Thank you, good morning and welcome to the Practice third quarter, 2024 conference call. This best squad to remain laser focused on advancing our pipeline as we gear up for next year to have four programs in registration totaling to a substantial multi billion dollar opportunity.
The phase three study in essential tremor essential three for lead program, Ulis account mind continues to progress. Well, we have confirmed all aspects of the internet analysis and are now updating the plans to have the results in Q1 2025.
Both studies are well powered and controlled for success because there's a range of outcomes for each study as well as the interim analysis. In the coming months, we decided that we will only share an update on timing for both study one and study two. Once we have evaluated the recommendation from the interim review board for the interim analysis in Q3. We're very excited to report the positive top line results for another asset in our pipeline Vormatrigine in the phase two NB trial in CN two A and CN eight A G.
In the 15 patient study liturgy demonstrated an impressive 46% reduction in motor seizures versus placebo with third of the patients achieving an unprecedented seizure free status based on those results, we initiated a second registrational cohort of the study which has already started screening patients just weeks after completion of the prior cohorts in common Vormatrigine or metro previously known as practice 6 to 8 is starting out of the gate. Strong in all areas of our Comprehensive Energy Clinical Program.
The innovative observational study and power, a first of its kind in collaboration with the epilepsy study consortium launched in the third quarter in this short period of time, attracted the interest of over 1,000 patients who registered in the study.
We expect the key learnings for empower to impact the entire energy program.
The phase two radiant and the phase 23 power one trials are on track for top line results next year, rounding out our portfolio as a nurse and begin dosing patients in Brazil in the second quarter for the EMBRAVE study. And we continue to engage with regulatory agencies in Europe and in the us to finalize the development plans in a two gain of function patients with our strong balance sheet, we continue to be fully funded as we pursue our vision to deliver precision therapies for patients with CNS disorders.
Let me now focus some more on Alexa, our innovative essential three program in et is the biggest and most comprehensive program conducted. Today.
We began recruiting for the two phase three studies just about one year ago and have seen tens of thousands of patients interested in participating.
This vibrant participation highlights the significance and met needs for the millions of patients with essential tremor in their physicians and caregivers who are seeking a therapy that will allow patients to perform daily activities without impairments.
The need for treatment and essential tremor continues to be more defined as we advance this program in a survey we conducted with over 400 patients up to 77% of the respondents said they do not feel their et symptoms are managed with current treatments.
In a separate survey we conducted with 150 treating physicians. They share that 85% of their visits with 50 patients are focused on looking for treatment. Clearly, there is an incredible need here and we look forward to shortly completing the essential three study with the goal of bringing an option to the market as a quick refresher. The essential three program has two simultaneous phase three studies being run concurrently. 31 is a 12 weeks two arm placebo controlled parallel group study and study two is a 12 week randomized study. Both studies used as primary assessment, the change in the modified activity of daily living and they are both run entirely decentralized as in the patient's home rather than at a clinical site.
We share in our last quarterly call that we decided to trigger a pre plans analysis. When 50 to 75% of the patients have completed the 12 weeks that you want, the analysis will inform us whether we should continue the study throughout completion. If the primary end point is met, to consider seizing the study or to consider enrolling additional patients to ensure it's sufficiently powered for success.
Based on the expectation for the sufficient number of patients who complete the study cleaning of the data execution of the statistical testing and analysis by an independent boards and our internal operations. As well as considering the operational impacts in the study. Completion of 32 we will be finalizing the internet analysis in the first quarter of 2025.
Given the range of outcomes, we will not speculate on scenarios or timing for results of 31 and 32 until we hear from the internet and review boards at which time we will be better informed to provide an update regardless preparations continue to file the ND A as expected in 2025.
Now, moving on to our highly differentiated epilepsy portfolio Vormatrigine previously known as plastic to A is a next generation functionally selective small molecule being developed as a once daily oral treatment for adults with epilepsy.
We know that treatment options for common sis are lacking in both efficacy and tolerability. And we believe the profile emerging with romaine will provide a highly differentiated paradigm shifting way to treat this disease.
Last quarter, we introduced our broad energy clinical program for Vormatrigine inn focal and generalized epilepsy.
And I'm glad to share that the ambitious multi study goal we aim to achieve are advancing. Well.
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 our metro gene.
Three trials of energy are to evaluate the efficacy and safety.
The first of these is radius, an open label study that will enroll patients with either focal or generalized epilepsy who receive me for eight weeks with a safe follow up of two weeks.
We are on track to deliver on topline results in the first half of 2025 which should help us better understand the effectiveness levels of our metro and its pharmacology in the patient population.
The power one and power two studies are 12 week phase 23 studies in patients with focal seizures. Power one is underway and we anticipate top line results towards the end of 2025 we will slightly stagger the initiation of power two to begin recruiting in the first half of 2025 the combined studies are expected to enroll approximately 500 patients globally as we consider other areas where Vormatrigine can play an important role. It's clear that it's activity in NAV 1.7 and NAV 1.8 coupled with fast acting pharmacology and safe profile could play an important role in pain management.
We are concluding our assessment about the potential role of our Vormatrigine in pain and we'll be sharing more in the near future.
Now, turning to Relutrigine a functioning state modulator that is formulated for pediatric use in these a group of severe epilepsies, caties by developmental delays with early onset with CN two A and SN eight A being one of the most severe and refractory forms of these.
And we're currently there is no approved treatment as a reminder, Relutrigine has orphan and rare pediatric designation for these two indications.
We're thrilled and humbled to share the unparalleled results we observed in phase two involve trial cohort one in SN two A and eight a last quarter where lit demonstrated a number of impressive and unprecedented data points.
This two arm study was run over 16 weeks with 44 week periods. Patients in the placebo arm were admins placebo for one period and were littering for the other three periods and neither the patients or investigators were aware which period was on placebo.
15 patients completed the study and patients had the option to continue to an open labor extension. After the 16 weeks, a robust 46% placebo just a reduction in motor seizures over the period was observed with 33% or five out of 15 patients achieving seizure free status that notably was never seen before in this severe patient population.
In addition, we saw a disease modifying impact noted in the study by both caregivers and clinicians with leveraging leading to meaningful improvements in overall well being of patients in areas of seizure severity and intensity alertness and other important measures.
It is also very impressive and encouraging finding given not only the severity of the disease but also the lack of improvement in these areas with currently available treatments.
Lastly, theine was generally well tolerated with no drug related series of events or those reductions required during the study.
These results further set up RLI as a potential first and best in class treatment. And following the successful proof of concept, we initiated screening for cohort two of the study which aims to enroll 80 patients and has been receiving interest from physicians and caregivers moving us closer to our goal of bringing a potential precision therapy for those severe patients.
In addition, across all these which affected nearly 200,000 people in the US. 70 to 80% of the patients are currently on a surge channel block.
When we see the data from Relutrigine, which use a more target approach on the south channel mechanism. Of action. We believe there is a broader potential for Relutrigine across ogs.
With that in mind, we're already diligently working with the regulatory agencies to finalize the Emerald Study Protocol for all G. We expect to finalize by the end of this quarter and initiate in 2025.
We're very excited by both the potential and the progress of our so channel modulator for metro gene androgen.
And there's a lot more to come in 2025.
Running out our clinical epilepsy program is our first AO as a nursing designed to selectively decrease the expression of the SN two A gene and directly target the underlying cause. In early on that seizures in CN two a last quarter, we continue part A of the EMBRAVE Protocol in Brazil. This part of this study will provide important control data, examine the safety and effectiveness of nursing in a very severe disease population.
This continues to be an exciting time for practice. In 2024 has been a transformative year. Looking ahead to 2025 we have a number of inflection points and you remain the rigorous focus on execution.
We look forward to our potential. First of many ND A submissions in 2025 with that in mind. Let me now turn the call over to our Chief Financial Officer, Tim Kelly Tim.
Thanks Mario and good morning everybody and thank you for joining today's call. I'll provide a quick summary on our third quarter. Financials. In Q3, our operating expenses were $57.1 million but $41.9 million of that R&D and the remaining $15.3 million for GN A and reflects an increased amount of clinical activity in our movement disorder and epilepsy programs.
During the third quarter, Prax has spent $27.7 million in operating cash similar to the second quarter of 2024 and it reflects our focus on working capital.
We ended Q3 with $411.2 million in cash, cash equivalents and marketable securities which compares to $81.3 million of cash at December 31st 2023. With the increase primarily due to the net proceeds from practices follow on public offerings. Earlier this year, our cash supports the runway into 2027 and it includes funding all of the programs that Marcio discussed today through their readouts. Now, I'll pass it over to you Marcio.
Thank you (Operator Instructions)
Our first question comes from Ritu Baral with TD Cowen. When you may proceed.
Good morning guys. Thanks for taking the question. A couple questions on retro gene 550 for tee specifically, as you think about the 80 patients in the expanded cohort for 80 patient, expanded cohort sufficient for registration. Will the enrollment criteria for that 80 patients be any different than the original 15 patients? And it, so do you expect it to result in any or prospectively expected to result in any changes to Fathy or safety?
And then the second part of that question is you mentioned that you are seeking alignment with regulators in the first half. Can you talk to maybe any more specifics around that timing? How you might expect cohort to change based on feedback and any specifics on what you're asking on? Emerald? Thanks.
Marcio Souza
Sounds good. Thanks Rich for, for the question. So on the first one, for the 80 additional patients that are enrolling on the second cohort on the, on the study right now. So number one, like there are active patients. So we we've been screening those, those patients in and getting them into the study, which is very good news in our view, the the major difference I would call on this on this is that it's actually the start dose for the patients randomized to drug.
So starting on the previous study was that half a milligram per kilogram per day. And this one is 1 mg per kilogram per day. So it's straight up into the one we believe to be the most efficacious. So we believe the impact is going to be on that. It's just a fast or faster. May I say effect in terms of like separation in a deeper effect, possibly maintaining or even expanding the number of seizure free days and number of patients there no real major like change on the inclusion criteria. So, from a patient population perspective, we're not expecting to see a different one.
And then on the, on.
The timing for, for Emerald. So we do have a protocol, we are aligning on specifics there. I would say it's a little bit more. Maybe traditional is what I would call. We're expecting to run like a parallel, a group of 1 to 112 weeks. What we are aligning is really the inclusion of those patients. So our view and our position right now is that we can phenotypically define patients with, with the independently of their genotypical like geology.
And for as long as they have no sensitivity, the mechanism, number one and two seizure burden that are consistent with what we believe we can play a high impact that should be sufficient. So just double checking this like a number of like small details in terms of how to randomize and size and, and things like that, which should be done by, by the very end of the year and then we're going to be able to operationalize by the very beginning of next year.
Got it. So I want to clarify, you are going to genotype these patients, but all they need to have is a genetic mechanism that's rational for good.
Our next question comes from Yasmeen Rahimi with Piper Sandler Companies. You may proceed.
Good morning team. Thank you so much for all the thoughtful comments. A few questions on the interim analysis. I think investors were just wondering I think the interim was expected to happen end of year, maybe just some color around why it got a little bit moved into one Q2025.
And then it appears based on the remarks you've made that we're study two will not read out before the interim or at the interim. We'll get an insight about one and two. I just want to make sure just to go ahead and if you could just walk us through sort of the disclosures around both of the studies that, that could be helpful.
And then last question is I think you guys noted that upon the outcome of the data in A T, you would reinitiate a Parkinson's disease program in 2025. Could you maybe comment on like the success in A T would move you into Parkinson's or what would that be a phase two study? Phase three study? Any color around that would be helpful and I'll jump back into the queue.
Marcio Souza
Sounds good. Thanks, Yeah. So, start on the interim, right? So I'll, .
Start.
By saying we're very confident on, on the execution for, for the interim. I like every aspect that our monitoring and every discussion just increase our confidence on a successful like execution. Of course, it is biased towards our success to begin with and making sure we wrap up the, the program like concomitantly to slash shortly thereafter to the and then, and that was the, I would say the main driver here, right? So what what we're trying to do to take a step back if to deliver a successful program that we can file an ND A and can be incredibly clear the efficacy, the safety of helix aide hydrochlorate for this patient.
What when you look into that, that there was a number of things that were either bumping up in terms of availability of ID MC members, the their ability to conduct the analysis, cleaning of the data. And I would argue the most important factor here is the influence on study two. That is the second part of your question, right? In the eventuality, which is a quite possibility that the internet analysis work exactly as we expect so very positive. We wanted to make sure the result of study study two is about the same time too shortly there after number one but two, that there is no influence and by influence, I mean, negative influence on study to read out. So when you're looking into as a program, it made sense for us to to make this, which in our view is a small and slight chain. That is safeguarding the overall like positive results in the in our view of the combined studies, right? 3,132 it's combination and the package for for the ND A. So that that is the main rationale on our end, everything is progressing brilliantly so far.
Then on the, on the Parkinson's disease study, I think that as our content grows into the outcome on essential tr we need to really be ready to the expansion, right? Like time is an incredibly important asset on this business. We want to make sure that the an indication of value for ourselves for potential strategics and so on and so forth. I get off the ground. We had, I got some feedback from the ft a last time in terms of what they would like to see on AP this study. So we have a very good idea to design a phase two study in, Parkinson's that would significantly advance this program as well. So we're just restarting that in terms of the planning. So we are ready at that time to, kick off and, and restart. So we have a portfolio of indications and forex instead of just one.
Thank you.
Our next question comes from Joon Lee with Truist Securities. He may proceed.
Hey, thanks for the updates guys. Just a quick clarification. Will you be including Lentis Gesto in the broader DEE study? Because there's, you know, genetic basis for L gaso and you seem to want to stick to epilepsy based on your response to the question. And I have a follow up.
Marcio Souza
Sounds good.
So we will include LG patients on this who attempt to, the answer again to, reach you. Before we are providing and attempting to collect as much demo type information. Sometimes as you know, they're going to be Phenotypically Defined, clinically defined and not have like a final diagnosed there. But we believe that as these patients are right now, when you're looking to actually data on the literature on claims data for projects, one of the highest use of the actual channel mechanism with one of the highest issues in terms of tolerability, which we think is a, is a sweet spot for for our drugs. So we as we will be doing, but at the same time, that is part of like the entire discussion about inclusion criteria and measuring is the discussion we're having right now.
Great. So it's a true the E study?
Great. You know, for the interim analysis for essential program just wanted to clarify that you when you say refer to interim analysis, you're referring to the study one interim. So your withdrawal trial topline will depend on the interim from the parallel comparator trial. Is that correct? And then is, yeah.
Yeah. So, and, then number part part two is that or is there no inferiority analysis baked into that interim analysis?
Marcio Souza
Yeah. So the the interim analysis is on study one only as you mentioned, right? We, we don't believe that would be necessary or appropriate for, for an internal study too. The basically there's an alignment in terms of like database lock planning between the multiple events that we're talking here. So that is could be somewhat of an influence because those studies are recruited concomitantly, right? As you know, are from the same pool of patients and they are randomized to these studies. So that's why there could be some influence on depending on the outcome of the, of the internal as well. We will be reading out study to of course shortly thereafter on the inter that is easier one could argue study to monitor based on like event rates and, and things like that. So quite bullish about that to begin with.
Now, what was the second part of your question? About the inferiority or sorry.
So that is a futility margin on the, on the lower end of the conditional power as its standards, right on, on interim like that. So fairly standard in terms of the, of the bottom there, a very wide, I would say a size information zone. Because that's why the reason why they study or the that is well designed to begin with. And on the other hand, as well, which should be considered that is it's tough for overwhelming efficacy as well. You were wanted to balance all of that, of course, from an information fraction perspective and from a spending perspective and in the overall execution to drive to the successful outcome.
Right? And then last question, you know, as we look to the, you know, very likely approval of sugen from vtex in January, it's actually impressive that it even works at all because it only targets one of the three voltage gated sodium channels in the peripheral nervous system. So it's actually interesting that you're advanced looking at your, your formal in in pain as well, which targets two out of the three pain receptors or not receptors, but voltage gated channels, any anecdotal evidence of pain reduction from your phase one or any other.
Thank you.
Marcio Souza
Yeah. So the, the like we're.
Super excited about this as well, we've been looking to for a while. It, it's not something that made sense from a priority execution, capital location beforehand for us. But now we believe it does, we do have a very strong pre clinical evidence on
in pain models and in general like a very potent inhibitor of 17 and 18, as you know that mechanism and the duality of the mechanism is quite important in paying generally acute and sub chronic and chronic pain.
We thought that, yeah, we are, we're excited with what you're seeing and, and we think that what's most appropriate for us is just to finalize everything look into from a competitive standpoint, as well, make sure that would be competitive and then talk about our plan early in the year with all of you.
Thank you.
Our next question comes from Francois Brisebois with Oppenheimer, you may proceed.
Hi, thanks for the questions and thanks for kind of going through the, the potential scenarios here and the complexity and the dependence between the or the the impact of study one on study two. So, but in terms of, you know, what to share on the interim, is it, you know, could it go into data or that's actually a really good case scenario where we stop the study because things are working out or is it more, you know, it, can we be assured that the actual top line of study one will be after study two that might come short after the interim. Look just any any help there understanding the timeline of the top line versus the interim for study one.
Marcio Souza
Yeah, sounds good. And so the like I, I think the scenarios like if I think about boot camps here, so one a as you mentioned, the potential to to stop like for, for overall Masco that obviously is not the base case, let's just play that out. And then both studies would be having the results at the same time, right? Like study one and study two at that point in time, which obviously would be a quite positive complete package. And, and so on. I think that is now an opportunity as well to increase the size of study one. And, and on that case, the conversation we'll be having as we're moving that one forward, we're increasing the size. And for the study two, we should have the results like very quickly as well.
So that's when it associates the two that is the highest a priority probability that would happen is, is on that just because the range of the conditional power is the largest or the widest on that song. So I think that's the two, I would say we should plan the most around with the first one having the highest impact, right? In terms of like operationally making sure ready to like wrap it up the the other two studies and so on. So that's what we, one of the considerations and how, how we look into being ready for for the interim.
Okay. Thank you. And then on the de commercial front, there's a lot of different ways to look at this market. Can you help us understand, you know US, X US, how you think about the commercial potential here?
Marcio Souza
Yeah, the vast majority of the business and I would say from a dollar value perspective is in the United States, our modeling shows around 70% in, in the US. And then the about 30% outside of the US. For, for our pick. We're talking about a multi billion dollar pick here in GS, right? We just completed yet like another refinement of the epidemiology in the US and, and looking into the utilization of the mechanism, limitations and so on and it's a little bit shy of 200,000 patients in the US. When you consider that even relatively small market share gets you quite important figures in terms of like the potential big revenue. And then the outside of the US becomes a little bit more.
I'm going to call opportunistic from business perspective, obviously important to have access to patients as well, but not as important to get the drug off the ground and, and get quite meaningful revenues. So about two thirds in the west, third outside of the west. That's how we would be modeling.
Thank you.
Our next question comes from Yatin Suneja with Guggenheim. You may proceed.
Hey, guys, thank you for taking my question. Just a couple for me as well. Mostly on the ET side, could you provide us where you are, at least on the enrollment from like how many patients have been enrolled in study one and two if you could and then, you know, we understand this. In turn, could you also talk about and maybe put some numbers around the possible sample size adjustment ranges based on the pre specified plan? Like how long would that take at the maximum if, you decide to increase the size and, and let's say you go with the maximum of patients that are allowed, how long will that will that take, will that take?
Marcio Souza
Yeah, absolutely. So, I'll, give as much as we feel that we could give right now in order like to preserve all the optionality for us. So the the current study states I would say of patients, right? The way we look into is not on the top of the screening, but on patients being randomized per week. So when you look into what we can maintain constantly, is anywhere between 2030 patients per week, randomized new patient. So, if you fast forward to potential scenario here.
So I'm going to use like two scenarios where I can increase of 100 increase of 200 patients. You can see that that could be achieved in like anywhere between like 3 to 6 weeks of ization. Of course, you need 12 weeks after that to completion of the study, but it is very fast in terms of accruing new patients to the study if needed.
Thank you.
Our next question comes from Douglas Tsao with H.C. Wainwright & Co., LLC. You may proceed.
Hi, good morning. Thanks for taking the questions. Just to confirm what you just said. So I think you indicated 30 patients. Is that enrolled and randomized or is that simply enrolled into the study in the scenario that you expand the patient population for essential?
Marcio Souza
So that is the one we very, very comfortable from our like base of our organization that we can achieve very, I would say relatively easily. I'm not going to say easily because there's a lot that goes on on this randomized patients in a given week.
Okay, great. That's helpful. And then just if you could provide a little more color in terms of moving from trigen into these pain indications and what type of work you're going to be doing or need to do before coming out with a more sort of expanse or sort of coming forward with the full development plan.
Marcio Souza
So, we're working.
And, and I'll say thanks for others working on this space. Right. There's a, there's a lot that's been done on the last few years here as well. And when you look into the, what, what it's important for us, a couple of things, right? So one is the pharmacology itself, right? Like, can we have the relief of like kindergarten to CX and to relationships with cyex, like quickly enough for certain types of pain? What is the ideal types of pain? What is our confidence in terms of pre clinically and potentially early clinical data, biomarker data, et cetera? That could get us to a point that we're incredibly confident as we were in las for when we like moving into a focal to have a similar package.
I would say and, then like really understanding the impact that we're talking about here. And I think differently from other things being developed, both central and peripheral aspects of the disease. So how much more can we expect from this mechanism? What is again, ideal education, ideal study to show that and cost in that study and things like that. So that's the work is being done literally as we speak, a lot more to be finalized between now and the end of the year. And I think we're going to be in a very good position early in the year to showcase that to all of you.
Okay, great. And then just one more on (Elsa Urson), I think with last quarter, you indicated that the first patient was being enrolled in sort of the Global Registration study. But I think today you indicated that they're sort of being added to Embra. And I just want to understand if there's been any change as you think forward about the global registration program for that drug.
Marcio Souza
Yeah. So no, that that's a very important aspect as well. So the way we've been looking into I know since that two fold here, so one we consider to be important to explore particularly the safety at a different exposure levels. And that's a lot of it's being done in Brazil right now on the second cohort is I want you to rerandomize like patient cohort to drug or placebo or to drug or sham. On that case, we're exploring a range of those sequentially increasing the dose on those patients. We're doing all the other assessments as well as you can imagine.
So it was important for us to actually keep that separated from what we believe to be a very good long term ecas exposure. Those that is the 1 mg for a month for for the global study. We have very good alignment already in general what we is needed there. But we do have still a meeting pending this year with the FDA on finalizing which was likely a change on their end on, on the our expectations from, from when the meeting will appear. So nothing problematic there, but it's kind kind of drove the fact that we need just a little bit more time to make sure we have confidence on the final protocol so we can initiate it. So that is the, that's the bottom line for that one.
Okay. And so with the patients being studied in Brazil, now, are you, you're looking at some additional doses? And if the result, I mean, is there a scenario, I know you've been very confident in the 1 mg per K dose? I mean, is there a chance that if if results warrant that you would potentially look at higher doses in the US and European registrational studies?
Marcio Souza
Yeah, we must follow the science, right? So what we've seen so far on the patients in the US, which are continuing taking the drug and on the patient in Europe and in Australia that that actually took higher dose than in the US. It's not meaningfully different in terms of to control gains on like development milestones and, and, and things like that.
Now we gotta remain open to, to the possibility that yes, it's going to be meaningfully different fact or whatever. And if that's the case, we would be in a position to complement the the global study, either in its open label phase right after the control phase or even in a different cohort, if that is warranted. So will be driven by the, the results that we see here. But the time lines in terms of like the original four patients that they're going to be those that are perfectly aligned with the enrollment timelines we have for the global study. So it shouldn't be a conflict in terms of how to get to the best possible result for those patients?
Thank you.
Our next question comes from Kambiz Yazdi with Jefferies. You may proceed.
Morning team a couple of questions for me. The placebo response was pretty well controlled in essential one. Essential three has a more innovative decentralized design. What steps have you taken to control placebo response and study one in essential three?
And then as a second and a set of questions maybe on verme gene. What is sodium channel blockers demonstrated historically in PGTC seizures? And what would a registrational program consist of in a generalized epilepsy? Thank you.
Marcio Souza
Sure. Thanks came. So, placebo was already pretty well through, as you said, on on essential one. When you're looking to essential three, there was one aspect that, we wanted to add to further control that. So, what are you seeing? Is There is a I would say.
Slight but important, change on patients that are less stable at baseline. And what I mean by that is, there were, pre, screening, assessments or sorry, a pre mation assessment on study, on essential one in a baseline assessment. So when you look into those patients that vary more in between.
Those They tended to be a little bit higher on placebo. Now, that study was, again, at the end of the day, it is going to be like four times smaller than essential three. So we wanted to ask the question whether or not the influence is going to be similar, right? So we chose to actually add a maximum variability parameter between those visits and to formally have visits the pre organization one. We believe because you can monitor our patients for all the study and we know how long it takes for the drug to start working that we're very successful on on controlling that on making sure that the, the patients that are similar to the what we want from you.
One, right? We don't want to depart from the cohorts on one, but we want to make sure we tighten potentially variability that is not due to drug effect, but rather to placebo effects. So we're very, very confident on the measures that we put in place to to control placebo there.
And then on your second question on generalized by the primary or not. It's mixed the the results historically. And I think partially because that isn't really being a sergeant channel blocker that is very selective. And that really works on as these neurons are like firing a lot and, and expanding a lot in terms of like the loss of going through. I'm going to call on the on the action potentials that can really block the pathological events but not the physiological for this patient. That is a very good evidence with more selective or partially more selective drugs.
So we are interesting enough, I would say anecdotally, the conversations that we've been having like a lot of the conversations that get off the ground and I get excited. A lot of people are equally or more excited actually about the generalized. What was a little bit surprising to me that there is so much excitement on generalized with, with romaine.
And I believe it's because that is a huge amenity there. And obviously, those seizures are incredibly important as well when they happen from the severity and potential impact and in terms of fatality as well for, for this patient. So we, we're going to see soon enough, I would say from radiance, what kind of impact we can have there and radiance going to serve as a, as a kind of springboard for us. And to design. What we would expect to be a registrational phase study for, for generalized as well?
Thank you.
Our next question comes from Ami Fadia with Needham. You may proceed.
Hi, good morning. Thanks for all the updates. A couple of quick questions for me. Firstly, on Alexa, can you comment on the enrollment and and how what percent of patients have completed randomization relative to the target enrollment for the two studies? And was there a slowdown in the enrollment rate that caused the shift in the timeline?
Maybe I'll ask my next question after you.
Marcio Souza
This one. Sure. So I mean, we not going to talk about that right now as you mentioned, right on the, on the prepared remarks and in the press release. But what, what I can tell you that is no, is slow down on what we expected from randomization or from patients on screening. I think we continue and we, we saw historically, we expected to continue to see if we decide to increase the, size of the study in Q1, a fairly robust number of patients coming through. I think we intentionally being managing that. So we can get like the best possible outcome for, for the studies that are two positive studies at like right after the entrance. So it's been a lot on us and, and of course, the gathering of patients and things like that, which influence but not meaningful.
Got it. Okay. And then on Vormatrigine in the RADIANT study, can you talk about how many patients you're targeting or, or sort of the mix of patients between focal and generalized and, and how that might inform your plans to develop it further in generalized epilepsy?
Marcio Souza
Yeah. So the the goal is to have 50 patients on a what, what we are seeing again on the early days. But what we're seeing is about like the expected 30% generalized 70% focal interest for like in general, particularly like on, on the site we targeted here, we were, I'll say are relatively selective in terms of the number of sites because that is again a huge interest and we didn't want to completely, I'm going to say lose control of the number of patients and get significantly more than we expect here.
So we kept that a little bit tight in terms of the 50 or so patients that, that we expect to enroll that should be sufficient as we go like across. And it's an open label study, right? So we're continuously seeing and adapt as needed in, in terms of maybe reducing or increasing the num the total number of patients based on the overall interest. But 3,070 from generalized and focus is, is what we're going to expect to see at the end.
Understood. Maybe just a last question for me as you design the MD E study, what assumptions would you be making with regards to regulatory performance in this patient population relative to the data that you saw, you know, in sen two A&A?
Marcio Souza
Yeah. So arguably CN two NH A were the hardest of those conditions to treat when you, when you look across the board. Yeah, there are a few allergies that are incredibly difficult to treat, but those were definitely incredibly hard to see reduction to see your freedom mortality in Chile, for example, is like six times higher than right. So in, in infancy, so this is a complete like higher bar. So we expect FS are above the, the ay levels. They were saying of course, not powering the study for that. We're being a little bit more conservative, but I don't think it's unreasonable to assume that this would be best in class for this patients.
Thank you.
Our next question comes from Joel Beatty with baird. You may proceed.
Hey, thanks for the updates. The first one is on (eex callide) For how if the interim is successful, could we get final results at the same time that we learned the interim is successful? Or will there inherently be some amount of time between those two events?
Marcio Souza
Yeah. No, Joe, like thanks for that. If in the return, it's, successful. So it's designed for an equivocal accs it's cross we will have results at the same time.
Thanks and then in, DEEs, should we think about routine as kind of just working in, in patients who are already responsive to calcium channel blockers? Or could you talk about the potential to work beyond the patients who are responsive to those agents?
Marcio Souza
Yeah. So, it's quite interesting. I think that is like when you're looking to pre clinically and, and all the work we did, it does not look like it could or should be restrictive to patients who had prior response or that are expected to. If you look into all the work we did with the two compounds published a little back. The the results on actual the dynamics of the neurons among the animal model, for example, into the syndrome are quite as the als but unexpected meaning are significantly better than you would expect on that, which is there is a bias towards maybe some first generation. So channel blockers wouldn't work on that population, right? So clearly not the case here.
And then there's a few other ideas that would a priori expect to have AFAC that we're seeing AFAC on prepl models. And, and therefore, we should expect to have as well when a seizure is happening, right? If we could observe like the neuron, so channels are going crazy and that in a, in a very late term way to, to describe it. So stopping that activity is a very, very important for seizure control, independently of the the etiology of the seizure or a general even or origin in the brain anatomically. So we expect quite wide range here of Effy I think what we have to ask the question as well is how consistent is the seizure? Because we want to count them similarly, right? We're going to do one study. It can't be for example, some patients have clusters, others don't have clusters, so we shouldn't putting them together. So that's more of a restriction than anything else.
Thank you. And as a reminder to ask a question, please press star 11 on your telephone.
Our next question comes from Laura Chico with Web Bush Securities. You may proceed.
Hey, good morning very much. Thanks for taking the question. Two clarification questions for me first on the interim for let's call them. I I understand that the timing for the interim has extended to the first quarter 25. What I'm what I'm trying to clarify though is does it, does the actual at which the interim is executed, is that also changing? And I guess maybe asking it differently is if this was expected to be conducted at 50% for example, does this now shift to 60%? Ho hopefully that makes sense. And then I have a follow up.
Marcio Souza
Now, it makes a lot of sense. Thanks for, for the question are.
Now. So the the range that we gave for the information fraction, right? That if I understand correctly, that your question was between 50% and, and 75%. So the the range for, for the information does not change. Of course, it is a range because like depends on the exact day of the data transfer and the calculations by the AD MC. But we did not change that.
Okay. That's helpful. And then I guess I understand your comments also about with respect to study, conduct and integrity and the ramifications to study too. My understanding was that these are conducted under the same protocol. So I'm trying to understand the the separation of the release of results. And have you had any feedback from FDA on how they would like to see result communication? Thanks.
Marcio Souza
Yeah. So the last part is easy. So we did not and I don't think they often opine on how results should be communicated. They did though review the data, as I said is a plan which analyzed these studies separately. And and then there's another yet another analysis plan just for the internal analysis that that was revealed and we received it back many months ago from, from the FDA of that. So call on that. So the the influences last operation on the I like definition of operation, meaning you're absolutely correct. The, the studies are patients are randomized to one study or to the other.
It's more on the influence of a potential impression of failure by patients who are on study tube as they finalize the study by a potential needles. Since they wouldn't know their own study tube or study one. So we didn't to unduly influence or create a quasi placebo effects by potentially in the positive case. To be perfectly H1st, here, creating a potential impact on, on what we expect to be applied successfully study. That is a study too. So maybe overly cautious on our end. But again, trying to safeguard the integrity of the entire program.
Okay. That's helpful Marcio. And maybe the last question for me, I, I think I missed this and I know you commented that earlier, but could you expand a little bit more on the rationale that we start in the Parkinson's indication? I guess I'm, I'm trying to better understand what would be the mechanistic read through from the ET studies to Parkinson's. Thanks very much.
Marcio Souza
Yeah. No, no, absolutely. So, I think the from a scientific ration I was very strong to begin with in Parkinson's right where the last time when we actually stopped the, the Parkinson's study had very little to do with our expectation in terms of results for that study and a lot to do with availability of capital. I think as we fast forward that we have significantly more safety data. Of course, we are excited. And, and we expect the study one and study two to be positive for essential timer. The data from a scientific standpoint did not get weak where they got stronger from a Parkinson's rationale.
So why you not going to be like using like significant amount of capital to actually re initiate before the results? We want to be ready at the time of the essential three results to reit so maybe that's more of the message there than to have a delay and not necessarily use the mechanism. I think there is a far that.
Is both go to market strategy here where while movement disorder specialists only have about 5 to 10% of the patients, those five to 10% of the patients co exist a lot more with Parkinson's patients. So that is a kind of a penetration of the market strategy that that is important and the other is just the engagement in general opinion. Leaders. Of course, it goes without saying that we think we can have a meaningful impact on, on parking some patients as well.
Thank you. I would now like to turn the call back over to Marcio Souza for any closing remarks.
Marcio Souza
Thank you so much. I really appreciate Everyone joining the call and, and stay with us as the, as the company continued to to evolve quite positively was a lot went on on the last 10 months and nine months if comes departure, in terms of the transformation of the company for what is going to be next year for registrational programs and, and potentially one MD A submitted mid year or so for account model as we continue to progress, millions of patients will be positively impacted by those drugs and, and billions of dollars and in value will be created to all of us shareholders. So we'd appreciate it looking forward to providing more updates in the near future. And I'm sure we're going to be in touch. Thank you so much.
Operator
Thank you. This concludes the conference. Thank you for your participation. You may now disconnect.