Q2 2024 Praxis Precision Medicines Inc Earnings Call

August 13, 2024

Okay.

Operator: Ritu Baral, Marcio Suneja, Good day. Thank you for standing by. Welcome to the Praxis Precision Medicine Second Quarter 2024 Corporate Update Conference Call. At this time, all participants are in a listen-only mode.

Speaker Change: Good day, Thank you for standing by welcome to the practice of Medicine second quarter 'twenty 'twenty four corporate update 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. Just a question. During the session you will need to press star one on your telephone you well done.

Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1-1 on your telephone. You will then hear an automatic message advising your hand is raised.

Yohanan Sways: The automatic message advising Yohanan sways. Please note that today's conference is being recorded.

Operator: Please note that today's conference is being recorded. I will now hand the conference over to our speaker host, Daniel Perry. Please go ahead. Good morning.

Yohanan Sways: I'll hand, the conference I'll, let you speak of host Daniel Perry. Please go ahead.

Speaker Change: Good morning, and.

Operator: And welcome to Praxis Precision Medicine's second quarter 2024 financial results and business update conference. This call is being webcast live, can be accessed on the investors section. Praxis website at www.praxismedicine.com. This call is also being, Please note that remarks made during this call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These may include statements about the company's future expectations and plans.

Speaker Change: Welcome to practice precision medicine second quarter, 2024 financial results and business update conference call.

Speaker Change: This call is being webcast live and can be accessed on the <unk>.

Speaker Change: Yes, your section of practices website at Www dot practices medicines Dot com.

Speaker Change: This call is also being recorded.

Operator: Clinical Development Timelines and Financial, While these four looking statements represent practices used as of today. This should not be relied upon as representing the companies used in the, Praxis may update these statements in the future, but it's not taking on an obligation. Please refer to Praxis' most recent filings with the Securities and Exchange Commission, for a discussion of certain risks and uncertainties associated with the company. Leading the call today will be Marcio Souza, President and Chief Executive Officer of Praxis. Tim Kelly, Chief Financial Officer, will also be joining us.

Speaker Change: Please note that remarks made during this call may contain forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995.

Speaker Change: These may include statements about the company's future expectations plans.

Clinical development timelines and financial projections.

Speaker Change: While these forward looking statements represent practices is as of today they.

Speaker Change: This should not be relied upon as representing the company's views in the future perhaps.

Speaker Change: Practice may update these statements in the future, but it's not taking on an obligation to do so.

Speaker Change: Please refer to practices most recent filings with the Securities Exchange Commission.

Speaker Change: For a discussion of certain risks and uncertainties associated with the Companys business.

Speaker Change: Leading the call today will be Marcio, Souza, President and Chief Executive Officer of practice.

Speaker Change: Tim Kelly Chief Financial Officer will also be joining marcio.

Marcio Souza: After providing updates on our key programs, there will be a brief question and answer session. With that, My pleasure to turn the call over to Marcio. Thank you. Good morning and welcome to the Praxis second quarter 2024 conference call. Praxis is driven by our mission to therefore more, as we discuss throughout the call. We have organized today's call to provide you with a comprehensive update on recent progress on upcoming milestones for our key clinical progress. I'm very proud of the significant progress we have made so far, which set Praxis in a position to have up to four programs in a registrational phase by 2025.

Speaker Change: After providing updates on our key programs that will be a brief question and answer session.

With that it's.

Speaker Change: It's my pleasure to turn the call over to Marcio.

Marcio Souza: We continue to successfully drive our lead clinical program, Elixir Calcimide, towards results, including the execution of our Pivotal Essential 3 trials in essential tremor, which expected top-line results later this year. Additionally, following the positive VPR results in PRAC628, we have designed a comprehensive clinical program, including three interventional studies in epilepsy patients and a first-of-kind observational study in collaboration with the Epilepsy Study Consortium. We look forward to building on the encouraging preclinical and clinical data generated to date with top-line results from the first efficacy study expected in the first half of next.

Marcio Souza: Thank you good morning, and welcome to the practice of second quarter 2024 conference call.

Speaker Change: <unk> is driven by our mission should therefore more as we've discussed throughout the call today.

Marcio Souza: Switching to the upcoming readout this quarter, we remain on track to report top line results for the phase two and both studies of reletrogen or Prax562 in pediatric patients with developmental and epileptic encephalopathy. We're very excited about the upcoming readouts and the potential of reletrogen in SN2A and 8A.

Speaker Change: We have organized today's call to provide you with a comprehensive updates on recent progress on upcoming milestones for our key clinical progress.

Marcio Souza: We also look forward to further exploring this pipeline in the molecule opportunity across a broad range of indicators. With our strong cash position, we're fully funded throughout several key readouts, which will continue to position Praxis at the forefront of precision medicine for CNS disorder. Let me now spend a few more minutes on you.

Speaker Change: I am very proud of the significant progress we have made so far this year, which set practices in a position to have up to four programs in our registrational phase by 2025.

We continue to successfully drive our lead clinical program, you would expect out Mike's towards registration, including the execution of our people talked with central III trials in the central tremor, which expected topline results later this year.

Additionally, following the positive IPR, resulting practice six to eight we have designed a comprehensive clinical program, including three interventional studies in epilepsy patients in our first off kinds observational study in collaboration with the epilepsy study consortium.

Speaker Change: We look forward to building on the encouraging preclinical and clinical data generated to date with topline results from the first efficacy study expected in the first half of next year.

Speaker Change: Switching to the upcoming readout this quarter, we remain on track to report top line results for the Phase <unk> study this offer leveraging <unk> in pediatric patients with developmental and epileptic encephalopathy.

Speaker Change: We're very excited about the upcoming Readouts and the potential offer leveraging in that sense <unk> and eight eight but also look forward sports are exploring this pipeline in a molecule opportunity across a broad range of indications.

Speaker Change: With our strong cash position, we're fully funded throughout several key readouts, which will continue to position practice at the forefront of precision medicines for CNS disorders.

Speaker Change: Let me now it's been a few more minutes on the Alexa.

Marcio Souza: The unmet need for E.T. patients is undeniable, with millions of patients in the U.S. in need of a therapeutic option that allows them to perform daily activities without the impairment created by the coronavirus. With such a large market opportunity, the ET landscape has been ready for innovation. Eulexacultamide is a unique and highly selective small molecule inhibitor of T-type calcium channels designed to block abnormal neuronal burst firing.

Speaker Change: Matt need 42 patients is undeniable with millions of patients in the U S in needs of a therapeutic option that allows them to perform daily activities without the impairment created by the condition.

Speaker Change: With such a large market opportunity the ETE landscape has been ready for innovation.

Speaker Change: It looks like ultimate has a unique and highly selective small molecule inhibitor of T type calcium channels designed to block abnormal they're all now burst firing.

Marcio Souza: Which should lead, as you've seen, and you're going to be looking into the new study, to improvements of E.T. symptoms in patients. It has been only a short nine months since we started the biggest and most comprehensive IT program conducted to date with Essential 3, comprised of two simultaneous Phase 3 studies, including a 12-week parallel design and a 12-week randomized withdrawal. Essential 3 incorporates a decentralized design to reduce patient burden, which has been working super well, together with stratification of key parameters to maintain balance across groups and the implementation of a very comprehensive screening protocol to ensure suitable patients participate in their study.

Speaker Change: Which should leads as you've seen and you're going to be looking into the new study two improvements RPT symptoms in patients.

Speaker Change: It has been only a short nine months since we started the biggest and most comprehensive program conducted debates with essential III comprised of Q simultaneous phase III studies in closing at 12 weeks parallel design and a 12 week randomized withdrawal one.

Speaker Change: Essential III incorporates a decentralized designed to reduce patient partner, which has been working super well together with stratification of key parameters to maintain balanced across groups and the implementation of a very comprehensive screening protocol to ensure its suitable patients participate in the state.

Marcio Souza: We knew going in Essential 3 that the proper endpoint had to be the MADL11, as we discussed previously. And also the importance of putting in place the controls to minimize variability in placebo effect. And that was all done.

When you go in an essential III that proper endpoints had to be the <unk> 11, as we've discussed previously.

Speaker Change: And also the importance of putting in place the controls to minimize variability in placebo effect and that was all done.

Marcio Souza: While we are confident about the design and the execution of the program, we're also cognizant, of being the first in a space like essential tremor, and the responsibilities that are bestowed upon us to leave no rock unturned in order to maximize the program of success of ULA. With all of this in mind, we built in from the very beginning of the study from the onset a planned interim analysis for the parallel group study or study one in the Essential 3 program.

Speaker Change: Why we have confidence about the design and the execution of the program. We're also cognizant of being the first in a space like essential tremor.

Speaker Change: And the responsibility that are bestowed upon us to leave no rock unturned in order to maximize the program of success of elixir.

Speaker Change: With all of this the mines with Delta and from the very beginning of the study from the onset a planned interim analysis for the parallel group study study one India Central III program.

Marcio Souza: We have discussed this plan with the FDA, and we intend to complete the analysis in Q4 2024. The base assumption we've been using, and we're going to continue to use at this point in time, is that we would read out the study shortly thereafter.

Speaker Change: We have discussed this plan with the FCA and we intend to complete the analysis in Q4 2024.

Speaker Change: The base assumption who've been using and we're going to continue to use at this point in time is that we would readouts. They study shortly thereafter.

Marcio Souza: The strong participation we are seeing in Essential 3 continues to highlight the significant therapeutic needs for new therapies in essential therapy, and we really look forward to fulfilling these needs and filing our plan's NDA next year. I'll now move to our highly differentiated Eplapsi portfolio, beginning with Praxis. As a reminder, Prax2Aid 628 is a next-generation, functionally-selective small molecule from our cerebrovascular platform. Sexuates currently being developed as a once-daily oral treatment for adults with epilepsy.

Speaker Change: The strong participation and we are seeing essential III continues to highlight the significant unmet need for new therapies in essential tremor, and we really look forward to fulfilling this needs and filing our planned NDA next year.

Speaker Change: I will now move to our highly differentiated epilepsy portfolio, beginning with frac fixed rates.

Speaker Change: As a reminder, fluctuate six two axes of next generation functionally selective small molecule from our Seo broke platform.

Speaker Change: Six suites currently being developed as a once daily oral treatment for adults with epilepsy.

Marcio Souza: Building up these strong results into date with 6 to 8, both preclinically and clinically, we have started a comprehensive late-stage program in epilepsy, and we call this program anorexia. ENERGY is comprised of four studies aiming to build a strong base of patients for our trial while generating multiple data points over the next 18 months to support the differentiated profile of BRCA628. We're very excited to be collaborating with the Epilepsy Study Consortium in a first-in-kind initiative to characterize a very large group of epileptic patients and, amongst other things, assess the appropriateness of participation in clinical study.

Speaker Change: These are not these strong results seen to date with <unk>, both pre clinically and clinically we have started a comprehensive late stage program in epilepsy and recall this program energy.

Speaker Change: Energy is comprised of four studies aiming to build a strong base of patients for our trial, while generating multiple data points over the next 18 months to support the differentiated profile of Brac fixed rates.

Speaker Change: We're very excited to be collaborating with epilepsy study consortium enough, forcing kind initiative, Joe characterized a very large group of the flagship patients and amongst other things SaaS the appropriateness of participation in clinical studies.

Marcio Souza: This initiative is conducted under a clinical protocol called EMPOWER, which is expected to be up and running this quarter and to be active during the entire development program for practice. RADIAN is the first of three planned efficacy and safety studies we expect to start in the coming. Regents will enroll patients with either focal or generalized epilepsy who received 6 to 8 for 8.

Speaker Change: This initiative is conducted under a clinical protocol called empower which is expected to be up and running desk quarter and to be active during the entire development program for <unk>.

Speaker Change: Raytheon is the first of three planned efficacy and safety studies, we expect to start seeing the coming months.

Speaker Change: Ragan will enroll patients with either for our generalized epilepsy, who received fixed rate for eight weeks.

Marcio Souza: Site engagement and recruitment initiatives are underway, and we plan to enroll up to 50 patients and expect top-line results in the first half of 2025. Regencies expect to provide important safety, PK, and efficacy information about sexuation. We're really looking forward to it. Power one and two are our 12-week phase two, three studies in patients with full contact. Power One is expected to start enrolling later this year, with results expected by the second half of 2025.

Speaker Change: Site engagement and recruitment initiatives are underway and we plan to enroll up to 50 patients and expect top line results in the first half of 2025.

Speaker Change: Regency is expect to provide important safety PK and efficacy information about fixed rates and are really looking forward to it.

Speaker Change: Power, one and two on our 12 week phase II III studies in patients with focal onset seizures.

Speaker Change: One is expected to start enrolling later this year with results expected by the second half of 2025.

Marcio Souza: We expect Power2 to be initiated in the first half of next year, which we believe, together with Power1, will generate a robust efficacy package for practice. With that, I'd now like to turn to our Erythrogene program partner, which are a group of severe epilepsy characterized by developmental delays with early onset. Relutargene is a first-in-class small molecule and preferentially inhibits persistent sore incurrence, which has been shown to be quite a key driver in uncontrolled seizures in multiple D. The preclinical and clinical data we reviewed before for rilutragine supports a differentiated profile in these, particularly those without any effective and safe treat available.

We expect power to be initiated in the first half of next year, which we believe together with power one we generate a robust efficacy package putback fixed rates.

Speaker Change: With that I would now like to turn to our retro gene program part disease, which are group of severe epilepsy characterized by developmental delays with R&D offsets.

Speaker Change: <unk> is a forcing class small molecule preferentially inhibits persistent sorting clearance, which has been shown to be quite a key driver in uncontrolled seizures in multiple tiers.

Speaker Change: The preclinical and clinical data we reviewed before for re leveraging supports a differentiated profile of <unk>, particularly those without any effective in phase III avail.

Speaker Change: Available today.

Marcio Souza: We look forward to the top-line results from our proof-of-concept study in bold this quarter. We have been particularly humbled by the severity of the patients in this study and the urgent needs they bring to the table for better therapy. At the time of the readout, we expect to be able to share the efficacy and safety of the placebo control parts of the study, as well as available data from the long-term extension portion, as appropriate. We believe reluterogen has potential as a best-in-class option, serving as a backbone therapy across multiple deindications, and really look forward to discuss that further with you all in the near future.

Speaker Change: We look forward to the topline results from a proof of concept study and boards. This quarter has been particularly humbled by the severity of the patients in this study and the European needs day brings to the table for better therapies.

Speaker Change: At the time of the readout, we expect to be able to share the efficacy and safety of the placebo controlled part of the study as well as available data from the long term extension portion as appropriate.

Speaker Change: We believe <unk> has potential as a best in class option, serving as a backbone therapy across multiple indications and really look forward to discuss that further with you all in the near future.

Marcio Souza: Finally, I'd like to turn to Alzheimer's or Praxis 222, our ASO designed to selectively decrease expression of SCN2A gene and directly target the underlying cause of early-onset seizures in SCN2A-DE. In the second quarter of this year, we initiated the first arm of the Global Registration Study for Asylum Nursing in Brazil, which is expected to be followed shortly by the expansion of the program in Europe and in the U.S. later this year.

Speaker Change: Finally, I would like to turn to our nursing practice Ya Chu our ASO designed to selectively decreased expression of SCM to aging and directly targets the underlying cause of early onset seizures in <unk>.

Speaker Change: In the second quarter of this year, we initiated the first arm of the global registration study of <unk> in Brazil.

Speaker Change: Which is expected to be followed shortly by the expansion of the program in Europe and in the U S. Later this year.

Marcio Souza: This study builds on the very encouraging data from Part 1 of In, where patients achieving significantly seizure reduction and significantly increase in seizure-free days while being generally safe and well-tolerant. As we take all of the updates together, we anticipate all four programs to rapidly advance throughout late-stage developments, with multiple regulatory filings expected in the next few years, which is incredibly exciting. With that, let me now turn the call over to our Chief Financial Officer, Tim Kelly. Thanks, Marcio. And good morning, everybody.

Speaker Change: This study builds on the very encouraging data from part one of the bridge, where patients achieving significantly seizure reduction and significantly increase in seizure free base, while being generally safe and well tolerated.

Speaker Change: As we take all of the updates together, we anticipate all four programs to rapidly advance throughout late stage developments with multiple regulatory filings expected in the next few years, which is incredibly exciting.

Speaker Change: With that let me now turn the call over to our Chief Financial Officer, Tim Kelly.

Speaker Change: Tim.

Tim Kelly: Thank you for joining today's call. I'll provide here a quick summary on the financials for the quarter. In Q2, our operating expenses were $37.8 million, with $27.3 million of that for R&D, and the remaining $10.6 million for G&A.

Tim Kelly: Thanks, Marcel and good morning, everybody. Thank you for joining today's call.

Tim Kelly: Provide here a quick summary on the financials for the quarter.

In Q2, our operating expenses were $37 $8 million with $27 3 million of that R&D and the remaining $10 $6 million for G&A.

Speaker Change: During the second quarter practice spent $27 $4 million in operating cash compared to $20 $9 million in the first quarter of 2024 with the increase reflecting more activity for the essential three studies, while we continue to maintain our focus on optimizing working capital.

Tim Kelly: During the second quarter, Praxis spent $27.4 million in operating cash, compared to $20.9 million in the first quarter of 2020, with the increase reflecting more activity for the essential three studies while we continue to maintain a focus on optimizing working capacity. We ended Q2 with $433.8 million in cash equivalents and marketable security, compared to $81 million of cash and, The increase of $352.5 billion is primarily due to net proceeds from Praxis January 2024 and April 2024 follow on public offerings.

Speaker Change: We ended Q2 with $433 $8 million in cash equivalents in marketable securities compared to $81 million of cash in December the increase of $352 $5 billion is primarily due to net proceeds from Praxis January 2024, and April 2020 for follow on.

Speaker Change: <unk> offerings.

Tim Kelly: Our CASH report is a runway into 2027 and includes funding all studies that Marcio discussed today to their readout. With that, I will pass it back over to you. Thank you, Tim. We're now going to open the call for Q&A. Thank you. Operator. Ladies and gentlemen, to ask a question, you will need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, simply press star 11 again.

Speaker Change: Our cash reports a runway into 2027 and includes funding all studies the MRC, we discussed today to their readout.

With that I will pass it back over to you Mark.

Thank you Tim.

Mark: We're now going to open the call for Q&A. Thank you.

Mark: Operator.

Ladies and gentlemen to ask a question you will need to press star one on your telephone and wait for your name to be announced to withdraw your question simply press Star one again.

Operator: Please stand by while we compile the KNEVS. Now, first question coming from the lineup, Yasmeen Rahimi with 5 Percent Learning, line is open. Hi, good morning team and congrats on kicking off the energy program. Team, a few questions.

Speaker Change: Standby, while we compile the Q&A roster.

Speaker Change: No first question coming from the lineup, yes, Rahimi with Piper Sandler Your line is now open.

Rahimi: Good morning team and congrats on kicking off.

Rahimi: Okay.

Speaker Change: Energy program.

Rahimi: Two questions first one is you alluded to that I guess could you comment whether enrollment I guess it seems like it's still sort of finishing up if you could quantify sort of where you are in the cadence on getting a central done second as we spoke about an interim analysis.

Yasmeen Rahimi: First one is, you alluded to that, I guess, could you comment whether enrollment, I guess, it seems like it's still sort of finishing up if you could quantify sort of where you are in the cadence of getting essential done. Second, if you spoke about an interim analysis, could you maybe talk about what this interim analysis is you're referring to? Because it's maybe a new word that we just picked up on, would love your thoughts on that, what that analysis is and what will be unveiled.

Speaker Change: Could you maybe talk about what this interim analysis is you're referring to because it's maybe a new word that we picked up on.

Would love your thoughts on that what that analysis said somewhat will be unveiled.

Speaker Change: And then the third question is could you maybe talk to us about.

Marcio Souza: And then the third question is, could you maybe talk to us about. Given that RADIAN will read out in the first half ahead of the power studies, how predictive is going to be the RADIAN study in terms of read-through to power one and power two, given that it has maybe a more broader population and how you're thinking about enriching that group? Absolutely. Marnie asked, thanks for the questions.

Speaker Change: Given that radian will read out in the first half ahead of the power studies.

Victor: Victor is going to be the radiant study in terms of read through to power one and power.

Speaker Change: Given that it has maybe a more broader population and how youre thinking about enriching that group.

Marcio Souza: So on the first one, right, if you can, as we look into our slides, like eight in our corporate deck we posted this morning, you're going to see we're clearly maintaining the guidance that we had before. So it's by no means like a delay here, introducing the internet analysis. What I wanted to be clear here was going to segue to our second question. As we're looking for the study from the get-go, from the very beginning of the prepared remarks, we considered the possibility of adding an in-train analysis, and we did. That was properly discussed in the very first portion of the protocol, statistical analysis plan, and so on. Primarily for two reasons.

Speaker Change: Yes, absolutely.

Speaker Change: Thanks for the questions.

Speaker Change: So on the first one if you can.

Speaker Change: Ken.

Speaker Change: As we look into our slides like eight corporate that quick bolstered this morning, youre going to see you're clearly maintaining the guidance that we had before so it's by no mean like a delay here or there.

Sandy: Sandy the internal analysis.

Sandy: Wanted to be clear.

Speaker Change: Our year here, what's going to segue to our second quarter.

Speaker Change: As we're looking for this study from the get go from the very weak.

Speaker Change: And on the prepared remarks.

Speaker Change: The possibility of adding trend analysis in which adds.

Speaker Change: <unk> property to discuss.

Speaker Change: The very first version of the protocol Statistical analysis plan and so on.

Marcio Souza: One, obviously, things can go better than we expect, number one. And two, things could happen along the way that might consider, depending on the data, for us to do this analysis. Now, in turn, nothing happened along the way.

Speaker Change: Primarily for two reasons, one obviously things can go better than we expect number one and two things could have been a long delay.

Speaker Change: That might consider depending on that.

Speaker Change: For us to do this analysis now.

Speaker Change: Nothing happened along the way.

Marcio Souza: But we considered phase of enrollment, type of patient, characteristics of the patient, slide of data. It's all looking exactly as we expected here. So that is a check, and that would not be a reason to conduct an in-train.

Speaker Change: I don't see there based on enrollment type of patient characteristics observation blinded data.

Speaker Change: All are located exactly as we expected here. So that is a shack and that would not be a reason to conduct.

Marcio Souza: But externally, there are factors that have been happening and that might have influenced the way we think. So when the cost of something is very small, as it is the case here, but the upsides is very large, as is the case here, meaning if you were, for example, to exercise the ability to increase the sample size, in case, just like a recent readout from another competitive program, seems like placebo is slightly higher than expected, not what we are seeing, but we remain humble and diligent here, we might have the opportunity to do that, because we have tremendous interest in the trial, that wouldn't be really a problem for us whatsoever to do that at points, and really continue to study.

Speaker Change: But externally that are factors that being.

Speaker Change: And that might have influenced like the way we think.

So the one that costs.

Speaker Change: So something is very small as it is the case here, but the upside is very large.

Speaker Change: It is the case here, meaning.

Speaker Change: If you were for example to exercise the ability to increase the sample size in case, just like our recent $3 for an another competitive program.

Speaker Change: Seems like placebo was slightly higher than expected not what are we are seeing but we will remain vigilant.

Speaker Change: Diligence here.

Speaker Change: Might have to do that.

Speaker Change: Because we have.

Speaker Change: Tremendous interest in the trial that would be really problem for us whatsoever to that our parents.

Speaker Change: Any commentary or they started so.

Marcio Souza: So a big insurance policy on one end, and not really an indicator that there is anything happening with either the enrollments or the program itself. On the other end, felt appropriate for us, considering the responsibilities that we have right now to deliver this program, not only for all of us, at Praxis for all the investors, like you are representing here, but patients, right, that don't really have any other option in development now for them. So when you put that all together, increasing the probability of success of the overall program was a key driver, and we believe we're doing that by conducting this analysis. So that is on the second.

Speaker Change: Big insurance policy on one hands and not really an indicator that is anything happening with either the enrollments or the program itself from the other ends.

Speaker Change: Felt appropriate for us considering the responsibility that we have right now it's delivered this program not only for all of us.

Speaker Change: Our practice for all the investors.

Speaker Change: You are representing here, but.

Speaker Change: Patients that don't really have any other option in development now for down so when you put that altogether.

Increasing the program at a subset of the overall program was a key.

Speaker Change: Driver and we believe we're doing that by product into that analysis.

Speaker Change: So that is on the second.

Marcio Souza: On radiance, so radiance is I think a phenomenal study to be conducting right now. It adds an intermediate result for us, which obviously continues to build excitement of 6-2A, to generate data. There are a couple of points to generate more.

Speaker Change: Right yes.

Speaker Change: Right and just.

Speaker Change: I think thats a nominal.

Speaker Change: It should be conducting right now.

Speaker Change: In the intermediate results for us.

Speaker Change: Which obviously continue to bill <unk> of <unk>.

Speaker Change: <unk> and.

Marcio Souza: One, again, continue to build the success we're seeing now with patients that have non-controlled seizures, both with focal sets and generalized. But the second is we want to, and we believe that since we are accelerating pretty quickly to a potential NDA not in that far in the future, to continue to characterize PK in this population, which is not something fancy or that we often discuss that needs to be done, but needs to be done.

Speaker Change: To generate data with a couple of points.

Speaker Change: <unk> two <unk>.

Speaker Change: Generate more one.

Speaker Change: Again, it continues to build.

Speaker Change: It took SaaS, we're seeing now with patients that have no control seizures, both with focus on SaaS.

Speaker Change: Generalize.

Speaker Change: But the second is we want to and we believe that seems to be accelerating pretty quickly to a potential NDA filing.

Speaker Change: <unk> in the future to continue to characterize our PK in this population, which is not something fancy or whatever we often discuss that needs to be done, but the distributor and conducting that study.

Marcio Souza: And conducting that on my study, that is what makes operationally far easier is the second parameter. And it's our first foray on patients with generalized where we're going to get like an even potential for a second indication here in the future. So, understanding that as well. All of that done in an incredibly efficient way, right?

Speaker Change: Operationally far easier.

Speaker Change: As the second parameter and is our first foray on.

Speaker Change: Patients with generalized where we're going to get like an even potential for a second indication here in the future so understanding that as well.

Marcio Souza: The excitement from all the investigators we talked to is incredibly high. I think everyone is really looking forward to having their results, something as efficacious as it looks like it's going to be. So, it wasn't all in between.

Speaker Change: All of that on an incredibly efficient way, but the excitement from all the investigators without chew is incredibly high.

Speaker Change: I think everyone really looking forward to having.

Speaker Change: Some things.

Speaker Change: Efficacious as it looks like six way, it's going to be so it was a little bit in.

Marcio Souza: Of course, we're going to learn things as well on this study that is going to help the entire package. So, when you look into a potential package for registration here, power one, power two, and whatever we learned from safety and exposure relationships and so on on radiance should be that package in the near future. Sorry for the long answer there, and hopefully I answered everything you asked. That was great.

Speaker Change: In between of course.

Speaker Change: We're going to learn things as well on the study that is going to help higher package. So when you look into a potential package for registration here.

Speaker Change: Power, one power to and whatever we learned from safety and exposure relationships and so on on regions should be there.

Speaker Change: Package in the near future sorry for the.

Speaker Change: A long answer hopefully I answer everything you asked.

Marcio Souza: Thank you, Marcio. I'll jump back into the Q&A. Thank you. And our next question coming from the line up. Joon Lee withdrew his seal on his open.

Speaker Change: That sounds great. Thank you Marci I'll jump back into the queue.

Speaker Change: Thanks, Yes.

Speaker Change: Thank you.

Speaker Change: And our next question coming from the line of.

Speaker Change: Jim Lee with <unk>. Your line is now open.

Joon Lee: Anyway, congrats on the progress and thanks for taking our questions. And I think interim is a good, you know, it's part of good housekeeping. But if you do decide to resize the trial for any reason, I could potentially push out the timeline for study one with the randomized withdrawal trial, which I believe is study two, still read out by year end. I don't think that there is an interim for study two, I believe. And I have a follow up question.

Jim Lee: Congrats on the progress and thanks for taking our questions I think.

Speaker Change: And it's part of good housekeeping, but if you do decide to resize the trial for any leader.

Speaker Change: It could potentially push out the timeline, we're studying one.

Speaker Change: With the randomized withdrawal trial, which I believe is steady to still beat up by year end.

Speaker Change: I don't think that there is an RFP for a stage two I believe and I have a follow up question.

Marcio Souza: Yeah, so thanks so much, Joon. So study one and study two now are slided to readouts together, right, as you know. We're still expecting to be the case, as we do expect, as you properly were there, the interns just going to be a housekeeping exercise. But in the case, which we're not expecting to happen, but it could happen, that we need to slightly increase the size of Study 1, then they would be separated.

Speaker Change: Yeah. So thanks, so much jumped so steady one third each now are slotted.

Two readouts together, Brian as you know.

Speaker Change: We're still expecting to be the case as we do expect as you properly.

Speaker Change: Are there any.

Speaker Change: Trends, Joe is going to be a housekeeping exercise.

Speaker Change: But in the case, which we're not expecting to happen.

Speaker Change: But it could happen that we need to choose likely increase the size of study. One then they would be separate and we don't believe buyout very large period of time, because we do have sufficient patients are not going to be closing.

Marcio Souza: We don't believe by a very large period of time, because we do have sufficient patients who are not going to be closing the screening and pre-randomization work for Study 1. It would be quite fast if that happened.

Speaker Change: The screening and pre randomization work, Florida study wont be quite fast.

Marcio Souza: That was one of the motivations, to be honest, on our end. Since we have enough patients, there wouldn't be a delay to create a significant cohort effect. Great. That's a fascinating setup there.

Speaker Change: The half that was one of the motivations to be honest on our end.

Speaker Change: So we have like enough patients that would then be agile and creates like a significant cohort effects.

Marcio Souza: The follow up question is, you know, as we look forward to the relutrogen data in DE, help us assess some bar for what, You think is a good data and what you, you know, from FDM 2A and 8A, and you say that, you know, the opportunity in 2A and 8A could be just a tip of the iceberg for future application. Can you elaborate on that a little bit? For example, what other types of DEE did you have in mind? Thank you. Yeah, no, that's it.

Speaker Change: Great.

Speaker Change: Fascinating set up there.

Speaker Change: The final question is as we look forward to the <unk> data and B E.

Speaker Change: Help us set the bar for what.

Speaker Change: You would think is a good data.

Speaker Change: From <unk> a M.

Speaker Change: The opportunity in <unk> and <unk> could be just the tip of the iceberg feature application can you.

Speaker Change: To elaborate on that a little bit for example, what other types of <unk> did you have in mind. Thank you.

Marcio Souza: And thanks for that. So we continue to monitor the progress here. We are really very, very close to that readout, right? Incredibly excited.

Speaker Change: Yeah, no thanks for that.

Speaker Change: We continue to monitor the progress we are really very very close to that as readouts incredibly excited.

Speaker Change: There are two things that I mentioned on the.

Marcio Souza: But there are two things there that I mentioned on the, On the prepared remarks, just going to want to bring back. So one, those patients were far more severe than than we originally expected. And I think that is quite interesting from the to actually drive some relief for themselves, for their family, which is exciting for us.

Speaker Change: On the prepared remarks, so its going to want to bring back. So wanted those patients who are far more sit here than than we originally expected and I think that is quite interesting from.

Speaker Change: Let's see to actually drive some relief for themselves for their families.

Speaker Change: <unk>, which is exciting for us.

Marcio Souza: We guided before, we're going to continue to guide at this point. 20 to 30% seizure reduction, we think that would be quite phenomenal from the sample size we have, from the type of patients enrolled, of course, we want to see patients doing as well as possible. You might have caught as well the fact that you're going to have, in my view, a significant number of patients crossing the long-term extension, so we're going to be able to talk about what happens when they continue taking the drug and so on. So that is the there.

Speaker Change: We guided before we're going to continue to guide the disappointing.

Speaker Change: 20% to 30% seizure reduction I would think that would be quite phenomenal.

Speaker Change: The sample size, we have from the type of patients who enroll of course wants to see patients doing as well as possibly you might have caught as well the fact that youre going to have a.

Speaker Change: <unk> was a significant number of patients crossing.

Speaker Change: Long term extension, so wouldn't be able to talk about what happens once they continue they can the drug and so on so that is there.

Speaker Change: Are there.

Marcio Souza: Then when you open, I would say, the horizon here and you order the, A month for something like 300 genetically defined, it blaps is at this point in time, right? Like, incredible the growth that existed on understanding, since the pioneers on this field like Sia Petrou, that Goldstein and others started like looking to this in detail and Sam and other folks. But the use of fairly toxic, but still efficacious sodium channel modulators is pretty wide.

Then we will open.

Speaker Change: I will say the horizon here.

Speaker Change: The other <unk>.

Speaker Change: Okay.

Speaker Change: Now for something like 300 genetically defined epilepsy is at this point in time right.

Speaker Change: Credible growth that existed on understanding.

Speaker Change: Since the pioneers in this field like that through the Goldstein and others.

Speaker Change: <unk> like looking to this <unk>, Sam and other folks.

Speaker Change: The use of a fairly dark sick.

Speaker Change: But it's two efficacious southern channel modulators is pretty wide.

Marcio Souza: So, if you think nothing else but great, like patients trying to come to a mechanism that gives them some relief, but they really can't because there are limitations on both efficacy and safety. That alone, it is probably the largest opportunity in TE that anyone ever talked about. And as we look into that, what you're probably going to be hearing from us, it's a broader approach in terms of like patients who have very severe, uncontrolled, and Pediatric ID because that is the key here, right? So very different manifestations, they get older, probably not as severe as when they are young.

Speaker Change: So if you take nothing else but.

Speaker Change: Yes.

Speaker Change: Like patients trying to control mechanism that give them some relief.

But they really can't because there are limitations on both efficacy and safety.

Speaker Change: That alone.

Speaker Change: Is probably the largest opportunity in <unk>.

Speaker Change: Anyone ever talked about.

Speaker Change: <unk>.

Speaker Change: As we look into that.

Rob: Rob I believe going to be hearing from us. It's a broader approach in terms of like patients who have very severe uncontrolled.

Speaker Change: And did you answer it.

Speaker Change: Because that is the key here right. So a very different manifestations they get older problems.

Speaker Change: Probably not as severe as it when they are young.

Francois Brisebois: That number is pretty big, not only from our market opportunities, but from our unmet needs opportunities. And I think that that's focusing all right. Thank you. And our next question, coming from the lineup, Francois Brisebois with Oppenheimer, Yolanda Salter. All right, thanks for taking the questions. So just first of all, so you mentioned the 20 to 30 percent seizure reduction would be great, especially with this size of a trial, but should we be expecting a p-value here?

Speaker Change: That number is.

Speaker Change: Really big.

Not only from a market opportunity, but upfront unmet needs opportunities and I think thats focusing all right now.

With our questions.

Speaker Change: Thank you.

Speaker Change: Our next question coming from the line of Thanks, Rob missile bomb with Oppenheimer. Your line is now open.

Speaker Change: Hi, Thanks for taking the questions.

Speaker Change: So just first of all you mentioned that 20% to 30%.

Speaker Change: The reduction would be great, especially with this size of the trial, but should we be expecting a P value here just wanted to make it clear for expectations into the data.

Speaker Change: Yeah, so thanks for that.

Speaker Change: Good question.

Francois Brisebois: I just want to make it clear for expectations into the data. Yeah, so thanks for the question. The, so we are like, again, we keep guiding care. We're going to continue to for 20 to 30%. I think what I would like to see on top of that is the distribution of the patients. Right?

Speaker Change: So we are again guiding channel, we're going to continue to for 20% to 30% I think what we would like to see on top of that is the distribution of the patients right. So I think we're going to be talking about that.

Marcio Souza: And I think we're going to be talking about that. Like, that there are things that are more common, like, variable sample in some of those patients that are things that are uncommon, like, significantly reduction. Potential for periods, like, without and things like that.

Like that are things that are more come on like variable at some point some of those patients that are things that are uncommon like significantly reduction.

Marcio Souza: So we're kind of weeks away. I would say, since we got it for Q3. so I'm going to continue to to look into to that. When you think about tolerability.

Speaker Change: Potential part periods like we don't see it.

Speaker Change: And things like that.

Speaker Change: So.

Speaker Change: Kind of weeks away I would say since we guided for Q3.

Speaker Change: Political continue to.

Speaker Change: Looking to show that when you think about still durability big.

Marcio Souza: The go-to hypothesis on this study is that we would see a lot of issues with these patients. They are known for having very poor tolerability with any agents they take, and I can say because tolerability is not blinded, right? We're seeing this throughout the study. That is not the case. We're seeing very good tolerability with this drug, which gives us even more encouragement on how it can be used and explored for a controlled and uncontrolled case. So stay tuned. It's now our footstep.

Speaker Change: The go to hypothesis on this study is that we would see a lot of issues with this patient data.

Speaker Change: Unknown for having very poor to let's see.

Speaker Change: With any agent state data.

Speaker Change: And I can say because some of our business blinded right.

Speaker Change: For all of the study.

Speaker Change: That is not the case, we're seeing very good tolerability with this drug which gives us even more and encouragement on how it can be used and explored.

Speaker Change: For control then uncontrolled case, so stay tuned.

Marcio Souza: It's very close for us to be talking about this, so we're going to be having a fulsome discussion as the results are out. Okay, thanks. And then just in terms of the study design, just differences with others in terms of essential tremor, can you just help us understand, you know, maybe the differences and the thought process between doing parallel and randomized withdrawal and just overall just maybe going through the differences that make you feel comfortable with the readout or more comfortable than what others ran into here. Thank you.

Speaker Change: It's in our footsteps.

Speaker Change: Very close for us to be talking about this all going to be having a fulsome discussion. So as a result of our outlets.

Speaker Change: Okay. Thanks, and then just in terms of the study designs at differences with others in terms of essential tremor can you just help us understand you know me.

Speaker Change: Maybe the differences in the thought process between doing parallel and randomized withdrawal and just overall, just maybe going through the differences that make you feel comfortable with.

Speaker Change: With the readout or more comfortable than what others ran into here. Thank you.

Marcio Souza: Yeah, so the thoughts from from the get-go on the, I'll start with the randomized drug here, because I think it's quite, quite interesting, right? The way drugs are used in the market is a patient takes a drug, and if they respond, they stay on the drug, and if they don't respond, they discontinue. The way, and I know it sounds insanely odd, what I just said, but it doesn't feel like when we have questions like this on how odd it is, then you go back to how you test drugs and you just assign them to groups that would never actually behave that way, right?

Speaker Change: Yes.

Speaker Change: For further gas go on the I'll start with the randomize withdraw here because I think it's quite quite interesting right. The way drugs are used in the market as a patient hub.

And if they respond they stay on the drug.

Bonds.

Speaker Change: We continue.

Speaker Change: The way and I know it sounds sandy.

Speaker Change: Just that but it doesn't feel like one of the questions like this oncology as it is.

Speaker Change: Then you go back to Howard.

Speaker Change: Dogs, and new just assign them to groups that would never actually behave that way right like parallel groups and all their designs. So when we.

Marcio Souza: They like parallel groups and other designs. So when we discussed with the agency, when we discussed internally, that was quite important to establish like what happened with these patients. They maybe remind everyone that patients with essential trauma don't tolerate anything, they are giving like a lot of other potential therapies and they continue all of them. Like the terminal rate is like 70% of retention on treatment. So that was quite important.

Speaker Change: Because with the agency when we discuss internally that was quite important to establish like what happened with these patients.

Speaker Change: Maybe remind everyone that patients with essential tremor tolerate anything.

Speaker Change: They are giving like a lot of other potential therapies and all of that like the terminal rates of slide six 6%.

Speaker Change: The redemption of ultra has been sold.

Speaker Change: That's quite important now that is steady.

Marcio Souza: Now that this study is out, it's pretty straightforward in the sense that we size that significantly higher than we believe we need. So that's why we're continuing that, and that's why from the beginning, we never planned to do any potential adjustments with that. The Barlow Group.

Speaker Change: It's pretty straightforward and ourselves that we sized that significantly higher than then we believe we needs.

Speaker Change: So thats why were continuing to add thats why from the beginning whenever plans to do any potential adjustments with that.

Speaker Change: The parallel group.

Marcio Souza: The key for influencing that from the beginning is, There have been many, many discussions in the field. Essential tremor never had a pharmacological treatment approved, which is a very comprehensive study and analysis of essential wands. If we understand the groups really well, and we powered a trial and conducted a trial based on those learnings. Now, as we move forward to a much larger study, I think it was important and continues to be important to understand how this heterogeneous group of patients, since there is not a one determinant of essential tremor, behave when you expose them to a relatively long period of time, like three months now. And I look into what's happening in their study right now, it's... Presumably done.

Key.

Speaker Change: Our influence in depth from the beginning is.

Speaker Change: As being many many discussions in the fields.

Speaker Change: Essential tremor never have a pharmacological.

Speaker Change: Approved.

Speaker Change: Did a very comprehensive study and analysis of a central one.

Speaker Change #100: If we understand the groups really well.

Speaker Change: We powered the trial conducted a trial based on those learnings.

Speaker Change: Now as we move forward to a much larger.

Speaker Change #101: <unk> I think was important.

Speaker Change #101: It should be important to understand how does that <unk> genius group of patients since there's not a one determinants of essential tremor behave when you expose them to a relatively long period of time like three months now.

Speaker Change #101: And I looked into what's happening in the study right now.

Marcio Souza: It is done exactly the way we're expecting and all the indicators are as we expect. But we still have that unknown of Virginia's population that might influence things slightly one way or another. That's why we plan, that we are planning right now. This is a registrational package.

Speaker Change #101: Bruce Mcdonald has done exactly the way we are expecting.

Speaker Change #101: All the indicators as we're expecting.

Speaker Change #101: But we still have that I don't know.

Speaker Change #101: But a genius population that might influence things is likely one way or the other that's why we're planning that we are planning right now.

Speaker Change #102: This is a registrational package and we want to make sure as you heard in our disclosures our dealers in our slide deck on our website to file an NDA next year and you'll file that NDA, we need they stay distributions.

Marcio Souza: And we want to make sure, as you heard in our disclosures, and it is in our slide deck in our website, to file an NDA next year. And to file that NDA, we need the studies to be remediative. And that we're doing everything in our power to get the first pharmacologically approved treatments in recent decades for essential tremor patients. So that's how the project was designed. And our next question, coming from the lineup. Captain Suneja with Guggenheim, Yolanda Salke.

Speaker Change #102: And we're doing everything in our power to gas first pharmacologically approved treatments in recent decades.

Essential tremor patients. So that's how the progress is.

Speaker Change #102: Alright.

Speaker Change #103: Thank you.

Speaker Change #104: And our next question coming from the lineup.

Catherine <unk>: Catherine <unk> with Guggenheim. Your line is now open.

Yatin Suneja: Hey guys, thank you for taking my question. Just a couple of clarifications for me. So with regard to the interim analysis in study one, could you tell us what would be the sample size that will trigger it? So that's one. What exactly are you looking for? Is there a particular MADL11 delta you're shooting for there?

Catherine <unk>: Hey, guys. Thank you for taking my question just a couple of clarification from me with regard to the interim analysis and study one could you tell us.

Catherine <unk>: What would be the sample size that will trigger it.

Speaker Change #106: So thats one what exactly are you looking forward is there a particular, maybe at 11 Delta Youre shooting for there.

Marcio Souza: And then is there an alpha loss there since you do an interim analysis and what sort of an alpha loss? And then I have a follow up on the other program. So the interim is based, and while I'm not going to give you the information points here, you have to, and I'm sure you do, believe that it has to be sufficient for the estimation of the entire study. We are using like a promising zone approach to understand where we are, so the re-estimation won't exist, right, it's just a reminder that it's not our base assumption, the base assumption is.

Speaker Change #106: And then is there an alpha launch there since you do an interim analyses and what sort of an alpha launch and then I have a follow up on the other programs.

Speaker Change #106: Alright.

Speaker Change #106: So.

Speaker Change #107: The interim this base.

Speaker Change #108: While I'm not going to give you the information points here.

Speaker Change #109: You have to and I'm sure you do.

Speaker Change #109: And believe that it has to be sufficient for the estimation of the entire.

Speaker Change #109: His study.

We are using like a promising zone approach to to understand where we are so the re estimation. One exists right. Just a reminder, that's not our base assumption of the base assumption is.

Marcio Souza: Resolution without re-estimation, re-estimation happens, it's going to be based on the boundaries, the recommendation of the independent IDMC that we have now. It's all within the range of things we believe we can randomize quite quickly to like, increase the probability of success of the final trial. One of the constraints we've been working on, and one of the reasons why we didn't discuss this before, is final cohort enrollment is incredibly fast. So when you have a situation like that, the reduction of potential entrants, as we're doing in the final cohort, are pretty close together.

Speaker Change #109: Duration without re estimation.

Speaker Change #109: Re estimation happens.

Speaker Change #109: Based on the boundaries the recommendation of the independent GMC.

Speaker Change #110: That we have now it's all with them.

Speaker Change #110: The range of things, we believe we can randomize quite quickly.

Speaker Change #110: To like.

Speaker Change #110: Increase the probability of success of the final trial.

Speaker Change #110: One of the constraints, we've been working on and one of the reasons why wouldn't discuss is before us.

Final cohort enrollments is incredibly fast so when you have a situation like that the reduction potential interim as we're doing in the filings, but pretty close together.

Marcio Souza: So we are considering that as well as work on this study. Okay, for the final analysis, or let's say for the study readout, is there what is clinically meaningful in terms of MADL, both on from the absolute size or on and also on the placebo adjusted delta? Yeah.

Speaker Change #110: So we are delivering that as while as workloads.

Speaker Change #110: Okay.

Speaker Change #111: For the final analysis or let's say for the study.

Speaker Change #111: Readout is good what is clinically meaningful in terms of maybe.

Both of them from the absolute size of them and also on the placebo adjusted.

Speaker Change #111: Okay.

Speaker Change #111: Yeah.

Marcio Souza: When you look back, most of the work, if not all of the work, that was for clinical meaningfulness, follow the recent, like last year's, FDA guidance on patient-driven drug testing plans and on historical guidance in terms of how you anchor this endpoint. Intrinsically, when you anchor the MAGL to a known disability standpoint, like global depression, What you see is a perfect alignment between chains on the ADL and chains on the global impression.

Speaker Change #111: When you look back most of the work if not all of the work.

Speaker Change #111: For clinical meaningfulness.

Speaker Change #111: Hello.

Speaker Change #111: Sounds like last year's FTA.

Speaker Change #111: On.

Speaker Change #111: Patient driven drug.

Speaker Change #111: And our historical guidance in terms of how you anchor this endpoints.

Speaker Change #111: Intrinsically when do you anchor the <unk> too.

Speaker Change #111: Like there's a bit of endpoints like global impression.

Speaker Change #111: <unk> is a perfect alignment between.

James on the AGL.

Speaker Change #111: <unk> on the global impression.

Marcio Souza: It's actually quite obvious for us because when you talk to patients, and then describe what would be important, so talk to physicians, and you ask them what they think is important for their patients. They all describe the gain or maintenance of a function.

Speaker Change #111: It's exited quite obvious for us because when you talk to patients.

Speaker Change #111: Then to describe what it would be barcodes.

Speaker Change #111: <unk> talked to physicians and you asked them.

Speaker Change #111: Good thing to be important on their patients.

Speaker Change #111: They all describe.

Speaker Change #111: King our maintenance of a function.

Marcio Souza: When you go back to the ATL, that is one point. Will you transform that to the MATL-11 that is required on this study that is obviously dropped below one point? This study is well-powered beyond that, but that would be the logical and proper answer is. If we can't drink properly from a cup, and now you can.

Speaker Change #111: Let me go back to the Agi well that is one points. What are you transform depths to <unk> 11 that is required on this study that as others did drop below one points.

Speaker Change #111: This study is well powered beyond apps.

Speaker Change #111: But that would be the largest.

Speaker Change #111: And proper answer is if we can properly from a cup and now you can.

Marcio Souza: I challenge anyone to tell me that that's not how to a patient, is incredibly meaningful. That's a point or less. Now, what we are planning to see on this study is obviously more than that. But it's quite important as well that the proportion of patients gaining one point, two points, three points, whatever, are prehab. So it's not only a point estimation, but also like the proportion of that. And we're monitoring, of course, and we're going to continue to monitor and talk about that. If you're looking for a corporate DAC, it is meant of three points.

Speaker Change #112: I challenge anyone to tell me that does not come to our patients.

Speaker Change #112: It's incredibly meaning that's a points are lax.

Speaker Change #112: No.

Speaker Change #113: Why do we are planning to see after the study is obviously more than that but it's quite important as well as the proportion of patients gaining 1.2 points three points whatever our pre thought so it's not only a point of destination.

Speaker Change #114: <unk> like the performance there and we're monitoring of course and it will continue to talk about that if you look into our corporate deck.

Speaker Change #114: Net of three points with talk about proportion of patients that are there and so on so it's very clear.

Marcio Souza: We talk about like proportion of patients that are there and so on. So it's very clear that this is going to be a quite meaningful treatment for patients with essential tremor, especially the ones that are like with significant disability due to their condition. All right, maybe one more multiple part, like a classic CELFAC question. So, for the interim analysis, this is an efficacy analysis, not fertility analysis, to how you will disclose or what exactly are you willing to disclose to us when this interim happens, and when exactly is this happening? Is it a Q3 event or a Q4 event? Thank you so much.

Speaker Change #114: That this is going to be quite meaningful treatment for patients with essential tremor.

Speaker Change #114: Especially the ones that are like with significant visibility to their conditions.

Speaker Change #115: Maybe one more multiple park like a classic sell kind of question.

Speaker Change #116: So for me the interim analysis. This is an efficacy analysis not utility analysis to how you will disclose or what exactly are you willing to disclose to us blenders in time happened and when exactly what's happening with the Q3 lender can cortland. Thank you so much.

Marcio Souza: Yeah, absolutely. It's currently scheduled to happen in Q4. Like, just as a reminder, right, patients have to complete the whatever information points we determine that the data has to be cleaned, transferred to an external independent data monitoring committee, and then it has to be collected. So, and coming back to us and so on. It's a little while, that's why there are four at the time.

Speaker Change #117: Yes, absolutely.

Speaker Change #117: Currently scheduled to happen in Q4.

Speaker Change #118: Like just as a reminder rights patients have two completes the whatever information points we determined.

Speaker Change #118: That data has to be a cleaning transferred to an extraordinary independence. They.

Speaker Change #118: Data monitoring committee and then there has to be done.

Speaker Change #118: And coming back to us and so on.

Speaker Change #118: A little while that's why therefore the timeline.

Marcio Souza: The, what we intend to communicate at that point in time is what we're going to do, is the decision that is being held at that point in time with DNS. So, the, I'll argue the likely decision here is we will update all of you with the result when the full result for the study is going to happen. And in the eventuality that we believe is appropriate, as recommended by the IDMC, to increase the sample size, what is the increase, and we will be reading out that as well, which we believe evidently will increase if that is to happen. We will have quite shortly that. And our next question coming from the line of... Ritu Baral with T.D. Cowan, Yolanda Sulpin.

Speaker Change #118: Why do we intend to communicate point in time is what we're going to do is a decision that is being held at that point in time with Dennis So the.

Dennis: Arguably it likely decision here as we will update all of you with the result.

Dennis: The full results for this study is going to happen.

And in the eventuality that we believe is appropriate as recommended by the ITM see to increase the sample size.

Speaker Change #120: What is the increase.

Speaker Change #120: And we wouldn't be raising all that as well, which we believe is evident.

Speaker Change #120: The increase if that is to happen.

Speaker Change #121: Would have quietly quite sharply.

Speaker Change #121: Okay.

Speaker Change #122: Thank you.

Speaker Change #123: And our next question coming from the line of.

Mitchell barrel: Mitchell barrel with TD Colin Your line is now open.

Ritu Baral: Good morning, guys. Thanks for taking the question. I have got one last, on Elixir, and then a bunch.

Mitchell barrel: Good morning, guys. Thanks for taking the question I have got one last question on helix.

Mitchell barrel: <unk>.

Marcio Souza: So, for the withdrawal study, I know that sometimes FDA imposes a, Official or unofficial requirement on the initial response rate for those patients going in that are defined as responders before the actual withdrawal portion is Conducted and analyzed. Have you spoken to FDA around the design of the withdrawal study specifically on that initial open-label Responder rate sort of what they're looking for even if and if there is even a hard requirement or just a soft Who would like to have?

Speaker Change #125: So poor the essential.

Speaker Change #126: The withdrawal study I know that sometimes FDA imposes a.

Speaker Change #126: Official or unofficial requirement on the initial response rate for those patients going in.

Speaker Change #126: Find as responders or for the actual withdrawal portion.

Speaker Change #127: Conduct group.

Speaker Change #128: All lines have you spoken to FDA around the design of the withdrawal study specifically on that initial open label responder rates sort of what they're looking for and if there is even a hard requirement or just a soft we'd like to have.

Marcio Souza: [inaudible] Thanks Ritu. From the beginning as well, even actually from the phase two, we had proposed the randomized one of the studies there. The parameters, as you wisely noted, there is the definition, right? randomize only stables or stable with another criterion, things like that.

Ritu: Yeah. Thanks Ritu.

Ritu: Okay.

Speaker Change #130: From the beginning is while we've been exiting from the phase two we had proposed that randomized that's one.

Speaker Change #130: One of the studies, there alright parameters SCO.

Speaker Change #130: As Lee noted there is a definition right.

Speaker Change #130: Randomized only stables are stable with another criteria and things like that.

Marcio Souza: And our proposal from the get-go, and what's being implemented in the central three, was that in the first eight weeks, they would be exposed to drugs, is a response criteria. Bilateral Response Criteria, meaning the criteria for increase and decrease is identical. If they cross that boundary, they're going to be disclosing shortly, as you can imagine that could influence some assessments, that's why we didn't disclose before. Then they can be randomized to stay on drug or to go on placebo, and for the following four weeks.

Speaker Change #130: And our proposal from the GAAP goal.

Lee: While it's being implemented in our central III, while setting the first eight weeks they would be exposed to drug.

Lee: As a response criteria.

Lee: <unk>.

Lee: Bilateral response criteria of meeting the criteria for <unk>.

Lee: Kris and decrease is identical.

Lee: If they cross that boundary gonna be disclosing sharply.

Lee: As you can imagine equity influence amongst estimates that's why we didn't disclose before.

Lee: Then they can be randomized to stay on drug or to go on.

Lee: On placebo.

Lee: And for the following four weeks in patients are not to meet the criteria at week eight and maybe that is what we haven't really talked much before.

Marcio Souza: If patients are not to meet the criteria at week 8, and maybe that is what we haven't really talked much about before, they are moved into the long-term extension programmatically, right? They don't know that they were excluded as the entire system remains blinded for the entire duration of the 12-week period.

Lee: They are moved into the long term extension.

Speaker Change #132: Programmatically right they don't know.

Speaker Change #132: There were excluded as the entire.

Speaker Change #132: It remains blinded for the entire duration of the 12.

Marcio Souza: So, only responders, are randomized after eight weeks, and therefore they are the only ones, quote unquote, at risk of losing the effect when they are randomized duplicity. But the original sort of open label response rate going in, there was no criteria, wired around. They are all randomized. They're all blinded already.

Speaker Change #132: So only responders.

Speaker Change #132: Our randomized after eight weeks and therefore, they are the only ones clinical at risk.

Speaker Change #132: Losing the effect when they are randomized to placebo.

Speaker Change #133: But the original sort of open label response rate going in there is no criteria for what was required around that.

Marcio Souza: Okay. Yes. Correct. Okay. Understood. Moving to 628 and the RADIAN studies. First of all, can we confirm that the Radiant and Power 1-2, those are placebo-controlled studies? Yeah, so radiance is not.

Speaker Change #133: They are all randomized.

Speaker Change #133: Shined it already okay, yes, correct.

Speaker Change #134: Correct, Okay I understood.

Speaker Change #134: 2628, and the Radiant study first.

Speaker Change #135: First of all can we confirm that the radiant and power one team does a placebo controlled study.

Yes, so <unk> is not.

Marcio Souza: Table Controls, Power 1 and Power 2 are on Table Controls. And then what doses are you using? Just given the, you know, very good safety that you've seen, what doses are you using in radiant and power too? So radiance, all patients are going to start at 30 milligrams. Powered 1 and 2, and we just updated the schematics in our PowerPoint and our website as well. Patients will start at 20 milligrams, four, six weeks, and then 30 milligrams for the four other. Six weeks on Power II, there's a lower dose as well just to fulfill potential requirements for a lower dose. Exposure there.

Speaker Change #135: As for controls power, one and power to our placebo controlled got it.

Speaker Change #135: And then what doses are you using just given the very.

Speaker Change #136: Very good safety that you have seen what doses, you're using ingredient and power team.

Speaker Change #135: Yeah.

Speaker Change #136: So radiance what patients are going to start at 30 milligrams.

Howard.

Howard: One and two.

Howard: Updated <unk> an hour.

Howard: Powerpoints and our website as well.

Speaker Change #139: <unk>, who will start us 20 milligrams.

Speaker Change #139: For six weeks and then a 30 milligram and support the four other six weeks on powered two there is a lower dose.

Speaker Change #139: As well just to fulfill potential requirements for Lowe's.

Speaker Change #139: Sure does.

Speaker Change #139: Exposure there.

Marcio Souza: The idea with radiance, there are more flexibility as well, so maximum efficacy should be derived from day one, but it's easier for investigators to make potential recommendations for adjustments, adjust other drugs that cannot be done in the study of a double-blinded study when you don't know if patients are on drug or which dose they are in because that could interfere. That is the idea. As you heard on the previous comments, we are collecting more extensive samples from this, so it becomes a lot easier for us to recruit them in general. Is there a minimum percentage of generalized epilepsy or maximum?

Speaker Change #139: The deal with reagents that are more flexibility here.

Speaker Change #139: That's why also Maxim, Alaska, which have been derived from day one.

Speaker Change #140: But it sure for investigators to make potential a recommendation for adjustments adjust other drugs that cannot be done in the Saudi offer double blinded study. When you don't always patients are on drug or which those they are in because the equity interferes.

So that is the ATI. It's also as you heard on the.

Speaker Change #140: The previous comments rides, we collect an extensive sample sprawl from this.

Speaker Change #140: It becomes a.

Speaker Change #141: A lot easier to recruit them in general.

Speaker Change #141: Is there.

Speaker Change #143: Minimum percentage of generalized epilepsy or maximum.

Marcio Souza: Generalized Epilepsy, I'm sorry, Epilepsy that you have in mind for RADIANT. We're asking just because when we did our doc checks, some of our KOLs were particularly excited about the potential. It was a, I'm glad you bring that up because one of the motivations I believe for includes originally, we thought about only conducting folk onsets, but that is a very, very clear excitement about six to eight on the investigators in general, when they look into highly translatable preclinical models across the board, I think what they are imagining, and that might be a for me at least, is even beyond what we are imagining, potential of this drug, potential for seizure from the board and things like that, that I think we're humbled by and confident about drug developments in general. So that is clearly a push.

Speaker Change #144: Generalized ethics ethics, I'm, sorry, epilepsy that you have in mind for radiant.

Speaker Change #146: Asking just because when we did our doc checks or as some of our kols, particularly excited about the potential for some rate in this population.

Speaker Change #144: It was.

Speaker Change #147: Glad you bring that up because one of the motivations accurate.

Speaker Change #150: Fluids, originally we thought about.

Speaker Change #148: Only conducting focal onset.

Speaker Change #149: It is a very very clear excitements about six to eight funding.

Speaker Change #149: Investigators in general.

Speaker Change #150: When they look into highly translatable preclinical models across the boards.

Speaker Change #150: Simple they are imagining.

Speaker Change #150: And that might be.

Speaker Change #150: EMEA is even beyond what we are imagining finish off this drug a potential for Cedar fair.

Speaker Change #150: The board and things like that that I think.

Speaker Change #150: <unk> bye.

Speaker Change #150: And then the bulk drug development in general.

Speaker Change #154: So that is clearly of course, we do expect by the conversations we have with decides they're going to be enrolling and the investigators in general they're going to follow the general proportion.

Marcio Souza: We do expect, by the conversations we had with the sites that are going to be enrolling and the investigators in general, they're going to follow the general proportion of patients in the clinic, so about 30% or so should be generalized, and the main reminder of that should be focal. Got it. Got it. And then final question. Thanks for your patience. Other than the dosing, do you see in the design? Are there any major differences between power one and power two?

Speaker Change #150: Patients in the clinic.

Speaker Change #150: So about 30% of our social be generalized M D.

Speaker Change #150: <unk> remain a reminder of that should be our focus.

Speaker Change #155: Got it got it and then final question. Thanks for your patients other than the campaign can you see in the design are there any major differences between power one on power Q of note.

Marcio Souza: So, at this point in time, there are no major differences. The power one, the reason why we are really pushing that ahead before power of two as well, is one, taking one study off the ground, or in the case of race, or one, it's obviously operationally simpler. The second is that it's overlap, in terms of fight, expected places we want to go to. And we wanted to make sure the way of the enrollments are on Power One. At the moment, we we start that if not complete. So we wanted to stagger to give the maximum opportunity for patients to enroll on Power One. That was the main motivation.

Speaker Change #156: So at this point in time, there are no major differ.

Speaker Change #155: Difference.

Speaker Change #155: The power one.

Speaker Change #155: The reason why we're really pushing that I had before power too as well.

Speaker Change #155: Yes.

Speaker Change #155: Taking one study off the ground or in the case of raising our wanted obviously operationally simpler.

Speaker Change #155: Second is that is overlap in terms of sites expected.

Speaker Change #155: Expected places we want to go.

Speaker Change #155: <unk>.

Speaker Change #155: And we wanted to make sure by the way the enrollments are on par with.

Speaker Change #155: At the moment, we started that.

Speaker Change #155: It's not complete.

Speaker Change #155: So we wanted to show a staggered to give the maximum opportunity for patients to enroll.

Speaker Change #155: <unk> that was the main motivation here.

Marcio Souza: Understood. Thanks for taking, Of course, our pleasure. Our next question coming from the line up, Joel Beatty with Bayer, the line is open. Hi, thanks for taking the questions. A couple on Essential Three.

Speaker Change #157: Understood. Thanks for taking all the questions.

Speaker Change #158: Of course, our pleasure.

Jonathan <unk>: Thank you and our next question coming from the line of Jonathan <unk> with Baird. Your line is now open.

Joel Beatty: The first is what's the next update for us to expect from the Essential Three program? Would it be an announcement on the completion of the planned enrollment? Or would the next update be the implications from the interim analysis? And then as a second question, has the data from Essential Three been able to be looked at on a blinded basis, perhaps to assess things like whether the variability of the data is in line with expectations? Yeah. Hey, Joel.

Jonathan <unk>: Hi, Thanks for taking the questions a couple on essential III.

Jonathan <unk>: The first is what's the next update for US Thats back from the Central III program would it be an announcement on the completion of the planned enrollment or with the next update would be.

Speaker Change #161: The implications from the interim analysis.

Speaker Change #162: As a second question.

Speaker Change #163: Data from our central <unk> been able to be looked at on a blinded basis, perhaps things like whether the variability of the data is in line with expectations.

Marcio Souza: So, I'll tackle the second question here first. So, yes, we continuously look into the data in a blinded fashion, and I can tell you the variability is actually, as expected, lower in terms of the patients coming in, number one, and then in the studies, the randomization is actually lower, sorry, is actually, as expected, lower beforehand. So, fairly stable patients coming in, as expected patients during the study. So, all systems are green there. That is not the motivation for the plans in trend to do.

Joe: Yeah, Hey, Joe so.

Joe: The second question here first so yes, we continuously look into the data.

Joe: In a blinded fashion.

Joe: The variability actually as expected and are lower in terms of the patients come in number one and then in the studies the randomization exactly lower sorry.

Joe: As expected lower beforehand, so fairly stable patients coming in as expected patients. During this study. So all systems are go green there.

Marcio Souza: On the next updates, we do have to talk about when we are, when we have completed all the next stages of the program, and also we should see. Updates coming up soon, not only on enrollment, but on the initiation and completion of the interim analysis. Great, thank you. And our next question coming from the line up. Ami Fadia with Needham Ilanithou, Hi, good morning.

Speaker Change #165: That is not the motivation for Ford the plans and trends to date.

Joe: On the next updates we do yes.

Speaker Change #165: Can you talk about when we are when we have.

Joe: Completed all the next stage.

Joe: And also we should see.

Joe: Updates coming up soon.

Joe: Not only on enrollments, but on the initiation and completion of the after the interim analysis.

Speaker Change #165: Great. Thank you.

Speaker Change #165: Thank you.

Speaker Change #165: And our next question coming from the line of Amit.

Speaker Change #165: <unk> with Needham Your line is now open.

Ami Fadia: Thanks for taking my questions. Firstly, just a, Follow-up on 6 to 8, what is the gating factor for initiating a pivotal program for generalized epilepsy and is radiant meant to inform the dose that you would study in that epilepsy type? and then I have one or two other quick follow-up. The motivation here for including Generaliza, you might recall, is fixuated quite broadly. Pepsi.

Amit: Hi, Good morning, Thanks for taking my question Firstly E.

Amit: Following up on extra weight, what is the gating factor for initiating a pivotal program or generalized epilepsy.

Speaker Change #169: And we didn't meant to inform the adult study and that epilepsy types.

Speaker Change #170: And then I'll have.

Speaker Change #170: I wanted to one other quick follow up.

Speaker Change #171: Yeah, the motivation here for including generalized.

Speaker Change #171: Recall.

Joyce: Thanks, Joyce quite broadly.

Marcio Souza: So this is the first. I would describe as the terminal value of this model here, right? So when we start with patients that are, I would say, struggling to respond, but likely to respond, in our view, and that's the way we're thinking about Raytheon, to understand whether or not we can really drive the efficacy of this drug. Now what? when you are powering a double-blind study, but really driving the potential maximum here.

Speaker Change #170: Biopsy.

Speaker Change #173: So this is the first.

Speaker Change #170: Chen.

Speaker Change #170: While we are trying to look into is the.

Speaker Change #174: I would describe as determined overvalue off this motto here right. So when we start with patients that are I would say.

Speaker Change #174: <unk> responds, but likely to respond in our view and that's the way we're thinking about raise yen.

Speaker Change #170: <unk>.

Speaker Change #175: Just to understand whether or not we can really drive that went up because of this drug.

Speaker Change #175: No.

Speaker Change #179: One of our borrowing that.

Speaker Change #175: Double blind study, but really driving the potent maximal here almost be better safety.

Marcio Souza: Obviously, that safety collection here that would add to a safe database, that's quite an importance. But maybe even primarily, I keep going back there, but we don't want to, throughout your study, keep collecting more and more PK samples from patients. And I know it sounds minimal, but as we're accelerating towards a potential MDA spectrum, that becomes a quite important consideration as well.

Speaker Change #175: Collection here that with ads.

Speaker Change #180: Data base.

Speaker Change #182: That's quite an important but maybe even primarily I keep going back there, but we don't want to have Roger steady kept like collecting more and more PK samples from patients and I know it sounds minimal, but moderating towards a potential NDA.

Speaker Change #180: Tom.

Speaker Change #180: That becomes quite important consideration as well.

Marcio Souza: And as we want to expand the program, right, after Power One or Two, very, very likely, we'll be running another study in generalized epilepsy, so we wanted to start getting some experience with that patient population. That was the motivation here.

Speaker Change #183: And as we wants to potentially expensive program right after power for two.

Speaker Change #183: Very very likely timing.

Speaker Change #185: The other study in.

Speaker Change #186: Generalized epilepsy, so we wanted to start getting some experience with.

Speaker Change #185: With that patient population that was the motivation here I think the bonus to all of us.

Marcio Souza: I think the bonus to all of us, particularly our investors, is another milestone here, an intermediate readout before Power One, which should obviously give more confidence in the overall problem, particularly on our end, right? We're working on this program with very high confidence in the readout.

Speaker Change #185: Similarly, our investors this ah another milestone here and and intermediate like Readouts are before power, one which should obviously some more confidence.

Speaker Change #185: On the overall problem.

Speaker Change #186: Articulated on our hands right.

Speaker Change #185: This program, which are very high confidence.

Speaker Change #185: On the results.

Marcio Souza: That's, that's quite helpful. Um, with regards to PrATS 562, um, can you talk about how age, and baseline severity impact how much seizure reduction we could expect to see, also how could we how should we think about read through into other DEs based on the data that you will share with us on the two DE subtypes. And then maybe I'll just plug it in here.

Speaker Change #186: Got it.

Speaker Change #186: Quite helpful with regards to Fracs by six two.

Speaker Change #186: Can you talk about how age.

Speaker Change #186: Baseline severity impact how much seizure reduction we could expect to see.

Speaker Change #186: Also how could we how should we think about.

Speaker Change #188: Visa into other DTE is based on the data that you will then share with that.

Speaker Change #186: <unk> subtype.

Marcio Souza: A quick follow up on Alexa. Is the interim analysis likely to drive a statistical penalty or not? Yeah, sure. So when you're looking involved in the upcoming results, I think we absolutely should look into this and how it extrapolates to other deeds. The world of G is being dominated by this, by Drophea, number one, and then two, by these buckets of unknown things that we call GFs, or Lennon-Gastaut, most recently, some instance.

Speaker Change #189: And then maybe just plummet in here a quick followup on Alexa.

Speaker Change #189: He is the interim analysis likely to drive a statistical penalty or not thank you.

Speaker Change #190: Yeah sure. So so we're looking for.

Speaker Change #190: Involved in the deal.

Speaker Change #189: Coming of Readouts.

Speaker Change #191: I think we're absolutely should look into this and how it extrapolates to two other ges.

Speaker Change #191: The award of G is being dominated by this.

Pfizer: Pfizer a fair number one a.

And then to buy these buckets of unknown things that recall.

Pfizer: GFS or our limo Gus starts most recently.

Pfizer: Instance.

Marcio Souza: But there are far more patients, that are, have no alternative. That was a reduction, as little as it might look or not look, right, we're obviously not expecting for little reductions here, we're expecting for significant reductions, would significantly change, one, their lives and their parents' trajectory, but the second is their survival. So we're absolutely sure that we're going to be talking during extrapolate beyond that. And that brings me back to our first question about the age. Is your burden there?

Pfizer: But far more patients.

Have no alternative.

Pfizer: That was a reduction as little as it might look our nonmarket price. We're obviously not expecting four littoral reductions you're expecting significant reductions with significantly changed one their lives in their business trajectory, but the second is their survival.

Pfizer: So we are absolutely assured then we're going to be talking with extrapolate beyond.

Speaker Change #194: That's coming back to your first questions about the age seizure burden there.

Marcio Souza: I know encephalopathies are not taking encephalopathies are a disease of childhood. When you look into the patients that enrolled in our study, as you're going to see pretty soon, we're talking about pretty young kids, seizure burdens that are very, very high, a disability that are quite prominent. When you see gains there, as we told you... Therapy from this patient that is incredibly meaningful because their body is still developing, their brain is still developing, and there's a huge opportunity here to continue to help them throughout their lives. It's exciting to see that.

Speaker Change #195: Development opportunities are.

Speaker Change #196: So I've taken several offices are disease childhoods.

When you look into the patients that enrolled in our study as youre going to see you soon.

Speaker Change #197: We're talking about pretty young kids.

Speaker Change #196: These are important that are very very high.

Speaker Change #196: Disability.

Speaker Change #198: Quiet prominence.

Speaker Change #198: When you see gains there as we've told you to see.

Speaker Change #198: <unk>.

Speaker Change #198: These patients there is meaningful because there are still developing there.

Speaker Change #198: Developing and there is like a huge opportunity here.

Speaker Change #198: To to help them for all their lives.

It's exciting to see there.

Marcio Souza: And we believe it's quite translatable to a very large number of Gs that don't really have any opportunity to have similar characteristics. High seizure burden, very low ability to treat, mostly because of safety and tolerability. Thank you. And our next question coming from the line of... Douglas Tsao, H.C. Rembrandt, D'Lenna Soltan, Hi, good morning. Thanks for taking the questions. Just maybe starting with Radian.

Speaker Change #198: And we believe is quite is translatable to a very large number of Tvs that don't really have any opportunities that have similar characteristics young.

High seizure burden very low ability to three it's mostly because of safety and tolerability drugs.

Thank you and our next question coming from the line of.

Speaker Change #198: Douglas Tsao with H C. Wainwright your line is now open.

Douglas Tsao: Hi, good morning, Thanks for taking my questions, just maybe starting with radiant.

Douglas Tsao: You know, I think, given the PPR results, there was a lot of interest in terms of the 6 to 8 effect in generalized epilepsy. I'm just curious, why not just do that study with generalized epilepsy patients? And also, I'm just curious in terms of the dosing between Radiant and the power studies. For power, you start at 20 milligrams for six weeks and then move to 30. Why in Radiant are you going directly to 30 without sort of a titration period?

Douglas Tsao: I think given the PPR results there was a lot of interest in terms of 68 effect in generalized epilepsy I'm just curious why not just do <unk>.

Speaker Change #201: That study with generalized epilepsy patients and then also I'm just curious in terms of the dosing between radiant and E power studies power Youre, starting at 20 milligrams for six weeks and then moving to 30 Y in Radiant are you going directly to the thirties.

Speaker Change #202: Without sort of a titration period. Thank you.

Marcio Souza: Thank you. Yeah, thanks, Doug. So we have a lot of flexibility on radiance to, as we go through the study, we're going to provide periodic updates on how things are going on that study to potentially actually spend at a cohort. So we're not quite there, but your thought about why not just run a generalized epilepsy in six months, that's what we're going to be talking about. We're going to be talking about starting that controlled study in generalized.

Speaker Change #201: Yeah.

Speaker Change #203: Thanks, Doc so we have a lot of flexibility radiance too.

Speaker Change #203: As we go for this study is going to provide periodic updates.

Speaker Change #204: On how things are going on that study to potentially actually spend at our cohorts. So we're not quite there but your.

Speaker Change #205: <unk> thought about why not.

Speaker Change #205: I generalize it biopsy.

Speaker Change #205: In six months, that's why we're going to be talking about going to be talking about starts.

Speaker Change #205: So all of that controlled study in in generalized Ah.

Marcio Souza: I think, first, we wanted to understand the impact we could have, which we believe is going to be fairly large in both focal and generalized epilepsy. The second question on the dose, I mentioned before, we want to drive the maximum potential efficacy here, which by definition, the highest concentration. At the same time, we have far more flexibility on radiant than we have on Power One.

Speaker Change #205: First we wanted to understand the impact we could have which we believe is going to be fairly large in both for coal and.

Speaker Change #205: Generalized epilepsy.

Speaker Change #205: Second question on the adults.

Speaker Change #205: As I mentioned before we want to drive the maximal potential efficacy here with the definition.

The highest consensus.

Speaker Change #205: At the same time, we have flexibility.

Speaker Change #205: Flexibility on region than we have on power one chip.

Marcio Souza: We do need to have some, like, data on the different concentrations in the reduction in seizures. For example, we do believe that 20 milligrams for six weeks is going to be a scatia. And that's sufficient. And that's going to be a quite important discussion and decision with regulators once that is significant, and then the 30s.

Speaker Change #205: We do needs to save.

Speaker Change #206: Some like data on all the different concentrations and the reduction in seizures. For example, we do believe that's 20 milligrams for six weeks is going to be efficacious and that sort of is sufficient.

Speaker Change #206: And that was going to be a quite important discussion decision with regulators once that is significant and then the authorities. So why did they start the.

Marcio Souza: How do you actually treat patients? But after regents, if you see, let's call just for scenario planning, a very significant number of seizure-free patients. Then we must rethink what a labeling language could be in the near future.

Speaker Change #207: How do you activate patients.

Speaker Change #208: Dr Regency PUC, let's call just before.

Speaker Change #209: Scenario planning, a very significant unknown seizure.

Speaker Change #210: As you freed up.

Speaker Change #210: Then we might have to rethink what our labeling.

Speaker Change #211: Languish it could be in the near future. So it's all complementary I think has drug developers with we need to think about the piece of the puzzle they're going to allow for the best possible decision by the regulators and the physicians and that's the that's how radio plays a role here.

Marcio Souza: So it's all complementary. I think as drug developers, we need to think about the piece of the puzzle that will allow for the best possible decision by the regulars and the physicians. And that's how Radia plays a role here. And our next question coming from the line up. Kambiz Gazi with Jeffrey C. Alana Salter, Morning, team.

Speaker Change #212: Thank you.

Speaker Change #213: And our next question coming from the lineup.

Speaker Change #215: And this yesterday with Jefferies. Your line is now open.

Kambiz Gazi: For PROC 628, in terms of local patient enrollment, how will you prioritize it between Power One and Radiant? And then maybe you can go into more details of the Empower observational study. And then for another program, Elsa Nersen.

Speaker Change #214: Good morning team.

Speaker Change #216: For <unk> in terms of local patient enrollment how will you prioritize it between power one and Raytheon.

Speaker Change #217: And then maybe you can go into more details of the empower observational study.

And then for another program.

Speaker Change #217: And Ericsson.

Marcio Souza: What feedback did you receive from global regulators to initiate a pivotal study in Brazil and what kind of what remains required to advance the program in the U.S. and Europe? Thank you. Sure. Thanks. Thanks, Kambiz. So, Power One and Radiant are not, I would say, competitive internally from a resource or externally.

Speaker Change #218: Feedback you received from global regulators to initiate a pivotal study in Brazil, and kind of what remains required to advance that program in the U S and Europe. Thank you.

Marcio Souza: They just go through a much larger initiative, as you can imagine, Power One. So, all the administrative stuff that has to happen takes a little bit longer. It's a smaller number of sites for Radiant, so that's part of that as well.

Speaker Change #219: Sure. Thanks, Thanks, Kevin.

Speaker Change #220: So power one in Reagan.

Speaker Change #221: I would say competitive internally.

Speaker Change #221: Thus far our external they just goes through.

Speaker Change #221: It's a much larger initiative as you can imagine power one.

Speaker Change #221: So all the administrative stuff that has to happen it takes a little bit longer.

Speaker Change #221: It's a smaller.

Speaker Change #221: Number of sites or for agents. So that's part of that is while our AMD patient characteristics, we biting rose slightly different that's also worth trying.

Marcio Souza: And the patient characteristics we provide in Rho is slightly different as well. So, we're trying to actually… I'm going to be perfectly honest, on making sure that both studies recruit quite excellently as we expect to. So again, no competitiveness there whatsoever.

Speaker Change #221: Felipe.

Felipe: Triple word.

Felipe: But to be perfectly honest.

Felipe: That both studies recruits quite excellent fleet.

Felipe: We expect to see.

Felipe: So.

Speaker Change #223: Again, no no competitiveness there.

Marcio Souza: I think your second question about nursing, we do have obviously full feedback from Brazil. We're able to start the study there. I believe that cohort is going to be quite complementary to the initiatives that we're having outside of the US. We do have some preliminary and should be final soon from Europe as well, which aligns with how we are thinking about this. We're moving and that's why we're guided for, more global parts, including the Iran part that starts later this year, and in this similar process with the FDA. We know it's a complex program with multiple variables here.

Speaker Change #224: So ever since your second question about the nurse and.

Speaker Change #225: Do we do have obviously, a full feedback from them for in Brazil, We're able to two.

Speaker Change #225: <unk> they started there.

Speaker Change #225: That cohort is going to be quite complementary to up to the initiatives that we are having outside of the U S.

Speaker Change #225: We do have some preliminary.

Speaker Change #225: And should be final assume frontier.

Speaker Change #225: So in Europe, as well which are.

Speaker Change #225: Now aligns with how we are thinking about.

Speaker Change #225: Moving and that's why we guided for.

Speaker Change #225: More global box, including Europe part of that starts later this year and in the similar process with with the FCA.

Speaker Change #226: No it is a complex.

Speaker Change #227: Program, where like multiple variables here are the most important of that is just how safe year those patients are.

Marcio Souza: The most important of them is just how severe those patients are, so we're taking one step at a time on that program. Thank you. I'm showing no further questions in the queue at this time.

Speaker Change #227: So we're taking one step at a time on that project.

Operator: I will now send the call back over to Marcio Souza for any closing remarks. Thanks, everyone. Sincerely appreciate it, joining the call and all the questions, or having quite importantly as well, the support for Praxis and all the patients we serve. As you heard at the beginning, we do dare for more. And oftentimes that materialize on actually looking at ourselves in the mirror and seeing what is best for the patients we serve. In the case of this call, it's really delivering successful studies for patients with essential tremor. We feel it's a customized hydrochloric, as we will later this year.

Speaker Change #227: Thank you and I'm showing no further questions in the queue. At this time I will now turn the call back over to Marcio Souza for any closing remarks.

Marcio Souza: Thanks, everyone sincerely appreciate them, joining the call and all of the class chance or having them quite importantly is wildly supports.

Speaker Change #228: If our practices and all of the patients we serve as you heard at the beginning we do therefore more.

Speaker Change #228: And oftentimes that materialize I'm actually looking at ourselves in the mirror and see what is best for the patients we serve.

Speaker Change #228: <unk> of this call is really delivering successful studies for patients with essential tremor with Felix compromise hydrochloric acid. We will later this year.

Marcio Souza: I hope everyone is as excited as I am about the upcoming results. And just a reminder, in a few short weeks, before the end of the quarter, we're going to be talking about our results for our previous 5.6.2, the reletrogen now, as we're calling, which brings a quite important upside for all of us, in terms of, from an investor perspective. But most importantly, SN2A, SN8A, have no treatments either available, approved, or in development.

Speaker Change #229: I hope everyone is as excited as I am asked that upcoming Readouts and just a reminder, in a few short weeks before at the end of the quarter Youre going to be talking about our results for our previous 562.

Speaker Change #230: Illiterate gene Ah now as we're calling which brings a quite important upside for all of us in terms of from Investor perspective, but most importantly, <unk> eight eight.

Speaker Change #230: No treatments.

Speaker Change #230: Either available approved or in development.

Marcio Souza: Radar at the break of being potentially approved. So to have that discussion, to have that coming up in a matter of weeks, in front of it's quite exciting and, Then without saying on how excited we all are by the number of questions in today's call of 6 to 8, 6 to 8 is moving at lightening speeds, as you can all see, I have, I have worked in many programs in my life.

Speaker Change #230: At our at the break of being potentially approved so to have that discussion to have that coming up.

Speaker Change #230: In a matter of weeks in front of us.

Speaker Change #232: Quite exciting and then they'll say on how excited we are by the number of questions in todays call of six to eight.

Speaker Change #233: <unk> is moving at lightning speeds as you can see I have worked with many programs in my life I haven't seen as much excitement about our progress from the investigators perspective, as we see it with fixed rates.

Marcio Souza: I haven't seen as much excitement about a program from the investigators perspective as we see with 6 to 8, and we're excited on not only getting that to the clinic. Potentially in the next few years, bringing markets and revolutionizing the way epilepsy is treated. So again, for the support, look forward to having follow up calls with you and we'll see you soon. Ladies and gentlemen, that's the end of our conference for today. Thank you for your participation. You may now disconnect. Sex of the Sleeper, Thank you for watching!

Speaker Change #234: And we decided on not only getting that to the clinic.

Speaker Change #234: <unk> potentially in the next few years, bringing markets huh.

Speaker Change #234: Revolutionizing the way <unk> is treated.

Speaker Change #235: You can't afford to support look forward to having follow up calls with you.

Speaker Change #235: And we'll see you soon.

Speaker Change #236: Ladies and gentlemen.

Speaker Change #237: Conference for today. Thank you for your participation you may now disconnect.

Speaker Change #237: Hum.