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

Good morning, and welcome to the Praxis Precision Medicines PRAX-628 program update. [Operator Instructions] As a reminder, this call is being recorded, and a replay will be available on the Praxis website following the conclusion of the event. I'd now like to turn the call over to Marcio De'Souza, President and Chief Executive Officer at Praxis Precision Medicines. Please go ahead, Marcio.

Thank you, and good morning to all of you. Appreciate you joining us today. We're excited to discuss our PRAX-628 program, particularly the top line results from our PPR study, we're releasing this morning. Before we begin, I would like to remind you that today's presentations contain forward-looking statements. Please refer to our disclosures in the SEC website for the complete disclosures. For today's prepared remarks, I'll be joined by our Co-Founder and Chief Scientific Officer, Steve Petrou. I would like to outcome and introduce Dr. Dan Friedman, Professor of Neurology at NYU Grassman School of Medicine. Dan was recently named the Director of the NYU Comprehensive Epilepsy Center, he's also the Vice Chair of the Epilepsy Consortium. He specialized in the treatment of teenagers and adults with difficult to control epilepsy and his research focused on novel treatments and tools to manage such patients. He is the principal investigator of several studies and has altered over 106 peer review papers and several book chapters. As a reminder, at Praxis, we're developing treatments driven by the genetics of epilepsy, enabled by our small molecule platform, Cerebrum, and our antisense oligonucleotide platform, Solidus. For our 2 platforms, we have a portfolio of precision therapies for CNS disorders, including 4 clinical stage assets in a multitude of rapidly advancing early-stage programs. It's an exciting and eventful year for us at Praxis, with upcoming readouts in our PRAX-562 program, ulixacaltamide later this year. Let me focus the next few minutes in the opportunity for PRAX-628 and why we believe we are positioned to revolutionize epilepsy treatment paradigm of fabs. Praxis has the largest and most comprehensive epilepsy portfolio in the industry. Which combined with our scientific and fiscal discipline, is enable the unlocking of market worth over $3 billion. Across the areas of epilepsy, we focus and despite the growing number of therapies, patients and providers are in needs of more effective and safer treatments. Our focused approach, anchored by epilepsy genetics, aims to change this paradigm. It's important to remind everyone why we are so excited about PRAX-628. From the discovery stage, we are looking for a molecule with very unique and differentiated properties, aiming at the ideal treatments. What PRAX-628 brings to the table is a significantly more potent compounds in highly relevant animal models, combined with the ability to dose once a day, in patients. And yes, achieving or surpassing therapeutic levels expected to significantly impact the control of seizures while remaining well tolerated. I'm happy to stand here today having achieved proof of concepts in the PPR study and getting one more step closer to positively impacting the life of patients with epilepsy. The MES model, as we all know, is well understood for its ability to translate to efficacy in patients with epilepsy. PRAX-628 is an average tenfold more potent than current treatments in clinical use and new treatments in development, creating a class of its own. Importantly, patients need a treatment that give them peace of mind by rapidly achieving therapeutic levels, with a dose regimen that's simple and convenience. PRAX-628 is expected to reach therapeutic levels at Day 1 and to be administered once a day, a significant advantage comparing to current treatments. One of the limitations of the current treatment is the inability to deliver the best possible response to patients, primarily due to narrow therapeutic margins. Based on our translation models and Phase I results in our volunteers, we project PRAX-628 abilities to significantly exceed the therapeutic concentrations needed to generate response in patients, while being well tolerated. For example, at a daily dose of 20 or 30 milligrams of PRAX-628, we're able to achieve drug levels that consistently exceed tenfold of the MES equivalent in humans. And today, we're proud to announce the top line results of our PPR study, which adds yet another building block to the success of PRAX-628. We have evaluated 8 patients with epilepsy, who also had a consistent response to photo simulation. Similar to our health volunteer study, concentrations of PRAX-628 significantly exceed the expected therapeutic range. Most importantly, all 8 patients or 100% responded to treatment with PRAX-628s. I want to take a moment to thank all patients who participate in these studies. We couldn't be standing here without all of you. Thank you. Let me now hand it over to Steve to review in more detail on the PPR study and its results, as we get even closer to revolutionize the epilepsy treatments with PRAX-628. Steve.

Thank you, Marcio, for that introduction and setting the stage for a deeper dive into the data underlying our key messages. I'm Steven Petrou, a co-founder and the Chief Scientific Officer here at Praxis, and I'll be delving deeper into our PRAX-628 program, an example of innovation derived from our Cerebrum small molecule platform. Specifically, PRAX-628 with its novel functional selectivity profile represents a significant advance in our quest to overcome one of the most daunting challenges in the management of epilepsy, achieving high efficacy and treatment outcomes while simultaneously ensuring patient tolerability. This initiative marks a significant stride towards redefining the standards of therapeutic care in epilepsy treatment. These findings signal a pivotal moment for PRAX-628, thrusting it into the next stage of its development journey. Our study was carefully designed to evaluate efficacy and optimal dosing of PRAX-628, implying 15-milligram and 45-milligram dosage arms. Over a detailed 24-hour observation period for each intervention, we conducted exhaustive assessments focusing on those participants displaying a baseline photoparoxysmal response or PPR, a critical metric for gauging treatment efficacy. Treatment responses were carefully classified as either partial or complete, reflecting the degree to which the treatment was successful in mitigating baseline levels. In addition to efficacy, our study placed a strong emphasis on safety and pharmacokinetic evaluations, ensuring a comprehensive understanding of PRAX-628's pharmacological profile. The concept of photoparoxysmal response, while complex, fundamentally pertains to an EEG anomaly precipitated for intermittent photic stimulation or IPS. Our study participants were equipped with EEG recording equipment and exposed to stray of lights of varying frequencies, allowing us to observe the transition from normal EEG pattern to distinct PPR responses. This rigorous protocol assessing multiple EEG [ waves ] and a range of light pulse frequencies provided an in-depth look at PRAX-628's therapeutic impact through EEG observations, showcasing its translational potential to revolutionize epilepsy treatment. Now focusing on the demographic makeup and overall composition of our study, we screened 30 participants with 10 meeting the criteria for inclusion into our treatment arms. Within Part A, 6 participants were deemed eligible for safety assessments with 5 undergoing PPR evaluations. For Part B, which involved the 45-milligram dosage arm, 4 participants were included in the safety cohort, with 3 being assessed for PPR. The study comprised the balanced demographic profile in terms of age, weight, body mass index and duration since first epilepsy diagnosis. Significantly though, our study predominantly involved female participants addressing a notable research gap in this area. The inclusion of background medications offer preliminary insights into the additive benefits of PRAX-628, suggesting its potential to improve upon standard of care. The preliminary safety and tolerability profile of PRAX-628 was nothing short of exemplary. With an absence of concerning safety signals and an adverse event profile comparable to that of placebo, the patient cohorts tolerability to 628 was convincingly demonstrated. Moreover, the data unveiled a remarkable finding. The majority of participants achieved a complete response to treatment, with only a solitary partial response noted in the 15-milligram dosage group. Impressively, every participant evaluated responded favorably to PRAX-628. All individuals on concurrent background medications experience an enhanced benefit from the co-administration of PRAX-628, a result that exceeded our expectations and solidified the program's potential for future success. Before I hand over to Professor Friedman, allow me to share a striking example, EEG recordings taken before and after PRAX-628 treatment, vividly illustrating the elimination of PPR responses. This remarkable result underscores PRAX-628 transformative capacity for patients suffering from epilepsy. It's now my distinct pleasure to introduce Dr. Dan Friedman, who will guide us through the next part of our presentation, summarizing the urgent clinical needs for epilepsy patients and highlighting the potential of PRAX-628 to significantly improve the quality of life for these patients suffering from epilepsy. Dan, the podium is yours.

Hi. I'm Dan Friedman, I'm Professor of Neurology at NYU and Vice President of the Epilepsy Study Consortium. I spent much of my professional time treating teens and adults with epilepsy, and my research focus is on improving outcomes for people living with epilepsy. One question that arises in epilepsy drug development is why should we continue to invest in drugs for treating focal seizures and epilepsy? Focal onset seizures remain the most common types of seizures that affect epilepsy patients worldwide. In the U.S., estimates suggest that 1.6 million to 2.6 million adults and about 200,000 children have focal onset seizures. The incidence of focal epilepsy increases with age. So these numbers are expected to go up, as our population ages. About 1/3 of these patients are not fully controlled with available current therapy. And 10% to 40% of patients report side effects from their medication, and that number actually goes way up, if you perform structured interviews. For an established seizure type, epilepsy type, there's little comparative data that suggests that one drug is more effective than another. So as clinicians, we often choose our initial treatment accounting for individual factors and circumstances of the patient. In an ideal world, we want the initial therapy to be best matched for the patient and ensure long-term success and tolerability. In the next few slides, I'll illustrate how even with 18-plus drugs available on the market, some of our patients are left without an ideal treatment. So in this case, we're faced with a 28-year-old woman with newly diagnosed focal epilepsy. Some of our medications are less effective for focal epilepsy or they're contra indicated as first-line treatment for women of childbearing age because of a high teratogenic risk. She also has co-morbid depression, which may be actually exacerbated by some of our medications. Some of our drugs have significant drug-drug interactions and may interact with her oral contraceptive, lowering its efficacy or they may have undesirable side effect profiles. Some drugs do not have enough data to support their safety during pregnancy or breast-feeding. And some drugs have slow titration schedules that preclude their use in settings where you might want to institute effective therapy quickly. The lack of ideal treatment options for this patient highlights that several gaps exist in our current therapeutic landscape and why we still need more choices. In the next session, I will discuss potential areas where therapies could differentiate themselves from current treatments. In this conceptual diagram, I state a simplified view of how epilepsy, the brain condition which gives rise to spontaneous seizures, impacts outcomes. I'll use this diagram to highlight different targets for improving the quality of life and health outcomes for people with epilepsy. The first target of intervention is seizures themselves. That is the target of our current therapies, but there continues to be room for improvement. Specifically, medications can be more effective. Seizure freedom remains the biggest driver in quality of life in adults with epilepsy, as this analysis from drug-resistant focal epilepsy patients in participating in trials shows. It's only patients that actually became seizure-free during the trial that experienced the greatest improvement in quality of life. Despite the fact that we've had over century and half of anti-seizure drug development, that proportion of patients that has become seizure-free remains disappointingly the same. So over the past century, there have been 26 marketed antiseizure medications in the United States. And the impact of these drugs has been studied for over 40 years. And in the early 2000s, when the rates of seizure freedom were examined with the available therapies at the time, only 64% of our patients were seizure free. Disappointingly a decade later, that number remained unchanged. Until recently, the proportion of drug-resistant patients with focal epilepsy became seizure-free and randomized blinded add-on trials, it's fairly low, approximately 5% in most studies. A recent trial of cenobamate showed a higher rate of seizure freedom during that blinded observation period, suggesting that advances in efficacy are possible and providing hope that new therapies will improve efficacy outcomes for patients with drug-resistant focal epilepsy. Another area for improvement is the treatment themselves, drug side effects, [ pharmacokinetics ] and drug-drug interactions, all impact quality of life. Tolerability is a major concern for people with epilepsy. You have to take medications daily to maintain seizure control. Adverse drug effects are a major contributor to negative quality of life. And there are several forms of drug adverse effects, both related to both acute treatment, as well as chronic administration. Some of these are CNS related and due to the drug mechanism action itself, where others are idiosyncratic and due to the molecule. For some drugs, it may be that tolerability is actually a barrier to achieving maximal efficacy, as off-target CNS side effects can limit the maximal dose that patients can use. For instance, in lacosamide trials, there was evidence of maximal benefit at a dose of 600 milligrams per day, but the adverse effects of this dose were high and current labeling actually excludes this dose. Another key area for improvement on therapies that target epilepsy co-morbidities, another key driver of outcomes. Depression, anxiety, memory dysfunction are all common among people with epilepsy and their impact is even higher in drug-resistant patients. Co-morbidities may arise from the consequence of seizures, medication side effects or the underlying biology of the epilepsy. Epilepsy is a disorder of brain circuits and the same circuit dysfunction that leads to seizures can also lead to other neuropsychiatric symptoms. Therapies that do not exacerbate and even ameliorate these co-morbidities would be well received. Finally, the holy grail of epilepsy therapy development are treatments that can modify the disease process that gives rise to epilepsy and especially drug-resistant epilepsy. Current therapies are symptomatic. That means you have to take them daily to prevent seizures. They don't address the underlying mechanisms that lead to altered seizure thresholds or the co-morbid symptoms of the epilepsy. They need to be taken chronically and therefore, there are no treatments that change the underlying mechanism, prevent epilepsy after a high-risk injury such as traumatic brain injury or even turn drug-resistant epilepsy into drug-sensitive epilepsy. Finally, other gaps include insufficient treatment options for people with generalized epilepsies or multiple seizure types. We need more safe and well-tolerated options for people that have a broad spectrum of efficacy across seizure types, so we can help patients no matter what kind of seizures they're having. And we also need more options for medications that are safe to take during pregnancy and breast feeding. So in conclusion, despite the fact that we have 18 plus marketed antiseizure medications are focal in generalized seizures, options fall short for many of our patients. We lack efficacy for a substantial proportion of our patients. Majority of our patients may experience intolerable side effects. There are limited choices for people who may become pregnant. And patients with epilepsy have to suffer the burden of that taking medications daily. The shortcomings of available antiseizure medications present opportunities for the differentiation of new therapies.

Thank you, Dan. For making so clear the unmet need that still remains for patients with focal epilepsy and epilepsies at large. We're proud to be here today delivering one more step towards PRAX-628 fulfilling the needs of those patients in a manner that is convenient, but also deliver the efficacy and safety they've been looking for. We're now going to open the call for Q&A. Operator?

[Operator Instructions] So our first question comes from Yasmeen Rahimi at Piper.

Dr. Friedman, thank you so much for your thoughtful analysis and thank you to Praxis team for the outstanding data. Dr. Friedman, I think, what would be really helpful is if you could talk about the translation of the PPR study, 2 treatment effects of focal epilepsy. If you could maybe help us understand because I think a lot of investors on the call are trying to figure out with really 100% complete responses, what would that translate in a product profile? What would the efficacy be in seizure reduction? And you also noted that given the clean safety profile one could dose optimally high and further get cleaner. So if you could talk about that, that would be really helpful. And then for the Praxis team, I guess, what are the next steps here, right, with this data? What are the doses could you contemplate running 2 Phase IIb studies for potentially that could become pivotal? And if you could kind of give us some broad strokes of the design, that would be helpful, and I'll jump back into the queue.

Thanks, Yas. It's very exciting indeed. And I'll hand over to Professor Friedman to talk a little bit about how the model is being used, not only I think in pre-conversations we had -- you mentioned a little bit about the broader use of the model as well. So it would be great to answer your question, Dan?

Yes. So the photo practicable model is a very useful model for first-in-patient proof-of-concept studies because it has predictive ability for drugs that are ultimately efficacious in the clinic, especially those with broad-spectrum activity, meaning that they can treat both focal onset seizures and generalized onset seizures. So as an example, several drugs that are currently on the market have initially demonstrated very good efficacy in the PPR model, such as cenobamate, brivaracetam, levetiracetam. And with varying degrees of suppression of the PPR response. We don't have a really good relationship between the degree of suppression, we see in these relatively small studies with a heterogeneous group of patients with a specific type of epilepsy, usually a generalized epilepsy and ultimate efficacy in the clinic. So for instance, cenobamate in their photoparoxysmal study, only 1 out of 4 patients achieved complete suppression, although that drug proved to be pretty efficacious in the clinic.

And maybe to the second part, thanks, Dan, for your question. We were expecting when we designed this study, right, to retail thresholds where we could see very clear signal, very clear suppression, as we did. And that would allow us to decide whether or not those concentrations would be sufficient to get to the next study, which will be an efficacy, as you said, Yas, an efficacy study in focal epilepsy. Our previous model, as I mentioned on the prepared remarks, was that we would be way above in terms of the exposures with the 15 milligrams but on the -- I would say, the lower end of that as a single dose than we expected. When you look into 20 milligrams or 30 milligrams every day, considering the dynamics of those in our drug every day, the potential accumulation that does exist, although minimal with this drug. And obviously, concentrations at steady states are much higher, we're going to be really well covered at those dose levels for focal epilepsy patients or even other types of epilepsy as Dan just mentioned, that is clearly a potential to use beyond focal here. So our next study is going to be square then, and I would say very clearly, an efficacy study. We're going to be giving more details pretty soon. But you should expect a dose of 20 milligrams for certain to be used to start that study, which we believe, going to be reaching unprecedented levels in terms of multiples of the MES EC50, that is a great surrogate for where we started those and we're going to be well above what a lot of people had started before and reaching levels that are not only safe for these patients, but should drive even higher efficacy than seen previously. And that should start later this year.

Our next question comes from Ritu Baral from Cowen.

I want to add my congratulations on this data. Praxis team, could you please go through the background meds that some of these patients were on? And then, as you think about the Phase III, we had spoken about the guidance that FDA has issued on Phase III development. But as you think of that design, given what Dr. Friedman said about the unmet needs, teratogenicity, et cetera, are there any aspects that -- of the Phase III design that you are thinking of, that could clearly differentiate 628 from the landscape?

Yes, absolutely. Thanks so much, Ritu, appreciate it. When looking to the background, as Steven presented, right, we had a mix of patients without treatment on this study, which was great to see as well. What happens on someone that is not tolerating any drug right now, is not willing to be on a treatment and would be willing to be on a treatment like 628 was quite actually rewarding to see because that was the feedback actually through the investigator we got from the patient as well. So I think that it starts to answer your question in terms of where this treatment can go. And then you look into the other 3 treatments that were on top. One was Briviact, widely used SV2A molecule in the U.S. and elsewhere are very effective on actually suppressing PPR. So when you got a patient that is on a stable dose, therapeutic dose and actually while showing a PPR response that screening a baseline that got eliminated with 628. I think it's all to say something about the potential for this drug as an adjunctive therapy. That's how everyone starts. And then we had a very classical combination with lamotrigine here. While small study, we explored the gamut of the use, which allow us to basically now go to the efficacy study later this year, with a lot more confidence in terms of, one, the ability to drive higher efficacy as an adjunctive but also the ambition for this molecule to really become standard of care, to really become a drug that's not only experts like Dr. Friedman, who are seeing these patients than in and day out and know these patients really well. But also the neurologists, right? And I actually would like Dan to comment on this because the dynamic of treating a patient that is like very severe, very refractory and the dynamic of treating all patients in the country. There is just not enough epilepsy experts to treat all of those patients. So how the dynamic and how a drug like 628 could play a role there. I think it's going to go in to answer part of your question Ritu. So Dan, maybe if you could elaborate there.

Yes. I mean I think there's a lot of value in -- like I said in my talk, in the ideal world, the first drug that you place somebody on will be the drug that they will stay on. And because the majority of patients with epilepsy are treated not by epilepsy experts, but by a general neurologist, there's a real need for medications that can be used easily. Meaning they don't have a complicated titration schedule. That they have efficacy at the initial dose, giving patients protection as soon as they leave the office. And that are well tolerated. So I think molecules such as this, may be important to differentiate itself from other new entities coming out in the market or available in the market that are more complicated for the general neurologists or the primary care doctors even to use.

And a quick -- very quick follow-up, if I may. When 628 was added to patients with background meds, especially those at the same class, was there any increasing of severity of the side effects of note of mechanism, including fatigue, headache, et cetera?

Yes, super important question, right? The -- to that as well because we want to make sure that you're getting the maximum possible efficacy for that given patient and at the same time, remaining fairly safe as you've probably seen on our slides on the safety was -- I would say, I wouldn't call uneventful because like you wants to see something, and I think we did. But it was not exaggerated, was not increased on the specific patients that got those on both cohorts with lamotrigine as the baseline. We haven't seen an increase or an issue with the safe profile, which was very good for us to see. It's a patient that's being on a consistent dose. It's a young female also has the entire life ahead of her, and we hope that we're going to play a very positive role for herself and her peers living with this condition.

Our next question comes from Doug Tsao at H.C. Wainwright.

Congrats on the data. Maybe starting for the Praxis team, the PPR model is known to be very good for generalized epilepsy. And I think Dr. Friedman mentioned it, and I think you've sort of suggested that was an avenue in the past. I'm just curious how you're thinking about pursuing the generalized epilepsy opportunity? And then maybe for Dr. Friedman, I'd just be curious to hear his perspectives on the unmet need for therapies in generalized epilepsy versus focal onset epilepsy.

Yes. Thanks, Doug. Our original idea here once we're planning this study before the result, right today was to, I would say, take a steady course from focal running 1 or 2 studies in focal and then expanding to generalize. That I think is a more throttle path. As we now sit back and look into what we are seeing, and it probably heard, as I'm sure you did, Steve, talking about what we're measuring this generalization in the brain, we're seeing a very consistent response on suppressing that it begs the question, right? So why not go faster since the unmet needs, as I'm sure Dan is going to talk a little bit about that, is huge on those patients. From a science perspective, from an unmet need for patients, which should drive all of us in this business, it's very clear that we should try to accelerate as much as possible. But then when you add the [ Acto ] financial part of this, right, there are about 30% excess patients there when it accounts for focal. So we're growing the available pool by at least 30%. That is a fair bit of upside, and we are now running the numbers and working everything inside to look into how we can accelerate towards that indication as well. I think it's very, very clear what's been the path for different drugs to achieve that. And we're looking forward to getting a development program that can cover not only focal but also like generalized as well. Dan, do you want to comment a little bit on the second part of the question?

Yes. I mean I think there is a tremendous unmet need in generalized epilepsy. We tend to think of especially the idiopathic generalized epilepsies as being relatively treatment sensitive. But I think that's an artifact of the fact that their seizures are less frequent, although they are equally disruptive. They tend to be tonic-clonic seizures. These patients have increased risk of mortality as well. And -- and the treatment options are not ideal, while valproate is probably the most effective treatment arm, and obviously, it has a lot of problems, not just in women of child-bearing potential, but across the spectrum, in fact, even in the U.K., it's now being severely restricted for men because of potential issues affecting sperm. And the rest of the drugs currently on the market just don't have that efficacy. So we still need effective drugs for this patient population. We need more choices. We need choices for patients who you don't know what kind of epilepsy they have. They only have had tonic-clonic seizures. They may not have EEG abnormalities to confirm their epilepsy syndromes. So you need to -- need to start them on an agent that works in a broad spectrum way. So I think the problem has always been in this population is that it's a somewhat trickier population to do clinical trials in because of the seizure frequency requirements. Though now there are some novel trial designs like time to event that may make recruiting these kinds of studies a little easier. And I applaud all of the companies that are engaging in studies in this population even before their compounds on the market.

Our next question comes from Asim Rana at Truist.

Congrats on the data, it's awesome on for June. Just one quick question. Marcio, you mentioned going forward with a 20-milligram dose for the efficacy study. Figures given today's data, why not go with the 45-milligram dose or possibly higher given the tolerability of this PPR study?

Yes. No, absolutely, and thanks for the question there. When you look into our previously published Phase I results for 628 right, the -- at 20 milligrams daily considering about a 1.3 accumulation to steady state. We're actually going to be reaching therapeutic exposures that are actually higher than what we're seeing with 45 milligram here. So since we're looking for the chronic treatment of these patients, not for the one dose as we did here, experiments, it's more appropriate to look into the final expected concentration, and we are surpassing any of the expected concentrations right now with 45 milligram, by giving 20 milligrams every day. So we're not given in or -- are giving up all the potential efficacy there, we're just actually surpassing that. We're more than comfortable with 20 milligram and 30 milligrams and the levels that we're achieving there, to an average of 10 to 15 fold, what is expected to be therapeutic. So we are really well covered.

Our next question comes from Kambiz Yazdi at Jefferies.

Congratulations on the results. Maybe Dr. Friedman, one question for you. How -- what is the importance of therapeutic margins and speed of achieving therapeutic concentration for anti-epilepsy medication? And then maybe for the team, investors I spoke to are curious about kind of the precise definition of a partial response. Does that mean the kind of a limited range of frequencies of IPS stimulation, they are exposed to that they would not have a PPR?

Sure. So maybe I'm just going to start with the second part there and hand over to Dan. So why don't we see, we simulate the patients right upwards from 0 hertz and then downwards from [indiscernible] and we define a range at baseline. What you're seeing on the sole partial response here on the first patient is a reduction in the range. So it means that at frequencies that previously triggered the PPR response was not triggered. But that range did not go to 0. In all the other instance, including on that same patient at 45 that went to 0. So very consistent, very clear. Our previous bar that we discussed with all of you was you have 2 partial response as they go ahead in either cohort. So I think we're well passing path what would be unnecessary range here to move this program successfully forward. Dan?

Yes, I actually think it is very important for broad acceptance of a medication that it has rapid onset of action. So when you see -- especially if you see a patient in the emergency room setting or in the hospital that has new onset seizures, you don't know their trajectory necessarily. And you want to discharge them with a treatment that will be effective from day 1 because you're not certain how soon it will take them to get a follow-up appointment and anything can happen. So the reason why medications like levetiracetam or lacosamide have such significant market share is because the emergency rooms and other doctors can start them quickly and not worry about leaving the patient unprotected. They're also easy to use. You don't need to have a complex titration schedule. There's no drug interactions to worry about. So all the things that a molecule can have that makes primary -- the primary frontline caregivers for people -- doctors and other clinicians treating people with epilepsy comfortable with its use are going to be important for its adoption.

Our final questions come from Laura Chico at Wedbush.

I have one clarification on the 15 mg patients moving into the 45 mg cohort. But first, I wanted to ask a little on the AE with respect to sleep paralysis. Just any additional commentary there? And yes, first on the sleep paralysis.

Yes. No, absolutely. Thanks, Laura. The -- so the AE of sleep paralysis occurred a significant time after the last dose. So we're actually not expecting to have any dose in the system at that point in time. That patient had a history of sleep disturbance, as well. It was ruled as non-related and also resolved immediately for every instance. So we're not assessing right now as related. There is no expected mechanistic and there was no drug concentrations in the system in relation to that. So that is, I would say, pretty clear right now. The question about the first patients, just trying to understand what exactly we're trying to understand there, if you don't mind repeating.

Yes. Thank you. So if I'm reading correctly, there were 3 evaluable patients in the 45-milligram cohort that came from the 15-milligram cohort. So I'm just trying to understand the 3 patients from the 15-milligram cohort that moved into the 45-milligram cohort, what are their responses in the 15-milligram?

Yes, no. Perfect. Perfect. Thank you so much for repeating. So one of them was actually the very first patients, are enrolled in this study, came at 15 milligram, and she had like a very pronounced PPR, it's actually an adult women, there's been avoiding any lighting stimulation her entire life according to the narrative we received because it triggers like very clear generalization on her brain. She had a reduction on the range at 15 milligram, actually had a very benign safety profile, came back about 3 months later, a little bit over 100 days later for the 45 milligram and had a complete suppression. For all the others, they all have complete suppression. So they were -- was the same. But the one was interesting and while the bar for us was always to have a partial, it was interesting to see her response increasing with the exposure as well.

So this concludes today's question-and-answer session. I'll now turn the call back over to Marcio for closing remarks.

Yes. Thank you very much, and thanks, everyone, for joining again. And most importantly, I thank for all the patients who participate on the trial, got dose, but also the ones that didn't participate but went through the screening and really dedicate their time and efforts here to science. They are the real winners today. As a reminder, we have a very or we're going to call eventful year. We're happy to start with these results for 628 today which enable really driving this drug towards its full potential later in the year. But we do have several others coming up. Our results for 562 are coming soon, we are equally excited about the potential there on QGs, initially that really don't have any other treatment options right now, there incredibly refractory and nothing that is in development or right now in the market can help these patients. So excited for that result soon. And quite importantly, as well, we might have seen on our most recently disclosures on how much interest, we've been having on the enrollment for our essential tremor patients for the Essential3 program. We continue to plow through, working very hard. I want to thank everyone at Praxis, involved in all these programs and looking forward to have those 2 Phase III results later in the year as well. So much more to come appreciate everyone's interest and looking forward to talking to all of you subsequent to this call. Thank you.