All right, good afternoon, everyone. Welcome to Guggenheim Emerging Outlook, Biotech Summit 2026. My name is Yatin Suneja, one of the biotech analysts here at Guggenheim. Our next presenting company is Praxis Precision Medicines. It is my pleasure to host this fireside chat session with two executives from the company. We have the Chief Executive Officer, Marcio Souza. We also have Chief Financial Officer, Tim Kelly. Marcio, lots happening at the company. You think so? I do. Tough to keep up on the updates that you're providing. But why don't you maybe just talk about for five minutes, like some of the key things that you think investors should be focusing on, and then I want to spend time on ET, mostly on the commercial side. Mm-hmm, mm-hmm. I don't know if you saw, we put out a piece recently, so we're gonna touch on that, and then we go into the epilepsy programs after that. Yeah. That's okay. No, it's always good to be here, and sorry for starting with a joke. Yes, there is a lot going on. It is a combination of course, we all here work very hard, right? We work particularly hard on developing these drugs to patients with CNS, such a huge area, and we're focused on a small sliver of that. It just happens that there are so many patients there, and I'm sure we're gonna be discussing a lot about each one. Yeah, I did see your report, and I appreciate it. And maybe I will start there, 'cause it brings the perspective of probably what we want to talk more about. The essential tremor, particularly since a lot of the focus on the report was going to the fields for the ones who didn't read yet, and really understanding the dynamic of how these patients present and how they are treated, and what a drug like ulixacaltamide hydrochloride would be able to deliver to these patients. And it's very consistent, right? In a sense, it's catching up to what we've been saying all along. It is a sad realization when you look into about 2-2.5% of the U.S. population, which means probably one, if not more of us here, in our lifetime, are gonna develop essential tremor, or gonna progress to a more severe or debilitating part of essential tremor is gonna require some sorts of treatments. There is nothing really right now that is effective, that is safe, that is able to deliver for those patients. While we spent a lot of time, and I would even argue rightly so, in the past, talking about how to develop drugs for essential tremor, particularly because that is only, like, in the-- only failures, right? There was a pile of failures in the past here, lack of understanding of the pathophysiology or mechanisms that could address. Now we are on the other side of that with a very effective, potential drug, as soon as Malcolm Woods gets approved in the U.S., so we should be talking about how the drug is gonna be used. There is no way... It's one of those indications that no matter how many haircuts one apply to it, we're still talking about a very, very significant number. We're, of course, quite interested here on the commercial potential, but I, I would urge you to think about the human behind that dollar value as well, particularly like our parents and our grandparents, that since that tends to manifest, like, quite severely, on the older patient population, you see, on that, and, and just what it is to bring function back to their lives. And when you do that, and you might have seen the results of our Essential3 program, both studies positive, it's quite meaningful, the what we bring back. Like, we look into those numbers, and you try to contextualize what they mean, and I think some of the physicians on the survey that you conducted, Yatin, did a really good job contextualizing, like, what a function is. On a new disease with a new endpoint, oftentimes it's just hard, like- Yeah. Anyone here can talk about, like, a number of drugs. Like, I think we all became, like, weight loss in terms of what, like, percent of the original weight, what is good and what's not good because of all the revolution that happened with GLP-1s, but we have no idea what is good- Yeah ... in Essential Tremor. So the focus is really commercial, and I think what we want to talk a lot more about moving forward. Yes. I think one of the thing in our research that we found out, and which I was positively surprised, is that, I mean, you can always think about, "Hey, look, it's 2-3% of the patient population, so it's a very large number." But we found out there are 80,000 scripts every month for ET coming only from neurologists. Forget about PCP, because we don't know. Yeah. So that was a big surprise, and so would you agree with that type of number, or that's what your research is saying? Yeah, we do, and as I jokingly said, we're all just catching up to what I've been saying, right? I'm just gonna recap what I've been saying all along, just because I think it's important, right, from a credibility perspective. Between 1 and 2 million patients in a 1-3-year rolling basis, because scripts data is not perfect either, claims data is not perfect either, are actively seeking treatment for essential tremor in the United States. There is no other indication this large without a solution for patients. None, zero in the U.S. right now. 80%-85% of those patients are solely asking about treatments when they go. When you actually buy scripts, because you can, right? And transcripts from these conversations, anonymized, of course, that's what they wanna talk about. Mm. What do you have for me?" And physicians, and I'll give them a lot of credits, they try... they try with other things, off-label use things, it's, they're just not good enough for these patients right now. So not surprised, probably on the low ends. We know that script data from, like, Medicare, for example, is quite complex, right? It's not, it's not readily available as, Yeah ... as private plans. So when you actually consider the age of the population, I would say you're probably wrong by a factor of 1.5 per month, which of course makes this a lot more interesting. And you've got to consider the families here. 70% of the patients with essential tremor have 1-2 members in the family with essential tremor as well. So when you consider that and the fact that they're not as engaged as the older member, the potential to increase this market is tremendous. Got it. So how are you gonna go after this patient population? I think you've said 300 patients, sorry, 300 people sales for. Is that enough? Just articulate for us, because there is some database that you have built internally, right? To talk about that, just exactly how we should think about the launch dynamics. Yeah. Yeah, absolutely. This is not a condition that we can just go and, like, call a limited number of physicians and just, like, call it a day. In a sense, we do need to solve for what I call solving for zip codes, right? Like, we need to, like, look into every zip code in America and say, what is the kind of solution we need there from a sales force perspective. I think we have very good people in the company thinking about this. We're bringing good expertise to maximize. Also, taking the approach at this point in time, at least, of course, we're gonna be evolving between now and the launch, to... If we believe that we need one, we probably need 1.3- Mm-hmm ... or 1.2, meaning we don't want this launch to be limited, because we don't have the capacity to actually be calling on the physicians. So that's number one. I think number two, and equally important, is we're very, one could argue, successful, I definitely would, on mobilizing patients to go to our clinical studies. Yeah. Was about 5-7 times faster than anyone else. Much larger companies, done studies in movement disorders, was not even close, right? 500% is not a small number, and it was mostly because we understood what's the online behavior and what's the office behavior for these patients and what they were looking for. Yeah. This is gonna be amplified during the launch. So there's gonna be a lot, as you're gonna see more and more, particularly after NDA, a lot more of the patient messaging out there, bringing to a single database. That's what we do really well, increasing our current database, and then making sure that if themselves and their physicians believe that it looks like ulixacaltamide is right for them, that they actually have a conversation about that. So trying to get the, the two having a conversation there. And of course, coverage, right? And making sure that at time of launch, there's not gonna be an impediment from a payer perspective. It's normally not the case in situations where there's not available treatments, as here, but we're very cognizant of that as well. Got it. Maybe a couple more questions then- Please ... we move to other stuff. How should we think about pricing here? I think in our research, I mean, physicians don't really care as long as the copay for patient is manageable, right? Mm-hmm. Mm-hmm. Mm-hmm. Just, can you put that in perspective? What do you think the copay would be, and where you should think the pricing could be, or- Great ... the brackets around? Great perspective from the treating physicians here. So we've got to separate the populations here, right? So the private payer population, so it's about 30%-40% at time of launch, very easy to manage, through copay programs. Mm. Can imagine that it would be incorporating that in our, like, cost base or overall cost of launch base. So minimal to no- Mm-hmm ... copay to, to patients, that's the way we're thinking about that. That is a lot more complex for, for the Medicare patient population, so they have to go through, the first, which normally is around $2,000- Yeah ... for all the drugs, all the coverage they have, right? So the timing and how they start and when they start, and what we can do, it's very limited under the current regulations. We're considering things like the initiation not being considered paid drug. Mm. That helps best time in the year. They all utilize the system, so they all kind of get to the maximum that they have to. But on the checks we've done so far, there would not be a limitation. Okay. The copay for the drug itself would be relatively small. Okay. But when you are dealing with an older population, we gotta consider the entire burden for that person, not only on the drug we're like dispensing to them. Got it. And then the range on the pricing front? Yeah. So, I look into your, like, maybe to speak about your own model here, right? I think we have $6 billion peak sales for ulixa, which I obviously disagree. I think it's too small, but let's assume it is. But let's assume it's correct. I'm 60% there. I think you've said more than 10. I'm saying more than 6. It's okay. The one thing I know is that we are both wrong, but and that the number is very big. But to get to about, like, that, that number that you have, that's where I was going, is you probably can have a price as low as $20,000 per year, which would be too low- Yeah ... here. Absolutely too low. That's no need whatsoever. That's the point that we're leaving money on the table, and money on the table in our business means less innovation to patients. Mm-hmm. So it's not only about profits at the end. Probably around 40-60 is a sweet spot at one point, with the potential to even go higher, depending on the dynamics of the launch. So it is a little early for us to just put a number on the table, but you can see how we are thinking about this. Got it. I think when we contextualize it, I think when we put TD, tardive dyskinesia- Mm-hmm, mm-hmm ... as a benchmark, I think it resonates. But obviously, you also there don't agree because you're saying that's just not even the size. No, I think it's a good analog. Good analog? Yeah. Okay. Now, maybe just procedurally, what needs to be done? You have breakthrough designation. Number one, do you expect ad comm? When will you file? What's left from a filing perspective? Yeah, absolutely. So, we guided, file, like, around, like, mid-February or so. I think some of you reminded me that's kind of upon us. Yeah. I don't know, I don't know which day is today. I should know which day is today. It's the eleventh. So we are—we remain on track- Mm ... as you can imagine, for what we disclosed previously, publicly. You've got to remember two things: we might not make it to the other drugs by the 11 minutes we have left. But we do have two NDAs being- Yeah ... filed on the same office with the FDA at the same time, give or take. Yeah. It's a big effort for a big company. It's definitely a huge effort for, for a company like us. We wanna make sure everything is, is correct. Having said that, the plan was all along to be filing right now. Mm. That is what I can tell you at this point in time, that there is no components, like no piece of any of the applications that is missing. There is no, like, documents that is in initial altering, things that would guide it- Mm ... to where we are with this, and there is no intention whatsoever. This is being webcast, the Reg FD call, so there are certain obligations as well, as you all know. There's no indication whatsoever that we're gonna miss the ability to file within the guideline that we gave. So very, very confident we're- Would you seek for Priority Review there, given Breakthrough Designation or-? So, would we ask for it, it may be the question, right? Because we have to take those forms and to issue there. This is the calculus in our minds right now. It's a lot on what I just said. Two drugs, same office, and we know there's a lot of shared resource there. And one drug that we're trying to get as quickly as possible to the markets, with relutrigine, and one drug that we're trying to get to the maximum overall bene-- economic benefits and humanitarian benefits- Mm ... with ulixacaltamide hydrochloride. The equation has to consider all of that- Mm ... and has to consider our understanding on what is best for us and what's best for the FDA. Now, there is no doubt whatsoever, no doubt in my mind, no indication from the agents whatsoever, that if you were to ask, wouldn't be granted. Like, again, there is such a huge overlap between the criteria for breakthrough designation and and all the other designations, including fast track and priority review. It might not be on the best economic benefits of the drug to do so, and that is a calculus that we take very seriously, right? So if we consider this drug to be what we consider to be $10 billion-$15 billion plus peak sales, economic overall benefit matters. And I'm more than happy to explore with all of you individually why we feel that way. So we're you gotta, in a sense, I don't do the trust me, because I think that's a little shallow, but I'm gonna do this right now. Trust us that we're making the best decision for the drug and for the overall economic impact of it. Got it. Very helpful. Thank you. Then moving to... I'm gonna skip Rylofentor, I'll come back to that. But relutrigine, obviously, that's the NDA. It seems like that's where you wanna get it out to the market very fast, for the priority review. When are you filing that? And then can you maybe help set expectation for the EMERALD study? Because I think that just opens up a significant market in DEE for DEEs. Yeah. So it's not quite a race. I said this the other day to the regulatory leads, but they are like, "It's not quite a race between the two." They're like, "Oh, it is a race." So, it's basically neck and neck, the two NDAs. So we should consider when we said mid-February, that we meant both. Both. Days apart, not even weeks apart, the filing. Very confident. Much smaller package, right? Yeah. Mm. So in a sense, like, what's easier to put together and things like that. In general, it's smaller by definition. It's smaller. There's less studies, less patients, less everything, less sites, manufacturing, everything else. There, SCN2A and SCN8A, I think it's very clear the benefits. As you might recall, we chose to go with a disease that had a very, very high bar, like these are uncontrollable seizures since birth for all those patients with severe developmental delays. When we expand it to Emerald, which is the larger DEE population, we're really borrowing like an idea here from a lot of experimentation, like a lot of animal models, a lot of human understanding of the biology here, but fundamentally, the fact that we need these channels to actually propagate seizures or even initiate seizures, sometimes. So it was a very fundamental mechanism. The study, Emerald, started not that long ago. It's going, it's on fire. That's the way I would describe it, and in a good way. It's being, there have been days that it's been harder on us to actually handle and process all the interest from the PIs and the patients coming in. We mentioned before, I'm gonna reaffirm right now, that we're gonna be finalizing this study in the second half, likely reading out this year. There are two things here, right? So one is the population is so much larger, it shows- Yeah ... the benefits there likely. But the second as well, let's assume it's gonna be positive, since otherwise, why wouldn't we, why would we run this study? If it is positive as we expect, it's we're almost a perfect case for the STAR program situation. Like, the agency, I don't want to put words in their mouths, but in the public reports, it seems they've been struggling to find a case that fits the criteria, where the evidence is limited on the new indication, and the package is likely the same as contemporaneous, and so on and so forth. They can use to accelerate the second indication, right? So you can look it up. It's called the STAR program. No one qualified so far. We believe strongly this would be like when you—we're a textbook case for qualifying on this, which would mean the sNDA would be a lot faster than a regular sNDA. So we can imagine a situation where readouts submit pretty quickly and then have that expansion of the label earlier next year. This is all assuming that the current NDA would be approved. Of course ... of course, this year. But, very, very exciting. I don't see any scenario that we don't finish this study. Yeah ... this year. So, that just enough, EMERALD could just be sufficient to broaden to massive market? No reason whatsoever to believe otherwise. Yeah. Yeah. Yeah. Okay. What is the size of SCN2A and SCN8A? Yeah ... how many patients are there? Yeah. How should we think about, I mean, then what about, do you need a separate sales force for that? So we the needs versus want or believe- Mm ... is correct. It probably it's those are different things. I think we're pretty set that we're gonna have a small specialized, like, field force, because it's not only sales, right? Medical affairs and other things as well, that goes there. Particularly because the overlap, for example, if you're talking about vormatrigine, it's huge overlap with the neurologist treating ET. It's a little bit smaller for the pediatric, or a lot smaller for the pediatric one, and it is a process that takes a little bit more time. This patient's incredibly fragile. They're on several medications, so I think it deserves a slightly different conversation. Also, launching two drugs at the same time just needs the effort for the individual drugs- Yeah ... we believe. So much smaller overall numbers here, but same coverage in general. The way we're looking to SCN2A and SCN8A in the U.S., it's like anywhere between 3.5-10,000 patients that would be addressable at the end, right? So they're not total numbers. They are much bigger total numbers. These are addressable patients, and virtually all of them are identified today. The reason why they're all identified today, differently than other rare disease that you might be familiar with, manifestation is very clear, very early, and unfortunately, they die very quickly, meaning in teenage years. Which means that the people who are alive right now, the patients who are alive right now, they came after this genomics revolution and the identification. So it's not like patients from 20 years ago that might not have had a genetic diagnosis in the United States. If you're talking about other countries- Mm ... the picture is not quite as developed, but in the U.S., that's our key markets, is really well developed. So it's just a matter of the conversation with the physician and the parents in this case, because the majority of them are kids and really decide whether or not it makes sense to add a medication or switch a medication. Got it. Helpful. Two minutes, vormatrigine. POWER1 is expected to read out, but I think your official guidance is first half, but I assume it's coming relatively soon. What the expectations are, if you can help us understand, how should... And you've been very confident that the discontinuation rate will be much more managed in this study versus RADIANT study. So what are the expectations? Yeah. So I think we, we all know, and we're very happy there are other folks developing drugs for focal onset seizures. A huge unmet needs affect a very large proportion of the U.S. population, very likely some of us in this, in this room here. Not a zero-sum game, right? Yeah. You can have... There are 25 drugs approved right now. If there were 25 more, probably all of them would be successful as well. It's all to say that while we had very impressive results before with RADIANT, both on the short term and on the long term- Yeah ... the bar for success here is not that high. Yeah. When you look into placebo-adjusted, it's like anywhere on the high 20s to, like, mid-30s%. So about 40%-50% drug alone would be quite exquisite, I would say. I think we guided for around that before. There is no reason to change right now. The ultimate positioning for this drug is to move to first line, right? Mm. Starting in third line and then moving slowly to first line. It's probably the only drug that could do that by its potency and mechanism, the ability to dose patients safely in a different dose range. So the limitation was the question you ask, is, like, can we manage the discontinuation better? Mm ... than RADIANT? And I can say quite definitively that yes, and we're very confident and very happy with what we were seeing POWER1... but we're gonna see this first half of the year, it's yet another multi-billion dollar opportunities that we can add to the portfolio. It's the POWER3 that could move you to the front line, right? Like, some sort of a unique design. Correct. Okay, Elsunersen, the plan is for an NDA next year. Would that cannibalize the relutrigine SCN2A market? Oh, we don't believe so. And, like, these patients are so, so severe with 2A E, that it's actually probably would be irresponsible for any of us to say monotherapy is ever gonna be an option for, for some of those patients. Combination therapy in general is gonna be the case. Mm. There are obviously patient preference as well, on all sort of things. These are markets that, as mortality is likely reduce, as one would expect, the market's gonna grow quite disproportionately from where we are today. And, we believe those two drugs have complementary, features, I would say, and we have some experience on combination- Mm. I think that's where it's gonna go. Got it. Tim, quick one. How's the pro forma cash position? How are you funded? And also, how many priority vouchers are you eligible for? So we currently have about $1.5 billion in the balance sheet. Thank you to Guggenheim for your help earlier this year, and some of you in the room. So very well-funded to support the launches. Also, I think Marcio outlined some of that. We can have the launches that we need to have for these drugs. We expect our runway gets us into 2028, and likely to be enough to get us to break even as well. And then the vouchers, I think with the extension of the program, very, very exciting for the rare disease space. I think 2 right now is conservative, is what we have in mind for that, between relutrigine and then also elsunersen. Alsinerksen. Very good. Thank you. Thank you, gentlemen. Thank you. Thank you!