All right. Good afternoon, everyone. My name is Cindy Xu. I'm an associate at the JP Morgan Investment Banking team. Our next presentation will be Praxis Precision Medicines, and the presenter from the company is the President and CEO, Marcio Souza. With that, I'm going to hand over to Marcio.
Thank you. Thank you, Cindy. Thank you, everyone. A real pleasure being here. A lot of you here in the room and, I guess, on the webcast know me, so know this is not my voice. This is my J.P. Morgan voice, although, I guess, a lot of people are telling me it's an upgrade to the regular one, so talk a little bit about Praxis and why this might be the most exciting thing, if not the most exciting thing I've ever done in my life, and trust me, I did a lot of exciting things before because we're really revolutionizing how drugs for this incredibly meaningful disease to patients can be treated in a quite unique way and quite a meaningful way.
We always say we dare for more, and I hope you're going to see during this conversation, which I prefer to be versus a presentation during the next several minutes, why we believe that we're really going to be daring for more for patients with CNS conditions. We're going to be making some forward-looking statements. Please refer to our SEC disclosures, and as I'm sure you're going to do that, to be up to speed with those. Why are we so excited? Maybe first and foremost from a value proposition perspective, and particularly for investors as we start this year on the heels of what was a quite phenomenal year last year. So we have four programs in late-stage developments. I think for any company out there, that would be quite exciting.
It is incredibly exciting for all of us, particularly more exciting for what we're referencing here in the headline that is those patients that are bringing these therapies for. On top of that, the sum of what I would argue fairly conservative estimates for each one of those programs are bringing over $9 billion in potential revenue. We always see, I definitely do, a way to continue to invest in innovation by bringing results for all of you as our investors and for society so we can develop more and more drugs for patients. So that is just a metric of how much more we can do throughout the years and hopefully be quite successful, all of us. This year itself, and one could argue last year, was quite meaningful as well from a number of things that happened and quite a transformation for the company.
Continue to advance each one of those programs in a quite meaningful way, and we're going to go through some of those milestones in the following slides, which is quite phenomenal as well since it's not only high value, late stage, but everything is advancing quite meaningfully as well. How can we do that? Of course, the first thing, and maybe that's what should be here in this slide: these patients are out there. They need us. The second thing is that it's an incredible group of people that supports the efforts that we're doing every single day relentlessly, and we created two distinct platforms to deliver on this. We asked the question in the brain, as we're going to see in a second, how can we address that? We're agnostic to the tool that we use afterwards, and we decide what is the best way to modulate it.
From a cash perspective, we're very well capitalized. We're very disciplined on the use of capital for the company. We have been very disciplined for a long time. And that brings us generating all this value, all these programs advancing to completion of the clinical studies or NDA filing until 2028. So very, very strong position to start and to be with right now. The four major principles that we utilize in the company to move these programs forward to derisk is first looking to genetics, but instead of looking into that in a one-to-one relationship, we get inspired by genetics. And it's going to be pretty clear why I'm saying that later. Asking what happens when there are disturbances and try to adjust our programs in relation to that.
Use to its maximum translational tools we are very committed to be efficient and rigorous when it comes to the execution, to asking the questions, to questioning the assumptions, but most importantly, as I mentioned a number of times today already, truly patient-guided, and patient-guided oftentimes means doing things that have not been done before because we're answering really the question for all of us that are patients at one point in our life, but primarily the people who are not in the room when we're making these decisions, so what we have right now, and we'll spend just one second here, as you can see, it's an incredibly busy, one could call meaningful, which is what I would refer to, but a number of assets that are incredibly high value.
That is a lot of focus on the top here of the platform, one of our Cerebrum platform, which is our small molecule modulator of different targets in the brain, particularly the most advanced programs, the top three here. Ulixacaltamide for movement disorders, the first indication being essential tremor, PRAX-628 for epilepsy, particularly in adults, relutrigine for developmental epileptic encephalopathies, so very, very severe disease of childhood, and then many other indications. So I'm going to focus on the top of the funnel today because we wouldn't possibly have enough time to explore each one of them in just a few minutes. When I mentioned at the beginning that we will be progressing each one of those programs this year, I think that's, here's the illustration, right?
There's a lot of focus as we speak and a lot of conversations during this meeting in relation to the very first program. I think it's quite natural. Essential tremor, as again, we're going to see in a minute, is an incredibly large opportunity, one that is wide open. And we are reading out two Phase 3 programs imminently, including an interim analysis for the parallel group study this quarter. So no doubt that that would be something of focus for all of us here in this room and in the industry in general. We intend, since we expect those studies to be positive, to file an NDA this year.
There is always a lot of questions about the different scenarios that can come up out of the interim, but in any scenario, as I'm sure we're going to explore, the NDA is still being filed based on the two studies being positive later this year. It's incredibly important for us as well. When you move into the focal and generalized epilepsy program, they're progressing incredibly well. We have the most differentiated program in focal epilepsy ever developed, and we're going to discuss that a little bit in the future of this presentation as well. We've read out both in the first half and in the second half of the year. As a group, the developmental encephalopathy programs are all advancing quite nicely with some readouts coming up in several months as well.
So very meaningful, very active number of inflection points for patients, ourselves, and particularly investors with Praxis. So spending a few minutes on movement disorders, specifically on essential tremor. Essential tremor is the most prevalent movement disorder affecting Americans. People in this room have essential tremor, I am pretty certain. And if there is no one here in this room right now, we know someone. There is someone in our households. There is someone who is our neighbor who has this condition. It's a progressive, but there is no degeneration. And I would say that that's good news and bad news. The good news is that it tends to get worse, but not necessarily, unfortunately, as other progressive diseases with degeneration like completely destroy part of the brain. But the bad news is that took a lot less attention throughout the years in terms of how to address that.
Right now, in any point in time in the United States, there are over 2 million patients seeking treatment. The only thing we can offer them as a society right now for a very, very small number is a first-generation beta blocker that barely works and works just in a very small part of that. It's a wide open market with massive unmet needs that is robbing the ability of many patients to function every single day. Then if we transform that to dollars at the end, since that's part of the equation as well for innovation, it's over $4 billion in total, and I would say in a very conservative way.
When we design the phase three studies, which I'm going to discuss a little bit with all of you, the key question, and we're incredibly happy that we are aligned with the FDA on this, is how are lives of those patients affected? And then we measure the way it's affected. Luckily enough, it's actually pretty simple because patients with essential tremor lose function. They lose the ability to simply grab their cup of tea or coffee and have that drink and enjoy that drink or eat by themselves or go out with their family. So the scale that is utilized in the phase three study is based on the ability to perform tasks. Incredibly easy to understand, incredibly easy to derive meaningfulness. Because one function, one point, restore one point, restore one function.
If you cannot drink coffee in the morning and now you can, I doubt that any of you would tell me that that's not meaningful because that is not only a translation for the coffee in the morning, but it's a translation for a lot of other things that you can do in your life. Why are we excited about the program move forwards? In our phase two study, using exactly the same endpoints, but a much smaller sample size since we are trying to understand at that point in time what we call the Essential1 , what would be the magnitudes of effects that we would have with this drug? We're seeing a quite meaningful, one would argue, I certainly would, large separation between drug and placebo, and a nominally significant P-Value here, as you can see in the bottom.
Based on those results, we had discussions with the FDA, and we designed a very innovative phase three program, which we have here in front of you. So let me walk you through a couple of elements of this program because I believe it's quite important to understand considering that we have an imminent inflection here in Q1. This is the first time in neurology that two studies are run in parallel, truly in parallel, where patients are unaware of what study they are participating in. Patients are randomized to the study before they get re-randomized into the specific control in the study. That allows for a direct comparison throughout the study for better monitoring, for more homogeneous patients in general. It's a very tall order. The reason why many companies don't do that is because it's incredibly difficult.
We're talking about 600 patients being enrolled on a study versus 400 or 200. So it's a tall order. One that we strongly believe, and even more so today, that was necessary to continue to give us confidence as we progress with this study because there are many things, and I know a lot of people listening to this in the room are drug developers, and you can see already the benefits of being able to monitor these studies as we go and to make estimations and to potentially make adjustments, which we haven't made but could have been made. But it answers multiple questions as well. What is the separation on the more classical parallel design that is the one on the top? What happens when you keep these patients on drug and you remove the drug is the one on the bottom.
What happens when they put them back on the drug when you do the rescue in the long-term safety extension? Questions that physicians and patients grapple every single day when they are using a drug. So it's incredibly informative from a regulatory perspective and eventually from a commercialization perspective. For Essential3, we took the recruitment into our own hands, and what it generated was over 130,000 patients reaching out and going through pre-screening in our pre-screening system to participate in a study. I am unaware, and I would love for any of you to tell me that if that ever happened before of any condition, let alone in CNS, where over 100,000 patients have reached out to participate in a clinical study. This just showed the number of patients out there, number one, validation of the size of the market that we discussed before, but just the unmet needs.
We're incredibly rigorous on how to enroll this study. We are now at a point that we're going to be conducting this interim analysis imminently to decide whether or not we stop the study for efficacy, we continue the study as planned, or if for any reason, since this is the very first Phase 3 study in essential tremor, if we need to make adjustments from sample size re-estimation. In any of those scenarios, I believe it's a win for the fields, and it certainly is going to be a win for Praxis and all of us in this room. We're very excited coming up later in Q1. Moving on to epilepsy quickly, it's not less excited from a science or from a business opportunity perspective.
When you look into our three molecules in the clinic right now, and we have a number of them preclinically, and you see the numbers here by yourself in the slide, each one of them addresses very high medical unmet needs, large number of patients in some of them, some are rare indications here, but in a very differentiated way. I think that is the most important point to highlight. There are many ways to address seizures. There are many ways to address developmental encephalopathies, the 30 years or more of development in this space. The question that one must ask is, are we doing a good job today, and we are not doing a good job today. There are many other companies, and I applaud each one of them advancing treatments on this area as well, and we need it.
We're certainly going to play a huge role here on addressing these markets. PRAX-628 is one of our lead assets and arguably the second largest indication here that we have. When you look into the profile of our PRAX-628, being the most selective, most potent drug ever developed in epilepsy. A lot by design, a fair bit by luck. I think we should always be a little bit humble and say when you got lucky in certain things, we definitely got a little here, but a lot of that by design, by targeting specific properties of the channel that have not been properly targeted before. What we see is sodium channel modulation work, but why do we have to stop treating patients with this? For multiple reasons. Sometimes convenience, not the case here for PRAX-628, can give once a day.
Sometimes it's too hard to titrate, not the case here, direct therapeutic levels at the first hour after dose. Sometimes for efficacy, and that is one of the biggest issues. 30% to 40% of patients with focal and generalized epilepsy fail every day. It's a rotating merry-go-round of having seizures. I hope you never had one. I hope you don't know anyone who had one. It completely stopped their life on its track. It's not either fun or, most important, it's very dangerous. When you compare with drugs that are being either very successful as cenobamate or drugs that I expect to be very successful as the drug candidate Xenon for focal epilepsy, you can see why we are so excited. We're pushing every single time in drug development for epilepsy, the efficacy very, very close to toxicity. What we see with PRAX-628 is quite the opposite.
We can go way beyond what anyone has ever seen from a potential efficacy perspective without reaching the maximum tolerability or even close to the maximum tolerability, so what did we do with that? We did a lot of Phase 1 work. We did a lot of early Phase 2a study, but where are we right now? We have an Empower program, very excited. The person who named this is in the room here, and I'm very excited to acknowledge that as well, and we decided to do a number of things with this program, so the first one is try to get as many patients characterized before they get into the trial, and that's what Empower is. Empower is a way to understand the space better and then allow them to choose to be in a clinical study.
We have several thousand patients right now that raised their hands and said, I want my seizures better characterized, and I want to think about participating in a clinical study. That at least partially resolved the problem of enrollment in epilepsy studies. That's at least what we're aiming for and we believe so far being very successful. Then we have Radiant, which is reading out this half of the year. Quite meaningful as well is the first time there is a combination of primary generalized and focal onset seizures in the same study since we believe it's going to significantly address both of them. Again, coming up pretty soon. And by the end of the year, we're going to have Power1 . Power1 is your more traditional, if I may, parallel group, 12 weeks, median seizure reduction, 28 days adjusted study.
What we expect from this program is not what we've been seeing before with drugs in this space. We expect really to create a revolution in terms of how these patients are treated. We know we cannot cure this disease with those molecules, but we want to give them a chance to be there when potentially a cure is going to be available for these patients. And we believe we're going to be a lot closer than we are today after patients are taking this molecule. Moving on very quickly to our relutrigine, the concept is incredibly similar. So we have one molecule that does a phenomenal job modulating these channels for larger indication and one that we designed specifically for patients who seize continuously, 10, 20, 30 seizures per month, per day, sometimes, unfortunately, per hour.
The properties are very similar, but the pharmacological properties are tailored for patients who are pediatric. They can be given orally or not orally, like through a tube. They last a very long time. So these patients, if they miss a dose, they're still on the therapeutic level, and they're obviously incredibly potent and allowing to. We run a Phase 2 study, a proof of concept. And what are you seeing? And just to contextualize, those 15 patients at baseline, which is only 28 days, four weeks, had almost 1,800 seizures. So just think for a minute because having one seizure is one too many. Having 1,800 at baseline is certainly something not to joke about. And we're seeing quite unprecedented results here, 46% placebo-adjusted seizure reduction. That alone would have been incredibly meaningful.
But what really humbled all of us was that 33% of those patients in four months, in the four months of the study, became seizure-free. So imagine a family with 100 seizures in the previous month have zero seizures for the following four months. I know most of us here, our parents are definitely young and how meaningfully that would be. The progress that I was seeing is equally impressive. Looking to placebo here, the minimums, right? You can't really fake it. You can't really try to. Those kids are nonverbal. We're really seeing all of that happening. In the very first time, when you compare one month, just one direct month comparison, it is larger than other trials run for 12 weeks, for three months, for four months. In the very first time when you compare side by side with them in one of the periods on the study.
But when we keep them for nine months on drug, you see a phenomenal 77% reduction. And of course, a number of those patients are seizure-free. All of that we were expecting. I know it sounds quite extraordinary, but we were expecting. What was surprising, and not surprising because we didn't think we're going to affect, but surprising because it is surprising, is to have a disease modification with a small molecule. And what we're seeing independently by caregivers or clinicians, not on the same day, not in the same room, not looking to each other and asking the questions, but independently assessing items that are incredibly important, like disruptive behavior. When our brain's on fire, when we seize a lot, we become very disruptive. And these kids, unfortunately, are very important. Improving communication.
I'm going to ask you again to imagine the parents that cannot communicate with their child and now can increase the communication. It's quite, quite meaningful, incredibly meaningful. Severity and intensity of the seizures, it goes with the territory. Reduced seizures, reduced severity was good to see, but was expected, and alertness is counterintuitive because one would expect, and particularly with the drugs in development right now, that you dampen, you reduce hyper-excitability, you reduce alertness, and what we've seen is bringing these kids back, like unlocking these individuals on their body, so incredibly excited, so what do we do when we are excited? We keep going, right? We amended this protocol. We added registrational cohorts, which is here on the top. This registrational cohorts is ongoing. It's going incredibly well. I would say partially because when you have incredible results, people get excited.
They work more with you. We announced on Sunday in our press release that we intend to use the data from that study, assuming to be positive as we are right now, to file an NDA next year for this indication. It's a good reminder that we have pediatric designation for this drug. So that gives not only the ability to give these drugs to patients, but really to help us fund the next wave of innovation as well without continual fundraising for that. So quite meaningful. But maybe even more important is that when we looked into the mechanism, we start asking, could this work across the board in GEs? The current definition of GEs and the subdivisions that we all make are actually quite recent, right? We start like splitting hairs not that long in the past.
But fundamentally, when there is dysfunction in the brain, these neurons are firing in an aberrant way. There is always one type of mechanism that is present that is important, and it's sodium channel modulation. One could argue, and maybe some of you would argue with me, that GABA as well on the other side on the inhibitory part, and it would be correct. But one that we can titrate, meaning we can modulate. So what we decided after doing a lot of preclinical work was really to talk to the FDA as we are doing it as we speak, and start a larger study in what we're calling all GEs on phenotypically defined GEs.
So we are going from a market opportunity perspective from a few thousand patients, five, seven thousand patients on the top to 190,000 patients on the bottom in the United States alone, helping more people, generating more opportunity and revenues, and investing on the next wave of innovation as well as a company. So just going to end with, it's incredibly exciting. We went through about half of what we are doing right now. Everything is moving tremendously. We're very, very thrilled, and I'm particularly incredibly excited about this quarter as we're going to be talking about essential tremor. This half, we're going to be talking about Radiant and how we help patients with focal and generalized epilepsy and the remaining of the year as we start to dream about really creating this fundamentally different company in CNS and helping patients, helping our employees, and helping shareholders. So thank you.
Thanks for joining us all, and I appreciate your presence.
All right. Any questions from the audience?
Hi. Can you tell us what were the, you know, remember following up with you before on the components of the essential tremor score? This is now a modified score. What did you take out, and what was FDA's reaction on taking these things out? I know, you know, Spiral was part of it. I don't know how wedded the FDA was to Spiral. I'm sure that I think there were three or four other components too. Just love to get a little bit more of an understanding of the new score.
Yeah, absolutely. So there are two major scales on essential tremor, right? One that we call the TETRAS ADL, and it's what we are looking to here, the activities of daily living, and the TETRAS Performance Scale, or PS. What we're referring to is the fields, and I mean the movement disorder physicians historically had been more prone to looking to the performance scale. And I actually think that's quite obvious because the performance scale resembles a neurological exam, like the patients, and it's great to assess a patient whether or not they have essential tremor or a parkinsonism or any other movement disorders. It's not very adequate. I'm going to even go as far as to say it's horrible to assess progress over time. The very first discussion we had with the FDA about two and a half years ago or so, we actually proposed the performance scale.
Like that's the prevailing scale out there. The agency was quite clear with us that that would not be adequate, that we had to measure the activities of daily living. If we so wished, we could add a few items from the performance scale. The ADL itself, and I believe that is incredibly important here, is always assessed as 12 items with a 4-point dynamic range, 0 to 4. Any of our investigators right now on Essential3, on Essential1, on any other study, when they are assessing the patient, are 12 items, 4-point dynamic range, 0 to 4, no impact at all, and complete impact you cannot conduct on the 4. That's the dynamic range. The agency asked us and others in the field to, after the collection, mathematically transform the score.
I think that is a quite important notification or clarification because a lot of people think that the actual scale is modified, but one could argue that it's the results of the assessment of the scale that are recalculated. The dynamic range reduced. The hypothesis being that zeros and ones are pretty similar, so we should try to put them together, and that the social impact, which is the item 12, is not that reliable. That was the assumption from the FDA. While I don't believe that there is evidence, scientific evidence for the social impact not to be relevant, that is the agreement we have with the agency to use the 11 items from the scale and the three dynamic range. Quite importantly, though, going back, I should use this other thing I forgot.
Those results from the previous study are on the exactly same collection, protocol, training, and calculation as the current study. There is no modification between the two. The two items that were not included here, that were included in a previous study, are the items six and seven of the scale, which are the Archimedes spiral. So it's the ability of patients to draw a spiral, which for us is actually pretty simple, considering that we are neurotypical here. For patients with essential tremors, incredibly difficult. And we're still conducting that. It's not an endpoint. It's not a formal ranked endpoint. To answer a different question, humans, and I'm sorry for all of us limited humans in this room, we cannot discern in a dynamic range for spirals from patients in a linear scale between zero and four. But we believe computers can.
So we're doing experiments, and was a discussion we had with the agency. It would be interesting if there is a way to discern. That is not an endpoint, a formal ranked endpoint in the study, but it would be a good scientific question to answer. I think both ourselves, and of course, I cannot speak on behalf of the FDA, but I believe by what they said, they agree. The handwriting sample that was the other item is just completely garbage, and it should not be used in any study. And not garbage because a patient did or a physician assessed from an endpoint perspective. It cannot be assessed. So unfortunately, may I say, because it would be good to have other assessments. So this is the endpoint that we agree with the agency that's going to be used, is being used on both studies.
Both studies being positive at our end of Phase 2, the discussion was that would be used to support the NDA that we intend to file later this year.
Other companies that are doing essential tremor, are they also doing this new scale?
Yeah.
Versus the old scale?
Yeah, so I think as of today, for good and for bad, there is no one else in late-stage developments in essential tremor. If I was a betting man, I would tell you that the next one will because that is an endpoint that is intrinsically meaningful. The FDA really likes it, and it's very reliable, and I think when we are developing drugs, we want reliable endpoints as well.
I guess we have five more minutes left in the Q and A. Maybe one last question from me. For essential tremor, could you talk a little bit more about the scenarios that you mentioned for the interim analysis that we expect in Q1?
Yeah, absolutely. Thanks, Angie. When we started this study, we were the very first, as I mentioned before, Phase 3 program in essential tremor. So one must ask, I believe at least, what can go wrong when you are doing something like this? We had many assumptions before, and if you were like 18 months ago, two years ago, ask me and say, we believe we controlled all the controllables, there is one thing we don't know, is how big should this study be? How is the variability going to be on that study? When we went to the Phase 3 study, that is the ones we're discussing right now, we asked the question, in the eventuality that something happens in between and we might want to increase the sample size because the estimation is a little bit wrong, what is the proper mechanism to do that?
From the get-go, from the very beginning, we discussed that with the FDA and we added an interim analysis in the protocol. We continue to monitor the program. We until recently decided we're not going to trigger the interim because everything is really going as well as one can imagine to be. And then there was a competitive, right? It's your question. There was a competitive program until recently, and while we know very little about the results, one of the things they said is the placebo effect was a little bit bigger than we expected. So we decided to, while we have no evidence whatsoever that that's the case for us, we believe that's coming mostly from ex-US sites. Our study is exclusively in the U.S.
We decided that for the price of the premium of the policy, the reward on the other side of the policy was more than worth it. So what scenarios we have right now based on that? It's a biased scenario as a biased interim analysis towards continuation of the study as is or sample size re-estimation, meaning over 80% of the probability is within those scenarios. Independent Data Monitoring Committee reviews the data and makes a recommendation to us. And the recommendations are likely, and I'm going to say in order of a priori, probabilistically likelihoods. The first one is continue the study and just finishing. The second is stopping the study early for efficacy, what we call overwhelming efficacy in a scenario like this. And the next one is increasing the sample size.
If they were to offer to increase the sample size, trust they are also going to be suggesting how many more patients in 50-patient increments. To give you an idea, I talked about over 100,000 patients that reached out to participate in the study. Currently, we have an ability to randomize around 15 patients per week in the low end, so we would be 50, it would be three, four weeks. If it's 100, it's a little bit more than that, so it's a very unique situation, right? Because most times when companies run an interim analysis, they are like so far from completion of the study that they need to calculate whether or not it's worth it from a cash burn, from other things. We don't because we are really there.
And if they recommend as we expect, and I don't expect because of anything else other than the fact that it's probabilistically more likely that they ask us to or suggest, since it's non-binding, to just finish the study, it's a matter of weeks, not months. And that's a luxury that we have for phenomenal execution, as I believe that that was the case here.
Is futility also a fourth?
Yeah.
Yeah.
Yeah. So the last side of the boundary, every time you have efficacy on the top, you have futility on the bottom. It's a priori less than 3% probability of being futile the way it was designed. But yes, it's always a probability. Good. I guess we have 30 seconds. Appreciate everyone here. Hope you enjoy the conference and looking forward to a great year.