Praxis Precision Medicines, Inc. (PRAX) Earnings Call Transcript & Summary

Good day, and thank you for standing by. Welcome to the Praxis Precision Medicine's Essential1 Top Line Results Call. [Operator Instructions] Please be advised that your conference is being recorded. I would now like to hand the conference over to your speaker today, Alex Kane, Vice President, Investor Relations and Corporate Communications. Please go ahead.

Hi, everyone. Good day, and thank you for joining us. We are pleased to be with you today to discuss the top line results from the ulixacaltamide Phase IIb Essential1 study for the treatment of essential tremor. With me on today's call are President and Chief Executive Officer, Marcio Souza. We will be joined by additional members of the Praxis management team for a live Q&A session following today's prepared remarks. Please note that today's remarks will reference the press release issued earlier this morning and the slide deck accessible through the Investors & Media section of our corporate website, which was posted in conjunction with the call. We will be making certain statements that are beliefs, forward-looking and subject to various risks and uncertainties. For additional detail on forward-looking statements and the risks associated with our business, I encourage you to consult our SEC filings. I will now turn over the call to Marcio. Marcio?

Thank you, Alex, and good day to everyone joining us today. It's great to be here to share the results from the Essential1 study assessing ulixacaltamide in patients with moderate to severe ET. Before reviewing the top line data, I want to take a moment to acknowledge and thank the patients with essential tremor who participated in this important study. Without their sacrifice and dedication, we could not be standing here today. My gratitude extends to all the investigators and the study personnel involved in the conduct of Essential1 as well as, but not the least, the outstanding team at Praxis. We believe that ulixacaltamide has the potential to transform the treatment of essential tremor. Today's results reinforce our perspective. Essential1 demonstrated a profile for ulixa or PRAX-944 that us, together with the essential tremor community, excited about progressing this program to Phase III. Essential tremor patients have waited more than 50 years for new treatment for their disease and have never had the benefit of a precision medicine targeted for ET, such as ulixa. We are working urgently to deliver a potential treatment for the more than 2 million patients in the United States diagnosed with essential tremor. Looking at the efficacy data in aggregates, we observed placebo-adjusted improvements in multiple endpoints that have direct functional relevance for patients, which give us confidence in the drug effects. We also continue to observe a well-tolerated safety profile that is clearly differentiated relative to existing options. We learned important information throughout this study as well, giving us a clear understanding on the path forward. As you hear, the results inform our perspective on exposure and dose for Phase III on endpoints, trial design, patient certification and other finds that we believe will be critical to running a successful registration study. And ultimately, getting ulixa to patients in need. Turning to the study. As seen on Slide 3, Essential1 is a randomized, double-blinded placebo controls trial evaluating the efficacy, safety and tolerability of once-daily treatment of ulixa compared to placebo after 56 days. Patients meeting eligibility requirements for Essential1 were randomized 1:1:1 to receive 60 or 100 milligrams of ulixa or placebo taking orally once daily in the morning. The primary endpoint was the pooled analysis for the change from baseline to day 56 in the mADL scores for ulixa-treated patients relative to placebo. We also assessed safety, PGI and CGI as well as additional sub items in the [ data ] scale. Following study underlining, post-hoc, we explore the impact of treatment in the mADL without the addition of the TETRAS performance scale items. As well as potential prognostic factors, which could be relevant to the population study. We expect that this [indiscernible] will be relevant for our Phase III plans. Patients in Essential1 were required to have a clinical diagnose of ET for at least 3 years and be considered moderate to severe in nature. Concomitant propranolol use was allowed as long as patients remained on stable dose. On Slide 6, you see that a total of 132 patients were randomized and treated in this study. And of those, 116 met the criteria for the primary analysis, which we refer to as the mITT population. In the mITT population, 78 patients were randomized to ulixa and 38 to placebo. In terms of baseline demographics, the groups were generally well balanced with the population randomized to ulixa exhibiting characteristics is slightly different than placebo in family history and background propranolol use. The key parameter used to assess efficacy, the TETRAS-ADL, was well balanced between the group. It's important to notice that since the ADL is composed of several items, modifications to the items or how they are assessed influence the aggregated baseline and eventual chains. General need in essential tremor is not only for effective drugs, but ones that are well tolerated. In Essential1, patients treated with ulixa experienced rates of treatment emerging adverse events consistent with the previous profile of the drug. No drug-related serious adverse events were observed, and the AE profile were generally mild to moderate in severity. Discontinuations due to AE were 12% in the ulixa group and mostly occurred during the first month of treatment. As you can see on Slide 9, there was no pattern associated with those discontinuations. I now would like to focus on the efficacy analysis for the primary population. As noted, the primary endpoint for Essential1 was the change from baseline to day 56 on the modified ADL. We also discussed the effect on clinical and patient global impression as well as subscales of the TETRAS. As a reminder, as seen on the left side of the slide, the TETRAS-ADL subscale is composed of 12 measures directly impacting the ability to function for patients with a total possible score of 48 points. The modified ADL scale in Essential1 excluded social impact, one of the original items in the ADL scale and included 2 items from another scale, the TETRAS performance subscale, specifically the handwriting and spirals items. The modified ADL is also scored differently with transformation resulting into a maximum score of 42 points. We have included feedback received from the FDA in relation to endpoints for the key trials in our public filings with the SEC today. So we can more fully appreciate the advice we received from the agency in the past. Moving now to the analysis of the ADL items. As you can see on Slide 13, we did not achieve the level of statistical significance the study was designed to meet in the primary end points. While the numerical change from baseline was in favor of ulixa-treated patients with patients improving their mADL score by 3 points and placebo patients improving by 1.44 points, the p-value for comparison between groups was 0.126. We will make reference to p-values in other analysis and end points throughout today's presentation. They should all be considered nominal. When examining the change in the untransformed TETRAS-ADL scale on the right-hand side of the slide, we observed a difference of more than 2.5 points in favor of ulixa which is considered clinically meaningful. When observing the distribution of individual patients on drug and placebo in the waterfall plot on Slide 14, you'll notice a large proportion of patients with improvements in the ulixa arm compared to placebo. In order to better understand the change between the 2 scales, we plotted the difference between each item, as you can see here in Slide 15, for the ADL and the mADL scales. It becomes clear that the effect was diluted by the addition of the performance scale items, predominantly the left-hand spirals. Of note, more than 90% of patients in this study were right-handed. The performance scale items has been historically unreliable to assess patients' progress in clinical trial studies. And while we expected that our enrichment criteria, careful site selection and [indiscernible] review, would have resulted in a more reliable measure, the data indicated that our assumptions were incorrect. As you reflect on the next steps for the program, we believe that the feedback we previously received from the agency would be supportive of removing the performance scale items from assessments in clinical trials. We intend to make this proposal to the agency in the forthcoming end of Phase II meeting. When the performance scale items are removed, one can observe a clear and consistent response to treatment with ulixa in the ADL items. We referenced this endpoint as mADL 11. Those results are supported by the improvements noted by both patients and clinicians in the global impression scale, PGI-C and CGI-S as reflected in Slide 16. After reviewing this data internally and with support of key opinion leaders in the field, we have concluded that there is a clear signal of efficacy for ulixa, warranting advancing the program. Because we intend to focus moving forward on the 11 items in the ADL scale, for which we previously received feedback, I would now like to discuss the change in those items in the mITT population. As displayed in Slide 19, we observed a clear and consistent change in the mADL 11 for this population, not only at day 56, but throughout the course of treatment. As you can see in Slide 20, the effect was consistent with the expected exposure response to ulixa is starting when patients reach therapeutic drug levels and maintained during the course of treatment. The effect was not dependent on whether patients were randomized to regimen 1 or 2 of treatments. As part of our post-hoc exploration of this study, we conducted a review of additional prognostic factors, which could have influenced the performance of patients in our study. One such factor was the presence or not of intention tremor, which is described in Slide 22. This clinical manifestation was assessed in addition to the diagnose of essential tremor for the patients in this study. Intention tremor has the potential to make assessments like the ADL more variable and harder to assess over time since it could directly interfere with the measured task. And therefore, it's important to consider its impact. Removing essential tremor patients presenting with intention tremor, generated a more homogeneous group in the analysis, which also resulted in an improved ability to observe drug effects. We will continue to evaluate how to control for the presence of such patients in future trials. In Slide 24 and 25, we'll be able to observe the trajectory of this group of patients over time when treated with ulixa adjusted to placebo as well as their ADL profiles for the 11 items previously described. It's certainly reassuring to see that in a more homogeneous group, the effect is even more clear with ulixa. In summary, we have learned a lot with Essential1 and remain excited to move the program forward. While the primary endpoint did not formally achieve the expected significance level, the effect of the drug in this population in our view is very clear. We additionally achieved important objectives for this Phase II study, gaining significant insights into the use of the scales in essential tremor as well as key elements to progress the drug to Phase III, including dose, safety and the ability to define a better population. We plan to meet with the FDA shortly in the end of Phase II meeting and advance the program to Phase III by the end of this year. I'll now turn the call back to Alex to cover Q&A with the operator. Alex?

Thank you, Marcio, and thank you to everyone for listening today. [Operator Instructions] With that, operator, please feel free to open up the line for questions.

[Operator Instructions] And our first question comes from Yasmeen Rahimi with Piper Sandler.

I guess the first question that on everybody's mind is, based on the KOL discussion and interactions that you've had since this data, like what is the probability that the FDA will grant you the green light to move forward with the ADL without the PS scoring? And then 2, why did initially the FDA really assist on changing into that modified definition including it? And then maybe the third one is just any color in terms of how soon you're going to get details on how you plan on communicating it with the [ Street ].

Thanks for the questions. They are quite important. So I appreciate starting with that. So I'll break that on the 3 buckets, right, then put it there. Key opinion leaders view, the ones that we presented -- independence to our view, they gave us the advice. This is clearly a drug, they'll clearly use on the majority of their patients and what they are seeing in the clinic where it's really impacting these patients' lives are really the ability to conduct tasks, not like necessarily a clinical termination. So that is quite positive on that regard, and I'm sure we're going to hear the same when we talk to them. I encourage you and everyone else to read the full feedback that we posted with our Form 8-K with the SEC today in relation to the FDA response to our question. The reason why we wanted to give the full context, as you're going to notice there, they are very clear about the 11 items on the ADL and also very clear in our understanding and our interpretation that, that could be used at the endpoints. The other questions, the other answers there, what I mean are in relation to the question we asked that was originally in relation to the performance scale so they did not oppose to do the handwriting assessing the clinic first, the handwriting as impact on the patient's life because there are 2 of them, as you know, and today spirals, although they're [ losing ] clients in relation to the spirals as you're going to read yourself. So when you look into the feedback, becomes -- again, quite clear that we went with the most comprehensive version. We look into how these patients behave. And what we learned here is that the assessment -- neurological assessment in the clinic is just not reliable. I think we've seen this in other clinical trials in the space, both in neurology at large and specifically in essential tremor. And they made the assumption based on the data set we had before, where being a smaller data set, may be less size was a little bit more stable. So our degree of confidence is very high and that's based on the feedback we have from the FDA to date, they want to encourage you to take a look at. In terms of the timing, we're going to be meeting with them ASAP. As you know, it's a special type of type B request at the end of Phase II meetings, 70 days from the time of the request that is granted. We're working diligently to put the package together to submit to the agents. That's why we gave the 100 days-ish deadline there and we're going to be communicating to all of you shortly thereafter on their understanding, which we, again, strongly believe it's going to be an agreement with us.

Our next question comes from Myles Minter with William Blair.

Taking the first question, I believe the prior Phase IIa, that one of the signals that could have confounded not getting more responders was like dizziness and confusion. It does seem to be popping up again in this trial despite the slower titration. So I just wanted your thoughts on whether you thought that those AEs impacted the ability of a trial participant to perform on those TETRAS PS items that seem to be trending in the wrong way from the ADLs. And if the slower titration achieved the improvement in AEs that you were hoping for in this trial?

Thanks, Myles. I'll start with the last part of your question there. So the slower titration did not improve, I would say, in general. I think what we learned is a little bit more idiosyncratic than necessarily titration-related here. Definitely, you shouldn't start with a high dose, but probably would have been fine to just start with 20 milligrams for example, as before. The advance of dizziness that you mentioned, they are very short in duration. And just a few of them all last to discontinuation that any lower -- than we're expecting much lower than any other competitive trial in the space. We do not believe that there was that anything general that affect the assessments. We believe the problem is with the assessments. As you recall, in another trial in this space that's been reported previously, the 2 different assessors have discordant views on the performance scale. As you're going to read on the feedback from the agents that we posted with the SEC today, the FDA probably seen that as well and warrants that is more chance to unreliable assessments. When you look throughout the time, obviously, we are looking for an aggregate number here at the variance, it's actually bounced back and forth a lot more inconsistently in terms of the PS assessments in general, which handwriting was part of for subjectives of daily living were really clearly more on the impacts. I'll point it out to one specifically. The handwriting as assessed by the patient, right? As the -- during the last 7 days, the activities to write and general test, general life, things that you and I do, taking notes and so on was positive across all the analysis. When you look into the writing of the core set name in front of the physician, the assessment was basically new. I don't believe that those things are the same. We don't believe those things are the same. And they -- as you've seen now, as we learn from this trial, they have less sensitivity in general. So not putting too much emphasis on the side effect profile, what was very mild, but rather on the assessment itself.

Okay. Cool. And then just a quick follow-up. You've measured both TETRAS PS the entirety of that scale and the entirety of the ADL that calculated the modified version of it. What was the data looking like for the entirety of the performance scale? Were the parameters all like not improved to worsening as you're saying with the 3 that we've seen today? Or did it paint a different picture?

Yes. So we included in the appendix of the slides that we posted on our website today, and I'll point you to Slide 29 there, where the 3 items, the 3 ways to analyze the PS, right? We have seen no change on the performance scale in aggregates. The point estimate is really around 0 out there. We are seeing no change on the combined upper limb. Same thing, high variable point estimates and a slight change on the upper limb, which as you recall and discussed before, was never seemed to be reliable. So the overall what I would call neurological examination that is assessed as an endpoint did not perform reliably here.

And we have a question from Douglas Tsao from H.C. Wainwright.

Good to see the data. And so Marcio, it sounds like -- and it looks like there's a pretty significant discrepancy between the response patients with and without intention tremor, resulted from ulixa. I'm just curious if it looks like about 18 patients had intention tremor in the study. Just curious, is that relatively reflective of the broader population of the essential tremor population at large and to confirm, would you be looking to exclude those in the Phase III study?

Yes. Thanks, Doug. So in vision term and maybe to be clear here, I know you got it, but just like for the broader audience, right? All those patients in the trial had essential tremor for more than 3 years and so on. And since 2018, so it's like relatively recently, the Movement Disorder Society guideline included this other like specifiers in terms of other confounding tremors and we assess that, we check that at baseline, right, that screening, and we carry that to baseline. So that's how we have the data to look. The first trial that collects the data prospectively since it's the first one after 2018 that follows the MDS guideline here. So I want to make that point. When you look into those patients and we look into the literature that is very scarce because there's not a lot of data being followed, what we're seeing is that the fact that the tremor amplifies towards the objects can confound the assessments. And I think that's the point we're trying to make. So we will exclude them moving forward from primary analysis. We still might include them in a trial side of our primary analysis. We do not believe we're harming these patients, right? We now believe that they would benefit as the essential tremor components but they are, from a clinical development perspective, not a good source of patients because they add a significant amount of variability. To your question about the prevalence of that feature with essential tremor patients, I think the question is up in the air. I don't think it's unreasonable to estimate between like 15%, 30% at this point in time based on the data you've seen, but that is not something that is clear in the field at this point in time.

Okay. And then to clarify, Marcio, you do think that they drive a clinical benefit. It is just largely from a clinical trial execution standpoint that they are bad candidates for ulixa.

That's correct. That's correct. And let me give a little bit more color, right? We look into that analysis excluding them, as you've seen on this study because we just cannot control for the variable, so that's the most proper way to do it. But when we compare them, just a group of patients who had intention tremor and essential tremor, there is no harm towards using ulixa. It's actually a small benefit that we're seeing there. It's just so in balance because they changed like in a lot more erratic way, I would call than the patients we expect that they're not proper to be analyzed. Have we known this before this trial has -- there was no literature for us to base. There was no other drugs for us to base, who obviously would have excluded them? Maybe a note here or a color is -- in the 2:2:1 data set, which was basically what we used to define this drive, as you recall, the previous Phase IIa study, there were 2 patients with this feature. It went back to the data set, we collect that data there as well. And those 2 individuals, they stayed online for [ 4 ] after the randomized withdraw and one has been a good responder, another one not. So they kind of cancel out, so all the calculations we made based on the randomized withdraw are still pretty much valid, and they were all driven by the patients who are the pure essential tremor patients, the ones we're showing without the analysis here. So that was what drove us. So they're back to -- and I know a posteriori it's easy, and I'm not trying to make an excuse whatsoever, you know me well, we're looking into this, it was the intended population that we wanted to treat when we remove those patients.

Our next question comes from Tazeen Ahmad with Bank of America.

I have a few questions. Maybe can we just start off with your decision to move -- to propose to move straight to Phase III. So just based on the data that you presented today, it does seem that you may still have some questions that need to be sorted. So I guess, why not just do another Phase II to answer these questions rather than, in a sense, risking it on moving to a Phase III, which could be costly for the company? And then I have a couple of follow-ups.

Yes. Tazeen, first and foremost, right, I actually don't believe that is such a thing as questions last year to move to Phase III. This is -- the results of a Phase II are to inform basically 3 effects, right? One, exposure response, we check that box. Is there a minimum dose that drives the effects and 60 milligrams clearly does. The second is, is there a new safe signal or additional incidents of a safe signal that we should be looking for the size or moving forward or the safe database and we check that box. And the last one is, can we define one, a clear population and two, a clear endpoint that to power the Phase III and to move forward. And we have both of those as well. So that is -- actually would be maybe disingenuous not to move forward. Now how to power that trial, what is the exact duration and the design, I think those are open questions for us to discuss with the FDA, and that's what we're saying, the proper past year is an end of Phase II meeting not like another Phase II. I'm actually curious on what another Phase II answer that would have answered at this point in time.

Yes. I asked that just because maybe do you want to have a better sense of what the titration schedule should look like? And I guess related to the population, you just said it was the intended population. I think in the past, you assessed that older patients might skew the results a bit. So did you have a good distribution around each in this particular study?

Yes. And thank you so much for clarifying that, Tazeen. The titration, we did not explore much, so I understand why you would ask the question. The titration actually is very clear that after 20 milligrams, the patient starts responding, they can go there to individual response up to 60, but not beyond that, there's no additional response. So we're pretty clear on that titration, and we chose not to show all the data today since we're already being quite comprehensive. You are correct in relation to the age as it relates to severity. In the proper way to control for that moving forward is really using certification factors, and we're going to continue to do that.

Okay. And then just on the total enrollment of patients was 132, right? You included 116. Just wanted to see what that delta was.

So the -- from the very beginning of the analysis, the full analysis set or what we call mITT here, where the patients were enrolled under version 4 of the protocol and what version 4 means is after we amended the protocol for efficacy as the end point, they had to had a minimal severity in terms of the ADL and the global severity as moderate to severe. It has to be randomized to either placebo, 60 milligrams regimen or 100-milligram regimen. So that analysis set was defined prospectively and allowed for patients who were previously enrolled to be included as well. Now trial was blinded. So we didn't know how many was previously enrolled. So we made an estimation. If you look back to the posters that we presented at the MDS conference last year, going to see that, that analysis was pretty clearly defined there. So we did not change that. The difference was some patients were randomized to 20 milligrams since at one point in time, there was a 20-milligram arm and a few patients who did not meet the severity criteria for the analysis sets.

Our next question comes from Ritu Baral with Cowen.

A couple on my part. One, looking at Slide 15, I guess I'm trying to figure out the scales here. I'm looking at the different bars on Slide 15. Are we looking at effect size on improvement? Because even relative to each other, say, dressing in using key, it looks like the bars are of different proportions amongst the items of benefit between the 2 analysis? And then as a follow-up to that, in the meeting minutes, FDA clearly has social impact, not important. Conversely, are there other portions of the meeting minutes that are more important to them that there's some minimal threshold because using keys sound terrifically important, but so does something like working or feeding with a spoon, which shows less impact on this.

Yes. So thank you so much, Ritu for that. When you look into the bar, what you're trying to show here, right, the impact at baseline for each one of those items is different. As you can imagine, and that's why we are looking to the difference, the adjusted difference between placebo and drug to give an idea if that is -- what kind of magnitude it is. We're going to continue to present this data at AAN and other scientific conference. So we're going to see a little bit more. Your second question is, yes, it's very clear on the social impact. It was not clear, it was not called out by the FDA on any other item. Now I'll give you color on things that are important to discuss by the deals. The average age of those patients is 70, as you saw at the demographics. Working is different as we age in society so we don't consider necessarily that to be negative or less impact, but just the amplitude of the impact versus continue to dress as we all dress in the morning and sometimes more times in the day, dependent of our age or using keys and other small objects or the general disability impacted by this disease and so on and so forth. They all need, as you know, the criteria function under 21 CFR.

Got it. And then do you think some of this -- as you think about the reliability, do you think this is a function of sites? Do you have to think about which sites and maybe do some more site evaluation, for lack of a better term, for the Phase III?

Yes. So the patients are reported parts, right? The ADL was very, very reliable, but that's -- I'm not answering your question because you're asking about the site. So our patients with essential tremor who comes to our site and assessed the last 7 days and talk about they were very, very reliable. We see that between screening and baseline, broad visits, other incredible subjects to participate in this trial. The sites did very good quality work here as well. I do believe when you look into data that is not here, but I'm going to talk to you about screening to baseline, it is just very difficult for these physicians. So I'm not saying the quality of the site was low because it was not. They did a very good job. But whether how difficult it is to turn a neurological exam into a score. And I think that's what a little bit of the FDA was trying to warn us as well on the communications, we probably read out. Could other measures fix it? I think both ourselves and others attempted to do video. We did on this study. We observed the video. We lose one dimension, the displacements and things like that. There are central raters. We use a central QC for screening, and I can go on and on. And we are trying to fix a broken endpoints. So I think the best way for us and it is to move on is to really now look back on the performance scale and abandon once and for all, something that's not adding value to the fields or to those patients.

Got it. And very last question, I promise. Any fall seen in this study?

Would you say it again, please?

Any falls -- patient falls as a side effect.

Falls, no. Yes, relevant -- incredibly relevant, right? This is another patient population. We had a little bit of dizziness. No, no, we did not have falls. We did not have fractures. We did not have anything that would be problematic here, I would say, thankfully, and I'm very happy for their safety as well.

And we have a question from Laura Chico from Wedbush.

I'm going to ask probably a naive one, but can you remind us when the FDA feedback that you [ AK-ed ] was provided?

Yes. It was about 1.5 years ago for the -- we requested the feedback in Q1 '21 and took a little while, I think, to get the response and obviously when we got the response was about when we were running the IIa. And I would say just back then for context, right, as the field was always influenced a little bit by the literature in the field. Everyone is looking to upper limb and measures on upper limbs. So our question or briefing book was really based on that. And I think they came and gave us the response that you're seeing that they don't really like the upper limb, and we checked that out -- that one out. And I think we've talked before, but then we're looking and we're working with them, I would say, on the rest of the scale on things that could be relevant. And as we know right now, I think we can just put a nail in the coffin of it, yes and maybe invalidate that scale.

Okay. That's helpful, Marcio. And then I guess, following up on the other question, just with respect to trying to get certainty around what constitutes an approvable endpoint for a regulatory path here. Would you seek an [ SPA ] from the agency?

Yes. Yes. I think we -- first, we're endeavoring the feedback as one should, right? In the paragraph that they say has the potential to be acceptable clinical endpoint, that is as regulatory language goes, as strong as it gets. So I don't think that is a margin of error here for using the ADL. Now in an end of Phase II meeting, as we're ready to proceed there and we start the Phase III, that is the endpoint we are proposing as well in front of them. We think that is incredibly high certainty that they would be okay with it.

And then last question, just circling back to the AEs. This has come up a few times now. This is going to be an elderly population. What stood out on some of these discontinuations though was due to kind of these cognitive-related adverse events such as hallucination, feeling abnormal. I guess in terms of a final target product profile, how does this influence your thoughts about positioning in the marketplace? And I guess does that ultimately impact the view on what the ultimate addressable population would be used in?

Yes. We're looking into that or like these 4, right, before the trial and looking to assessing -- I would say the feedback we got from the key opinion leaders, this is pretty much par for the course in terms of like CNS-active drugs as used in this patient population. Not really concerned. We're looking for upwards of 20% has been meaning the target profile here. So we are way short of that. Those are short in duration as well, so not impacting them in terms of loan duration in general. So from a market perspective, from a safety perspective in general, we are not concerned with what we're seeing. It's also -- competitively when you look into the other drugs in development are quite favorable. The one point I would like to make is patients with essential tremor were moderate to severe as the ones we've seen here. When you give them drugs that really give them effect, right, to reduce significantly the disease, they tend not to tolerate and discontinue. And discontinued rates that are much larger than the ones we're seeing here. So the excitement, I believe we heard from the key opinion leaders is it's transient, it's less a day or 2. If they cannot tolerate, they cannot tolerate sure, they just discontinue. But if they stay, it goes away, number 2. And then second, they respond. So that is a really big deal for them because they don't have that kind of option at this point in time. I believe that was the feedback we got and very exciting to hear that because it's easy for us to get excited about a drug, but it's good to see the field getting excited about it as well. And as I hear this morning from a patient, after we release the data with the excitement on that kind of drug would be very important on the person's life. That's what we -- meant a lot for me. And I know it's one person reaching out. But at the end of the day, that's what we are trying to do as a company is to help people.

One moment. We have a follow-up from Tazeen Ahmad from Bank of America.

Maybe Marcio, just for clarification. When you talk about the composite primary endpoint for TETRAS, does that include the performance scale items? Or is that excluded like the spirals and the handwriting?

Yes. So when we talked about the primary that we use right now, it does include the performance. When we're talking about moving forward, we're not going to be including the performance scale. So that's the -- I think that's the divider there. And if you exclude the performance scale as you probably saw on the slides, it becomes a lot more uniform, the groups and a very clear separation. And not only separation, not only moving forward because it's positive for the drug, the overall behavior of the groups, the overall distribution of the groups is very clear like placebo is not supposed to move in this patient population. And that's why we see a much more homogenous versus like up and dollars you see on the other scale. I hope that makes it a little bit more clear. I appreciate the follow-up.

And there are no other questions in the queue. I'd like to turn the call back to Marcio Souza for closing remarks.

Thank you so much, and thanks, everyone, for asking the question then. I think I would like to close with 3 points here. So first, everything we do is going back to whether or not we're helping patients here at Praxis. Today is a big day for that and for patients with essential tremor and we are really moving forward to help them expeditiously and to get this drug to Phase III. The second is the certainty around moving to Phase III that I wanted to convey. Right we checked the boxes, as one could say, in terms of the exposure response, the dose titration, this drug being active, the endpoints being certain and really having the ability and the means to move to Phase III enabled by the end of Phase II meeting with the FDA that is forthcoming. And the last one is while today, we are excited about Essential1 and what enables us to do for those patients, we remain equally excited about the milestone that we have for the remainder of the year for our epilepsy programs, helping patients at larger CNS conditions is key for us. And we have 3 other programs in the clinic in epilepsy, addressing specific populations that are going to have updates and readouts in the next several months between now and the end of the year. And we really believe that that's going to bring significant value to the target of this call, our investors, [ rose to ] patients at large that is what it really means for us. So exciting rest of the year for all of us here, I appreciate everyone's support and questions and looking forward to continuing interacting with all of you.

This concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.