Praxis Precision Medicines, Inc.

Good day, ladies and gentlemen, and thank you for standing by. Welcome to the Praxis Precision Medicine's first quarter 2026 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question, you will need to press star 11 on your telephone keypad. 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 Medicine's first quarter 2026 financial results and business update conference call. This call is being webcast live and can be accessed on the investor 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's 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' most recent filings with the Securities and Exchange Commission for discussion of certain risks and uncertainties associated with the company's business. Joining the call today are Marcio 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 Petra, President of Research and Development, and Megan Sinicinski, 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 elixir-cultamide and relutrigine accepted by the FDA, and Piduphidate-Seth, we're ramping up commercial efforts to support the two potential U.S. launch within the next eight months, while also making significant progress with our other clinical programs. It was incredibly exciting to announce that we have completed recruitment for the Emerald study in the broad DE 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 PowerOne study for brometrogen 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 halosinursin in SCN2A early onset GE and substantial reduction in monthly seizures, amongst 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 just start with Ulexa. The FDA acceptance for Ulexa's NGA marked a meaningful step forward for the 7 million Americans living with essential tremor, who currently have no ET-specifically developed treatments approved. We estimate that about 2 million of those people living with ET are in immediate need for therapy that can clinically improve their daily life. 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 a 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 higher 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 E.T. and elixir chalmides. We surveyed more than 2,300 U.S. physicians who collectively managed tens of thousands of patients. The results were beyond encouraging. They validated the Ulexacalpamide profile across efficacy, the breadth of benefits, and tolerability, reinforcing the more than $10 billion peak sale potential and the needs for a drug like Ulexa in the markets. Importantly, We also wanted to hear in more detail from patients and conduct a similar work with over 1,300 ET patients, which further validated the agreements between the needs of patients in terms of their functional benefits with the results of the Essential 3 program. It's truly exciting to be in a place of such alignment amongst treating physicians, patients, and the results of our program. We're also very pleased with a robust presence at the American Academy of Neurology Annual Meeting last month, with 15 scientific presentations, including a plenary presentation highlighting the Essential 3 program results, which received the AM's Abstract of Distinction in Movement Disorder Award, which underscore the strong interest and engagement of the medical community. To further enhance our engagement with healthcare professionals, we have launched the Essential to Me disease state campaign. Let's now move to our epilepsy programs. As we shared in March, in another pivotal moment for praxis and patients, the FDA has accepted, with priority review, the NDA for relitrigine for seizures associated with SCN2A and ADE. Those are severe patients. affected early in life and where the seizures are intractable from the very beginning. It's important to highlight that if approved, religion would be eligible for a pediatric review voucher. With the PDUFA date of September 27, preparation for launch are moving fully steam ahead. We've 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 on the clinical potential for LetroGene and the benefits to the broader DE population. With recruitment in Emerald study now completed in record time, it's clear that patients and investigators share our view. The potential launch in SCN2A and 8A will build the foundation, and the results of the emerald later this year, if positive, will significantly expand the commercial potential for lethargy by several folds, considering the broad DE population is comprised of over 200,000 patients in the United States. Let's now talk about vormetrogene. the most potent and selective sodium channel modulator ever developed for the three and a half 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 readouts of the Power One phase three study later this quarter. Then the initiation of the Power Three study, a milestone in the community using all the exciting features of vermatrogen to deliver on what the majority of the market really needs. And then, later in the year, the completion of the Power 2 Phase 3 study, which is evaluating those of 20, 30, and 40 milligrams once daily. Enrollment is progressing well in our own track to finalize the study this year and report early next year. Lastly, let's talk about alginersin, the first ASO in our platform. Alginersin also has a rare pediatric drug 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 enrolls nine children aged 2 to 12 to randomize 3 to 1 to alginersin or SHEM over 24 weeks. We're 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 the 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 potentials of this drug. In conclusion, we're off to a great start for momentum continuing to accelerate across our clinical portfolio, preparations for commercial launch of elixir-cultimide and erythrogen well underway, the completion of the Emerald study enrollments, Power One 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. And I'll 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 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 31st, 2026, are expected to fund operations into 2028. With that, I will hand the call back to Marcio.

Thank you, Tim. Appreciate the review. I'm going to now move to a Q&A. Howard, maybe you can compile the queue for us.

Ladies and gentlemen, if you have a question or comment at this time, please press star 1-1 on your telephone keypad. If your question has been answered or you wish to remove yourself from the queue, simply press star 1-1 again. Again, if you have a question or comment at this time, please press star 1-1 on your telephone keypad. Please stand by while we compile the Q&A roster. Our first question or comment comes from the line of Yasmine Rahimi from Piper Sandler. Your line is now open.

Good morning, team. Thank you so much for all the great updates. Maybe also congrats on Emerald bringing to the finish line enrollment and data in 4Q as it's an important readout this year. Maybe remind us, right, what is the data that we have to support Rithlut-Judeen working in a broader DE 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 on a high success in the Emerald study? And I'll jump back in the queue.

Sounds good. Thanks, Yas. I'll take a step back here and maybe talk a little bit about the genesis of going to the broad DE. population, right? When you look into seizure activities, particularly on those intractable conditions like these, we know full well just how difficult those patients are to control. Also know that when they can have at least some partial control for the most part is because that is a way to inhibit or block, better modulate their sodium channel. Activities like you You simply cannot have seizure activity without participation of those channels. So when we were conducting the in both program for SCN2 and NHA, the number one question we're getting from physicians back then is like, when are you going to expand this beyond this? So we'll take that in mind in terms of the overall clinical proof of concepts, their 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 in our website, a fair bit of the work in terms of different animal models, which are incredibly predictable 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. And then the last part, we had to make sure that the FDA was in agreement that we could study in this population, right? Safety is paramount, making sure that we're actually understanding the populations we're in. So when we checked all those boxes, we were able to initiate the study. I think what is incredible, I would say, is just the level of interest. If you look into ourselves, if you look into other studies in DEB40, if you look into and I'm going to put that very loosely, the award studies that are going right now, there was no interest on those others. It's kind of pretty obvious by the pace of enrollments that is happening with us and with others out there. And the number one reason why is, like, physicians are very confident on the ability here, just like we are. So it gave us, of course, this extra... to move the things forward. But if I can turn to the business for a second, right? We are in the business of helping patients, but at the same time, the only way to continue to helping them is by continuing to generate proper positive returns to invest in the future. The actual expansion towards GE, broad GE, is like 20-fold what it is, the initial application for SCN2 and ASA, 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. And then lastly, I know we keep filing catalysts throughout the year. 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, it gives the FTA a lot of flexibility to actually look into just the additional data and potentially even qualify to certain accelerated mechanisms that have been available. So, all in all, we see these are tremendous and maybe the key updates today that we're giving in terms of value inflection for investors.

Thank you so much. Thank you.

Thank you. Our next question or comment comes from the line of Ritu Baral from TD Cal. Your line is now open.

Good morning, guys. Thanks for taking the question. A lot of client questions 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 power two and three studies given the different doses in those studies and the different um dosing paradigms yeah the great great set of uh of questions there we too

So I think let's just start with the baseline, but that's what you mentioned, right? So if you look historically, at least in recent history, baseline for focal fat seizures in the refractory population, so one to three ASMs, and you know the drill there on the other criteria, being hovering around like nine to 11, 12 countable seizures on the previous 28 days, right? And I think we're probably a little higher than that, a tiny bit here for power one, which was kind of what we were aiming for, right? We knew these patients are fairly refractory or very confident about the drug. We wanted as well to make sure that once we establish there in 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 patient with focal contact seizures and in the future other types of seizures as well. That brings you to a second part of your question, that is the expectations. And I think that it's always dangerous to talk about expectations and setting bars, artificial bars, this late in the game in terms of like literally like weeks, I would say, before a readout. But we've been fairly consistent. on the expectation here for all the years is, number one, as the severities increase, I think this is one of the few areas, and you've got to be very excited about science, that the new drugs still deliver a lot. And we just see that recently with another program who expects to see the same, like here, drug delivery despite being piling up on a lot of other drugs for all the years in a higher baseline, so more severity. And we've historically been giving that kind of baseline, not baseline, sorry, 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, right, as you mentioned. And we're very confident about the safety profile of this drug, both what we've seen in the blinded based on power one, but also what we are seeing on a blinded based on power two. That was the very last topic you mentioned. So fairly comprehensively, I think we're excited about the upcoming redoubts and other cards to flip, another program to hopefully accelerates to bring to patients, and power two 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, to think about a potential third or fourth drug or potential third submission of an NGA or four official accounts for this NGA 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.

Yeah, no, no, no. Like, there's Nick there and one there, huh? Like, I think, again, we should unblind it. I do feel the number one thing is really to make sure we have very solid reduction. But, of course, we want to see seizure-freedom here as well. It's important. It's something we saw on the RADIANCE data, right, that when you treat patients longer, Like by week 10, 12, their median seizure gets to 100% of the reduction. So, of course, we want to see the more we treat them, the longer we treat patients, a very deepening of effect. That's what we're seeing. And I'll leave it like that, but we're excited with the overall profile.

Thank you.

Of course.

Thank you. Our next question or comment comes from the line of Tiago Faust from Raymond James. Your line is now open.

Great. Thanks so much for taking the question. I had just one quick one on Elixir. It's also related to the communication plan to the street on the regulatory interactions. It's 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 discussion, CMC inspection scheduling, or anything related to that? Thank you.

Thanks. Thanks, Tiago. So maybe, again, I'll take another step back here as well, right? So we are, of course, being communicated by the FTA when the expected mid-cycle meetings are going to happen for both programs, their communication pattern with us, when label negotiation is going to expect it to be started and completed, the entire cycle. So we have very good visibility from the agency's goals and from the conversations with us in relation to that. Although I can tell you that throughout this process, I think a very good shift I would say on the FTA is just their 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 gonna be cautiously optimistic here, about 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 Or in our end, is that they're going to be like no major concerns, like keep reviewing, keep like finalizing, crossing the T's and dotting the I's. And if that's the case, I think we should expect very little from us. Of course, if something meaningful happens on those meetings, either on the view of like maybe they want to say something or the opposites, they are moving faster and maybe they 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 applications to be able to have a discussion. I know you asked, Alexa, but I want to make sure our equally loved child gets some attention here with religion.

Fair enough, fair enough. Thank you so much.

Of course.

Thank you. Our next question or comment comes from the line of Francois Brisebois from LifeSite Capital. Your line is open.

Hey, thanks for the question, and congrats on the emerald recruitment there. I was just wondering maybe if you can help us understand. Obviously, the patient population size is quite different between 2A and 8A and then going to broad, but I was just wondering on the broad side, how different are these patients? And my question is geared towards expectations. Is it you know, that the 2A and 8A are so severe that if we look at that data, that kind of sets these, you know, artificial bars or whatnot on expectations for the broad DEs, or is that a dangerous game based on maybe the heterogeneity of the patient? Just a little more understanding on who are you going after with these broad DEs.

Yeah, and I'll take something. I'll split that question in two parts, right? So one, it is kind of insane to think this way, but it is the reality of the markets, right? When you go to these patients and to the physicians and we understand their clinical course and just how the diseases are downward slope, it only gets worse over time for those patients, unfortunately, leading to all sorts of complications and so that and so on. It is very clear that A, improvements, any improvements would be the bar. meaning stat sig is the bar for this, for the enrolled study, right? 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 bars. And as I said, in relation to the previous study with power one on Richard's question. So here we are in a situation that is a very large market, but that is nothing. It's kind of the end of the line, right? If you think about the these patients and for all the times we expect to give them a lot, but I think for this study, we need to be happy if we see statistical significance as we expect to and some improvements. Now, to go to the other side of the questions like how heterogeneous is this population, our recruitment strategy was very clear. We want these patients to be diagnosed with DEs, so that's very serious, has to be early, has to have a developmental impact together with seizure onset and a number of countable seizures at baseline. Having said that, we want 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 2A and 8A are harder two treats, but this is more heterogeneous two treats. So if you can see like even half, I would say what we're seeing on in bold would be just, it's even hard to imagine how big of a market that would be, but if we see just stabilization and improvements on these patients, that would be incredibly meaningful. So on setting it up, what is meant to be a really major opportunity for all of us.

Maybe if I could sneak in. On AAN, obviously, I think the plan area was packed, like about 8,000 people attending. And so, can you just talk about your interactions with neurologists and movement disorder specialists? Does that trigger any interest for XUS? Can you share what you guys are thinking on the XUS stage for ulexacaltamide?

Yeah, thanks for reminding us of things that I think we get so excited and so wanting to move forward as always that sometimes don't stop, slow down and smell the roses. Yeah, being on that plenary at AEN in Chicago a couple weeks back and with like about 8,000 physicians attending, being the first one recognizes the most important clinical study presented at the meeting. It was very emotional for some of us, for me, certainly. But the cool part, the most cool part, was actually the number of people who came afterwards to us and wanting us to go to their practice with our medical affairs team and present to the entire practice and for them to start thinking and so on. So it just reinforced the part. Now, there is a huge interest on XUS, as you can imagine. We believe... To be very clear, this is first and foremost a U.S. opportunity right now. We're putting our heads down and we're executing in the U.S. There are multiple implications of current policies in the United States, particularly pricing policies that I would say don't excite us too much on explore split strategies for 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. And of course, we're planning to eventually get there. But we're not really too excited about splitting the geographies with anyone else.

Thank you. Thank you. Our next question or comment comes from the line of Yatin Suneha from Guggenheim. Your line is now open.

Hey, guys. Can you hear me? Yep. Yep. Perfect. Hey, guys, congrats. Very nice update. Maybe two questions for me. Marcia, you addressed the expectations for Power 1, so the follow-up question I have there is that at least in Power 1, we're going to get data on the 30-milligram QD dose. Could you maybe talk about the potential to capture additional efficacy with the 40 milligram in power too? Just love to hear from you. How should we think about the 30 and the 40s if there is any potential there? And then, you know, a broader question on the commercial side. I mean, obviously you are undertaking two big launches in the next, let's say, six months or so. Could you talk about the manufacturing, supply chain, all of that stuff? Where do you stand there? Thank you so much.

No, of course, Yaten. Maybe even starting with that, right? So we imagine when we're planning these launches, we're like, okay, what is likely to happen? And that's how we set our base and how we set the financial expectations and you see in our forward-looking statements and overall what you're saying there. And then we go and we talk to the market and we're like, starts to be maybe a little conservative on some of those. And what if we're wrong on the upper side of that? And then what if you're wrong by several faults on the upper side of that? And that's how we have to plan supply in our view. And that's what we've been doing. We're blessed to, for Elixir, for example, to have dual, like two completely dependent drug substance manufacturers They are being rock and rolling drug for us to have inventory. We're talking about metric tons of drugs here. Alexa, just to give you an idea of scale, this is not like a small scale in general. It's like a very large scale. And we're also quite happy with the fact that the process is relatively, I'm going to say in the grand scheme of things, simple. and we've been able to align that with the FTA before the submission. So we're good there. Relateragene, of course, the scale is smaller for 2N8A, but it's not small for GEs. So we're thinking about that as well, and we prepare for that for the launch, too. Very different distribution strategies, as you can imagine. It's like a much more full white glove, like... one-on-one interactions, all the way to the point of use with the Rilutrigine app, and we're building like that. And then on the Ulixa, we want to do a one-to-one as well, but of course there's a little bit less downstream here. So both inventory and management of the patient taking the drug have been quite sorted out. If I go back to our Power One, Power Two interrelatedness question, 20, 30 milligrams per one, I believe we're going to see very, very strong results there. But that begs the question, is that even more to come? So if you look into recent history, very, very recent history, what we're seeing is companies dabbling with the issue of even a little bit more drug and you trip the wire and then the drug becomes completely useless from a clinical practice perspective. We saw that in our results a few weeks back. when there are two dose and the top dose cannot be used at all by patients, just by delivering a little bit more efficacy on paper. But that is not the case here, right? We know that that is not the limitation with vermatrogen. So, when you think about the ultimate need of patients and the 3.5 million, not the 30,000 that maybe others are going after. That is the real market we're going after, and it requires to understand the heterogeneity of all those patients. That's why having the ability to deliver meaningful, either at 20, at 30, at 40, you name it, is so important. So not to create expectations that it could be even better, but of course, by definition, it could be even better there on power two. So we'll get there soon, and we're going to be able to review it. I hope I answered your questions.

Thank you so much.

Thank you. Our next question or comment comes from the line of Kambiz Yazdi from BTIG. Your line is now open.

Morning, team. Thank you so much for the questions. Three for me. On ULIXA, with the Essential to Me Disease Education Campaign launched in April, can you give us a sense for the early response from healthcare providers and how you think this initiative is going to translate into kind of the top of patient funnel heading into the PDUFA. Maybe briefly on relutragine. I know you touched base on MRCO, but how were you able to enroll Emerald so rapidly compared to competitors in the DE space? And lastly, on vermatrogene, you commented a little bit about blinded, power one, power two safety. How are you handling investigators option to reduce dose of background medication in power one relative to the RADIAN study. Thank you so much.

Sounds good. I'll try to tackle all of them so I can move on. So essential to me was something we developed with patients and the way they see themselves and I think once the reaction from the providers are being fantastic, like people really love it, they see their patients, it reminds them to act, and so we're very happy with this. It will, and it's already doing it, like a great job on building further our database pre-launch to understand really who would be kind of the first in line here, both on the providers and on the patient. I'm going to give more of an update that next quarter as well. How did you enroll Emerald, right? I would say to go back in time and people would ask and maybe I'm going to be criticized by this comment, but I'm going to give it a try. Who asked Jordan how he could be Jordan, right? He would go back to the court and would train and would understand the shots that worked and the ones that didn't. And it wouldn't take any win as a win. But it's an opportunity to, the next one, to work. And I think we're never going to be as good as Jordan was, but I think we're pretty serious about every single day asking ourselves how can we do better because these patients need us. And we're pretty good as well on actually getting sites that have a large number of patients and therefore have the ability to enroll and they understand us from the beginning. meaning they understand that our expectations is highest quality, first and foremost, but also high speeds in terms of you don't sit on queries or don't sit on eligibility form. You don't sit on a meeting that's going to happen next week. You need us, we're there immediately. And I think our team is just, if I were to say fantastic, they would be out fantastic on doing all of this. because everyone is here for one single reason is to help this patient. So that's as simple as that. And I think there was a last question that I actually forgot now.

Yes, just briefly. You, on vermatrogen, you talked a little bit about blinded power one, power two. Got it. Tolerability. How are you handling the investigator option to reduce dose and background? in Power One relative to what was observed in Radiance. Thank you so much.

Yeah, absolutely. So what we learned from Radiance, right, we got like a both pragmatic and programmatic reduction system in Power One. One must be very confident on what the investigational drug does to allow for the background to be reduced. Others reduce the investigational drug, as you know, because they don't trust the drug so much. not our case. So we allowed that to happen. I'll tell you, it happens partially, which is obviously very important, but I think was very effective as well. It's the same algorithm for Power 2. I think physicians are very happy with how it's done. It's very safely done, also very logical the way it's done, and it considers the fact that the background sometimes on placebo creates, like, as well, which is required. So, keeps the blinds, keeps the integrity, but at the same time, manage the study in general. So, super happy with that as well.

Thank you so much.

You bet.

Thank you. Our next question or comment comes from the line of Ami Fadia from Needham & Company. Your line is now open.

Hi. This is Purnah on for Ami. Thank you for taking our question. For focal onset epilepsy, are there any first-to-market dynamics you see if Phenon's product is first-to-market? Our KOL checks have been overwhelmingly positive for vomatogene, but just wanted to understand if there are any other factors that may have an impact here. And also, have you had any early discussions with payers on what data you may need to generate to support early-aligned use? Thank you.

Yeah, so I think when you look into the overall market, right, and we did a lot of work on this, It's very sad in a sense that when you go outside of the very small number of patients that are treated at level four epilepsy centers, and you go to a much larger market outside of that, these patients are failing at very high proportions. They are switching medications, like they're adding on top of that, and so on. So I said this before, I don't believe that it's possible one winner game here that if we had 10 other drugs in focus at seizures uh that would be needed right what we have right now is completely inadequate having said that uh the biggest complication for all the years is when you get like a drug and and you really can't like allow the physician to have flexibility to tailored for their patients needs and i think what we've seen with formatrogen is that it gives a lot of flexibility in terms of what can be done, as we just discussed on the previous question, for example. And it's not the case for other potential competitors here. But also pretty confident about our overall pace, right? Like being a few months behind, remind all of you, we were way more than several months behind the other DE study not that long ago. We're reading out soon when the other studies not even reading out until late next year. So I'm not sure if a few months is really a first mover advantage. And I don't believe there was ever a mechanistic sodium channel modulator removed from the markets, but there certainly was for the other mechanism that you mentioned. And all the safe signals are showing up there as well. So I think the physicians we talked to are happy on having more options, but cautious about things that they've seen before not happening too well or working so well for patients on the safety side. So we'll play that. We'll play full-court press on the markets, and I have no doubt we're going to win.

Got it. That makes a lot of sense. Thank you.

Thank you. Our next question or comment comes from the line of Andrew Tsai from Jefferies. Mr. Tsai, your line is now open.

Hi, good morning. Appreciate all the updates. I know we've talked a lot about Emerald Study. I did have one small pointed question about it. When you guys shared the 2AAA data, 53% placebo-adjusted reduction overall, I'm curious if you saw a consistent seizure reduction in both or each of the two DEE subgroups. Maybe that can give investors confidence. You'll see robust and consistent efficacy across broader DEE subgroups. So would it be possible to share the seizure reduction in both subgroups? And then for ET, appreciate all the AN analyses and so forth. And maybe 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 Ulexa responders could be on the drug for? Thank you.

Thanks, Andrew. Maybe I'll start with ET, and then we can move back to 2AMH, Aon and Bolts, and in general. So when you ask physicians, right, and we had a number of advisor boards, and this insanely large overall observational study, we asked them on how they would manage and what the expectation is. And I think the positive surprise for us was just like how comfortable they were on managing what we know to be a tolerability concern that happens on the first few days and first few weeks of this drug. We're going into this launch fully aware of that being the single most important driver of retention of patients in the long run. And they're incredibly comfortable and we're actually telling them the things that we thought they could do in terms of like calling these patients and then advising them better and so on and so forth. So, very comfortable with that. Now, how does that translate to overall retention over time and financials? There are two approaches here that we can take. One is saying what are the things we're thinking about? And that is your classical oral chronic therapy compliance and retention. So starts anywhere there on the 60s to 80%, right? That just overall numbers all there. And then what is the minimum to sustain the forecasts we put in front of you all to be over $10 billion? That number is way smaller. So I'm not saying the number will be smaller, I'm saying we're going to have to believe on something to go into a forecast, and we don't need to believe a lot to go to 10 billion plus. And that gives us insane comfort. We also have hundreds, hundreds of patients in the SAFET database, as you know, that have been on this drug for six months, one year, two years. So that gives us a very good indicator on how persistent all these patients are. On the second question, it's very actually appropriate to be asked right now, the results on 2A and 8A, despite the fact that the manifestations in the elastophysiology and the overall clinical manifestation of NAV1.2 deregulations and NAV1.6 deregulations are very different. The results are quite similar and very good in terms of the overall reduction, developmental gains, and seizure freedom. So it gives us the same comforts that it is so similar across to ANFA as well. Very good points. Thanks for reminding us to make the highlights.

Thank you, as always.

Of course. Thank you. Our next question or comment comes from the line of David Hong from Deutsche Bank. Mr. Hong, your line is open.

Great. Thanks for taking my questions. So I just had a couple here. Maybe back to vermatrogen in focal epilepsy across Power 1 and Power 2. I know you're looking at three doses, 20, 30, 40 mg. 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 Power 3 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 vermatrogen and why aren't other sponsors pursuing monotherapy studies like that? Thanks a lot.

Thanks. Thanks so much for the question, Dave. So 20-30-40, when you started at 20 for a part one, and the thought is like normally people start, if you go to the public documents for like other sponsors, for example, everyone's going to be like, how close to the MES CC50 can I get when you translate that to humans? And I'm going to be pretty close to that because I can all go much higher. We can go much higher here. So we're like, where do we start that the drug's going to be clearly effective, right? So that's where we start to that. And where do we end for now when we believe that's kind of the maximum efficacy? And I think that's the bookends that you're seeing. But a pretty big feedback from the thousands of neurologists that treats these patients is, Flexibility is important for them as they're going through different patient types and different comorbid conditions. So we intend to bring all of those to the market because we believe that gives the highest flexibility to physicians and our largest ability to obtain and keep market share. Power 3 is a different animal. Power 3 requires... the profile for metrogen. So the answer to your question why others are not doing it is because they cannot, right? Because you would be able to, you need to be able to use the drug as monotherapy. Now, there's steps towards monotherapy, right? It's not an immediate reduction to monotherapy. It has to be done pretty safely, pretty thoughtfully. But that patients fail because they can't be on one mechanism. mechanism that can, if tolerated, as we believe here, hormatogen can truly stop any seizures is by acting on the IS and by modulating these channels. And we're the only ones that do that right now. Like everything else is upstream of that mechanism. So that's why the confidence when you have a drug like hormatogen, as I said in my prepared remarks, this is the most potent and most selective ever developed. So we have this data publicly available for anyone to scrutinize. So that is the confidence there. What it does is to move from what has been a little bit of the definition of insanity on how these drugs are developed to get more and more severe patients, smaller pools of patients, and they no longer represent the broader markets on those refractory studies. And you're never really addressing the true markets, the true amenities that are those patients who are struggling to go back to work. struggling to stay driving, struggling to have concentration. Significant number of patients with epilepsy go into disability state costs themselves and the healthcare system and the social security system. Insane amount of resource because the drugs they were put in are compounding the issue with the condition. And I think we have an obligation as a company with such a potent, such an interesting drug to go there and change and revolutionize, as we say, the treatments of epilepsy. That is the long answer to the question.

Thanks a lot.

You bet.

Thank you. Our next question or comment comes from the line of J. Olson. I'm sorry, Olson J. from Opco. Your line is now open.

Oh, hi. Thanks for taking the question and congrats on all the progress. This is Chen on the line for Jay. Maybe a couple from us. First, on the OLIX commercialization, just to start with the feedback from AAN and market research you conducted, kind of what do you view as the most important driver of adoption? And then I think at AAN you also presented some data so then channel model later in pain. So I'm just also curious about related thinking around this opportunity and if there's anything we should expect in the near term. Thank you. Yeah, yeah, of course.

Thanks, Shane. So the most important thing for physicians, right, when you rank, and as I mentioned before, and I appreciate you bringing up the question, was very extensive testing and really understanding the details from them. And there are a number of things they really like. They really like the fact that they never had something targeted for essential tremors, so having something that's the most fundamental mechanism is T-type calcium modulation, and now they have something for that, or soon they're going to have something for that. The second was actually a little bit surprising to all of us. They absolutely love the fact that in two weeks, for the majority of the patients, you have the ability to have a conversation with the patients, and they really have an effective They just don't have that right now in a sustainable manner. They like the fact that we tested the durability of effects on study two. And I would say all those things together, there are many others, really are going to be key drivers of adoption. And as I mentioned in one of the previous call about like inventory and building, if anything, they're giving us indications they're going to prescribe to way more patients than were originally thought there. And then the second part of your question about our paying program, well, I think we've been, as you can imagine, right, we're a CNS company. We need to look into areas of science that make sense for us based on our technology. On one end, on another end, we do have a fair bit of things that are moving forward, as we discussed today, many more catalysts to come. So we've been taking a measured approach in terms of exploring a number of other areas in science that our molecules and our platforms can play a significant role. And at AAN, we did present some of the work we've been doing in pain. And you will hear more from us in the future about how we are advancing quite significantly on that regard as well.

Got it. Thank you so much. You bet.

Thank you. Our next question or comment comes from the line of Douglas Sal from HC Wainwright. Your line is now open.

Hi, good morning. Thanks for taking the question. Hello, can you hear me? Yes, we can, Donald. Sorry about that. You know, Marcio, just starting with Emerald, I'm just curious, congrats on completion of enrollment. Obviously, demand was very strong. I'm just curious if you have insight in terms of the subsets of patients that you received, and were there any particular Ds where you saw very strong demand to reflect sort of the magnitude of unmet need, because obviously for so many of these, there's no approved therapy, and physicians are just basically trying to figure it out as they go along using sort of off-label ASMs.

Yeah. So I'm going to be honest. Like, when we went to the sites and we talked to physicians who presented the protocol, maybe what I haven't said in the call so far is, We disappointed a lot of physicians by telling them, no, no, no, you've got to stop. You can't enroll more patients on this study. They really got there pretty fast because exactly, and it seems like you have a deep understanding of this, exactly what you just said. There is so many patients out there that there is very little or nothing they can do, even patients who have other drugs technically approved, but they failed already. or they try to have some optimal response. So it is very broad, both phenotype and genotype of patients we got here, and it is within what we expected. And unfortunately, maybe this is a mea culpa, an apology, we couldn't get all the patients that wanted to be on the study, but I think our promise is if the drug works, we're going to get the drug to them in the near future. really, really happy on everything and all the dynamics here.

Okay, great. And if I can, on a follow-up in terms for vormatrogene, just with power one, I'm just curious, do you have any insight in terms of the discontinuation rate so far? Because obviously, I think in radiant, there were some discontinuations, but we certainly heard from clinicians that, you know, they sort of had patients who may be dropped out, who if they would have provided some additional counseling, just given the robustness ultimately of the drug, it would maybe sort of encourage them to stay in as long, additionally, given the fact that you sort of titrate up in power one, you know, if we're seeing any evidence that that is having an effect. Thank you. Yeah, absolutely.

So, uh, or, Pretty happy with how it got reduced, I would say, the overall discontinuation here in terms of the historical with the program. I think some of the points you mentioned, right, people get more experience with the studies and so on. They get more comfortable managing. So, I'll say, I think we're very comfortable with that. I think we're very comfortable with the new benchmark as well. When you consider like drugs, people are excited about have like 22 to 25% discontinuation. with further 25% dose reduction on the top dose, that's definitely not what we are seeing. So we think we are very, very competitive here, considering recent competitive events.

Okay, great. Thank you so much. Of course. Thank you. Our next question or comment comes from the line of Danielle Brill from Truist Securities. Your line is now open.

Hi, Tyler here for Danielle. Thanks so much for taking our questions. My question is regarding the total addressable market in essential tremor. So up to 7 million patients have essential tremor, but you've recently said that there are approximately 1 million actively seeking treatment. So what's this gap between the predicted prevalent population and the seeking treatment? And with that, is education still needed in the field for more accurate diagnosis? And do higher volume academic centers typically have that more accurate diagnosis?

Yeah. So there's about like two to two and a half million patients right now either who are being like treated and seeing a physician at this moment or just done it and are sitting on the side. So when you go from seven to let's say two to three, it is a drop. It is not unheard of. I'll say there are many, many reasons here. It is not a misdiagnosed problem. And I want to clarify that as well. This is mostly like something they know, and they're either not speaking publicly or disclosing or discussing because they know there's a stigma, there's a fact. I think we just saw this week Senator Collins speaking about her diagnosis of essential tremor in defense of people attacking that she might copy fits, which obviously is absurd, right, because this is a progressive disease only of movements. For example, but people are afraid of talking about things like that. It is a disease that for the most part runs in the family, so people are aware. It is a combination of two factors. One is the progress, so it's how quickly and how far the disease patients are. We call that the level of disability, and that's what gives us about three million. And the other is society sometimes not being too ready for someone to raise their hands and say they have a condition. And I think the last one is when you have two or three family members and a physician tells the first one, there's nothing I can do right now because there's no good alternatives available, you disengage the other family members. With Ulexa Caldmite coming to the market hopefully soon, all those dynamics change, right? So we bring this to the forefront. One of the reasons why our campaign is called Essential to Me Because it's really what is essential for that, for the patients. That's what we want to awaken on that.

Thanks so much.

Of course. Thank you. Our next question or comment comes from the line of Brian Scorny from Baird. Your line is now open.

Hey, good morning, team. Thanks for fitting me in here. You've alluded to the opportunity to develop Ulexa and the role of T-type calcium channel antagonists and indications beyond ET. Obviously, you're pretty full with two NDA reviews and running another few capital studies, so maybe it's a little bit on the back burner, but just wondering if you have any updated thoughts on the exploration of other indications where Ulexa could have an impact and if there's any timeframe you can provide where we might hear an update on that.

Yes, Brian, we did select two other indications we're going to be going through. We're just going through the last, I'll say, checking everything here, ticking and tying, and making sure that we can discuss a little bit more publicly. We're discussing the format of that as well, if it's an R&D day or if it's maybe a series of calls and experts with us. So sit tight just for a bit, and you're going to be able to talk about that. We are very excited, both scientifically, patient side, and market potential for either of those indications.

Great. Thanks for the update.

Thank you. Thank you. I'm afraid that's all the time we have for Q&A at this time. I would like to turn the conference back over to Mr. Mauricio Souza for any closing remarks.

So thank you very much, everyone. I'm sorry for the questions we couldn't take on today's call. I think we're running a little bit ahead here. Like, incredibly exciting way to start the year, right? As you think back on the last 12 months, so much happened in really moving the needle for so many patients. Yes, another study, they were finalizing, making sure that we flip the card, make sure that If there is a benefit, we're going to get that as quickly as possible. This year already, with Embrave Part A being positive, Embrave 3 recruiting really well, Emerald coming up, Power 1 coming up, Power 2 coming up, new indications, as Brian just asked. So we're fully steam ahead. The focus is very clear. It should deliver as much value for everyone, including our shareholders. And we promise you we'll have our heads down on the execution here and getting everything done. Thanks for the interest, and we're going to be talking 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. Speakers, stand by.