PRAXIS PRECISION MEDICINES, INC. (PRAX) - GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - PRAXIS PRECISION MEDICINES INC

All right, I think we're live now. Good morning, everyone. Welcome to our third annual, or Guggenheim's third annual health care innovation conference. My name is Yadin 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 is 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 NDA under review, and there's is a lot more happening. Why don' you maybe start on the regulatory side from an upfront, from an update perspective, and then we go into some Q&A? MARCIO MARQUEZ- Yeah. Thanks so much. Always great to be here. And thanks for everyone in the room and on the webcast. Q&As is not for the faint of heart, right? think we talked about that before you might have read our press release this morning we intentionally kept very thin just to be 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 The conversations with the FTA, as you would expect at this point in time, are fairly advanced. I will start with arguably the most important here, as Ulexa Kautmaid, 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's, almost a year ago now, granting a breakthrough designation for us that they actually understood the IMAT needs and the potential that ulexacultamide hydrochlorate 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 the late cycle meeting with the FTA, and I can tell you that, in a sense, not that common, but most of the conversations, if not all of the conversations and during the the LCM meeting with the agents were about labeling which our reads of that not extending 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 and 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 and why I'm not going to expand any further on that what I can say is being fairly aligned with all the conversations we had from the last several months the application has been there so it's not possible to have left the building there are the agents with any other filling but the one that comes January you're gonna be getting this drug approved and of course launching shortly thereafter not with the proper caveats that are making a looking statements and they can change and they're not entirely on our control so very very good with religion we had the life cycle a delayed cycle sorry ironically it's called LCM that's why sometimes I call life cycle the the late cycle meeting there as well a little behind into when you compare with with Felix 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's an earlier PDUFA but seems to be a little bit behind in terms of the review cycle or the like finalization of the cycle and I think that would be a proper representation of what happened. If we didn't have two we wouldn't be able to compare. I strongly believe both of these drugs are gonna 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 don't have visibility for that but nothing on those two meetings change the plans that we have there is really moving forward with the launch moving forward we've all the prep that we have ahead of us got it very helpful and these are like some really important update. So, Marcio, you just mentioned end of the process for Ulixa twice, and I'm surprised you have already completed the LCM or the late stage meeting or you've already gone through it. So I'm not going to ask you about the label because I don't think you can comment much. So the simple question is, if the FDA acts fast, are you able or are you, how fast can you launch? Yeah. So we're planning to launch, like today. If you are so blessed, I do not believe this is going to happen before people start including this in the small. If you're so blessed on receiving that NG approval letter, we would just be able to execute the launch 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 is going to be scheduled. We discussed back then that we recommended no scheduling. The no scheduling is based on a full eight-factor analysis that shows, in my view, that there would be no needs. We also acknowledge, as we've always done, that some of the AEs are ones that historically the agents actually being a little bit more guarded and recommended to HHS and then to GA for scheduling. I think once again, at this point in time, there were some conversations about that, and 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, we're going to be ready. There are certain things that can be done before the final scheduling, but you cannot commerce, right? You cannot actually market 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 we ship the drugs, I would say it's largely irrelevant for this application. But we're gonna 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 correct. But, you know, 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. So four or five, I think that would be the maximum that could be there. I'm still hoping that our arguments for noise scheduling is going to be the case, mostly just because it's a little easier on the supply chain. It has nothing to do with the actual launch performance, but in the supply chains, a little bit easier here. But nothing more than that. Got it. Got it。 So you mentioned, I think I'm going to ask it, you mentioned on the labeling that you are in the lab, that's one topic, right, the titration. So are there elements of the label that matter from a launch perspective? Like what does a good look like versus a great? Any potential for ramps? Yeah. Well, we don't have the red line yet, right? I think that's 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. So 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 in another, right? Like, the population is the population. 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 this 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 ofthe 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 is 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 as well here that we propose. And with all of that, we believe the discontinuation that we're seeing on Essential 3 to be fairly similar to Essential 1, which just for people that are not that tuned in, it was about 70% less in Essential 1 than on Essential three so all if anything i think the current indications is for uh possibly more positive i want to argue than the initial conversations got it then one more question then i want to discuss retrogene both for the review and the emerald in de so the question is on on on your licks are there any requirement for post approval studies I would say not yet nothing agreed yet if there were and don't hold me to this because at the latter we're gonna guess the final ones I think we might have certain studies like preclinical or special populations or things like that that might be required here if I were to try to imagine but nothing of impacts Got it. With regard to religion, you mentioned it's a little bit behind, but do you still feel good about, you know, the PDIFA data 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 uh information requests leading to and they tend to be i would say i see late uh questions and that's why we said it's a little bit behind we normally i would like to be with everything resolved uh on that the conversations themselves at the late cycle were more about uh questions that we still have to resolve before the approval. So one could argue a little bit more of uncertainty on that than on Elixir, very high certainty on Elxir and a little less. I believe they are all based possibly on some of the lead review recently retired, so there is a little of that as well, people catching up To that step, one of my hypotheses is 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. And while we thought that was a good day in terms of like this RAG-FT call, we announced and we thought that would be a good idea to give a full some 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 his own is on track and everything is the same but since we had such a positive interaction for for Ulexa, 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 aren't meaningful for relutrigine would be good to give the differentiation. Very good. Thank you for all that, Kala, I really appreciate it. Okay. Now, with regard to the MREL study, would you announce data while the NDA is under review? I understand different indication, but... Yeah. Yeah, we would. And I would say it's based on two premise here. One, we are in that phase on MREL right now where less patient, less visits has occurred. Yeah. There is a lot of stuff that happens between less patient, less visits, and the actual readouts, as you all know. Historically, we try to do that very quickly. We try to doing that in weeks, but this is a large study on a fragile patient population. a lot of data to be QC. We take the approach, not everyone does, to actually QC every enter, like every form, every field in the forms, which takes time, right, to make sure it's the highest possible quality of the redoubt. 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. And 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 informed the most prescribers it gives not only the initial readouts but later so we've been cleaning in the data throughout including several visits on the open label so which puts a lot of a lot strength on the on the site and on the team internally it's by no mean an excuse what I'm doing here it's actually quite the opposites we want to come up with the strongest package when it presents to all of you and 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 gonna be whatever pick a date any dates between now the end of the year and then one or two 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's going to be like, oh, something bad happened. And no, it's just logistics. It's just something that's going on with the study. So we were intentionally a little bit more vague. We do not believe that there has any bearing on the current application, but it is a study about the same molecule in adjacent indications. So who am I to say what the agents is going to think about that? Got it. Got it now. When you make the disclosure, what's 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? Just like and what is a good effect size? Yeah. So embold is is a very unique study. right and I think for everyone that is always wondering how we analyze them balls just don't in on Thursday and you're gonna tell you the but in both is that population is so so fragile we're always very scared about what's gonna 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 So comparing the studies by themselves is incredibly difficult here. Also here from physicians, as you're going to also hear on Thursday, some quantitative data about how they feel about this. And the good news is they feel just like we do, like stat-sick is the bar. We're going be showing you the baseline seizure burden for these patients later this week. And I hope that you all are 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 is going to be undeniable that if we see any reduction here, as we expect to see a very clear reduction, it's to be meaningful it's going to be used and maybe the last points there right we're going from a population that while fairly large for a rare disease uh five to ten thousand patients in the u.s with scn2a and 8a the d total uh it is 30 times bigger than that uh so there is a lot of needs 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 benefits we're bringing also what is the overall potential revenue we're bringing on the other side for every percent points that we gain in market share here and 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've said they are well representative of somebody that will respond to a sodium channel. So maybe give a little bit flavor there. How are you are maximizing the enrollment? Is it etiology driven, syndrome driven in this case? Yeah, etiology-driven, right? That's how the study was set up. GE is largely, it's geologically 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 this historically may be the biggest concern that we hear from investors is like, well, SCN1A, historically, there's some concerns about maybe patients there. And 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. So the concerns, I think, probably can be put to bed at this point in time. Got it. And 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, response? like 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 gonna be showing some data on the long-term, above and beyond what has been shown, what was shown before on Thursday. And 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. So I know for SCN 2A and 8A you've talked about, or, you know, I think the pricing range would be pretty significant. Do you think that will hold, let's say, if you move to DE, which is, you knows, close to 200,000 to 400,000 patients? Yeah, so we're going to move this approach once again on Thursday from opinion to data, which I always prefer to be at. And 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 5, 10, 20, someone just around the corner throughout the years. and without any price change. So I think that is a stupid argument, and maybe you're going to put such a bad this week. Got it. Final question on this, because there is 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 SCN 2A and 80 approved, like just one study? That's being 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, got it. Then moving to Elsa Narsen real quickly in the next, let's say, one minute or so, how does the breakthrough designation shape up your discussion with the FDA? And then there's Embraer F3 alone sufficient from an NDA standpoint, expectation timeline very very high likelihoods in brave 3 alone is gonna 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 design an analysis plan that we believe is aligned with the agent'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 RometraGene, anything you are willing to say about the Power 2, Power 3, the modification, when they're going start? Yeah, Power 2 is up and running, so we're out there we're going to talk a little bit more about this uh soon as well power three uh we just had like some phenomenal uh key opinion and advice on how to start that uh we're gonna be starting that next year uh move a little bits there to give us more time to to really have the best possible uh study uh on that regard so something else that's moving and as you're gonna learn later this week a number of other things that are moving they're going to create significant value to society first and foremost and to all of you as investors got it tim final question for you so you have two launches coming up you have potential third snda or you know sort of mrsnda then the power studies are starting or have started um 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.