercial commercialization in the U S.
That means that we're not going to commercialize in other jurisdictions and we've talked about that at some point, although <unk> as a wholly owned asset that we own no downstream economics in terms of royalties to anyone at some point, we would look at ex U S partnerships in terms of accessing those markets commercially so nothing has changed there.
We see a lot of our focus over the last couple of years is in preparation for commercialization in epilepsy, but we've done enough work to feel that we're comfortable that we could do it in depression as well there would be a timing difference. There obviously, where we are in the epilepsy program that would launch first and and we could step into commercialized.
<unk> in depression, and Chris can provide a little bit more layers of details from those comments.
Yes building on what Ian said we've spent.
The majority of my time.
Since joining xenon preparing for commercialization here in the U S in the epilepsy space in.
There are several examples of companies of our size and scale that it launched in the epilepsy arena with a meaningful commitment from a commercial standpoint, but also a very significant support from a medical affairs standpoint to help with communication of the key data stemming from both our clinical trials and our support of work.
Over the last several years as we've executed against those plans I think we have great comfort that we can be a meaningful player in that space.
Both with.
The team we've built to date as well as what we think will be required to successfully commercializing in the epilepsy Arena, which is folks know are big but still a manageable commercial.
Commercial space with probably less than 10000 prescribing <unk> here in the United States.
The advantage of adding ex Nova data really goes in two directions first we can't lose sight of the fact that the pressure remains one of the most important comorbidities within the epilepsy space in that.
Potential data supporting that patient population is something thats very interesting within the epilepsy arena, but more to the point. There are examples of companies who are our size and scale, who have also successfully launched in major depressive disorder. In exome is doing a phenomenal job right now with their early launch with a more.
Our targeted approach than what's been seen with past MDT products.
So both markets are here for us as we continue to build the addition of Julian and adjusting to the team from a from a director standpoint, only enhances our planning and execution over the coming years.
Thank you Phil.
Thank you so much.
Today's conference call you may now disconnect.
[music].
Okay.