Prepared remarks
Good day, ladies and gentlemen, and thank you for standing by. Welcome to the Praxis Precision Medicines First Quarter 2026 Financial Results Conference Call. As a reminder, this conference call is being recorded. At this time, I would like to turn the conference over to Mr. Dan Ferry of LifeSci Advisors. Sir, please begin.
Good morning, and welcome to Praxis Precision Medicines First Quarter 2026 Financial Results and Business Update Conference Call. This call is being webcast live and can be accessed on the Investors section of Praxis' website at www.praxismedicines.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 timelines, and financial projections. While these forward-looking statements represent Praxis' 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 Praxis'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 Praxis, and Tim Kelly, Chief Financial Officer. After providing updates on our key programs, we'll move to a brief Q&A session where Marcio and Tim will be joined by Steve Petrou, President of Research and Development, and Megan Sniecinski, Chief Operating Officer. With that, it's my pleasure to turn the call over to Marcio.
Thank you, Dan, and good morning, everyone, and thanks for joining Praxis' First Quarter 2026 Conference Call. Building on a remarkable 2025, we have continued executing across our portfolio in our journey to become a commercial company with strong momentum building across four late-stage assets, representing more than $20 billion in peak sales potential. With the NDAs for ulixacaltamide and relutrigine accepted by the FDA and PDUFA dates set, we're ramping up commercial efforts to support the two potential U.S. launches within the next eight months while also making significant progress with our other clinical programs. It's also incredibly exciting to announce that we have completed recruitment for the EMBOLD study in the broad DEE population, with top-line results expected in the fourth quarter of this year, which we expect to support a potential supplemental NDA next year. We're also on track to report results from our POWER1 study for vormatrigine later this quarter. We also made exciting progress with our solids ASO platform with the positive results from the EMBRAVE Part A showing a disease-modifying effect of elsunersen in SCN2A early-onset DEE and a substantial reduction in monthly seizures, among many other results. With key hires made in our commercial organization and a strong financial foundation, we're accelerating the delivery of life-altering treatments to patients with CNS disorders. Let me provide a bit more detail on each one of our programs. Let's start with ulixacaltamide. FDA acceptance for Ulixa's NDA marks a meaningful step forward for the seven million Americans living with essential tremor who currently have no ET-specifically developed treatments approved. We estimate that about two million of those people living with ET are in immediate need of a therapy that can clinically improve their daily lives, representing a potential for over $10 billion in peak sales. To unlock the benefit for patients and the value, we have been diligently preparing for our commercial launch based on the PDUFA date of January 29 next year. The commercial leadership team is in place with our field force plan to be hired and trained in advance of the launch, and we continue to expand and build the commercial infrastructure across multiple areas, like operations, marketing, access, and compliance. We have also successfully established a distribution network to ensure drug availability at launch at successful levels. Earlier this year, we conducted a very comprehensive observational study with physicians to understand their view of ET and ulixacaltamide. We surveyed more than 2,300 U.S. physicians who collectively manage tens of thousands of patients. The results were beyond encouraging. They validated the ulixacaltamide profile across efficacy, the breadth of benefits, and tolerability, reinforcing the more than $10 billion peak sales potential and the need for a drug like Ulixa in the market. Importantly, we also wanted to hear more details from patients and conduct a similar work with over 1,300 ET patients, which further validated the agreement between the needs of patients in terms of their functional benefits and the results of the Essential3 program. It's truly exciting to be in a place of such alignment among treating physicians, patients, and the results of our program. We're also very pleased with our robust presence at the American Academy of Neurology Annual Meeting last month. With 15 scientific presentations, including a plenary presentation highlighting the Essential3 program results, which received the AAN's Abstract of Distinction and Movement Disorder Awards, which underscore the strong interest and engagement of the medical community. To further enhance our engagement with health care professionals, we have launched the Essential2 Me disease state campaign. Let's now move to our epilepsy programs. As we shared in March, in another pivotal moment for patients and practice, the FDA has accepted with priority review the NDA for relutrigine for seizures associated with SCN2A and SCN8A DEE. These are severe patients affected early in life, in whom the seizures are intractable from the very beginning. It's important to highlight that if approved, relutrigine would be eligible for a pediatric review voucher. With the PDUFA date of September 27, preparation for launch is moving full steam ahead with continued hiring of commercial roles, building sufficient inventory, establishing a comprehensive patient support program, and engaging with payers to ensure timely access upon potential approval. We remain confident in the clinical potential for relutrigine and the benefits to the broader DEE population. With recruitment in the EMBOLD study now completed in record time, it's clear that patients and investigators share our view. The potential launch in SCN2A and SCN8A will build the foundation and the results of the EMBOLD later this year; if positive, it will significantly expand the commercial potential for relutrigine by several folds, considering the broad DEE population is comprised of over 200,000 patients in the United States. Let's now talk about vormatrigine, the most potent and selective sodium channel modulator ever developed for the 3.5 million people living with epilepsy in the United States. We have three key milestones in the near future for the program. The first is the readout of the 401 Phase III study later this quarter. Then the initiation of the POWER3 study, a milestone in the community, using all the exciting features of vormatrigine to deliver on what the majority of the market really needs. And then later in the year, the completion of the POWER2 Phase III study, which is evaluating doses of 20, 30, and 40 milligrams once daily. Enrollment is progressing well, and we're on track to finalize the study this year and report early next year. Lastly, let's talk about elsunersen, the first ASO on our platform. It also has a rare pediatric disease designation and is being developed for the treatment of early seizure onset patients with SCN2A mutations. We have recently reported the results of EMBRAVE Part A, which enrolled nine children aged two to 12 who were randomized 3:1 to elsunersen or sham over 24 weeks. We are thrilled with the impressive 77% placebo-adjusted reduction in monthly seizures and the disease-modifying components seen across multiple domains in those patients, while maintaining a generally safe and well-tolerated profile. The overall data from both the EMBRAVE program, open-label extension, and emergency use program globally highlight durable seizure reduction and meaningful global gains, which further underscore the transformational potential of this drug. In conclusion, we're off to a great start with our momentum continuing to accelerate across our clinical portfolio, preparations for the commercial launch of ulixacaltamide and relutrigine well underway, the completion of the EMBOLD study enrollment, POWER1 top-line readout coming up, and many other achievements to come. Backed by a strong balance sheet and a long, multilayer IP portfolio across the programs, we're focused on rigorous execution and driving progress across our innovative first- and best-in-class portfolio of CNS therapies. I'll now hand over the call to our CFO, Tim Kelly.
Thank you, Marcio. Good morning, everybody, and thank you for joining today's call. I'll provide a quick summary of our first quarter financials. In Q1, our operating expenses were approximately $106 million, with $78 million of that for R&D and the remaining $28 million for SG&A, driven by ramping activities and hiring related to commercial launch preparations. During the first quarter, Praxis spent $86 million in operating cash compared to $53 million in the first quarter of 2025, reflecting greater clinical trial activity, headcount growth, and commercial launch preparations. As of March 31, 2026, Praxis had $1.4 billion in cash, cash equivalents, and marketable securities compared to $926 million as of December 31, 2025. This increase of approximately $474 million was primarily attributable to net proceeds from Praxis's January 2026 follow-on public offering and interest income on marketable securities, partially offset by the previously mentioned cash used in operations. The company's cash, cash equivalents, and marketable securities as of March 31, 2026, are expected to fund operations into 2028. With that, I will hand the call back to Marcio.
Thank you, Tim. I appreciate the review. We're going to move now to Q&A. Howard, maybe you can provide the queue for us.
Questions and answers
Our first question or comment comes from the line of Yasmeen Rahimi from Piper Sandler.
Maybe also congrats on EMBOLD bringing to the finish line enrollment and data in Q4 as it's an important readout this year. Maybe remind us, what is the data that we have to support relutrigine working in a broader DEE population, both across preclinical and clinical data? And then also, what do you see on a blinded basis across safety and efficacy that continues to give you confidence in the high success in the EMBOLD study? I'll jump back in the queue.
Thanks, Yasmeen. I'll take a step back here and maybe talk a little bit about the genesis of going to the broad DEE population. When you look into seizure activities, particularly in those intractable conditions like DEEs, we know full well just how difficult those patients are to control. I know that when they can have at least some partial control for the most part, it is because that is a way to inhibit the block, better modulate their sodium channel activity; you simply cannot have seizure activity without participation of those channels. So when we were conducting the EMBOLD program for SCN8A, the number one question we're getting from physicians back then was, "When are you going to expand this to this population?" So we'll take that into mind in terms of the overall clinical proof of concept, payer idea, and the needs that we're seeing. But we had to slow down a little bit and do a lot of work. And you might have seen, and it's available on our website, a fair bit of the work in terms of different animal models, which are incredibly predictive in epilepsy, on understanding whether or not there was a good scientific rationale on top of the electrophysiology rationale, on top of the molecular rationale to go to this. Then, in the last part, we had to make sure that the FDA was in agreement that we could study in this population. Safety is paramount, making sure that we're actually understanding the populations we're in. So when we checked all those boxes, we're able to initiate the study. I think what is incredible is just the level of interest. If you look into our studies and other studies, there was no interest in some of those others. It's pretty obvious by the pace of enrollment that is happening with us and with others out there. And the number one reason why is that physicians are very confident in the data here, just like we are. So it gave us, of course, this extra ability to move things forward. But if I can turn to the business for a second, we are in the business of helping patients. But at the same time, the only way to continue to help them is to continue to generate proper positive returns to invest in the future. The expansion towards the DEE is like 20-fold what the initial indication for SCN2A and SCN8A is, which is incredibly important. But the second part makes not only scientific sense, but it's a tremendous upside in terms of the potential of this drug. Then lastly, I know we keep piling catalysts throughout the year, and you guys might be tired of us having so many readouts. But we thought it was very important to get that, shortly thereafter, to really, with a fresh, hopefully, approval at that point in time, give the FDA a lot of flexibility to actually look into just the additional data and potentially even qualify for certain accelerated mechanisms that have been available. So all in all, we see this as a tremendous and key update today that we're giving in terms of value inflection for investors.
Our next question or comment comes from the line of Ritu Baral from TD Cowen.
A lot of client questions are just around the upcoming POWER readout and what our expectations should be. Knowing the baseline and knowing the relative baseline of other competitive therapies, how should investors, how should we be looking at placebo-adjusted seizure reduction, the safety profile? And then how might that data then frame the POWER2 and POWER3 studies, given the different doses in those studies and the different dosing paradigms?
Great set of questions there, Ritu. So, I think let's start with the baseline, that's what you mentioned. So if you look historically, at least in recent history, baseline for focal seizures in the refractory population, so one to three ASMs, and you know the drill there on the other criteria, have been hovering around nine to eleven, twelve countable seizures on the previous 28 days. And I think we're probably a little higher than that, a tiny bit here for POWER1, which was what we're aiming for. We knew these patients were fairly refractory or very confident about the drug. We also wanted to make sure that once we establish there and have very clear efficacy as we expect, allow us to move incredibly quickly as well towards the ultimate goal of this drug that's being widely available for any patients with focal seizures and in the future, other types of seizures as well. That brings us to the second part of your question, which is the expectations. And I think that it's always dangerous to talk about expectations and setting artificial bars this late in the game, in terms of literally weeks before readouts. But we've been fairly consistent on the expectation here throughout the years: number one, as the severity increases, I think this is one of the few areas, and we're going to be very excited about science that the new drugs still deliver a lot. We just saw that recently with another program; we expect to see the same here, a drug delivered despite being piled up with a lot of other drugs. It is at a higher baseline, so more severity. And we've historically been giving that adjusted by placebo around 30% or so as quite meaningful because when we talk to physicians, when you look into the active prescription pattern, that seems to be a number that lands incredibly well. And then the last part is safety, as you mentioned. And we're very confident about the safety profile of this drug, both what we're seeing in the blinded data based on POWER1, or also what we are seeing on a blinded basis in POWER2, which was the very last topic you mentioned. So fairly comprehensively, I think we're excited about the upcoming readouts, another card to flip, another program to hopefully accelerate to bring to patients. POWER2 is going really well. So, as you saw as well in the press release, we reiterated finalizing the study by the end of the year and reading out early next year. So all in all, thinking about a potential third or fourth submission of an NDA in 12 months is no joke, and we are very, very proud of that.
Given that baseline, what about seizure-free, Marcio? Last question, I promise.
No, no, that's a good one. I think, again we should unblind it. I do feel the number one thing is really to make sure we have a very solid reduction. But of course, we want to see seizure freedom here as well. It's important. It's something we saw in the RADIANT data, that when you treat patients longer, by week 10, 12, your median seizure reduction can reach 100 percent in some patients. So of course, we want to see the more we treat, the longer we treat patients, a deepening of effect. That's what we started seeing. And I'll leave it at that, but we're excited with the overall profile.
Our next question or comment comes from the line of Tiago Fauth from Raymond James.
I had just one quick one on Ulixa. It's also related to the communication plan for the Street on the regulatory interactions, which is still a huge area of focus with investors. So I'm curious what's the level of detail that the Street can expect around mid-cycle review, labeling discussions, CMC inspection scheduling, or anything related to that?
Thanks, Tiago. So maybe, again, I'll take another step back here as well. We are, of course, being communicated by the FDA when the expected mid-cycle meetings are going to happen for both programs, their communication pattern with us, when label negotiation is expected to start and be completed, and the entire cycle. So we have very good visibility from the agency's goals and from the conversations with us in relation to that. I can tell you that throughout this process, I think a very good shift on the FDA is just the ability to really try to keep communicating with the companies throughout the process, and we are seeing that in both programs, which gives us — I'm going to be cautiously optimistic here — a good level of comfort on how the process is moving on both drugs. Having said that, I think it would not be appropriate for us to give play-by-play. And at the mid-cycle, I think the expectation on our end is that there will be no major concerns, keep reviewing, keep finalizing, crossing the Ts and dotting the Is. And if that's the case, I think we should expect very little from ourselves. Of course, if something meaningful happens at those meetings — either they want to see something additional or the opposite where they are moving faster and maybe want to accelerate things — I think it would be appropriate for us to have a discussion. But we need to get to that point with both submissions to be able to have that discussion. I know you asked about Ulixa, but I want to make sure relutrigine gets equal attention as well.
Our next question or comment comes from the line of François Brisebois from LifeSci Capital.
Congrats on the EMBOLD recruitment there. I was just wondering, maybe if you can help us understand, obviously, the patient population size is quite different between SCN2A and SCN8A, and then going to broader DEEs. But I was just wondering on the broad side, how different are these patients? And my question is geared towards expectations. Are SCN2A and SCN8A so severe that if we look at that data, that kind of sets artificial bars on expectations for the broad DEEs? Or is that a dangerous game based on the heterogeneity of the patients? Just a little more understanding of who you are going after with these broad DEEs.
Yes. Thanks. I'll split that question into two parts. One, it's kind of surprising, but it's the reality of the market. When you go to these patients and to the physicians, and we understand their clinical course and just how the disease is a downward slope, it only gets worse over time for those patients, unfortunately, leading to all sorts of complications. It is very clear that improvement, any improvement, would be the bar, meaning statistical significance is the bar for the EMBOLD study. Of course, we want to deliver the best possible results for those patients, but I also think we have to be very careful about setting up the bar. As I said in relation to the previous study with POWER1 on Ritu's question, for this study we need to be happy if we see statistical significance as we expect to and some clinical improvements. Now, to address how heterogeneous this population is: our recruitment strategy was very clear as to what we wanted these patients to be diagnosed with. So that's very specific — an early diagnosis, developmental impact together with seizure onset, and a number of countable seizures at baseline. Having said that, we wanted the most diverse group of patients possible because that's what we're going after. That's what no other drug can do right now. And we accomplished that. By definition, one could argue that SCN2A and SCN8A are harder to treat, but the broader DEE population is more heterogeneous to treat. So if you can see even half of what we're seeing in SCN2A/8A on EMBOLD, it's hard to imagine how big a market that would be. But if we see stabilization and improvement in these patients, that would be incredibly meaningful. So it is meant to be a really major opportunity for all of us.
And maybe if I could sneak in on AAN, obviously, I think the plenary was attended by about 8,000 people. Can you just talk about your interactions with neurologists and movement disorder specialists? Does that trigger any interest for ex-U.S.? Can you share what you guys are thinking on the ex-U.S. strategy?
Yes. Thanks for reminding us of something that I think we get so excited about and sometimes forget to highlight. Being in that plenary at AAN in Chicago a couple of weeks back, with about 8,000 physicians attending, and being the first one to recognize the most important clinical study presented at the meeting, it was very emotional for some of us, certainly for me. But the most important part was actually the number of people who came afterwards to us and wanted us to visit their practice with our medical affairs team and present to the entire practice and start thinking about adoption. So it reinforced that there's huge interest ex-U.S. as you can imagine. To be very clear, this is, first and foremost, a U.S. opportunity right now. We're putting our heads down and executing in the U.S. There are multiple implications of current policies in other regions, particularly pricing policies that don't excite us to explore split strategies outside of the U.S. We wouldn't put at risk the U.S. business. So this is something that someone has to do globally. Of course, we're planning to eventually get there, but we're not really excited about splitting the geographies with anyone else at this time.
Our next question or comment comes from the line of Yatin Suneja from Guggenheim.
Congrats. A very nice update. Maybe two questions for me. Marcio, you addressed the expectations for POWER1. So the follow-up question I have there is that at least in POWER1, we're going to get data on the 30-milligram once-daily dose. So could you maybe talk about the potential to capture additional efficacy with the 40-milligram in POWER2? Just love to hear from you how we should think about the 30 and 40 milligram doses, if there is any potential there. And then a broader question on the commercial side: you are undertaking two big launches in the next, let's say, six months or so. Could you talk about manufacturing, supply chain, and where you stand there?
Of course. Maybe even starting with manufacturing and supply. When we are planning these launches, we ask, what is likely to happen? That's how we set our base and financial expectations. We're conservative in planning, and then we prepare for upside. That's how we have to plan supply in our view. For Ulixa, for example, we have two completely independent drug substance manufacturers. They are being readied for us to have sufficient inventory. We're talking about metric tons of ulixacaltamide to give you an idea of scale. This is not small scale; it's very large. We're also quite happy with the fact that the process is, in the grand scheme of things, relatively simple, and we've aligned that with the FDA before the submission. So we're good there. Relutrigine, of course, the scale is smaller, but it's not small for commercial realities. So we're preparing for launch for that too. Very different distribution strategies, as you can imagine: a more full white-glove one-on-one interaction for relutrigine, and Ulixa will also have tailored support. Both inventory and patient management have been sorted out. On your POWER1 and POWER2 interrelatedness question: 20 and 30 milligrams in POWER1 — we believe we're going to see very strong results there. But that begs the question: is there even more to come? If you look into recent history, we've seen cases where the top dose can't be used in practice despite delivering a little more efficacy on paper. That is not the case here. We know that that is not a limitation with vormatrigine. When you think about the need of patients and the 3.5 million people, that requires understanding heterogeneity. That's why having the ability to deliver 20, 30, or 40 milligrams is so important. So it may be even better at higher doses; we'll see that with POWER2. We'll be able to review it soon.
Our next question or comment comes from the line of Kambiz Yazdi from BTIG.
Three for me. On Ulixa, with the Essential2 Me disease education campaign launched in April, can you give us a sense for the early response from health care providers and how you think this initiative is going to translate into the top of the patient funnel heading into the PDUFA? Maybe briefly on relutrigine: how were you able to enroll EMBOLD so rapidly compared to competitors in the DEE space? And lastly, on vormatrigine, you commented a little bit about blinded POWER1 and POWER2 safety. How are you handling the investigator's option to reduce the dose of background medication in POWER1 relative to the RADIANT study?
I'll tackle all of them. Essential2 Me was developed with patients and reflects how they see themselves. The response from providers has been fantastic. They really love it. It reminds them to act, and we're very happy with it. It's already building our prelaunch database to understand who would be first in line, both on the provider and patient side. We'll give more updates next quarter. How did we enroll EMBOLD so rapidly? We focus on continuous learning and improvement. We would go back to the core, train, and understand the approaches that worked and those that didn't. We don't take any wins as a final win but as opportunities to improve. We're very serious every single day about how to do better because these patients need us. We're also good at engaging sites that have large numbers of patients and therefore the ability to enroll, and they understand our expectation for high quality and fast turnaround on queries and eligibility forms. Our team is highly committed to these patients. On the investigator option to reduce background medications in POWER1 relative to RADIANT: what we learned from RADIANT led to both pragmatic and programmatic reduction systems in POWER1. One must be confident in what the investigational drug does to allow background medications to be reduced. Others reduce the investigational drug because they don't trust it; that's not our case. We allow dose reductions when appropriate. It happens partially, which is important, and it's the same algorithm for POWER2. Physicians are happy with how it's done. It's done safely and logically, keeping the blind and the integrity of the study while managing patient safety.
Our next question or comment comes from the line of Ami Fadia from Needham & Company.
This is calling in for Ami. For focal onset epilepsy, are there any first-to-market dynamics you see if a competitor's product is first to market? Our KOL checks have been overwhelmingly positive for vomacigine, but I just wanted to understand if there are any other factors that may have an impact here? Also, have you had any early discussions with payers on what data you need to generate to support earlier line use?
Yes. When you look into the overall market, and we did a lot of work on this, it's unfortunate that outside the small number of patients treated at Level 4 epilepsy centers, in the larger market these patients are failing at very high proportions. They are switching medications, adding on therapies, and so on. I don't believe it's a one-winner game where one drug suffices. If we had 10 effective drugs for focal seizures, that would be needed. The biggest complication is when a drug doesn't allow the physician flexibility to tailor therapy for the patient's needs. With vormatrigine, it gives a lot of flexibility, for example regarding dose adjustments and background medication reductions. I also feel confident about our overall pace. Being a few months behind a competitor is not necessarily a first-mover disadvantage. Physicians we talk to want more options but are cautious based on prior safety experiences. We'll play our cards in the market, and I have no doubt we'll be competitive.
Our next question or comment comes from the line of Andrew Tsai from Jefferies.
Appreciate all the updates. I know we've talked a lot about the EMBOLD study. I did have one small pointed question about it. When you guys shared the SCN2A data, 53% placebo-adjusted reduction overall, curious if you saw a consistent seizure reduction in both of the two DEE subgroups. Maybe that can give investors confidence that you'll see robust and consistent efficacy across the broader DEE subgroup. Would it be possible to share the seizure reduction in both subgroups? And then for essential tremor, based on your ongoing work on a friendlier titration schedule, ultimately, should this be approved, what kind of compliance rate do you expect to see in the real world? How long do you think Ulixa responders could be on the drug for?
Thanks, Lin. On essential tremor and the AAN engagement: when you ask physicians, and we had extensive advisory boards and the large observational study, we asked how they'd manage and what expectations are. The positive surprise for us was how comfortable they were managing the tolerability concerns that happen in the first few days and weeks of the drug. We're going into this launch fully aware that early tolerability is the single most important driver of long-term retention, and physicians are comfortable with strategies to support patients, like proactive outreach. That gives us confidence in retention prospects. Regarding compliance and retention, classical oral chronic therapy compliance and retention starts anywhere from the 60s to 80% in general; that's an external benchmark. The assumptions we need to reach the more than $10 billion peak sales number are not excessive, so we have comfort. We also have hundreds of patients in the safety database who have been on the drug for six months, one year, two years, which helps indicate persistence. On the DEE subgroups, the results in SCN2A and SCN8A, despite different electrophysiology and clinical manifestations, were quite similar and very favorable in terms of overall reduction, developmental gains, and seizure freedom. That gives us strong comfort that the effect may be seen across those subgroups.
Our next question or comment comes from the line of David Hoang from Deutsche Bank.
So I just had a couple here. Maybe back to vormatrigine in focal epilepsy across POWER1 and POWER2: I know you're looking at three doses, 20, 30, and 40 milligrams. How many of those doses would you like to actually take to market? And what do you think would be the best number for commercial viability? And then in terms of the POWER3 study, the monotherapy study that you also intend to conduct, could you talk a little bit about how that fits into your broader plans for vormatrigine? And why aren't other sponsors pursuing monotherapy studies like that?
Thanks, David. On 20, 30, and 40 milligrams: when we started dose selection, we wanted to pick doses that are clearly effective but offer room for flexibility for different patient types and comorbid conditions. Feedback from thousands of neurologists is that flexibility is important, and we intend to bring multiple dosage options to market to give physicians that flexibility, which we believe improves commercial viability and helps obtain and keep market share. Now, POWER3 and monotherapy: POWER3 is a different animal. POWER3 requires the profile of vormatrigine to allow progression to monotherapy. Others are not pursuing monotherapy because they cannot safely deliver a drug that can be transitioned to monotherapy. You need the right efficacy and tolerability profile. There are steps toward monotherapy — they must be pursued safely — but the idea is to address a much broader market, including patients who are trying to return to work, drive, and manage daily life. That broader unmet need is what we believe vormatrigine can substantially impact.
Our next question or comment comes from the line of Olson Jay from OpCo.
Congrats on all the progress. Maybe a couple of us. First, on the Ulixa commercialization: curious about the feedback from AAN and the market research you conducted. What do you view as the most important driver of adoption? And then you also presented some data on the calcium channel modulator in pain. So I'm curious about your latest thinking around this opportunity and if there's anything we should expect in the near term?
Thanks. The most important things for physicians, when we rank feedback from our extensive testing, were: one, having the first targeted therapy for essential tremor; two, seeing a benefit in two weeks for many patients, which allows for early conversations about effectiveness and tolerability; and three, the durability of effect, which we tested in Study 2. Those factors together are key drivers of adoption. Inventory planning and distribution preparations reflect these expectations. On the pain program: we're a CNS company and explore areas of science that make sense for our technology. We presented some work at AAN on pain and are advancing that work. You'll hear more from us in the future on how we are advancing pain programs; we're taking a measured approach while focused on current late-stage catalysts.
Our next question or comment comes from the line of Douglas Tsao from H.C. Wainwright.
Marcio, just starting with EMBOLD, congrats on completion of enrollment. Demand was very strong. I'm curious if you have insight into the subsets of patients that you received? Were there particular ones where you saw very strong demand that reflect the magnitude of unmet need, because for many of these there's no approved therapy and physicians are using off-label ASMs?
Doug, to be honest, when we went to the sites and presented the protocol, we quickly reached enrollment capacity. We actually had to tell some physicians we couldn't enroll more patients because we filled the study rapidly. There are many patients out there with few options, including patients who have failed approved drugs or had suboptimal responses. We saw a broad range of phenotypes and genotypes within our eligibility criteria, and it was within expectations. Unfortunately, we couldn't accommodate all patients who wanted to be in the study, but if the drug works, our promise is to get the drug to them as quickly as possible.
If I can follow up on vormatrigine and POWER1: do you have any insight into the discontinuation rate so far? In RADIANT there were some discontinuations, but clinicians have said they might have counseled patients to stay in. Also, given titration in POWER1, are you seeing any evidence that the titration scheme is having an effect?
We're pleased with how discontinuation has been reduced compared to historical experience with the program. With experience, sites get better at managing tolerability and counsel patients appropriately. Recent competitor experiences had 22% to 25% discontinuation and additional dose reductions at the top dose; that's not what we're seeing. We believe we're very competitive on tolerability and retention given our current protocols and titration schemes.
Our next question or comment comes from the line of Danielle Brill from Truist Securities.
My question is regarding the total addressable market in essential tremor. Up to seven million people have essential tremor, but you recently said there are approximately one to two million actively seeking treatment. What's the gap between predicted prevalent population and those seeking treatment? Is education still needed for more accurate diagnosis? Do higher-volume academic centers typically have more accurate diagnosis?
There are about two to 2.5 million patients who are either being treated or have sought care; dropping from seven million to this range reflects a combination of factors. It's not primarily misdiagnosis. Many people know they have tremor but may not seek care due to stigma or because they were told there were limited options. Essential tremor can run in families, and when one family member is told there are no good alternatives, others may not seek care. Our campaign is called Essential2 Me to awaken awareness. Education remains important, and bringing a targeted therapy to market should change care-seeking behavior over time.
Our next question or comment comes from the line of Brian Skorney from Baird.
You alluded to the opportunity to develop Ulixa in indications beyond essential tremor. You're quite full with NDA reviews and running a few pivotal studies. But wondering if you had any updated thoughts on the exploration of other indications where Ulixa could have an impact? Any timeframe where we might hear an update on that?
Brian, we have selected two other indications to explore. We're completing the final checks and deciding on the best forum to share more publicly, whether an R&D Day or expert calls. We expect to discuss those plans in the near future. We're excited scientifically and clinically about both indications and will provide more details when we're ready.
That's all the time we have for Q&A at this time. I would like to turn the conference back over to Mr. Marcio De'Souza for any closing remarks.
Thank you very much, everyone. I'm sorry for the questions we couldn't take on today's call. It's an incredibly exciting way to start the year. As you think back over the last 12 months, so much happened in really moving the needle for many patients. We have another study finalizing, making sure that if there is a benefit, we're going to get that to patients as quickly as possible. This year, with EMBRAVE Part A being positive, EMBRAVE Part B recruiting really well, EMBOLD completed enrollment, POWER1 coming up, POWER2 coming up, and new indications in planning, we're full steam ahead. The focus is very clear: deliver as much value for everyone, including our shareholders, and keep our heads down on execution. Thanks for the interest, and we're going to be talking to you soon.
Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect. Everyone, have a wonderful day.