Okay, welcome everybody. I'm Doug Sow, Senior Analyst at A.G.P. / Wainwright . We are thrilled to have with us Praxis Precision Medicines, represented by the company's CFO, Tim Kelly, and Marcio Souza, the company's CEO, is supposedly en route, so he might join us midway through the presentation. You don't have to worry if somebody barges in and sits down.
So it's Marcio versus the trains this morning. I think he's going to win.
You know, Tim, it's obviously been, you know, a very eventful couple of years for the company. You would probably say it's been an eventful, you know, five years for the company as a public company. You know, maybe as a starting point, it might be helpful to just lay out the next 12- 18 months from a data and milestone standpoint.
Absolutely. Very glad to be here. Thanks to everybody for joining today. Really, really important next 12- 18 months. I think you highlighted for us where the focus of the company is right now is on executing really across the whole portfolio. We have four programs in late stage. All four of them will get to a point of de-risking and be in the pre-commercial stage over the next 12- 18 months. The first one coming up will be Vormatrigine, and this is our program in common epilepsies. This is a sodium channel modulator that we're investigating in focal and generalized epilepsy right now. The upcoming catalyst there that we have is a phase II open-label study called Radiant, where we are investigating Vormatrigine at a 30 mg dose in up to 50 patients with focal or generalized epilepsy.
We will get the data from that by mid-year. The next study that we'll have for Vormatrigine will be in the second half of this year, which is the first of the two registrational studies that's called Power1 . We will be in a place of having a lot of data for Vormatrigine. The second registrational study called Power2 , we will initiate that in the second half of this year. We will be staggering POWER1 and Power2 for two reasons, mainly. One is that outcome from the Radiant study will inform the dosing that we use in the Power2 study. The second is the focal epilepsy space is fairly competitive right now. We didn't want to be competing with ourselves for patients. We're staggering the enrollment there.
That's the Vormatrigine asset, quite a lot coming over the next through this year, and then more as we get into next year. The next asset where we will have data this year is with Elixir Caltimide. This is our program in essential tremor. Many of you will know that we did an interim statistical review of the data earlier this year. The outcome that came from that, and this was just in one of the two studies that we're doing right now, the parallel control arm, the recommendation from the interim review board was to stop for futility. They also gave us guidance that we should evaluate the statistical model that we were using.
Given that the studies, both of them were fairly far along on enrollment, we politely declined their recommendation to stop, and we're going to continue those studies all the way through to completion and read them out in Q3 this year. That also gives us time to evaluate, are there ways that we can improve the statistical modeling that we're using in that first placebo-controlled study? The second study is a randomized withdrawal study, and we've used that study design a couple of times before with this drug with very good effect. We will share results from both of those studies we call study one and study two for Elixir Caltimide in Q3 this year. Another program that will be de-risked and will be at a decision point once we have that data to either proceed to an NDA filing or to stop development in that asset.
The next study or next drug where we will have data over the next 12- 18 months is our Ralutrogen program. Ralutrogen is a very similar molecule to Vormatrigine. It's also a sodium channel modulator, but it has some pharmacokinetic properties that lend itself to more of a sensitive pediatric population. We are looking at this in developmental epilepsies. We shared data from this drug in our Emerald study last fall, where when investigating the drug in 15 patients over a four-month period, we saw a 46% reduction in seizures. We saw that five out of the 15 children had at least one period, one month of seizure freedom. This comes from a baseline of roughly 55 seizures a month previously at that time of baseline, just a staggering seriousness of this disease.
We were very surprised, impressed, humbled by the data, and very quickly enrolled a second cohort that is registrational for this drug. That is actively enrolling right now, up to 80 patients focused on SCN2A and SCN8A developmental epilepsies. We are expecting to read that study out no later than the first half of next year. Another catalyst as well. What we shared recently at our developmental epilepsy analyst event a couple of weeks ago is in this cohort of 15 patients, there are still 12 of them who are enrolled in an open-label extension up to 11 months of dosing. We are now seeing around a 90% mean seizure reduction for these children. The baseline or the improvement in the days that are going between seizures went from three days at baseline for both placebo and the drug arms to now a mean of 67 days.
We continue to see improvement for these children as well as they continue dosing. What we also shared at this DE day recently was pursuing a much broader approach for Ralutrogen. While we've initially focused on SCN2A and ADA, and the reason we did that at the time also was we did not have a lot of money, to your point, on this being an eventful period for us. That was a very high bar for us to have a proof of concept study. We did that. The real opportunity with Ralutrogen as a sodium channel modulator is to look at all developmental epilepsies. What's common across all developmental epilepsies, regardless of their genotypic manifestation, is they all have sodium channel activity related to their seizures.
If you were to look at the idea of what we've used sometimes as a tree, where all the leaves are the various genetic mutations, but the trunk is the common sodium channel activity related to seizures, we believe that Ralutrogen—can you guys still hear me?—that Ralutrogen is applicable for all developmental epilepsies. We will be initiating in mid-year a much broader study called the Emerald study that will look at enrolling people based off of their phenotypically driven seizure burden, not genotypically driven. Based on that, we believe there's a much broader population of over 200,000 patients where Ralutrogen can be applicable. We will get that study up and going as well very shortly, but a much broader potential for Ralutrogen.
That's, I think, as we say, we're kind of rounding third and then coming home on our fourth asset in the clinic is Elsa Nursen. While our first three programs are small molecules, Elsa Nursen is an ASO. It targets the SCN2A gain of function mutation. What we saw in some data we shared a little bit over a year ago was out of four patients who were dosed over a four-month period, a 43% reduction in their seizures, a 48% increase in their seizure-free days, much better response than what we expected. We accelerated our plans to initiate a registrational study. Given the rarity of this disease, we do need to go to multiple regions. We spent a good part of 2024 harmonizing the trial design with the various regulators, and we got that alignment.
We will be initiating by mid-year what we're going to call the EMBRAVE 3 Study . This will enroll up to 40 patients in a cohort of children ages 2- 18 for a six-month period. We believe that's the shortest ASO trial that's been supported. There are also two additional cohorts, Cohort 2 that will enroll children ages one to two and Cohort 3 that will enroll children from birth to age one. I think it is a great endorsement that this is a program that we can enroll patients all the way from birth as well. We're looking to get that up and going by mid-year also.
With that, we've got one other aspect of the EMBRAVE Study also is we have a Part A currently enrolling in Brazil where we will share data again in the first half of next year also. There is a lot of data coming through as we go for these next 12-18 months. There's also much broader studies that we're kicking off mid-year this year, and we'll continue to give updates for those as well.
Okay, so that was very comprehensive. One thing I wanted to touch on, because this is a question I've gotten a lot from investors recently, especially over the last 10 days. Oh, there's a mic. You know, one of your competitors who's also running a focal onset seizure study pushed out the timeline for the readout for a little bit. The question I've gotten from investors is just given how quickly you are turning around or expect to both enroll and read out the POWER1 study , right? You're looking to basically complete this study within a year. This other company has been running their study for close to two years now, I think. What has allowed you to basically enroll so quickly while maintaining sort of what you would say data quality?
Thanks, Doug. Thanks for coming out a little bit late as well. Multiple things, right? It's never a one-dimensional system when you look into things like this. The very first thing I would say, maybe I know you're talking about Xenon. There's no point about, like, we have a lot of respect for them and the work they're doing in epilepsy as well here. This is difficult, right? I'm not going to discount any efforts being done in this space, but drugs and mechanisms have history, and they tend to influence. I would say that's the very first thing, the way patients are selected and the expectations that they will have and so on and so forth. I would argue the second issue here at play is Empower for us.
For the people who are not familiar with Empower, we have right now the largest, I'm going to call pre-screening, it is an actual study to understand the patients with epilepsy, their type of seizures, their medical records are reviewed by a central medical monitor. If they are likely to qualify, and I think likely is the important word here, they are referred to a site. What we are able to do is really complement the site with more patients that the site are going to go through the entire process, of course, as well, and add patients. That is important. It is about 30% or so of the throughput right now coming from that initiative. When you translate that, it is about three years or so that some of the other companies have been taking, it is an entire year that you wipe out of recruitments on that pace.
I think the second is I tend to refer to this as we are a massive pain in the neck. We are every single day really understanding what the impediments are. We have a process that we call preview awards for that. At the end of the day, it's every single day the teams are meeting and are moving things forwards. Not everyone subscribes to that. We do quite heavily. We believe micromanaging is the way to actually get clinical trials enrolled. Proudly so, we call it micromanaging. The last one is geography. We do have significant overlap. I think that was mistakenly said a few weeks ago by others that there's no overlap in epilepsy. It's completely a lie. There is significant overlap in sites, but there are sites that there is no overlap.
For as long as you pick them properly, we're going to get there as well. To address the quality parts, Doug, maybe just to finish on that, every epilepsy study, either by us, by Biohaven, we also respect, or by Xenon, they all go for the same quality process. I would say that that's probably not an issue we should be focusing on. These patients are suffering a fair bit. They're being educated in terms of the seizure type by the same central folks. That is not a concern whatsoever. Sorry for my voice. I probably need a little water for the run.
You know, Marcio, one of the things that I think we've talked about, the two of us over the years, is the choice between optimizing a program, say, exploring additional doses, sort of running a longer study to perhaps see additional, you know, characterize your clinical benefits more versus getting a drug to patients as soon as possible. You have obviously sort of always focused on sort of getting a drug to market and to patients as soon as possible, you know, the most number of patients as soon as possible. With a drug like Ralutrogen and what, you know, sort of Tim mentioned, the 11-month data and the magnitude of seizure reduction you're seeing, you know, how do you think about finding that balance, right?
Because there's a bar for getting a drug approved, but there's also a bar for really characterizing a molecule which will drive both clinician uptake as well as really also payers, right? You know, that's a reality that we have to think, you know, deal with. As your programs mature, how are you sort of thinking about that? Has your thinking evolved over time?
I think what's something super interesting about GEs, right, since they are on Ralutrogen, that maybe sometimes it's lost. There's a lot of great research being done in terms of everything else that affects these patients, right? When you look into the overall disability, the autism spectrum disorders that are quite present, mobility, you name it. Particularly an area that is of incredibly high impact, but not a lot of research is being definitively done, is early mortality. You can't trace a straight line between a patient either having pseudapp, and unfortunately, that is a consequence of seizures, or aspirating and have pneumonia and then dying as well. We forgot that all of the time. The risk of dying because a kid has a SCN2A mutation on a gene is six times larger than Dravet.
We talk a lot about Dravet and how important other things are. I'm not discounting Dravet syndrome. I'm just saying that it is a significantly bigger issue here. Those things do not take a lot of time, but they are incredibly heterogeneous. When you talk to your patients, your physicians, actually 40 hours ago or so, I was in Germany with world leaders on GE, having one of the most incredible meetings they have every other year with this community. It is very clear, like, we all want to solve the entire problem, but the problem is seizures. If you look into the literature, you only actually need three weeks to properly count seizures. When you are actually using 16 weeks, you are doing multiples of that quite accurately. I think we are actually well beyond.
Maybe quite importantly, both the FDA and payers recognize that as the most important thing we're trying to avoid because less seizures, less hospitalization, less interventions, less healthcare costs in general, utilization of the system, so on and so forth. It's perfectly aligned. I think with Ralutrogen, because the titration is self-titration, it's no change in dose, but the concentration grows or increases quite nicely over about three weeks, we have the beauty of examining the relationship between the concentration and the effects without having to go through multiple and many, many doses there as well. That is the feature of the drug. It's not present in every drug, but in that case, it helps quite a lot as well.
I think one other aspect I might just add there, I think Ralutrogen is a great example where what we want to do in drug development is achieve proof of concept and de-risk the asset before we start applying more shareholder capital as well. When you're always balancing what's the risk of shareholder capital and what's the return, what I think we've done well with Ralutrogen is we de-risk the asset with the SCN2A and SCN 8A populations in the Emerald study. We've been able to raise capital and appreciate Wayne Wright's contribution to that as well, but also in a place now where we can invest in a much broader study that can impact many more patients in a way that's also responsible to shareholders and maximum benefit to patients. These are the things we're constantly thinking about.
In the trial design and something like Emerald, it is a very elegant, straightforward trial design. I think that's a really important way also to think about how do you get the drug to patients for the best benefit. As Marcio said, there's an enormous unmet need.
I think, Marcio and Tim, we've sort of talked about Ralutrogen and Vormatrigine as sort of, to some extent, being your workhorse molecules. You know, you have said that you don't see it necessarily as a competing agent with, say, something like Elsa Nursen, right? Even though they potentially address similar patients. Given the potency you've seen with those two and sort of the fact that you would argue they could be backbone treatments for so many patients, does that push you or sort of a focus in terms of early stage development for the company back on sort of the ASO platform and refocusing on some of the very well-defined genetic epilepsies?
GEs, as we understand them today, it's incredibly different than we understood them about 15 years, 20 years ago, right? We're talking about a group of like a handful of conditions to about a thousand or so distinct conditions right now. They create kind of three different features here. One, it's incredibly exciting that we can address them directly, the market's incredibly large. The drawback is you might become enamored to all these tiny little things and chase them. I think the process we go quite constantly is to ask the question, which of those subgroups fits everything we're trying to do here? Health patients, first and foremost, meaningful benefit, clear shareholder and always stakeholders' return so we can do it again, right? It's part of our mission is to keep doing this again and again.
Some of those GEs fit that bill quite nicely. For example, our Praxis 100 program, which is in loss of function, causing for the gene causing for NAV1.2 receptor or channel, that is about 20,000 patients in the U.S. Absolutely nothing helps these patients. Now, they do not seize a lot, but they have a lot of intellectual disabilities, particularly ASD. When you look into that, nothing else, small molecules unlikely to help right now. If it is to help, probably going to come from us anyway. We can always like expense the markets later on. For other conditions, it does not make sense. We can use something that is incredibly broad and potent, like Ralutrogen, to address.
For as long as we believe that distinct needs and markets, since we all are here to give like returns to the community, particularly this one is investors' community here, and to maximize the well-being of patients, we're going to continue to separate them. As we look right now, there is not a lot of near-term limits for this model, but it is a balance. There are certain conditions, for example, SCN8A, that we don't believe an ASO is ever going to be viable because of the characteristics of the disease itself. On that one, Ralutrogen is going to be the molecule of choice. For certain others, we're actually excited about it's building muscle as well.
We can go from the GE and the different molecules we're working right now quite easily to a number of other conditions if time and capital and the science allow that are adjacent to GEs, but they're not necessarily seizure-like or developmental-like conditions that can use the same technology.
One of the things, you know, at the analyst meeting you recently hosted that you talked about was some of Steve's work in terms of modeling for neurons and the channels and the cell interactions. I'm just curious how mature that work is and how much further can you take it to increase even further the precision of the small molecules or ASOs to influence sort of seizure activity and as well as just developmental activity in these patients.
Yeah. There is a lot of work that is not disclosed right now. We've been using, I'm sure Tim mentioned this earlier today. We have a very good and tense collaboration in the company. We believe in health and vigorous debates in terms of prioritization of the assets on both the science and on the economic value. When you put on the matrix, it makes sense to move forward to what we have right now. You can imagine that there would be at least five- 10 other targets that would be ready to be pretty close to have leads and then a declaration of a candidate when the capital condition and the science and the structure of the company allows to do so. If there is an opportunity before that to partner or to do something else with these assets, we'd be happy to.
Expanding around, as you rightly said, on the incredible work that Steve's done throughout the years and enabled the company to be where the company is right now, going to continue to generate fruits for the time being.
With that I think we are out of time. Unfortunately, we'll have to stop there. It is great to get the update. Thanks for all the efforts in making the presentation. Thank you.
Thank you.