Praxis Precision Medicines Fourth Quarter and Full Year 2025 Earnings Call - Two NDAs Filed, Poised to Transition to a Commercial Company

Conference Operator: Good day, and thank you for standing by. Welcome to the Praxis Precision Medicines fourth quarter and full year 2025 earnings 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 during the session, you will need to press star one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today’s conference is being recorded. I would now like to hand the conference over to your speaker today, Dan Ferry, Investor Relations. Please go ahead.

Dan Ferry, Investor Relations, Praxis Precision Medicines: Good morning, and welcome to the Praxis Precision Medicines fourth quarter and full year 2025 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 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 us on today’s call are Marcio Souza, President and Chief Executive Officer of Praxis, and Tim Kelly, our Chief Financial Officer. After updates on our key programs, we’ll move to a brief Q&A session where Marcio and Tim will be joined by Steven 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.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Thank you, Dan. Good morning, and thank you for joining the Praxis fourth quarter 2025 conference call. Let me start by saying that 2025 was a remarkable year for Praxis. It was marked with the breadth of significant clinical achievements and regulatory events across our portfolio, with positive readouts and interactions for ulixacaltamide, relutrigine, and vormatrigine, as well as accelerated development plan for elsunersen. Standing here today, we deliver on our goal to submit 2 NDAs, one for ulixacaltamide in essential tremor and one for relutrigine in SCN2A and 8A DEEs. Just like 2025, this year will continue to enhance our clinical portfolio and mark our transformation into a commercial company. Next quarter, we expect to have the top-line results for POWER1 for vormatrigine in focal epilepsy and the elsunersen in EMBRAVE data.

In the second half of the year, we expect to complete enrollment for POWER2. The EMERALD trial for relutrigine in broad disease is expected to serve as the base of an sNDA by next year, and those are only a fraction of the deliverables expected in the next 12 months. We have the drugs, the people, and the capital to deliver yet another transformational year, bringing innovative treatment to patients with CNS disorders. Let me now deep dive a little bit on each one of the clinical programs. Now, focusing on ulixacaltamide. Last October, we reported the positive top-line results from the Essential3 program, with both studies delivering clinically meaningful and statistically significant results. Study 1 met its primary and all key secondary endpoints, with ulixa showing meaningful improvements in the MADRS-11, in the rate of disease progress, PGI and CGI.

Study 2 also met its pre-specified primary endpoint, with ulixacaltamide demonstrating a superior maintenance of effects during the randomized withdrawal phase. This was the first time an investigational therapy designed specifically for patients with ET showed positive results in a comprehensive clinical program. Based on this positive data and the fact that there is no other specific therapy delivering such results as ulixacaltamide, we were granted breakthrough designation by the FDA in December. Had a very productive pre-NDA meeting also in December with the FDA and worked diligently to prepare the NDA submission. We have recently completed the NDA submission to the FDA. Now, as we move towards expecting an approval in the near future, our preparations for the commercial launch for ulixacaltamide are well underway.

We estimate that more than 7 million people in the United States live with essential tremor, with about 2 million of them being an immediate needs for therapy or an addressable population, as we call. We’re excited about the opportunity to deliver a therapy that can meaningfully improve their daily lives. As we interact with more neurologists in this space, we continue to hear this is a drug that meets a large unmet need in their practice, and their interest continues to improve towards the potential use of ulixacaltamide when available in the future. We believe ulixacaltamide has a peak potential of over $10 billion annually.

Given the size of the population, the strength of the clinical data, the opportunity for a responsible price, and they recognize the value of the drug, we have been building our commercial organization infrastructure, including key hires and core aspects of the pre-launch plan, including preparing a comprehensive medical education campaign, which we plan to launch at the upcoming American Academy of Neurology annual meeting in April. At AN, we also share additional data from the Essential3 studies in multiple presentations. We look forward to interacting with our core audience in Chicago next quarter and share the exciting data from the Essential3 program. Moving on to our epilepsy programs. We start this discussion with our relutrigine program in developmental and epileptic encephalopathies, a group of severe epilepsies characterized by developmental delays with early onset, for which there are limited to no currently approved treatments.

In December, at the annual meeting of the American Epilepsy Society, we presented data from the EMBOLD study in SCN2A and SCN8A DEEs. We delivered overwhelming efficacy, with relutrigine treatments leading to a clinically meaningful and a statistically significant change in seizure and associated developmental endpoints, like disruptive behavior, alertness, and communication. Beyond the impressive overall results, the effect of relutrigine was rapid, durable, and continued to deepen with time. Given the strong efficacy results and the favorable safety profile underscoring relutrigine best-in-class potential, in alignment with the FDA, we have submitted the NDA earlier this year. It’s worth mentioning that relutrigine has Rare Pediatric Disease Designation, making it eligible for the Pediatric Review Voucher program upon approval. The initial addressable population for relutrigine for SCN2A and SCN8A DEE is roughly 10,000 patients in the US.

However, there are currently over 200,000 patients with DEE, for which we believe relutrigine could offer benefits. The ongoing EMERALD study is assessing relutrigine in the broader DEE population, and we’re on track to complete enrollments in this study this year. If the NDA in SCN2A and SCN8A we just submitted is approved and the EMERALD study is positive, we expect to submit a supplemental NDA for the treatment of broad DEEs by 2027. We believe the full potential of relutrigine in DEE space could be as large as $5 billion in annual revenue. Similarly to the efforts for ulixacaltamide in essential tremor, we have initiated pre-launch activities, including key hires and building sufficient inventory for a successful expected launch for relutrigine. Our team has been accelerating the efforts to ensure patients have access to this potential first disease-modifying treatment for SCN2A and SCN8A.

Moving on to vormatrigine. Our comprehensive energy program for vormatrigine, a next-generation, functionally selective small molecule in development as a once-daily treatment for adults with common epilepsies. At the December AES meeting, we shared the full data from our RADIANT phase 2 study, where vormatrigine demonstrated its best-in-disease potential in patients with focal onset seizures. Vormatrigine had fast-acting efficacy, with 58% of patients achieving at least 50% reduction in seizures at week 1, without the need for titration. This effect continues to increase, with patients who proceed to the early, were achieving 100% median weekly seizure reduction at week 9, which was sustained through week 16. Additionally, we saw that vormatrigine improved efficacy on top of other common anti-seizure medications patients were taking. We are on track for multiple readouts from the pivotal studies for vormatrigine in the next 12-18 months.

The next clinical update will be for POWER1, our study in focal onset seizures, which exceeded its original enrollment targets. We expect to share the top-line results in the second quarter of this year. The second phase 3 study, POWER2, has been enrolling patients and we anticipate enrollments to be completed by the end of the year. Those two studies, if successful, will serve as the base of a new drug application for vormatrigine. We’re also on track to initiate the POWER3 study, which will evaluate vormatrigine as a monotherapy in the first half of this year as well. Altogether, this is a very robust registrational program that we believe will demonstrate vormatrigine’s potential to address the significant unmet needs of approximately 3 million people in the United States suffering from common epilepsies, potential to achieve over $4 billion in annual revenue.

Turning to our fourth program in the clinic, elsunersen. Elsunsen is being developed for the treatment of gain-of-function SCN2A DEEs, a rare genetic epilepsy characterized by early onset seizures and very detrimental developmental impacts. This past September, we had a favorable meeting with the FDA, where the agency agreed to update the EMBRAVE3 registrational trial design, simplifying it by converting from the double-blind sham control design to a single-arm, baseline-controlled study, where approximately 30 patients will be enrolled. We are quickly enrolling this study and expect it to be completed later this year, with a potential NDA for elsunersen next year. While EMBRAVE3 is enrolling, we have some additional data from the EMBRAVE study, Part A, our phase 1/2 study evaluating the safety and efficacy of elsunersen versus sham procedure.

The trial is ongoing, and we’re on track to report the top-line results from the original 9 patients in the first half of this year. Elsunersen also has rare pediatric drug designation, and we qualify for a pediatric review voucher upon approval. Once approved, we believe elsunersen has the potential for over $1 billion in annual revenue. In summary, 2025 was a year of major portfolio advancements as we enter our pre-commercial phase. We started 2026 strong with 2 NDA submissions, and we are positioned for another catalyst-rich year with multiple readouts of our innovative pipeline. We are planning an R&D day next quarter to discuss our clinical programs and preclinical programs, and a commercial day to follow, where we’ll highlight our launch strategy, readiness, and more aspects of the launch for ulixacaltamide and relutrigine.

With a very strong balance sheet, we’re well capitalized and focused on discipline of execution to deliver on the preclinical, clinical, and pre-commercial activities this year to come, while unlocking the more than $20 billion opportunities across our comprehensive CNS portfolio. With that, I’ll hand over our call to our CFO, Tim Kelly. Tim?

Tim Kelly, Chief Financial Officer, Praxis Precision Medicines: Thanks, Marcio. Good morning, everybody, and thank you for joining today’s call. I’ll provide a quick summary of our fourth quarter and full year financial results. 2025 was a year of continued investment into the pipeline while maintaining rigorous financial stewardship. In Q4, operating expenses totaled $97 million, broken down to $77.5 million for R&D and $19.5 million for G&A. That compares to Q4 of 2024, where total operating expenses were $71.4 million, broken down to $56.3 million for R&D and $15.1 million for G&A. For the full year, operating expenses totaled $326 million for 2025, compared to $209 million for 2024.

The increases in both Q4 and full year were driven by an increased spend in our Cerebrum and Solidus platforms to progress the portfolio of clinical programs. As we go into 2026, we expect to have a significant increase in spend as we invest into our commercial launch activities that Marcio just discussed, as well as continuing to progress the pipeline. We ended Q4 with $926 million in cash, equivalents, and marketable securities, compared to $469 million as of December 31, 2024. This increase to $457 million was primarily due to net proceeds from Praxis October 2025 follow-on public offering, and net proceeds from the at-the-market sales of common stock, offset by cash used in operations.

Our cash position was further strengthened through proceeds from a public offering in January this year, which yielded $621 million. When added to our year-end position, our pro forma cash is approximately $1.5 billion, which is expected to fund operations into 2028. With that, I will pass it back over to you, Marcio.

Unidentified Speaker, Praxis Precision Medicines: Thank you, Tim. Going to now open the call for Q&A. Shannon, would you compile the queue, please?

Conference Operator: Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Yasmin Rahimi with Piper Sandler. Your line is now open.

Yasmin Rahimi, Analyst, Piper Sandler: Good morning, team. Congrats to the outstanding timing of the filing. So congrats. Two questions, one directed to Tim and one for Marcio. Tim, if you could maybe walk us through the pre-commercial activities that are going on currently and what the cadence are going to be throughout 2026, that’s very helpful. And then for Marcio, maybe help us understand sort of what additional new data we could, we could be seeing at AAN, and I’ll jump back onto the queue for respect to my colleagues to ask questions.

Tim Kelly, Chief Financial Officer, Praxis Precision Medicines: Yeah. Thanks very much, Yas. I’m glad to be talking about what we’re doing to prepare for two launches. As you can imagine, we’re at the stage now where we’re making some key hires and looking to build out the talent for our commercial organization. We’ve also been focusing on ensuring that we have sufficient inventory for what we expect will be, you know, good, strong launches, and we never want to run out. Be sure that we’ve got inventory on hand for all scenarios. That’s a long lead time activity, so very well at hand to ensure that that’s in good shape. And then also looking at for, particularly for ulixacaltamide, helping to improve awareness of the disease. And Marcio, in a moment, will talk about our activities at AAN and all the data we’re sharing there.

We’re also looking at that at a time when we can start sharing more about the disease and help patients understand about the innovative therapies we’re developing.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah, no, thanks, Tim. That’s, yeah, there’s a lot going on, as you mentioned, right? In terms of making sure that not only the highest quality and NDAs were submitted, as of course, was always our priority, but now moving on to making sure it’s a smooth review with the agency. On the other side of that, the prescribers really understand or potential prescribers really understand the disease in one hand, which they understand well, but there’s obviously a good reminder there. On the other hand, the clinical data for ulixacaltamide, and then relutrigine later in the year as well. In regards to the American Academy of Neurology meeting next quarter, we have about 15 different presentations going on at the meeting.

It just speaks about the number of things across the company. A number of them are about the Essential3 program and essential tremor in general. What we’re gonna be doing there, as you will see, and I hope to see you there, in Chicago, is oral presentations on the clinical data. And actually, it’s very nice for that because the presentations are reasonably long, so we can go into a fair bit of detail, on the clinical program, which, of course, very important for the 13,000 or so neurologists that are our audience. They’re gonna be there also to expand the understanding of the overall community of this very strong clinical data sets.

So we’re gonna be discussing, like, other aspects, like the response on the drug and what happens to these patients, and just how meaningful it is, the combination of all the endpoints, but particularly the primary measure here, that’s the MADRS-11. And you’re gonna see throughout all the presentations, there are very robust number of new data points. We put a lot out there. So it’s not to say that there is any scarcity of data on the Essential3 program, but it’s definitely more geared towards the future prescriber here, the neurologist. Incredibly excited, very grateful to the scientific committee of the AAN for giving us the podium there to present the strong clinical data.

Conference Operator: Thank you. Our next question comes from the line of Ritu Baral with TD Cowen. Your line is now open.

Athena Chin, Analyst, TD Cowen: Hi, guys. This is Athena Chin on for Ritu. Thanks for taking the question. I have another one on Relyxa. You previously indicated that the label may include alternative titration schedules. What is the status on this? And, are you currently running additional studies to support this? If the label doesn’t include these schedules, how will you be educating and guiding prescribers upon launch? And then I have another follow-up.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah. Thanks, Athena. So maybe I’ll break it down, if I may, your questions in two parts, right? So we’ve been discussing, since you asked about education, and surprisingly, I would say there’s very little education needed here. We’ve been presenting the data for advisor boards, for consultation meetings, to a number of key opinion leaders in the country, very top key opinion leaders. And it is very clear that they see this is incredibly robust and very, very easy to deal with the potential tolerability for a subset of patients here that we know might have that. Now, going back to the matter of the label, as we previously discussed, we propose not only submitted proposed label to the FDA, not only the standards titration that was done in the clinical study, right?

So 7 days, 20 milligrams, 7 days at 40, and then 7 days at a stable dose of 60, but also an alternative that we discussed with the FDA. I think as we move forward, as you continue to engage with the Agency here, that it’s now their view has to prevail in terms of what the final label is gonna be. So it would be pretentious of us to say what’s gonna happen there. But it came on the heels of discussions with them and alignment. The Agency was incredibly clear with us that they did not expect us to conduct clinical studies pre-approval in this regard. So as we always respect the opinion of the FDA and the guidance they give, of course, we’re not doing.

I believe, and now that’s my interpretation, that is because this is really not a safety issue, right? This, there is some tolerability that happens on a subset of patients. It’s very quick, it resolves very quickly, and the efficacy, most importantly, is very strong. So when you put from a benefit-risk perspective, that is both our interest, the prescriber’s interest, and the agent’s mandates, that is all maintained quite nicely. But we’re gonna see how this, this progress during the review, and we’re very enthusiastic about the ability to have serving not only the 70% or so of patients that stay and do really well, but hopefully, 100% of the patients that try this drug.

Athena Chin, Analyst, TD Cowen: Got it. As to the commercial prep for both Riluzole and Relyxa, how much capital allocation should we be thinking about between the two programs?

Tim Kelly, Chief Financial Officer, Praxis Precision Medicines: You know, I think in terms of allocation, you can imagine that with ulixacaltamide being a much broader market, we will be probably, you know, putting more of the allocation there. I think we’re looking at, as I said, the disease awareness campaign, probably a bigger field for us as we get into that part of the work as well. The inventory build is gonna be a bit bigger. So we want to be sure. I go back to the old line, you only get one chance to launch a drug, and we want to be sure we’re investing appropriately for a great launch. I think with relutrigine, when we look at that market, particularly focused initially on the SCN2A and SCN8A population, it is a bit more focused. So, there’s a lot of disease awareness for us to be doing there.

It’s a more focused effort, though, with those physicians, but we want to be laying the groundwork for the indication expansion that we hope will come in 2027 with the EMERALD study. So it’s a bit of a strategic move in how we will do the commercial prep for relutrigine also.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Got it. Thank you. I’ll hop back in the queue.

Conference Operator: Thank you.

Tim Kelly, Chief Financial Officer, Praxis Precision Medicines: Thank you, Tiana.

Conference Operator: Our next question comes from the line of Yatin Suneja with Guggenheim. Your line is now open.

Yatin Suneja, Analyst, Guggenheim: Hey, guys. Thank you for taking my questions. I have two questions. With regard to the POWER3 study, can you just articulate to us how will that study help you move towards the front line setting or to in FOS? So that’s one. And then the second question is around the review timeline. So we, I think Marcio, it’ll be good if you can address the review timeline for both the NDAs. We do get questions from investors in terms of priority review or not, so we’ll be able to sort of address it today. Thank you.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah. Thanks. Thanks, Yatin. The, so starting with POWER3, right? So just a reminder on what we are trying to accomplish here. So POWER1, as the, like, first study here for-- towards registration for vormatrigine, reading out, as we just narrowed here in Q2. The study enrolled a fair bit more than the original 230 patients that were planned. So we’re very, very happy with how enthusiastic the investigators were on enrolling patients on this study, particularly, like, when you consider comparatively how well this study enrolls, right? POWER2, as we’re enrolling quite nicely right now as well, would be the second registrational. But when you look into the markets, and it, it’s something quite interesting, what this goes on in focal seizures.

You do have, I would say, a part of this market that is the more refractory patients or going to even argue hyper refractory, being super treated, multiple ASMs, really struggling for years and years, possibly decades, here. And that’s where most of drug developments and most of what the level four epilepsy centers, the key opinion leaders in epilepsy have been focusing. But when you go to the rest of the market, and it’s probably the physicians to call rest because it’s the majority of the markets, are the patients that are 70, 80% of the patients with focal seizures. They still can’t strive, they still can’t carry on with their lives. There’s all sorts of restrictions because they’re having, like, breakthrough seizures, from time to time, and they’re really not doing well. That market has stayed untapped until now.

So speaking with those physicians and people who treat significant number of patients, right, which it is a different subset of the ones we’re looking, the needs there is for a drug that they can trust and understand how to remove the treatments, so they can be confident, and they are very enthusiastic about vormatrigine for that matter. So, we’ve been in consultation with them for finalizing this design. We’re getting this off the ground very soon. We thought today was the day to reinforce and celebrate submitting two NDAs, so we’re going to be talking about that more in the near future. But what it does to the drug, while not required for registration, right? This is not a requirement, as is the ever-evolving requirement for registration in the United States, as we are seeing this week. So we’re very excited about what’s to come.

But it is something we can see as moving to first line, potentially, this drug in the future, which is from a serving patients, is what we all should be aiming for. We’re just in a very privileged position that vormatrigine might be the drug that allows patients and physicians to do that. On your second question about the review timelines, you can imagine that the decisions we have to make are multiple folds, right? So one, obviously the timing of the submissions is now in the past. The second is the entire understanding and relationship and workload and and so forth with the agency. Good reminder here that while the NDA or Division of Neurology 1 and 2 are two different divisions, there’s a lot of shared resource.

We’re having two NDAs at the same time with them. Very obviously, raletrogene is easier. I’m going to say not because it’s easier from a clinical or anything like that, it’s just much, much less data, by single study, rare indication, and that by itself, from a workload perspective, is smaller. So we decided to request a priority review for that application, but we decided not to request for ulexakalmide for multiple reasons, right? Those that I just mentioned, but there’s a broader business reason, about the time of the launch and the maximization of the revenues over time for this drug, particularly around pick, particularly around payer and overall dynamics of discounting, and so on, that happens year later in the launch.

So on a drug that can be and will be as big as ulixacaltamide, we can’t pick up the dollars and forget about the millions on this one. So I think we need to be, and we were very focused strategically on the overall value here.

Andrew Sey, Analyst, Jefferies6: Very good. Thank you so much.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Of course.

Conference Operator: Thank you. Our next question comes from the line of Jun Lee with Truist Securities. Your line is now open.

Jun Lee, Analyst, Truist Securities: Hey, guys. Congrats on all the progress, and thanks for taking our questions. Just wanted to clarify the response from the prior question that you just answered. So you mentioned business reasons for not asking for priority review for ulixacaltamide in ET. Just to clarify, is that because asking for standard review as opposed to priority review would result in almost a year delay in being forced to negotiate under IRA? Question number one. Question number two, you know, looking forward to your presentations at AAN, can we expect any long-term follow-up data? The reason I ask is long-term efficacy came up as a key point for payer KOLs regarding reauthorization of Alysa in ET. And the last question is, you know, in the past, you’ve telegraphed around $50,000 list price for ulixacaltamide.

Is that still the case? And can you help us understand your thought process behind the pricing strategy? Thank you.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah. Jun, I think we are—you’re in the right direction there, right? In terms of what we are looking at and we’re forecasting this drug. Of course, there are multiple dynamics, and you just named some of them, right? Like, what payers and reauthorization, and like, potential step edits, and you name it. But, the Inflation Reduction Act and the and the dynamics of the act right now is important consideration as well as a very important consideration. This is a heavily, Medicare, Part D, population, so we want to make sure we’re both responsible on how we’re launching, we’re also maximizing and giving the proper value for the drug, and that includes looking to the life cycle of evolution of the current iteration of the act, when it impacts, when it kicks in. I believe that’s where you’re going there.

That is a pretty big difference in value, depending on when that negotiation happens. And it was a key consideration on our filing strategy. The second, on the data to be presented, I think multiple follow-up, yes, we’re always, like, gonna be presenting more and more data to reinforce the short-term and long-term value of ulixacaltamide in essential tremor. One point we believe there is still room to explore here is really how strong the data is. I know you recently spoke to some payers and, like, payer groups, and they, if I understand correctly, agree with how strong this data is and how high the potential for this drug is.

But it’s what the understanding is not clear yet in the market because we haven’t put this data out there, is just how deep the effect is on a very large proportion of patients. And when you look into drugs, it’s not one-size-fits-all. So we want to make sure that gets reinforced, that gets holistically reviewed. While we’re very excited about having our principal investigators presenting this data to their peers, they’ve been thrilled with the execution, with the results, and I think now is the time to let them take the stage and present this data as key opinion leaders in the field. So stay tuned. I know we’re trying to cover a lot in this call, but stay tuned for, for April. I’m sure we’re gonna be pleased.

Jun Lee, Analyst, Truist Securities: Thank you so much, guys. Looking forward.

Conference Operator: Thank you.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: All right. Thank you.

Conference Operator: Our next question comes from the line of Andrew Sey with Jefferies. Your line is now open.

Andrew Sey, Analyst, Jefferies: Hey, good morning. Congrats on all the progress. Appreciate the updates. Maybe, shifting to relutrigine, actually. You’re pursuing this broader label, the EMERALD study, for all DEE. So how many different DEE patients in the phase 3 does the FDA want to give you a broad label, and how many different DEEs have you enrolled so far? And secondly, for that study, as we think about what you want to see, is it fair that you might be expecting efficacy to be similar or even stronger, than what you saw in SCN2A? And maybe explain why. Thanks.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah. Thanks. Thanks, Andrew. So if you’re looking to EMERALD right now, right, let me separate a couple of things there. So one, as I mentioned in the remarks, and then Tim mentioned as well in one of the answers, the goal here, at this point in time, is to get that SMGA by next year. And it should give you the confidence on what’s happening on the study right now. Really incredible interest, incredible enthusiasm, and engagement from the physician that are referring to the sites or participating in sites in this study. We took a very basic approach, right? If you go and you look into the most recent definition of these, like Dr. Scheffers recently published around this, and really going back to the basics, right?

What is a developmental and epileptic encephalopathy? What are the drivers? Like, why should we be treated? And relutrigine sits, like, on that junction of really helping the broadest population, at least hypothetically right now, since we’re gonna have to see the results in GE. So we took the approach of phenotypically defined versus genotypically defined patients for this study. What I can tell you right now, without saying too much, is that it is a very diverse group of patients that we have on the study. Both enrolled studies and patients in screening, they are very diverse, not completely unexpected or unexpected at all.

When we position and we discuss this study with the agency, and I can never speak on their behalf, but I tell you our interpretation is that the idea here is to treat the disease, is not to treat the cause of the disease. Would be pretentious to enough of us to try to do that. The understanding is that you cannot have a seizure without participation of sodium channel in the neurons, and therefore, this is like omnipresence type of mechanism that we can use. So that is the definition right now. There is no subgroups, or there are no quotas for different, if I may, for different etiologies. So we’re really looking into, like, an overall effect.

When you go back to the last part of your question and what to expect here, the-- we need to go back to translation. We need to go back to the preclinical data since we do not have the clinical data yet. And when you go back there, and we look into all different models that we tested, all the fundamental electrophysiology and basic biology of the channel, deposition, the physical density of the channels in a critical juncture in the neurons, what we see is, like, quite overwhelming preclinical efficacy. So when we had that before, on SCN2A, on the different models with SCN8A, on the aldogenic model, I think the way we’re looking into that is, like, those are very good translational models.

Now we have clinical data on those indications that translated well, so we expect to translate well as well. I think it would be a little bit too early to guide on how well the translation would be, but you got to remember from an overall DEE perspective, there is basically nothing for these patients as well. So while I’m incredibly excited about showing results, maybe the same, maybe better than we’re seeing on 2A and 8A, it’s absolutely not needed to deliver a very fundamental change on the way these patients are treated right now. But as I said in the past, we’re going to see this soon enough. So we’re just going to keep our heads down, executing on EMERALD, and soon enough, we’re going to be discussing, hopefully significant benefit for patients on that population.

Douglas Tsao, Analyst, H.C. Wainwright: Makes sense. Thank you.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: You bet.

Conference Operator: Our next question comes from the line of Douglas Tsao with H.C. Wainwright. Your line is now open. Douglas, your line is open. Please check your mute button.

Douglas Tsao, Analyst, H.C. Wainwright: Oh, sorry about that. I was on mute. Marcio, maybe it’s a little bit of a follow-up on that last question in terms of relutrigine, and then I have a follow-up on vormatrigine. But just sort of when you anticipate utilization, do you see sort of utility across the entire DEE spectrum, and it sounds like you see utility across the entire DEE spectrum, and even in indications where there are sort of ASOs or sort of more targeted therapies being developed, and arguably, sort of relutrigine will sort of become a workhorse used, you know, regardless of what other therapies may also be deployed for particular patient populations. Thank you.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah, no, that, that’s a very good question, though. The, yeah, the, the workhorse, probably I wouldn’t use that term, but I, I’m glad you did, because I, I think that’s one way to look into a drug, like a, in a toolbox, like, like relutrigine, where physicians would have that available that they don’t have right now, right? They, they have to ask too many questions, too many tries. Like, unfortunately, a lot of those patients don’t have that time to keep trying and optimizing. And, and quite importantly, like there’s what, 20-25 drugs that are normally tried in this population, virtually none of them have been tried, and officially, like with randomized studies, properly developed in pediatric populations or in adolescents, on early adults here.

So we never talk about that other side of off-label use, that we really don’t know what you’re doing on those populations. So what we hear a lot from physicians here globally is that certainty of the drug that’s being rationally developed for this indication. So there’s a lot of enthusiasm there. Now, to think that this is a silver bullet would be, like, completely absurd. That is not such a thing as a silver bullet in medicine. I think we all wish there was, but there isn’t. So we do see this as a kind of an overall background therapy for some patients. Ideally, would be monotherapy. For other patients, they’re going to continue in other drugs. You mentioned ASOs particularly. I think ASOs are getting consolidated as kind of the second workhorse.

I think we’re finally beyond some of the dreams we had about other modalities on gene therapy, and really understanding that that’s a very, very good mechanism. So combinations between ASOs, for example, and others, and riluzole, we expect to be the norm, right? We look forward for the moments where these discussions are about how the use is happening versus all these hypotheticals, because these patients don’t have a lot of time, and really excited about helping them.

Douglas Tsao, Analyst, H.C. Wainwright: Okay. Great, Marcio, that’s really helpful. And then just on vormatrigine, I’m just curious, in the RADIANT study, as patients go sort of past that, the initial point and we’re in the open label extension, I’m just curious, have you gotten data or seen data of patients who are withdrawing some of their background meds, sort of a little bit of a preview or look, if you will, into the, the POWER3 study? And in particular, patients who are maybe able to go off, you know, sort of some of the more problematic, you know, sort of efficacious, but perhaps more sort of less tolerable drugs like cenobamate or carbamazepine, et cetera. Thank you.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah. We’re seeing across the boards reduction, elimination, removal of background therapies as patients continue to have experience on the open label with vormatrigine. That physicians are very excited about that, the possibility, and I would say patients are more excited about that. As you can imagine, of course, efficacy is king here, right? But the queen is safety for these patients, and it is very hard for them to daily operate as humans when they are, like, on all those medications. So it’s always a very important. It’s not only that, right? I think one of the drugs you just mentioned has just been, like, put on a new warning for drug-induced liver injury.

So you got to think about the long-term impacts of these drugs, and being vormatrigine, at least so far, like, so clean, it’s quite important for these patients as well. So we’re seeing more and more enthusiasm. Of course, every time you remove a drug, the first question you need to ask is: What happens to the primary measure? What happens to seizures? And I’m very happy to preliminarily report that we’re seeing exactly what we were expecting to, right? It’s maintenance of seizure control while really not being necessary to use. What, I believe you asked this from a clinical perspective, but I’m going to jump into here, into the commercial perspective.

As you believe the value proposition of, by the very first time on a drug, that you can sequentially reduce the use of other drugs is very different than a drug that you just throw on the top, get used for a little bit, and maybe removes. So very excited. I think we’re going to have more data and more discussions to talk about that, as when we have the POWER1 results as well, and giving an overall program updates.

Douglas Tsao, Analyst, H.C. Wainwright: Okay, great. That’s super helpful, and congrats on the progress.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Thank you.

Conference Operator: Our next question comes from the line of Francois Brisebois with Life Sci Capital. Your line is now open.

Francois Brisebois, Analyst, Life Sci Capital: Hi, thanks for taking the questions, and congrats on all the progress. It’s quite a 2025 for you guys. So maybe on elsunersen, there’s a lot to touch on, but I don’t think much has been touched on this one. Can you help us, you know, EMBRAVE data is coming soon, so just maybe set expectations there a little bit. And I think it, there’s so much going on with the company that maybe help us understand why it’s so important that the, you know, the update on just having a single arm comparison for EMBRAVE3 and what that means.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah. So, thanks for that, Frank. The— So elsunersen, or as we call it, like, elsunersen, it’s like, it definitely sometimes gets the backseat on these questions, so I appreciate. We see in a sense, right, with linking your questions to dual questions, this is like an ecosystem, all these drugs are all going to be used. They’re going to be different cases, in use one more and the other less or combinations, and you name it, in the future. So we have this cohort right now, 9 patients, 3-to-1 randomized, to sham or drug. Our intention there was to continue to understand the safety, the efficacy, the PK, of this drug.

But we’re very excited because every time you have control data independently or even open label data, independently of the number of patients, is yet another opportunity for us to understand the drug impacts. We know the study went really well with these patients, like, did really well from a safety perspective. Since then, we can monitor, like, generally, which is not a given, right, in any given disease, and we believe that it can be quite informative. The FDA left the door open for us on the discussions we had about the overall value of the data sets on the overall program, right? So we wanted to make sure we’re very respectful, and we were mindful of that, but it can have a very high value depending on the results here in the next few months.

Now, when you look into the-- we’re very pleased, and likely surprised that the agency was really pushing us to actually get EMBRAVE3 to be controlled on baseline. I think they’re definitely putting their money where their mouth is in terms of accelerating drug development for drugs with a high potential translatability, plausible mechanism, and this drug fits right in all of that. We did switch the study globally to a single arm, with the patients randomizing. Well, I guess not randomizing now, they’re dosing on the study. It’s been a great experience with all the PIs and all the patients globally.

So a little bit longer on the timelines, not really long on biotech years, but long for us since there’s a lot going on. But we do expect to be done with this study this year as well, which would potentially get another yet another NDA in the near future. Very different positioning, as you can imagine, commercially very complementary to the relutrigine efforts. They are doing same prescriber population, overall same patient population, so we can see how synergistic this can be on the overall life cycle of the company.

Francois Brisebois, Analyst, Life Sci Capital: No, that’s, that’s very helpful. And then on ulixacaltamide, I don’t think you mentioned anything about ex-US efforts. I was just wondering, such a big market here, I assume ET is everywhere else. Any thoughts there that you can share? And then the launch, obviously, without priority review, this is maybe a little premature, but you’ve had so many trials and, you know, so many patients on this. I’m just wondering, in terms of line of sight, you know, in terms of a launch trajectory off the bat, do we know where these patients are? Or, you know, any color there would be helpful.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah, yeah, absolutely. So, maybe the easiest part of the question here, absolutely know where these patients are. I think we have daily motivation as patients keep calling our IR line, keep sending us messages, and keep reminding us to keep pushing, that they are waiting. It’s quite motivating for me and for the rest of the team to keep moving there. And just like the millions of patients that we have mapped to prescribers in the U.S. That in a sense, I think it answers the second question or the first question that I’m answering second. While there is huge unmet need outside of the U.S., and we appreciate that, and we are very compassionate in relation to that, the focus of the company has to be in the U.S. right now.

We were laser focused on making sure the highest possible quality NDA was submitted. Now, we are laser focused that the highest possible quality launch is done for this. When looking to the magnitudes of this launch, I think it would be ill-conceived and intended for us to get distracted at this point in time with other geographies. So very good trajectory, very good number of patients, as you can imagine, on open label extension right now, which would expect it would transition right away to commercial. Other pools of patients that we believe are gonna be right before, and then just the spontaneous demands that we are seeing piling up on top of our database already for the launch.

So I don’t want to get over our skis here, but this is definitely trending towards a successful launch.

Francois Brisebois, Analyst, Life Sci Capital: Excellent. Thank you, this is it.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Thank you.

Conference Operator: Thank you. Our next question comes from the line of Amy Fadia with Needham and Company. Your line is now open.

Amy Fadia, Analyst, Needham and Company: Good morning. Thanks for taking my question, and congratulations on the submissions, both the submissions this month. My question is on vormatrigine and regarding how—what you assumed for your peak revenue potential, particularly regarding utilization in first line. And if you could provide some color on how you see utilization in earlier lines of therapy impacting persistency of patients and duration on of treatment, and how will the POWER program, you know, help you build the clinical data that supports or provides some color on how long patients stay on treatment as they get treated with vormatrigine in earlier lines of therapy? Thank you.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: No, thanks. Thanks, Amy. So the retention we are seeing right now, right, as an early indicator of what you are asking is, it’s incredibly high. And once we talk about POWER1 results, we’re gonna be able to talk about that as well. Patients not only participating on these studies, but really staying on the long run. So that gives us an early flavor of how retention in overall commercial is going to be. And of course, they are staying on drug differently from other drugs and different from other trials because they are having benefits, and because they’re having a safe experience with this drug. The way we currently forecast the movements between third line, second line, first line is actually very reasonable, I would say.

So we’re not looking for this at day one of launch. We’re not even looking to this at year one, at launch. We know it takes time for these things to happen. We know that the, the overall penetration is not like the highest, but when you look into our, peak revenue, right around $4 billion or so, in overall, like, you can imagine that we couldn’t just be hyper penetrating the, the first line, because otherwise this would be much, much higher than, than what we have right now. So there is a huge potential there for, for upsides, as you can imagine. But at the same time, as we-- there are many firsts that happened for us, in the last few years. And I think we’re always very responsible to say what we knew-... and what we didn’t.

I think what we know right now is that there’s incredible interest on utilizing this drug. What we don’t know is the dynamic of that. We are really keeping, I would say, very tempered our enthusiasm in terms of how the penetration is going to be there, and that’s reflected on our conservative to a realistic, one could call, peak revenue right now.

Andrew Sey, Analyst, Jefferies0: Thank you.

Conference Operator: Thank you. Our next question comes from the line of Brian Scorney with Baird. Your line is now open.

Brian Scorney, Analyst, Baird: Hey, good morning, everyone. Thank you, for taking my question. I guess we’ll get some guidance on NDA acceptance, but wanted to just get your preliminary thoughts on, on if the review division has given any indication on an advisory committee, for either relutrigine or ulixacaltamide. I mean, it seems that outcomes are getting more rare under this current iteration of the FDA. And relutrigine’s mechanism seems pretty straightforward with the data. It probably wouldn’t require one, but, but thoughts on, on ulixacaltamide in particular.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah. No, no indication whatsoever, at this point in time. One wouldn’t expect much of an indication before day 60s and day 74 interactions with the agency, but there is no indication right now, Brian.

Brian Scorney, Analyst, Baird: Great. Thank you.

Conference Operator: Thank you. Our next question comes from the line of Jay Olson with Oppenheimer. Your line is now open.

Jay Olson, Analyst, Oppenheimer: Oh, hey, congrats on all the progress, and thank you for taking our question. As you plan your pre-launch activities for both ulixacaltamide and relutrigine, can you talk about the potential synergies you can leverage between these two launches, and then eventually, how those synergies could help set up your future launches of vormatrigine and elsunersen? Thank you.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah, certainly. So I’ll take from the borrowing side, right? From an infrastructure perspective, back office perspective, lots of synergy, and, and on how things are set up, and we’ve been doing a lot of that on the backgrounds, like how the systems are set up and so on. Until not that far in the past, we were actually considering a lot more synergy in the fields as well and on the approach to the markets. Because we believed before the EMBOLD’s positive results last year, that we’d have a little bit more time with relutrigine, so we’d be able to leverage that. And that changed a lot once we are now really launching two drugs in about the same time.

While there is a very significant overlap in, I’m going to call it ZIP codes, right? Like with hospitals that have or clinics that have very high overlap of patients with ET and GEs or focal, we don’t believe that it’s prudent right now to take any distractions or taking a go-to-market strategy for both, for individually, for GEs and individually for essential tremor to maximize, each one of them. Now, since your question extrapolated to the future, Jay, when you’re looking to like focal seizures, for example, generalized seizures, you name it, other things that might come in the future, there is very, very high overlap, between prescribers for the majority of the epilepsy patients today and the majority of the essential tremors today in the markets.

So you can see how a practice presence might be beneficial at that point in time. Now, we are talking maybe 2 or 3 years from now, and that they’re going to be maximizing that. Now, let me bring back to, like, 60 days or so from now, when you’re going to be in Chicago with all these prescribers. If, if we were to count the universe of prescribers coming to the annual meeting of the Academy of Neurology, we’re talking about over 70% of the prescriptions for ET and focal in the U.S. are present at that meeting. So there is a natural overlap here. We’re just going to be maximizing that overlap more a few years from now than a few months from now.

Jay Olson, Analyst, Oppenheimer: Great. Thank you. Congrats again.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Thank you.

Conference Operator: Our next question comes from the line of Kambiz Yazdi with BTIG. Your line is now open.

Andrew Sey, Analyst, Jefferies0: Morning, guys. Congrats on the NDA submissions. Three questions on my end. First, can you provide an update on the essential tremor patient database? How is that already validated the size of the ET market? Second, the FDA’s default position is that one adequate and well controlled study, combined with confirmatory evidence, will serve as the basis of market authorization of novel products. How do you think about that with regards to vormatrigine and FOS? And then, my third and final question is, how should we think about the timing of relutrigine EMERALD top line? Would an interim analysis be a possibility for EMERALD? Thank you so much.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Thanks, Kambiz. I try to go through your questions here if I understood them correctly. Right. So on and I think I missed the very first one, so I might ask you to repeat which one was on ET.

Andrew Sey, Analyst, Jefferies0: Yeah, the first one was, can you provide an update on your essential tremor patient database?

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Oh, yes, the database.

Andrew Sey, Analyst, Jefferies0: How is that already validated the size of the ET market?

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: ... Yeah, so we’ll continue to both validate and grow, and, I think we intentionally didn’t talk about this, today, since now we are moving from the clinical focus one to the commercial focus, effort, and I’m gonna give, like, a larger update at our commercial day, in the near future there. So I’m gonna keep you holding your breath a little bit, in relation to that. I’m gonna go to the EMERALD, and then go back to, to the second question. So of course, there is always, an opportunity for, for interim. It’s not a current plan for EMERALD, and the reason why it’s not a current plan is, really the pace of enrollments, in EMERALD right now.

I think we’re being realistic, conservative about the timelines today, but that is really a very fast pace of enrollment that might not allow for that. And then on the last one, on how we think about generation of evidence vis-a-vis the commissioner, like New England Journal of Medicine yesterday publication, we applaud it. I think it can be and will be, I have the ultimate trust on this, on our company, that’s gonna be used responsibly. And we believe that in drugs where very clearly, like epilepsy, very clearly, the second study was not that necessary in the past. Those are good case studies and tests for the future. We could not possibly be trying to guide you today that that’s gonna be the standard for our drugs.

There’s a lot of water that needs to go under that bridge, but we are enthusiastic about what that can do for drug development and for Praxis, particularly in the near future. So stay tuned.

Andrew Sey, Analyst, Jefferies6: Thank you.

Conference Operator: Our next question comes from the line of Justin Walsh with Jones Trading. Your line is now open.

Andrew Sey, Analyst, Jefferies6: Hi, thanks for taking the question. With your clinical successes, have you been seeing increased attention paid to your Cerebrum platform? And related to that, can you remind us how both Cerebrum and Solidus are differentiated in their ability to select quality candidates for your pipeline?

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah, yeah, absolutely. We do. As you can imagine, that is, I think, Justin, like a renaissance, maybe I would say, on understanding that the best mechanism to address a lot of these diseases is through antisense oligonucleotides. So we’re seeing a lot of interest across the board actually on this. You’re gonna hear more in the near future about how we’re gonna maximize it. I also believe that there’s a different way. We talked about standards today, I talked about plausible mechanism today. There are different things there to maximize. We always follow two pillars, right? The biology, and what is the best way to address, and then the business on the other side. Without business, biology is irrelevant. Without biology, business is irrelevant.

So I think we try to, to do both of them, and that’s why we’re here today discussing the successes and the, the future success. So I think that is stay tuned, but there’s gonna be a lot more on, on that platform as well.

Conference Operator: Thank you. Our next question comes from the line of David Huang with Deutsche Bank. Your line is now open.

Andrew Sey, Analyst, Jefferies6: Hi there, thanks for taking my question. So maybe first one on ulixacaltamide and essential tremor. Could you just discuss a little bit about the distribution of the prescriber base? How, how well do you understand, you know, whether these prescribers will be based in, let’s say, academic centers versus community? Is this a product that would be prescribed by, you know, general neurologists broadly? And then one on vormatrigine. As we think about the evolving landscape and focal epilepsy, there’s several potassium channel-focused therapies that are in late-stage development and potentially coming to market soon. How do you think vormatrigine fits in amongst those products? And what, and what would docs look at when selecting a therapy? Thanks a lot.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Thanks, Dave. The, the distribution, and I would say the distribution of patients and the distribution of drug and the, the prescribing pattern is very well understood. I think we’ve been talking about that for a bit. It was one of the very first functions and knowledge that we built, in the company. I would arrogantly tell you that we have an exquisite understanding, on, on this, and, each one of the physicians that have case in the U.S. right now is the majority of them, the vast majority, are general neurologists, and they’re very eager and willing to, to engage with us. I think, on, on Vorma and the competitive, landscape, this was not and never gonna be a zero-sum game. We’re welcome. We are cheering for the next readouts, on the space, coming up soon.

And we believe that that is really, it’s in the best interest of patients that there are multiple positive readouts and drugs, and we can use them. And we just see the path to first line only happens with vormatrigine. So, competitively welcome, gonna have some competition on the refractory patients on the third line, but there’s no competition on the earlier lines. Yeah. Thanks for the question.

Conference Operator: Thank you. Our next question comes from the line of Ben Burnett with Wells Fargo. Your line is now open.

Andrew Sey, Analyst, Jefferies6: Great. Thank you so much. I want to come back to an earlier question on ulixacaltamide and just the potential to explore titrating patients. I think you mentioned an alternative titration protocol. I guess, curious if you could give us a little more color on this, and, and I guess would this alternative titration protocol start patients at a lower dose?

Speaker 3: ... I and then secondly, you also talked about standard review for ulixacaltamide, and I think you walked through a couple sort of business reasons for that. But it feels like it also would give you some time to maybe iron out a titration protocol, and was that also a consideration?

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah. Thanks, Ben. No, that was not a consideration, actually. I’ll say that was not an important consideration. Of course, it’s always up to the FDA if they want to discuss more. We had a very robust discussion about that topic with the agents before. It was very good to see that this is not a major concern, but there’s obviously an interest from us and from them when there is an efficacious drug that we try to actually expose and get the maximal amount of patients. That is the idea. It is not a lower dose, right? It’s starting at 20 milligrams. It’s just, it’s staying at 20 milligrams for longer.

Because what we see here is what looks like it is really just a few days that they stay longer on that dose, that tends to subside, the side effects, and then they have the opportunity to have the effects. So that’s the, that’s the idea there. I think, of course, there is thousands of things that can come up in conversations with the agency, but that was not one of them that we are planning as a main conversation, for sure.

Conference Operator: Thank you. I would now like to turn the call back over to Marcio Souza for closing remarks.

Marcio Souza, President and Chief Executive Officer, Praxis Precision Medicines: Yeah. Oh, thank you, everyone. I think we’re running a little bit even over the allotted time, so I appreciate you all hanging in with us here. All the enthusiasm shared by all the analysts and our shareholders. Can’t say how much I appreciate and all of us here at Praxis appreciates the patients that participate in all the studies, that continue to engage with us. As we are here, very humbly, submitting two NDAs, which I don’t believe has ever been done by a company in our stage on the same quarter.

The real motivation for everyone that worked, like, days and nights, on the last several years, but particularly in the last few months, has been the fact that there is someone, as we say, outside of the door, that we don’t know. They need these drugs. So just gonna dedicate these moments to all of them and thank them for participating in our studies. So looking forward to interact with all of you soon, and thanks for tuning in.

Conference Operator: This concludes today’s conference. Thank you for your participation. You may now disconnect.