My son couldn't find his calculator, so let me. We're ready to go. Okay, welcome, everybody. I'm Doug Tsao, Senior Analyst at H.C. Wainwright. We are pleased to have Praxis Precision Medicines up next, represented by the company's CFO, Tim Kelly, who I'm sure many of you know. It's been an incredibly eventful, you know, twelve-plus months for the company.
Mm.
When I think about where you were last year at this conference versus where you are today, you know, so as a starting point to maybe I think it'd be helpful to just provide a review of everything that's happened, right? We've seen ulixacaltamide move into phase III, data for 222, PPR data for 628, and now, most recently, the EMBOLD data for relutrigine, and where you are as a company.
Yeah. Thanks, Doug. Thanks very much for everybody joining today as well. I was thinking the same thing as I was coming into the hotel today about what it was like a year ago. At that point, we were trying to start our phase III programs in ulixacaltamide. We're now in a place where we've had over 75,000 patients come to the study website. We have two phase IIIs up and running very well right now, one placebo-controlled, one randomized withdrawal, and looking to, you know, still aim for our readouts by the end of the year.
We will, for one of those, you know, look to do an interim readout, but we continue to see very good participation interest from people in those studies, and I think it validates just how large the unmet need is in essential tremor, and how much we can be bringing to those patients. On the epilepsy side, the portfolio there has also been really exciting over the past year. Everything this time a year ago was on the verge of phase II data, and all of that's read out successfully. Our 628 program had a very successful PPR study, where we saw effect in epilepsy patients with our 628 program. And in that, it was a huge de-risking for us.
At the time we decided to do it, we did not have the resources we have now, and it was, I think, a more thoughtful, efficient way where we could get proof of concept. We saw that, and we've now launched what we call the Energy Program, which is three different efficacy studies that we will look to advance for 628. Our RADIANT study will kick off in the second half of this year and look to enroll 50 patients in an open label study and read out in the first half of next year. Then, we've started the first of our two registrational studies, called POWER 1 and POWER 2.
We'll start the first one the second half of this year, get the other one going in the first part of next year, but be on path very much there, where we can get our 628 program through the registrational studies phase, and I think also get some good data in the first part of next year. 562, or our relutrigine program, is a really exciting one for us, and many of you may have seen that last Tuesday, we shared the results from our EMBOLD study. This time a year ago, we were still enrolling and recruiting for that.
But those patients, out of 15 patients, we saw a 46% reduction in seizure, placebo-controlled, over the, the four months that patients were in the study, and 30% of the patients, or roughly five out of the 15, experienced prolonged periods of seizure freedom of at least one period or more. Each period for us was four weeks in this study. That's something that was really exciting to see. These are very, very serious patients, and we will be looking to now carry our relutrigine program forward into a registrational study for SCN2A and SCN8A patients, but also more broadly, looking at how sodium channels or the sodium channel approach can help other DEEs as well.
There’s, you know, over a hundred thousand patients we think can benefit from a better approach with a sodium channel modulator that relutrigine offers, and so that’s something that we’re gonna be looking to carry forward in what we call our EMERALD study, and getting that off the ground shortly. Then lastly, kind of rounding the third base into home, our fourth program, elsanorisen. This is a program we’re looking at. It’s an ASO and SCN2A gain-of-function patients. This time last year, we were still enrolling and dosing four patients in a small Part 1 cohort. What we saw in those patients in December of last year is that over a four-month period, they had a 43% reduction in seizures, a 43% increase in their seizure-free days.
Really strong results, and so because of it, we've decided to advance that program into a registrational study. And so given that this is a very rare disease, we will be doing a global study, and so right now, harmonizing that protocol across the EU and the U.S., and getting that off the ground shortly as well. We are continuing the Part 1 portion of the study that we gave results on last year in Brazil right now and already recruiting there also. So we're in a place now, you know, this time last year versus now, two phase IIIs up and going, and then our other programs all at a registrational phase. I think lastly, we've also had two very successful raises this year. Thank you for those of you that supported that.
Done a lot to not only ensure we fund our whole portfolio, but extends our runway into 2027 as well.
So, to maybe start with ulixacaltamide, and one of the more recent pieces of news was your decision to do the interim analysis, and I think, you know, that surprised some investors because I think we were all sort of prepared for just the final readout of the study. So maybe just walk through the reasoning for it and what this will allow you to do.
Yeah. So the interim analysis had always been part of our statistical plan. When we designed the study, we have done as much as we can to control the controllables in the study, and do that through a larger study design, the way we've set the powering assumptions. We believe we've got an endpoint that has performed well before, that will continue to measure well. And so we're feeling very good about how the study is going, the way that even our decentralized design is something that's a bit novel, but that's all performing very well also. So as we look at it, we feel like we've done as much as we can to reduce the risk of the study.
Now, I think one thing that we're mindful of, though, and particularly when we heard Jazz's study results and where they shared that part of what they saw was a higher placebo response, is we also recognize that there may be things that are beyond, you know, what we thought about, as much as we can. And so it would be a shame for us to get to the end of the study and find that we missed the placebo response by, you know, hit point zero seven instead of point zero five, for example. We would really kick ourselves for that. And so what the interim analysis allows us to do in this, you know, pre-specified statistical plan we have, is to evaluate the results, at the time that we do the snapshot.
So the interim review board will take a look at it at a time, probably between, you know, 50 and 75 percentile of the patients being completed, and they will inform us if we need to bring more patients into the study. And so for us, you know, we're executing everything very well. We will have those patients lined up and ready to go, but it's really a bit of an insurance policy. Given what we're doing, we thought spending a little bit more time if we needed to would be well worth it, given the long-term benefit for patients.
In the sort of scenario in which you do potentially need to enroll some additional patients-
Mm-hmm.
What is sort of the realistic impact in terms of the timing for the ultimate readout, the final readout?
I think in that circumstance, and overall, you know, we still believe the study we have is gonna be sufficient, but in that circumstance, I think part of it's dependent on when we get the report back from the interim review board, so that can take a few weeks. We are at a place right now, given the interest we've had in the study, we'll be able to activate patients who we could screen and bring in, but realistically, that takes, you know, at least the 12 weeks of their dosing and a few weeks of screening on either side. So that may move us more into, you know, the first part of next year, first quarter, first half, potentially.
I think, you know, the thing that we have talked about is once we get the results from the interim analysis, we'll update everybody on how that's going.
Okay. And you did note that there have, you know, that Jazz had a setback. There have been others. You know, essential tremor has proven to be really challenging over the last 12-18 months for many competitors in the space. What is that, John, or how has that influenced your thinking about the opportunity?
You know, I don't think it's done anything to diminish our sense of the opportunity. I think, you know, if anything, we are now hearing more and more anecdotes about how this disease is impacting so many people in their lives as they've come to the study. So I think we feel very confident that this is a huge unmet need that's ripe for innovation for patients.
Okay
and we're hoping we can bring that to them. I think what some of these studies have also, you know, made us mindful of, and we're always humbled to ensuring that we're doing as much as we can in the process of designing and executing a trial, so, you know, for example, we've added enough patients into the study that we think we're in very good shape from a statistical powering perspective. You know, we're not trying to cut any corners. We're ensuring compliance and quality are never compromised as we're going through this study. Those are the things for us as we hear about others having setbacks or failing. We want to understand why, and we want to ensure that we're doing as much as we can to mitigate that happening to us.
Turning to 562 or now relutrigine, as it's called, the data was really impressive in terms of seizure reduction. You know, you have spoken about this drug as potential sort of disease-modifying therapy-
Mm
which would sort of be, I think, different from most drugs sort of been treated, you know, sort of just basically focused on seizure control. How? What gives you that confidence, and how did, you know, EMBOLD inform you in terms of the drug's potential in that regard?
One of the data points that we captured through this was the global impressions from both the clinicians and then also the caregivers. As we were going through the readout and looking at the database, we were really struck by, and this data is all in our slides, by the proportion of both caregivers and clinicians. They reported positivity in seeing these children have improvements in alertness and reduction in the severity of their seizures in communication. These are things that, given the severity of how this disease manifests itself for these children, are really meaningful things to experience.
And so when we look at that on top of the seizure reduction and seizure freedom that some of the children experienced as well, we really think that there's an opportunity for this to modify the course of the disease. And that's something that we'll be looking to understand further as we go into the next trial.
When you go into the next studies, will those sort of endpoints be enriched in any way, or, you know, will you be basically replicating what you started to do on a more limited basis in EMBOLD?
Yeah, essentially carrying forward EMBOLD, and I think that's the nice thing about the design we have right now, is we are essentially extending the protocol for what we have. So continuing to capture safety, of course, but also seizure counts and then also the CGI, Caregiver Global Impression, as well.
You know, relutrigine is not your only drug for patients with SCN8A dysfunction. You also have elsanorisen, which you referenced, which also showed very strong reduction in seizures. I'm just curious, do you see how you ultimately see those two drugs sitting next to each other in the marketplace? You know, I think you've sort of hinted that it might not necessarily be an either/or.
Yeah, correct. And just to clarify, it's SCN2A gain-of-function-
Okay. Sorry
for those patients. Yeah, they both work in very different ways. So elsanorisen is an ASO. It works, if I were to say, maybe a bit more upstream, trying to, you know, mitigate the protein that's overexpressed. And so that's the part that reduces, you know, how the disease gets experienced by the body downstream? And then 562 works a bit more on some of the direct seizure-
symptoms. Given the severity of these diseases, and until we're at a place of complete cure, I think we're looking at this as being an additive approach. Maybe not for every patient, but being in a place where both drugs could be complementary to improving a patient's outcome.
And I guess, do you anticipate sort of sequencing with the two products in any way? Or are they, you know, sort of one more targeted for a certain subset of patients versus others, or potentially ultimately both getting both? But, you know, I'm just curious how you anticipate that translating in clinical practice.
Yeah, I think I have no better answer to this. It's probably too early to say right now. It's definitely early days. It's great to see the efficacy of both of these drugs, but in terms of what exactly it would look like to dose those, either sequentially or in process, that's definitely something we'd have to think about in the future. But we would, you know, lean into that.
You know, maybe going back to relutrigine, you did reference that you are looking at development in a broader DEE population.
Mm-hmm.
I guess maybe if you could help people understand exactly, you know, which sort of types of epilepsies and DEEs you're most focused in particular, and do you plan on enriching or excluding certain patients from that study?
There are over 900 genetically defined developmental epilepsies, and there may be more, you know, almost every day as we learn about more and more genes. We see that the patient population there is, you know, well over 100,000. And many of those patients, as part of their course of care right now, are given a sodium channel blocker. Roughly 70%, if not 80%, if not more, patients who already get some type of a sodium channel therapy. A number of those therapies are not very well tolerated and don't have great efficacy either. The promise that we see in relutrigine is to be, given the sodium channel modulator approach that it utilizes, potentially a more tolerable and better efficacy therapy for those patients.
So what we would be looking to do, and we still need to go talk to the agency about this, but a more phenotypically driven approach, looking at how we can, you know, add on or potentially replace the sodium channel therapy that those patients are receiving.
Mm-hmm.
We see it definitely as a substantial opportunity and one that we're looking forward to getting into.
Okay. And would you think, anticipate needing just one registrational study for that indication?
At this point, yes.
Okay, and I did mention elsanorisen, and I think you have begun enrolling patients in Brazil-
In Brazil
in Brazil for that study.
Right.
I'm just curious, you know, I think the original plan had been initiation of a global study, you know, sort of all at once. You know, so what has been the hold-up in terms of getting alignment with some of the different regions? I think you have PRIME designation for Europe. And how should we think about that progressing and impacting the timing, for that program?
Yeah. We are doing all we can to ensure that the agencies are aware of what we're doing and trying to push those timelines. I think sometimes we're not able to move how fast those agencies go as well. They have their own time clocks that we have to work with as well. What we're trying to do is ensure that when we interact with them, we're, you know, answering and addressing as many questions as possible, but sometimes it just takes a little bit longer. What's important to us is we get the right protocol, and we get alignment with everybody, rather than just trying to rush to meet a deadline. So, in the meantime, you know, we're able to get our vendors ready and identify where these patients may be, so we can recruit and enroll quickly as well.
But what's gonna be important is getting the right harmonized global protocol.
And so ultimately, even though you have started the study in Brazil, you ultimately expect that it will be just one study, fully harmonized, and suitable for registration across all those regions?
That's what we're working on, being sure it can work for everybody.
Okay, and you know, I think one of the things that's always impressed me is the breadth of the company's pipeline.
Mm-hmm.
You know, I think, well, months ago, as you referenced, you weren't in a position to necessarily talk about some of your even earlier stage programs, right? And I think you even partnered one of the assets, PRAX-020.
Right
because it had become sort of a lower priority.
Yeah.
I guess, Tim, I'm just curious, now that you're in such a different place, how you see the evolution of the company in bringing forward some of those assets, or are they still sort of maybe a little deprioritized as you try to get some of these sort of later-stage ones that have proof of concept, you know, across the finish line?
I think we're in a place right now where the best thing we can do for the whole portfolio is execute on what we currently have in the clinic, and in doing so, it will open up even more doors and opportunities for each of those programs. So, you know, for example, we had talked about Parkinson's before with our ulixacaltamide program. It's something that we deprioritized after our Essential1 readout. I think, you know, when we get favorable results from Essential3, that's something we would look to bring back in, for example. But in the meantime, you know, we would want to be sure. Right now, we're really looking to ensure we've got good focus and execution on the programs we do have in the clinic.
While we are also still thinking about how can the biology be extended and what other line extensions might we be doing, we've talked about with our RADIANT study in 628, that we'll be enrolling generalized epilepsy patients as well. That's a good chance for us to start experiencing that patient population, and then, you know, we may look at doing an additional study and generalized in the future. But right now, we have a very focused approach within the company to ensure we're executing on what we've agreed on, so we don't get distracted.
And in terms of six two eight, and you mentioned generalized epilepsy because I think you did have the successful PPR readout, which had relevance for both focal onset seizures as well as generalized epilepsy. Is it your thinking that for registrational purposes or getting labeling for generalized epilepsy, that you would only need one study on the back of the focal studies that are being run?
Probably. We haven't gotten that far yet. I think at the time, it would stagger behind the POWER 1 and POWER 2 for focal epilepsy, so we would have that data generated already.
Okay.
Probably be in a place where generalized would be more of a line extension on top of it, but not a... We haven't committed to that plan yet.
Okay.
We'll come back to you when we've got that one.
And then I know we're pretty much out of time, so maybe just quickly touch on the next milestones that everybody should be focused on.
Yeah. So coming out of our EMBOLD readout last week, which we were really excited to share, the next things will be our phase III readouts for Study 1 and Study 2, and the placebo-controlled and the randomized withdrawal. And then, going into 2025 , in the first half of the year, we'll share the data from our open label RADIANT study for PRAX-628, and then towards the back half of the year, the POWER 1 registrational study for 628.
Okay.
And in the meantime, we'll give updates as the other epilepsy studies get up and going.
Okay. Excellent. So with that, thank you so much.
Great. Thank you very much.