Praxis Precision Medicines Inc

NASDAQ:PRAX

Earnings Call Analysis

Praxis Precision Medicine Reports Progress and Strong Pipeline for 2025

In the third quarter of 2024, Praxis Precision Medicine advanced its pipeline, focusing on four programs targeting essential tremor and severe epilepsy. Key highlights include positive results from the Phase II EMBOLD trial of relutrigine, showing a 46% reduction in seizures, prompting a second cohort study to enroll 80 patients. The company also prepares for significant milestones in 2025, including the expected NDA submission for ulixacaltamide. Financially, Praxis ended the quarter with $411.2 million in cash, sufficient to support operations through 2027, as they aim for top-line results by the end of 2025 for both the RADIANT and POWER trials.

Transformational Progress in Pipeline

During the third quarter of 2024, Praxis Precision Medicine marked significant advances in its clinical pipeline, emphasizing four key programs aiming for registration in 2025. The Phase III study of ulixacaltamide shows promise, with updated results expected in Q1 2025. The company is focusing on achieving substantial revenue growth through its innovative treatments, positioning itself to address a multi-billion dollar market.

Exciting Developments in Seizure Treatment

Praxis shared positive results from the Phase II EMBOLD trial of relutrigine, indicating a 46% reduction in motor seizures for patients with SCN2A and SCN8A-related epilepsy, with one-third of participants achieving seizure-free status. Following this success, a second registrational cohort has already begun screening, further enhancing the drug's potential as a first-in-class therapy.

Broadening Clinical Impact

The EMPOWER observational study has attracted over 1,000 patients in a short span, enhancing Praxis's understanding and engagement in the epilepsy community. This crucial data is poised to impact their comprehensive clinical programs significantly as they look forward to delivering more precise therapies for severe epilepsies.

Financial Position Strengthens Future Endeavors

Praxis reported operating expenses of $57.1 million in Q3, with a cash reserve of $411.2 million, bolstered by recent public offerings. This robust financial footing allows continued support for clinical programs through 2027, facilitating the development and regulatory processes crucial for ulixacaltamide and relutrigine.

Strategic Focus on Regulatory Alignment

Praxis is keen on aligning with regulatory agencies to enhance its positioning for upcoming submissions. Guidance suggests a potential NDA submission for ulixacaltamide in mid-2025, contingent on the forthcoming data from the studies.

Expansion of Clinical Programs into Pain Management

Moving forward, Praxis is assessing the role of Vormatrigine in treating pain, based on its pharmacological efficacy in pain models. The results from ongoing studies, particularly RADIANT, will inform future development strategies, indicating a shift towards exploring pain management as a significant therapeutic avenue.

Confidence in Future Results

With positive expectations, Praxis anticipates 2025 to be a pivotal year, with combined top-line results from essential studies expected, potentially paving the way for multiple drug approvals. Their commitment to rigorous clinical execution remains evident as they navigate essential therapeutic developments.

Earnings Call Transcript 2024-Q3

[Operator]

Good day, and thank you for standing by. Welcome to the Praxis Precision Medicine's Third Quarter 2024 Corporate Update. Please be advised that today's conference is being recorded. [Operator Instructions]. I would now like to hand the conference over to your speaker today, Dan Ferry from LifeScience.

[Daniel Ferry]

Good morning, and welcome to the Praxis Precision Medicine's Third Quarter 2024 Financial Results and Business Update Conference Call. This call is being webcast live and can be accessed on the Investors section of the Praxis website at www.praxismedecines.com.

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, clinical development time lines, financial projections. While these forward-looking statements represent practices views as of today, they should not be relied upon as representing the company's views in the future. Praxis may update these statements in the future, but is not taking on an obligation to do so. Please refer to Practice's most recent filings with the Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with the company's business.

Joining the call today are Marcio De'Souza, President and Chief Executive Officer of Practice; and Tim Kelly, Chief Financial Officer. After providing updates on our key programs, there will be a brief question-and-answer session. With that, it's my pleasure to turn the call over to Marcio.

[Marcio Souza, executive]

Thank you. Good morning, and welcome to the Praxis Third Quarter 2024 Conference Call. This past quarter, we remain laser focused on advancing our pipeline as we gear up for next year to have 4 programs in registration tolling to a substantial multibillion-dollar opportunity. The Phase III study in essential -- Essential3 for our lead program, ulixacaltamide, continues to progress well. We have confirmed all aspects of the engine 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 analyses in the coming months, we decided that we will only share an update on timing for both Study 1 and Study 2 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 other assets in our pipeline, Vormatrigine, in the Phase II and EMBOLD trial in SCN2A and SCN8A-DEE. In the 15 patient study, relutrigine demonstrated an impressive 46% reduction in motor seizures versus placebo, with 1/3 of the patients achieving an unprecedented seizure-free status. Based on those results, we initiated a second registrational cohorts of the EMBOLD study, which has already started screening patients just weeks after completion of the prior cohorts.

In common Praxis, relutrigine previously known as PRAX-628 is starting out of the gate strong in all areas of our comprehensive energy clinical program. The innovative observational study Empower, 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 were registered in this study. We expect the key learnings for Empower to impact the entire energy program. The Phase II RADIANT and the Phase II/III POWER 1 trials are on track for top line results next year.

Rounding out our portfolio, elsunersen begin dosing patients in Brazil in the second quarter for the [ EMBRACE ] study, and we continue to engage regulatory agencies in Europe and in the U.S. to finalize the development plans in SCN2A 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 ulixa. Our innovative Essential 3 program in IT is the biggest and most comprehensive program conducted today. We began recruiting for the 2 Phase III studies just about 1 year ago and have seen tens of thousands of patients interested in participating.

This vibrant participation highlights the significant unmet 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 needs for our treatment in 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 ETF symptoms are managed with current treatments. In a separate survey, we conducted with 153 physicians. They shared that 85% of their visits with patients are focused on looking for treatments.

Clearly, there is an incredible need here, and we look forward to shortly completing the ESSENTIAL 3 study with the goal of bringing an option to the market. As a quick refresher, the ESSENTIAL 3 program has two simultaneous Phase III studies being run concurrently. 31 is at 12 weeks 2-arm placebo-controlled parallel group study and Study 2 is a 12-week randomized with [ dry ] study. Both studies used as primary assessments, the change in the modified activity of day living, and they are both on entirely decentralized as in the patient's home rather than at a clinical science.

We shared in our last quarterly call that we decided to trigger a preplanned interim analysis when 50% to 75% of the patients have completed the 12-week study 1. The analysis will inform us whether we should continue the study throughout completion if the primary end point is met to consider seizing this 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 the independent board and our internal operations as well as considering the operational impacts in the steady completion of we'll be finalizing the interim analysis in the first quarter of 2025.

Given the range of outcomes, we do not speculate on scenarios or timing for readout of Study 1 and Study 2 until we hear from the interim review boards at which time we'll be better informed to provide an update. Regardless, preparations continue to file the NDA as expected in 2025. Now moving on to our highly differentiated epilepsy portfolio. Vormatrigine, previously known as PRAX-628 is a next-generation functionally selective small molecule being developed as a once-daily oral treatment for adults with plenty. We know that treatment options for common [ eplaxis ] are lacking in both efficacy and tolerability. And we believe the profile of merging with from Vormatrigine will provide a highly differentiated paradigm shift in way to treat this disease.

Last quarter, we introduced our broad energy clinical program for Vormatrigine in focal and [indiscernible]. And I'm glad to share that the ambitious multi-study goal we aim to achieve are advancing well. Energy is comprised of 4 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 Vormatrigine. Three trials of energy are to evaluate the efficacy and safety. The first of this is RADIANT. An open-label study that will enroll patients with either focal or generalized epilepsy who receive our messaging for 8 weeks with a safe follow-up of 2 weeks. We are on track to deliver on top line results in the first half of 2025, which should help us better understand the effectiveness levels of our messaging in its pharmacology in the patient population.

The POWER1 and POWER2 studies are 12-week Phase II/III studies in patients with focal onset seizures. POWER 1 is underway and we anticipate top line results towards the end of 2025. We will slightly stagger the initiation of POWER 2 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 is clear that its activity in that 1.7 and NaV1.8, coupled with fast-acting pharmacology and sales 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 our relutrigine, a functional state modulator that is formulated for pediatric use in this, a group of severe epilepsies characterized by developmental delays with [indiscernible] with SCN2A and SCN8A being one of the most severe and refractory forms of this. And we are currently -- there is no approved treatment. As a reminder, relutrigine has orphan and rare pediatric designation for these two indications. We are thrilled and humbled to share the unparalleled results we observed in Phase II EMBOLD trial cohorts 1 in SCNA and 8A last quarter, where releveraging demonstrated a number of impressive and unprecedented data points.

This 2-arm study was run over 16 weeks with four 4-week periods. Patients in the placebo arm were minister placebo for one period and releveraging for the other 3 periods and neither the patients or investigators were aware which period was on placebo. 15 patients completed a study, and patients had the option to continue from an open label expansion after the 16 weeks. A robust 46% placebo-adjusted reduction in motor seizures over the period was observed. With 33% or 5 out of 15 patients achieving seizure-free status that notably was never seen before in the 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's 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, relating was generally well tolerated with no drug-related serious adverse events or dose reductions required during the study. These results further set up relutrigine as the potential first and best-in-class treatment. And following the successful proof of concepts, we initiated screening for cohort 2 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 this, which affected nearly 200,000 people in the U.S., 70% to 80% of the patients are currently on a sudden channel block. When we see the data from nitrogen, which used a more target approach on the southern channel mechanism of action, we believe there is a broader potential for relutrigine across all GEs. With that in mind we're already diligently working with the regulatory agencies to finalize the EMERALD study protocol for all GEs. We expect to finalize by the end of this quarter and initiates in 2025.

We're very excited by both the potential and the progress of our Southern China modulators for Vormatrigine and relutrigine, and there's a lot more to come in 2025. Running out our clinical epilepsy program is our first ASO, elsunersen, designed to selectively decrease expression of the SCN2A gene and directly target the underlying calls in early onset seizures in SCN2A-DEE. Last quarter, we continued Part A of the EMBRACE protocol in Brazil. This part of the study will provide important control data, examine the safety and effectiveness of elsunersen 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 we remain the rigorous focus on execution. We look forward to our potential first of many NDA submissions in 2025. With that in mind, let me now turn the call over to our Chief Financial Officer, Tim Kelly. Tim?

[Tim Kelly, executive]

Thanks, Marcio, 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 with $41.9 million of that R&D and the remaining $15.3 million for G&A and reflects an increased amount of clinical activity in our movement disorder and epilepsy programs. During the third quarter, Praxis 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 31, 2023, with the increase primarily due to the net proceeds from Praxis follow-on public offerings earlier this year. Our cash supports 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.

[Marcio Souza, executive]

Thank you, Tim. I now will now open the call for Q&A. Operator?

[Operator]

[Operator Instructions]. Our first question comes from Ritu Baral with TD Cowen.

[Ritu Baral, analyst]

A couple of questions on relutrigine, [indiscernible] specifically, as you think about the 80 patients in the expanded cohort for expanded cohort sufficient for registration, will the enrollment criteria for that patients be any different than the original 15 patients? And if so, do you expect it to result in any -- or prospectively expected to result in any changes to efficacy 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?

[Marcio Souza, executive]

Sounds good. Thanks, Ritu, for the question. So on the first one, for the 80 additional patients that are enrolling on the second cohort on the study right now. So number one, like there are active patients. So we've been [ eye ] screening those patients and getting that into the study, which is very good news in our view. The major difference outcome this study is actually the start dose for the patients randomized to drug. So starting on the previous study was at 0.5 milligram per kilogram per day and this one is 1 milligram 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 light separation and a deeper effect possibly maintain or even expanding the number of seizure-free days and number of patients there. no real major change on the inclusion criteria. So from a patient population perspective, we're not expecting to see a different one here. And then on the timing 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 as what I would call, we're expecting to run like a parallel group of 11, 12 weeks. What we are aligning is really the inclusion of those patients.

So our view and our position right now is that we can typically define patients with the independently of their genotypical, like geology. And for as long as they have not sensitive to the mechanism, #1 and #2 seizure burden that are consistent with what we believe we can play a high impact that should be efficient. So just double checking that like a number of like small details in terms of how to randomize and size and things like that, which should be done by the very end of the year and then we're going to be able to operationalize by the very beginning of next year.

[Ritu Baral, analyst]

Got it. So I want to clarify, you are going to geneotype these patients, but all they need to have is a genetic mechanism that's rational.

[Marcio Souza, executive]

That is right.

[Operator]

Our next question comes from Yasmeen Rahimi with Piper Sandler.

[Yasmeen Rahimi, analyst]

Two questions on the interim analysis. I think investors were just wondering I think the interim was expected to happen end of the year. Maybe just some color around why it got a little bit moved into 1Q 2025. And then it appears based on the remarks you've made that were steady to will not read out before the interim or the interim, we'll get an insight about 1 and 2. I just want to make sure just to get if you could just walk us through sort of the disclosures around both of the studies, that could be helpful.

And then last question is, I think you guys noted that upon the outcome of the data and you would reinitiate a Parkinson's disease program in 2025. Could you maybe comment on like the success in AT would move into Parkinson's or would that be a Phase II study, Phase III study? Any color around that would be helpful. And I'll jump back into the queue.

[Marcio Souza, executive]

Sounds good. Thanks, so in the interim, right? So I will start by saying we're very confident on the execution for the trend like every aspect that monitoring in every discussion just increased 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 program like [indiscernible]. And that will be, I would say, the main driver here, right? So what we're trying to do to take a step back if to deliver a successful program that we can file an NDA and can be incredibly clear the efficacy and the safety of ulixacaltamide hydrochlorates for these patients.

When you look into that, there was a number of things that were either bumping up in terms of availability of GMC 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 stature. That is the second part of your question, right? in the eventuality, which is quite a possibility that the interim analyses work exactly as we expect. So very positive -- we wanted to make sure the result of a study with about the same time to shortly after #1. But too, that there is no influence and by influence, I mean negative influence on Study 2 readouts. So when you're looking into as a program, it made sense for us to make this, which in our view is more and slicing that is safeguarding the overall like positive results in our view of the combined studies, right, Study 1 32, its combination and the package for the MDA so that is the main rationale on our end.

Everything is progressing brilliantly so far. On the Parkinson's disease study, I think that our confidence grows into the outcome on essential Terremark, we need to really be ready to the expansion alike time is an incredibly important asset on this business. We want to make sure that an indication of them for ourselves, for open strategics and so on and so forth gets off the ground. We had -- I got some feedback from the FDA last time in terms of what they would like to see on our PG study. So we have a very good idea to design a Phase II/III study in Parkinson's that would significantly advance this program as well. So we just restarting that in terms of the planning. So we already, at that time, to kick off and restart. So we have a portfolio of indications in Pollex instead of just 1.

[Operator]

Thank you next question comes from Joon Lee with Truist Securities.

[Joon Lee, analyst]

Just a quick clarification. Will you be including [ relutrigine ] in the broader EEE study because there's genetic basis [indiscernible] and you seem to want to stick to extended epilepsy based on your response to Ritu's question. And I have a follow-up.

[Marcio Souza, executive]

Sounds good. So, we will include LGS patients on there who will attempt to the answer again to reach you before we are providing an attempting to collect as much genotype information. Sometimes, as you know, going to be typically define 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 in the [indiscernible] on claims data for projects 1 of the highest use of the [indiscernible] mechanism with one of the highest issues in terms of [indiscernible], which we think is a sweet spot for our drugs. So yes, will be doing. But at the same time, that is part of like this entire discussion about inclusion criteria and measuring is the discussion we're having right now.

[Joon Lee, analyst]

Great. So it's a [indiscernible] study, great. For the interim analysis for essential program, I just wanted to clarify that your you referred to interim analysis, you're referring to the Study 1 interim. So you randomized withdrawal trial top line will depend on the interim from the parallel comparator trial? Is that correct? And then...

[Marcio Souza, executive]

Yes. Go ahead, Joon, sorry.

[Joon Lee, analyst]

Yes. So -- and the number -- part 2 is that is there -- or is there no inferior already analysis baked into that interim analysis?

[Marcio Souza, executive]

Yes. So the interim analysis is on Study 1 only, I mentioned, right? We don't believe that would be necessary or appropriate for an Interim Study 2. Basically, there's an alignment in terms of like database, not claiming between the multiple events that we're talking here. So that is could be some water and influence because those studies are recruited concomitant play, right, as you know, from the same pool of patients, and they are randomized to the studies. So that's why there could be some influence on depending on the outcome of the internal as well.

We will be reading out Study 2, of course, shortly thereafter on the trend that is [indiscernible] could argue study to monitor our base on like event rates and things like that. So quite bullish on that to begin where -- what was the second part of the third question about the inferiority -- sorry. So there is a futility margin on the lower end of the conditional power as it standards. Right on interims like that. So fairly standard in terms of the bond there, a very wide, I would say, [indiscernible] zone because that's the reason why they studied or the inter-analysis was designed to begin with.

And on the other hand, as well, which should be considered that if top for overall efficacy as our new work wanted to balance all of that, of course, from information fraction perspective and from a spending perspective and the overall execution to drive toward the successful all come.

[Joon Lee, analyst]

Great. And then last question. As we look to the very likely approval of [ sugetrigene ] from [indiscernible] in January, is actually impressive that it even works at all because it only targets 1 of the 3 voltage-gated sodium channels in the [ perpenervous ] system. So it's actually interesting that you're advanced looking at your formal thing pain as well, which targets 2 out of the 3 can receptors or not receptors, but voltage-gated channels. Any anecdotal evidence of pain reduction from your Phase I or any other study.

[Marcio Souza, executive]

Yes. So the -- like we're super excited about this as well, we look into for a while. It's not something that made some strong priority execution, capital allocation beforehand for us, but now we believe it does. We do have a very strong preclinical evidence on in paying models and in general, like very potent I mean, [indiscernible], as you know, that mechanism, the duality of the mechanism is quite important in paying generally acute tens of chronic and chronic bank we thought that, yes, we're excited with what we're seeing. And we think that what's most appropriate for us is just to finalize everything looking from a competitive standpoint. As well, make sure that would be competitive and then top of our plan early in the year with all of you.

[Operator]

Next question comes from Francois Brisebois with Oppenheimer.

[François Brisebois, analyst]

thanks for kind of going through the potential scenarios here and the complexity and the dependence between the impact of, say, one on Study 2. So -- but in terms of what to share on the interim -- is it -- could it go into data? Or is that's actually a really good case scenario where we stop the study because things are working out? Or is it more -- can we be assured that the actual top line of Study 1 will be after Study 2 that might come short after the interim look? Just any help there understanding the time line of the top line versus the interim for Study 1.

[Marcio Souza, executive]

Sounds good. Well, I think that in areas like if I think about ball cans here. So one, as you mentioned, the potential to stop like for overall [indiscernible] that obviously is not the base case, but let's just play that out, and then both studies would be having the results at the same time, right? It's like Study 1 and Study 2 at that point in time, which obviously will be quite positive, complete package and so on. I think that is now an opportunity as well to increase the size of Study 1.

And in that case, the conversation will be having as we're moving study or forward, we're increasing the size and for Study 2, we should have the results like very quickly as well. So that's when it dissociates this year. That is the highest our priority probability that will happen is on that just because the rate of the conditional power is the larger store, the widest on that zone. So I think that's the I'll say we should plan the most around with the first having the highest impact, right, in terms of like operationally, making sure ready to like wrap it up the other 2 studies and so on. So that's why we wanted the considerations and how we look into being ready for the interim.

[François Brisebois, analyst]

Okay. And then on the DE commercial front, there's a lot of different ways to look at this market. Can you help us understand U.S., ex U.S., how you think about the commercial potential here?

[Marcio Souza, executive]

Yes. 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 the U.S. and then the -- about 30% outside of the U.S. for PEC. We're talking about a multibillion-dollar back here in GEs? We just completed yet like another refinement of the [ epemiology ] in the U.S. 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 U.S. When you consider that even relatively small market share gets to quite important figures in terms of like the potential big revenue.

And then the outside of the U.S. becomes a little bit more, I'm going to call opportunistic from a business perspective, obviously, it's important to have access to patients as well. but not as important to get the drug off the ground and get to quite meaningful revenues. So about 2/3 in the 1/3 outside of the U.S. That's how we've been modeling.

[Operator]

Our next question comes from Yatin Suneja with Guggenheim.

[Yatin Suneja, analyst]

Just a couple for me as well, mostly in the ET side. Could you provide us where you are, at least on the enrollment front, that how many patients have been enrolled in Study 1 and 2 record, and then 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 prespecified plan like how long would that take at the maximum if you decide to increase the size and let's say, with the max number of patients that are not, how long will that take?

[Marcio Souza, executive]

Absolutely. So I'll give as much as we feel that we could give right now in order like to preserve the optionality for us a lot. So the the current study state, 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 confidently is anywhere between 20 and 30 patients per week randomized new patients. So if you fast forward to a potential scenario here, so I'm going to use like 2 scenarios where an increase of 100 and an increase of 200 patients you can see that, that could be achieved in like anywhere between like 3 to 6 weeks of [indiscernible]. 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 actually study if needed.

[Operator]

Our next question comes from Douglas Tsao with H.C. Wainwright.

[Douglas Tsao, analyst]

Just to confirm as what you just did. 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 ESSENTIAL3?

[Marcio Souza, executive]

Yes. So that is the one we we're very, very comfortable from a like pace of our organization that we can achieve very, I would say, relatively we, I'm not going to say easily because there's a lot that goes on this randomized patients in a given week.

[Douglas Tsao, analyst]

Okay. Great. That's helpful. And then just if you could provide a little more color in terms of moving Vormatrigine 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 -- sort of coming forward with the full development plan.

[Marcio Souza, executive]

So we're working, and I would say thanks for others working on this space, right? There's a lot that's been done in the last few years a year as well. When you look into what is important for us are a couple of things, right? So one is the pharmacology itself, right? Like can we have the relief of like [indiscernible] and to relationships with CEMEX like quickly enough for certain types of paying, what is the ideal type of thing. What is our confidence in terms of preclinical and potentially early clinical data, biomarker data, et cetera, that could get us to a point that were incredibly confident as we were last week for when we like moving into [indiscernible] to have a similar package, I would say.

And then like really understanding the impact what 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 at, again, [indiscernible] study to show that and cost in that study and things like that. So that's the work's 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 earning the year to showcase that to all of you.

[Douglas Tsao, analyst]

Okay. Great. And then just one more on elsunersen. 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 [indiscernible]. 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, executive]

Yes. So no, that's a very important aspect as well. So the way we've been looking into elsunersen are twofold here. So one we consider to be important to explore, particularly the safety at different exposure levels, and that a lot of what's been done in Brazil right now on the second cohort is want you to realize like patients or to drug or placebo or to drug or sham on that case. We're exploring a range of those sequentially increasing dose on those patients who are 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 cations exposure dose as the 1 milligram per month for the global study. We have very good alignments already in general, what is needed there. But we do have still a meeting pain this year with the FDA on finalizing which was slightly changed on their end on the -- our expectations from when the meeting was occurred. So nothing problematic there, but it's calling 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's the bottom line for that one.

[Douglas Tsao, analyst]

Okay. And so with the patients being studied in Brazil now, are 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 milligram per kg dose. I mean is there a chance that if results warrant that you would potentially look at higher doses in the U.S. and European registrational studies.

[Marcio Souza, executive]

Yes, we must follow the science, right? So what we see so far on the patient in the U.S., which are continue taking the drug and on the patient in Europe and in Australia that actually took higher dose than in the U.S. it's not meaningfully different in terms of [ Tier ] control gains on like development milestones and things like that now. we've got to remain open to the possibility that yes, it's going to be meaningfully different and meaningfully faster whatever. And if that's the case, we would be in a position to complements the global either in its open label phase are right after the control phase are all even in a different cohort if that's warranted.

So it will be driven by the results that we see here but the time lines in terms of like the original 4 patients, they're going to be dosed there are curtailed with the enrollment time lines we have for the global study. So it shouldn't be a complex in terms of how [indiscernible] possible results for those patients.

[Operator]

Our next question comes from Kambiz Yazdi with Jeffries.

[Kambiz Yazdi, analyst]

A couple of questions for me. The placebo response was pretty well controlled in the Central One. Essential3 has a more innovative centralized design what steps have you taken to control placebo response in Study 1 in Essential 3? And then as a second kind of set of questions, maybe on Vormatrigine. What have sodium channel blockers demonstrated historically in PGTC seizures? And what would a registrational program consist of in generalized epilepsy.

[Marcio Souza, executive]

Thanks, Kambiz. So placebo was already pretty well controlled, as you said, on the Essential1, when you're looking to Essential3, there was one aspect that we wanted to add to further home throw that. So what we're seeing is there is a -- I would say, a slight, but important chains on patients that are low to stable at baseline. And what I mean by that is there were streaming assessment -- or sorry, a [indiscernible] assessment on study on Essential1 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 the study was, again, at the end of the day, it's going to be like 4x smaller than Essential3, so we wanted to ask the question whether or not the influence is going to be similar, right? So we chose to actually add maximum [indiscernible] parameter between those visits and to formally have a visit the premium ammoniation ones. We believe because you can monitor patients from the study, we know how long it takes for the drug to start working that were very successful on controlling that on making sure that the patients that are similar to what we want from on, right? We don't want to depart from the cohorts only 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 control placebo there. And then on your second question on generalized the primary earnout, it's mixed the results historically. And I think partially because that isn't really being a surge channel blocker that is very selective and that really works on -- as these norms are like hiring a lot and expanding a lot in terms of like the loss of control, I'm going to call on the action potentials that can really block the pathological events, but not the physiological for these patients. that is a very good with more selective or partially more selective drug. So we are interesting enough, I would say, [indiscernible], the conversations that we've been having like a lot of the conversations that got off the ground and prices get excited.

A lot of people are equally or more excited actually about the generalize [indiscernible] was a little bit surprising to me that there is so much excitement on generalized Vormatrigine, and I believe it's because there is a huge amount there, and obviously, those seizures are incredibly important as well when they happen from a severity and potential impact in terms of fatality as well for those patients. So we're going to see soon enough, I would say, from RADIANT, what kind of feedback we can have there. And RADIANT is going to serve as a kind of a springboard for us and to design what we would expect to be a registrational phase study. for generalized as well.

[Operator]

Our next question comes from Ami Fadia with Needham.

[Ami Fadia, analyst]

A couple of quick questions from me. Firstly, on Ulixa. Can you comment on the enrollment? And how -- what percent of patients have completed randomization relative to the target enrollment for the 2 studies? And was there a slowdown in the enrollment rate that caused the shift in the time line? Maybe I'll ask my next question after you answer this one.

[Marcio Souza, executive]

Sure. So Ami, we're not going to talk about that right now, as you mentioned, right, on the prepared remarks and in the press release. But what I can tell you that is no slow down on what we expected proration or from patients in screening. I think we continue and we saw historically, we expect 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 been managing that so we can get like the best [indiscernible] for the study that are two positive studies have like right after the interim. So it's been a lot on us and of course, the scaling of patients and things like that, which influence but are not meaningful.

[Ami Fadia, analyst]

Got it. Okay. And then on relutrigine in the RADIANT study. Can you talk about how many patients you're targeting or sort of the mix of patients between focal and generalized and how that might inform your plans to develop it further in generalized epilepsy?

[Marcio Souza, executive]

Yes. So the goal is to have 50 patients on agent. What we are seeing, again, on early days, but what we're seeing is about what the expected 30% generalized 70% focal interest. For, like, in general, particularly like on the size of target that here we were, I would say, a 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 we got significantly more than we expect here. So we kept that a little bit tight in terms of the or so patients that we expect to enroll.

That should be sufficient as we go like across, and it's an open label study, right? So we continuously are seeing and adapt as needed in terms of maybe reducing or increasing the total number of patients based on the overall interest. But from generalized and Focus is what we're going to expect to see at the end.

[Ami Fadia, analyst]

Understood. Maybe just a last question from me. As you design the embed study what assumptions would you be making with regards to relutrigine performance in this patient population relative to the data that you saw in SCN2A.

[Marcio Souza, executive]

Yes. So arguably, SCN2A were the hardest of those conditions to [indiscernible] when you look across the board, yes, there are a few others that incredibly difficult treats, but those were definitely incredibly hard to see reductions to see [indiscernible] mortality in Chile, for example, is like 6x higher than right, so in infancy. So this is significantly like higher bar. So we expect at or above the efficacy levels that we're seeing, 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 these patients.

[Operator]

Our next question comes from Joel Beatty with Baird.

[Joel Beatty, analyst]

The first one is on ulixacaltamide, if the interim is acceptable, 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 2 events?

[Marcio Souza, executive]

Yes. No, Joel, thanks for that. If [indiscernible] is successful. So it's the buying grid for an equip efficacy is crossed, we will have results at the same time.

[Joel Beatty, analyst]

And then in DEE, should we think about relutrigine as kind of just working in patients who are already responsive to calcium channel blockers, or could you talk about the potential to work beyond DEE patients who are responsible to those agents?

[Marcio Souza, executive]

Yes. So it's quite interesting. I think that is -- like when you're looking to preclinically and all the work we did, it does not look like it could or should be restricted 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 results on actual, the dynamics of the neurons among the animal models, for example, point over syndrome are quite at the outer put unexpected meaning are significantly better than you would expect on that, which is there is a bias towards maybe some first-generation outside in general blockers wouldn't work on that population, right? So clearly not the case, here. The -- and then there's a few other ideas that would -- our priority expects to have efficacy that we're seeing efficacy in preclinical models, and therefore, we should expect to have as well.

When a figure is happening, right, if we could observe like a neuron, sodium channels are going crazy in a very late term way to describe it. So stopping that activity is very, very important for seizure control independently of the etiology of the seizure or general even or origin in the brain anatomically. So we expect quite wide range here of efficacy. I think what we have to ask the question is always, how consistent is the seizure because who wants to count and similarly, right? You'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 put in them together. So that's more of a registration than anything else.

[Operator]

[Operator Instructions]. Our next question comes from Laura Chico with Wedbush Securities.

[Laura Chico, analyst]

Two clarification questions for me. First on the interim for ulixacaltamide. I understand that the timing for the interim has extended to the first quarter 25. What I'm trying to clarify, though, is 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%? Hopefully, that makes sense. And then I have a follow-up.

[Marcio Souza, executive]

It makes a lot of sense for the question, Laura. So the range that we gave for the information fraction, right, if I understand correctly, that's your question was between 50% and 75%. So the range for the information does not change. Of course, it is a range because it depends on the exact day of the data transfer the calculation by the DMC, but we did not change that.

[Laura Chico, analyst]

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 2. My understanding was that these are conducted under the same protocol. So I'm trying to understand the separation of the release results. And have you had any feedback from FDA on how they would like to see results communication.

[Marcio Souza, executive]

Yes. So the last part is. So we did not, and I don't think they often opine on how results should be communicated, they did though reveal the data rate is from health plan, which analyzed the studies separately. And then there's another yet another analysis plan just for the internal analysis. So that was reviewed and we received it back many months ago. from the FDA on that. So a call on that. So the influence is let operational on the IT sensors, like definition of operation, meaning you're absolutely correct.

The studies are randomized patients are rhythmized 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 as they finalize the study by a potential meals since they wouldn't know their own study tube or Study 1. So we didn't unduly influence or create qualified placebo tact by potentially in a positive case, to be perfectly honest here, creating a potential impact on what we expect to be a quite successful study that study. So may be overly cautious on our end, but again, trying to set gardeners of the entire program.

[Laura Chico, analyst]

Okay. That's helpful, Marcio. And maybe last question for me. I think I missed this, and I know you commented on it earlier, but could you expand a little bit more on the rationale and the restart in the Parkinson's indication? I guess I'm trying to better understand what would be the mechanistic read-through from the ET studies to Parkinson's.

[Marcio Souza, executive]

Yes. No, no, absolutely. So I think from a scientific rationale is very strong to be in Parkinson's. The last time when we actually stopped the Parkinson's study had very little to do with our expectation in terms of results for that stay and a lot to do with availability of capital. I think as we fast forward, then we have significantly more safety data, of course, we are excited and we expect the ID-1 Study 2 to be positive for essential time the data from a scientific standpoint do not get weaker, they got stronger front of Parkinson's our rationale.

So why don't [indiscernible] like using like a significant amount of capital to actually reinitiate before the results, we want to be ready at the time of the essential 3 results to reinitiate Parkinson's. So maybe that's more of the message there than to have a delay and not necessarily use the mechanism. I think there's a far -- there is both go-to-market strategy here where while movement is other specialists only have about 5% to 10% of the patients, those 5% to 10% of the patients coexist a lot more with Parkinson patients. So that is kind of a penetration of the market strategy that is important. And the other is just the engagement in general in leaders. Of course, it goes without saying that we think we can have a meaningful impact on Parkinson patients as well.

[Operator]

I would now like to turn the call back over to Marcio De'Souza for any closing remarks.

[Marcio Souza, executive]

Thank you so much. I really appreciate everyone joining the call and staying with us as the company continues to evolve quite positively was a lot went on over the last 10 months and 9 months, if you count the quarter. in terms of the transformation of the company for what it's going to be our next year for registrational programs and potentially one NDA submitted midyear or so far ulixacaltamide. As we continue to progress millions of patients will be positively impacted by those drugs and billions of dollars in value will be created to all of us shareholders. So we appreciate it looking forward to providing more updates in the near future and I'm sure you'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.