All right, I think we're live now. Good morning, everyone. Welcome to our third annual, or Guggenheim's third annual Healthcare Innovation Conference. My name is Yatin Suneja, one of the biotech analysts here. Our next presenting company is Praxis. From the company, we have two executives. We have Marcio Souza, who's the Chief Executive Officer, and we also have the Chief Financial Officer, Tim Kelly, here with us. Marcio, I'm going to keep my comments very, very short because there's a lot going on at Praxis. Why don't you maybe talk about what's happening, how are things going. Obviously, you have two NDAs under review, and there's a lot more happening. Why don't you maybe start on the regulatory side from an update perspective, and then we go into some Q and A.
Yeah. Thanks so much. Always great to be here, and thanks for everyone in the room and on the webcast. Two NDAs is not for the faint of hearts, right. I think we talked about that before. You might have read our press release this morning. We intentionally kept very thin, just to be clear on why and two reasons why. One, we're having this conversation right now, which I think is going to be quite important, and then we have the investor day, which I would love for all of you to either show up in New York or tune in for the webcast. The conversations with the FDA, as you would expect, at this point in time, are fairly advanced. I will start with arguably the most important here is ulixacaltamide.
I can say I don't think I could be happier on where we are with those discussions, and it's always nerve-wracking as you're getting towards the end of a process and had a lot of conversations. We always strongly believe the agents understood this application after granting last year, it's almost a year ago now, granting a Breakthrough Therapy Designation for us that they actually understood the unmet needs and the potential that ulixacaltamide hydrochloride has on the lives of these patients coping every day with essential tremor. But it's good to come towards the end and realize that it still holds true on the agent side.
We have completed still the late cycle meeting with the FDA, and I can tell you that in a sense, not that common, but most of the conversations, if not all of the conversations, during the LCM meeting with the agents were about labeling, which our reads of that, notwithstanding that we don't actually control the outcome, of course, at this point in time, was very clearly that the agents really were more working with us towards what is going to be on the label, on the different sections, exposing their thinking about some of those things. I would say for all of you, the questions I get from all of you more recently tends to be titration, tends to be overall view of efficacy.
While I am not going to expand any further on that, what I can say is being fairly aligned with all the conversations we had throughout the last several months, the application has been there. So, it is not possible to have left the building there, the agents, with any other feeling but the one that comes January, you are going to be getting this drug approved and, of course, launching shortly thereafter. Now, with the proper caveats that are making forward-looking statements and they can change, and they are not entirely on our control. So, very, very good. With relutrigine, we had the late cycle, ironically it is called LCM, that is why sometimes I call life cycle, the late cycle meeting there as well. A little behind when you compare with ulixa.
The conversation was a lot more about some recent information requests the agents had to us, some questions they had, discussion open, some of the response we provided. So not quite there in terms of, I think you could, and probably rightly so, think that is an earlier PDUFA, but seems to be a little bit behind in terms of the review cycle or the finalization of the cycle, and I think that would be a proper representation of what happened.
If we did not have two, would not be able to compare. I strongly believe both of these drugs are going to be approved as we expected, but it is in a different stage. I would say from the conversations with us, it might be exactly the same stage inside the agents. We just do not have visibility for that. But nothing on those two meetings changed the plans that we had. Yeah, it is really moving forward with the launch, moving forward with all the prep that we have ahead of us.
Got it. Very helpful. These are some really important updates. So, Marcio, you just mentioned end of the process for ulixa twice, and I am surprised you have already completed the LCM or the late-stage meeting, or you have already gone through it. So, I am not going to ask you about the label because I do not think you can comment much. The simple question is, if the FDA acts fast, are you able or how fast can you launch?
Yeah. We're planning to launch, like, today. If we are so blessed, I do not believe this is going to happen before people start including this in the small. If we are so blessed on receive that NDA approval letter, we would just be able to execute the launch, yeah, immediately. One of the points that has been, and you might recall in our mid-cycle, we talked a little bit about that, is whether or not the drug's going to be scheduled, right?
Yeah.
We discussed back then that we recommended no scheduling. The no scheduling is based on a full eight-factor analysis that shows, in our view, that there would be no needs. But I also acknowledge, as we always done, that some of the AES are ones that historically the agents actually been a little bit more guarded and recommended to HHS and then to DEA for scheduling. I think once again, at this point in time, there were some conversations about that. While we don't have a definitive view on that, it is quite possible, I would say, in my view, that we would have, as we discussed before, and the reason why I'm bringing that up in terms of launch readiness, why we're going to be ready, there's certain things that can be done before the final scheduling, but you cannot commerce, right?
You cannot actually markets on the sense of being able to ship the drug until there is zero impact in the launch. I want to be incredibly clear from the get-go, we've been planning for that scenario. But whether or not we're going to be approved on or before January and be able to ship the drug, or it's going to be a few months before ship the drug, I would say is largely irrelevant for this application, but we're going to be ready either way.
Got it. I think it's generally about three months for scheduling. I might be wrong, but I think that's the number.
That is correct.
You said no impact on the launch, so I would assume, is it the five, which is the least one? Five or four?
Correct.
Something in that range?
Yeah. Our control drug in the human abuse potential study was a four.
I see.
Four or five, I think that would be the maximum that could be there. I am still hoping that our arguments for no scheduling is going to be the case, mostly just because it is a little easier on the supply chain. It has nothing to do with the actual launch performance, but in the supply chain, it is a little bit easier here, but nothing more than that.
Got it. You mentioned, I think I am going to ask it, you mentioned on the labeling that you are in the lab, that is one topic, right? The titration. Are there elements of the label that matter from a launch perspective? What does a good look like? What is a great? Any potential for ramps?
Yeah. While we do not have the red line yet, right? I think that is all the discussions in the meeting were about labeling.
Yeah.
That is, I think what I said, so we have as good of an indication of what it would be, that we don't have the text.
Yep.
We always have to be incredibly careful about that. But what I can tell you from my vantage points right now, that there is no zero, like, impacts, negative impacts. It's actually puzzling in one way and reassuring another, right? The populations, the populations, like those are adults living with essential tremor. We ran a very comprehensive analysis of any factors that might influence the efficacy on this. So did the agency. We agree that there is no actual factor that would potentially show the subgroup has less efficacy, the subgroups have more. So that broad label, therefore, is the overall assessment there. Of course, discontinuation was high on this study, so a lot of the focus has been, is this intrinsically high or is there things we can do?
I think on our ends of the table, on the agents' ends of the table, we work together and separately on trying to understand how we could reduce that. I think we all landed on a very similar place here that there's no clear factor that influence that. So we're going to have to just try and guide physicians, patients, and very, very likely the alternative titration is going to be on the label.
Got it.
As well here that we propose. With all of that, we believe the discontinuation that we are seeing on Essential3 to be fairly similar to Essential1, which just for people that are not that tuned in, it was about 70% less in Essential1 than on Essential3. All, if anything, I think the current indications is for possibly more positive one could argue, than the initial conversations.
Got it. Then one more question, then I want to discuss relutrigine, both for the review and the EMERALD in DEE. The question is on ulixacaltamide, are there any requirement for post-approval studies?
I would say not yet. Nothing agreed yet. If there were, and do not hold me to this, because at the latter we are going to get the final ones, I think we might have certain studies, like preclinical or special populations or things like that might be required here if I were to try to imagine, but nothing of impact.
Got it. With regard to relutrigine, you mentioned it's a little bit behind, but do you still feel good about the PDUFA date is in what, 45 days? December 27th, I believe. Are there any additional information that the FDA is looking for? Just a little bit there, if you could.
Yeah. I wouldn't say no IRs were issued at the late cycle. So, right now, no pending IRs. But we did have information requests leading to.
Yeah.
They tend to be, I would say, late questions, and that's why we said it's a little bit behind. We normally would like to be with everything resolved on that. The conversations themselves at the late cycle were more about questions that we still have to resolve before the approval. One could argue a little bit more of uncertainty on that than on ulixa. Very high certainty on ulixa, and a little bit less. I believe they are all based possibly on some of the lead review recently retired. There is a little bit of that as well, people catching up to that. One of my hypotheses, not what the FDA communicated to us, but my hypothesis that might have impacted a little bit. I don't personally see that impacting negatively. But it might. While we thought that was a good day in terms of this RAFT call-
Yeah
we announced, and we thought that would be a good idea to give a fulsome updates, particularly because they're back to back and we can compare them. I think in a vacuum, I would be telling you guys, "Oh, everything's fine and is on track and everything is the same." But since we had such a positive interaction for ulixa, such a clear willingness of my view of getting this approval by PDUFA, and no real open questions that are meaningful, and open questions that are meaningful for relutrigine, thought it would be good to give the differentiation.
Very good. Thank you for all that, Marcio. Really appreciate it. Okay. Now, with regard to the EMERALD study, would you announce data while the NDA is under review? I understand different indication, but I.
Yeah, we would. I would say it's based on two premise here. One, we are in that phase on EMERALD right now where last patient, last visits has occurred.
Yeah.
There is a lot of stuff that happens between last patient, last visits, and the actual readouts, as you all know. Historically, we try to do that very quickly. We try to do that in weeks. This is a large study on a fragile patient population. There's a lot of data to be QC'd. We take the approach, not everyone does, to actually QC every enter, like every form, every fields in the forms, which takes time, to make sure it's the highest possible quality of the readout. So, that's one.
The second is, something unusual in this study is that the pace of enrollments for the first half of the study and the pace of enrollment for the second half was very similar, which allow us to come out at the time of the readout with a fairly significant number of patients on the open label, having completed significant number of visits. The reason why we believe that to be important is, assuming, as our base case is, it's going to be a very clear positive study, that inform the most prescribers. It gives not only the initial readouts, but later. We've been cleaning the data throughout, including several visits-
Yeah
on the open label. This puts a lot of strains on the site and on the team internally. It is by no means an excuse, what I am doing here.
Got it.
It is actually quite the opposite. We want to come up with the strongest package when we present to all of you. One of the reasons why this morning, our press release, we were clear, but probably not as precise as most people would want us to be. Because to me, the worst thing is that we say, "This is going to be whatever, pick a date, any dates between now and the end of the year," and then one or two sites cannot finish the documentation, cannot finish signing the forms, and then we have to be a week or two later, and then everyone is going to be like, "Oh, something bad happened."
No, it is just logistics. It is just something that is going on with this study. So, we were intentionally a little bit more vague. We do not believe that that has any bearing on the current application, but it is a study about the same molecule in an adjacent indication. So, who am I to say what the agency is going to think about that?
Got it. When you make the disclosure, what should we anticipate from a disclosure standpoint? Are you going to give us an endpoint data which is similar to EMBOLD study so that we can do cross-trial comparison? What is a good effect size there also?
Yeah. EMBOLD is a very unique study, right? I think for everyone that is always wondering how we analyze EMBOLD, just tune in on Thursday and we're going to tell you. But EMBOLD is that population is so fragile, we're always very scared about what's going to happen when you don't allow for change in ASMs for a long period of time. So we limited placebo to four weeks. Here is very different.
Comparing the studies by themselves is incredibly difficult here. Also hear from physicians, as you're going to also hear on Thursday, some quantitative data about how they feel about this. The good news is they feel just like we do, like stat sig is the bar. We're going to be showing you the baseline seizure burden for these patients later this week, and I hope that you all going to agree with us and hope just because on this case, hope is a strategy because not everyone actually understand these things. But it's going to be incredibly clear how severe these patients are and how it's going to be undeniable that if we see any reduction here, we expect to see a very clear reduction, it's going to be meaningful, it's going to be used.
Maybe the last point there, right, we're going from a population that while fairly large for a rare disease, 5,000- 10,000 patients in the U.S. for SCN2A and SCN8A, the DEE total, it is 30 times bigger than that. There is a lot of needs there that is being unfulfilled right now, and maybe it's time that all of us start thinking a little bit more about that. Like, how do you fulfill the needs? What is both the humanitarian or medical benefit we're bringing? Also, what is the overall potential revenue we're bringing on the other sides for every percent points that we gain in market share here? They all converge to insanely interesting numbers.
Got it. Very helpful context. With regard to the patient mix in this study, I think in the past you have said they are well representative of somebody that would respond to a sodium channel. Maybe give a little bit flavor there, how you are maximizing the enrollment. Is it etiology-driven, syndrome-driven in this study?
Yeah. Etiology-driven, right? That's how this study was set up. GE is largely etiologically driven, it's not genetically driven. There's a fair bit of genetically driven patients in this study. We're going to provide a breakdown on Thursday as well of how those patients are. I think historically, maybe the biggest concern that we hear from investors is like, "Well, SCN1A, historically there's some concerns about maybe patients there." I can tell you it's low single digit percents for those patients, and they said they couldn't possibly change the outcome of this study.
Yeah.
The concerns, I think, probably can be put to bed at this point in time.
Got it. I think in the past, you have expressed high confidence based on sort of your view of the open label or the blinded data. Just curious, like, what is that driven by? Is it retention rate, relief response? What are you seeing?
Yeah. We are seeing something that has never been seen in these studies periods, from a disease, overall disease gain, and particularly from a seizure control perspective. We're also going to be showing some data on the long term, above and beyond what we've shown before on Thursday. I don't think it's going to take any genius to realize just how deep the impact it is for those patients.
Wow. Just a quick question on the pricing. I know for SCN2A and SCN8A, you've talked about, or I think the pricing range could be pretty significant. Do you think that will hold, let's say, if you move to DEE, which is close to 200,000-400,000 patients?
Yeah. We're going to move this approach once again on Thursday from opinion to data, which I always prefer to be at. Hopefully after that, there's going to be no more debate. I definitely will not going to tolerate more debates after that, because there are several drugs that increase by five, 10, 20, some more just around the corner, throughout the years, and without any price change. I think that is a stupid arguments, and maybe you're going to put such to bed this week.
Got it. Final question on this, because there's a lot, I don't have enough time. Is this EMERALD enough? From an indication that you can get or from an approval standpoint, assuming you get SCN2A and SCN8A approved, like just one study each?
Yeah. That's been from the beginning, the discussions with the agency. I think we always have the classical matter of review comments, so I can't comment for them, but that's the plan right now.
Got it. Then moving to elsunersen, real quickly in the next, let's say, one minute or so, how does the Breakthrough Therapy Designation shape up your discussion with the FDA, and then is EMBRAVE3 alone sufficient from an NDA standpoint, expectation timeline?
Very, very high likelihoods EMBRAVE3 alone is going to serve as the study for the NDA. We had a phenomenal meeting with the FDA recently, a comprehensive Type B meeting, and we are excited about answering some of the FDA questions about that and how to make. We designed an analysis plan that we believe is aligned with the agency's wills here, and we're going to provide an update on when we expect to be ready to submit an NDA for that drug on Thursday as well.
Got it. Wow, there's going to be a lot of update in a couple days. Finally, on vormatrigine, anything you are willing to say about the POWER2, POWER3, the modification, when they're going to start?
Yep. POWER2 is up and running, so we're out there. We're going to talk a little bit more about this soon as well. POWER3, we just had some phenomenal key opinion leader advice on how to start that. We're going to be starting that next year, move a little bit there to give us more time to really have the best possible study on that regard. Something else that's moving, and as you're going to learn later this week, a number of other things that are moving that are going to create significant value to society, first and foremost, and to all of you as investors.
Got it. Tim, final question for you. You have two launches coming up. You have potential third sNDA or sort of relutrigine sNDA, then the POWER studies are starting or have started. How should we think about the spend trajectory and the financial health?
Yeah, I think should feel very confident with it. We updated, we have $1.3 billion in cash. We continue the runway into 2028. It includes the launches as well as advancing the pipeline.
Well, very good, gentlemen. Thank you so much. Some very interesting updates today.
Thank you.
Thank you very much.
Thank you.