Good morning, and welcome to the Praxis Precision Medicines PRX-628 program update. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the formal presentations. 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 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'd 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'd also like to welcome and introduce Dr. Dan Friedman, Professor of Neurology at NYU Grossman School of Medicine. Dan was recently named the Director of the NYU Comprehensive Epilepsy Center and is also the Vice Chair of the Epilepsy Study Consortium. He specialize in the treatments of teenagers and adults with difficult-to-control epilepsy, and his research focus on novel treatments and tools to manage such patients. He's the principal investigator of several studies and has authored over 160 peer-reviewed 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 two platforms, we have a portfolio of precision therapies for CNS disorders, including four clinical stage assets and 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 and ulixacaltamide later this year. Let me focus the next few minutes in the opportunity for PRAX-628 and why we believe we are poised to revolutionize the epilepsy treatment paradigm with it. 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 markets 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 focus approach, anchored by epilepsy genetics, aims to change this paradigm. It's important to remind everyone why we're so excited about PRAX-628. From the discovery stage, we're looking for a molecule with very unique and differentiated properties, aiming at the ideal treatment. What PRAX-628 brings to the table is a significantly more potent compound in highly relevant animal models, combined with the ability to dose once a day in patients, and yet 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, in 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 gives them peace of mind by rapidly achieving therapeutic levels with a dose regimen that's simple and convenient. PRAX-628 is expected to reach therapeutic levels at day one and to be administered once a day, a significant advantage compared to current treatments. One of the limitations of the current treatments is the inability to deliver the best possible response to patients, primarily due to narrow therapeutic margins. Based on our translational models and phase I results in healthy volunteers, we project PRX-628 ability to significantly exceed the therapeutic concentrations needed to generate response in patients while being well-tolerated. For example, at a daily dose of 20 mg or 30 mg of PRAX-628, we're able to achieve drug levels that consistently exceed tenfold of the MES's effect equivalence in humans. 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 eight patients with epilepsy who also had a consistent response to photic stimulation. Similar to our healthy volunteer study, concentrations of PRAX-628 significantly exceed the expected therapeutic range. Most importantly, all eight patients, or 100%, responded to treatment with PRAX-628. I want to take a moment to thank all patients who participated 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 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, PRX-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 in 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, employing 15 mg and 45 mg 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 by intermittent photic stimulation, or IPS. Our study participants were equipped with EEG recording equipment and exposed to strobe lights at varying frequencies, allowing us to observe the transition from normal EEG pattern to distinct PPR responses. This rigorous protocol, assessing multiple EEG leads 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, six participants were deemed eligible for safety assessments, with five undergoing PPR evaluations. For Part B, which involved the 45 mg dosage arm, four participants were included in the safety cohort, with three being assessed for PPR. The study comprised a 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 offered 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 cohort's 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 mg dosage group. Impressively, every participant evaluated responded favorably to PRAX-628. All individuals on concurrent background medications experienced 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's 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 Daniel Friedman. I'm a professor of neurology at NYU and vice president of the Epilepsy Study Consortium. I spend much of my professional time treating teens and adults with epilepsy, and my research focuses 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 1.6-2.6 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 a third of these patients are not fully controlled with available current therapy, and 10%-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 or epilepsy type, there's little comparative data to suggest that one drug is more effective than another. So as clinicians, we often choose our initial treatment, accounting for individual factors and the circumstances of the patient. In an ideal world, we want the initial therapy to be the best match for the patient and ensure long-term success and tolerability. In the next few slides, I'll illustrate how, even with 18+ drugs available on the market, some of our patients are left with 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 contraindicated as first-line treatment for women of childbearing age because of a high teratogenic risk. She also has comorbid 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 breastfeeding. 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 illustrate 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. This 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 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 a century and a 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 anti-seizure 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 in randomized, blinded, add-on trials was fairly low, approximately 5% in most studies. A recent trial of cenobamate showed a higher rate of seizure freedom during that double-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 treatments themselves. Drug side effects, pharmacokinetics, and drug-drug interactions all impact quality of life. Tolerability is a major concern for people with epilepsy, who 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 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 mg per day, but the adverse effects at this dose were high, and current labeling actually excludes this dose. Another key area for improvement are therapies that target epilepsy comorbidities, 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. Comorbidities may arise from the consequences 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 comorbidities 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 comorbid symptoms of the epilepsy. They need to be taken chronically, and they're therefore, there are no treatments that change the underlying mechanism, prevent epilepsy after a high-risk injury, such as a 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 breastfeeding. So in conclusion, despite the fact that we have 18+ marketed anti-seizure medications for focal and 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. Patients with epilepsy have to suffer the burden of taking medications daily. The shortcomings of available anti-seizure 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's 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? Thank you, Marcio. So at this time, we'll be conducting a question and answer session with our speakers, so please hold for a brief moment while we poll for questions. So our first question comes from Yasmeen Rahimi at Piper. Please go ahead, Yas. Good morning, team. Hope you can hear me. Yeah. Okay, thank you so much for confirming. Dr. Friedman, thank you so much for your thoughtful analysis, and thank you to the 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 to 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. Then for the Praxis team, I guess, you know, what are the next steps here, right, with this data? What are the doses? Could you contemplate running two phase II-b 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. Thank you again. Thanks, Yas. That's very exciting indeed. And I'll hand over to Professor Friedman to talk a little bit about how the model's being used. And, not only, I think, in pre conversations we had, he mentioned a little bit about the broad use of the model as well. So it'd be great to answer your question, Dan. Yeah, so the photoparoxysmal 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, you know, several drugs that are currently on the market have initially demonstrated very good efficacy in the PPR model, such as cenobamate, brivaracetam, levetiracetam, and you know, 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, but usually a generalized epilepsy and ultimate efficacy in the clinic. So for instance, cenobamate in their photoparoxysmal study, only one out of four patients achieved complete suppression, although that drug's 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 reach 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 would be an efficacy, as you said, yes, 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, but on the, I would say, the lower ends of that as a single dose than we expected. When you look into 20 mg or 30 mg every day, considering the dynamics of dosing a 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 gonna 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 gonna be squared in, and I would say very clearly an efficacy study. We're gonna be giving more details pretty soon, but you should expect a dose of 20 mg for certain to be used to start that study, which we believe gonna 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 gonna be well above what a lot of people 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. Got it. Thank you so much, and I'll jump back into the queue. Appreciate it. Thanks for the questions, Yas. Our next question comes from Ritu Baral from TD Cowen. Please go ahead, Ritu. Good morning, guys. 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 of the phase III design that you are thinking of that could clearly differentiate six two eight from the landscape? Yeah, absolutely. Thanks so much, Ritu. Appreciate it. Well, looking to the background as Steven presented, right? We had a mix of patients without treatments 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 that 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 three treatments that were on top. One was Briviact, widely used as VPA 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 was showing a PPR response at screening a baseline that got eliminated with PRAX- 628, I think it's also 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 and then valproic acid, which are one of them, as you know, has significant liabilities for, for women of childbearing age and pregnancies, as well. So we explored the gamut here. While in a 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 day in and day out, and know these patients really well, but also the neurologists, right? And I actually would ask 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 PRAX- 628 could play a role there, I think it's gonna go into answer part of your question, Ritu. So, Dan, maybe if you could elaborate there. Yeah, I mean, I think there's a lot of value in—like I said, in my talk, you know, 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 general neurologists, 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, so giving patients protection, you know, as soon as they leave the office, and that are well-tolerated. So I think, you know, molecules such as this, you know, may be important to differentiate itself from other new entities on the coming out on the market or available on the market that are more complicated for the general neurologists or the primary care doctors even to use. A quick, very quick follow-up, if I may. When PRAX- 628 was added to patients with background meds, especially those of the same class, was there any increasing of severity of the side effects of note, of mechanism, including, you know, fatigue, headache, et cetera? Thanks. Yeah, super important question, right? 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'll say I wouldn't call uneventful, because, like, you want 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 safety profile, which was very good for us to see. It's a patient that's being on consistent dose. It's a young female, so has the entire life ahead of her, and we hope that we're gonna play a very positive role for herself and her peers living with this condition. Thank you so much. Of course. Thanks for the questions, Ritu. Our next question comes from Doug Tsao at H.C. Wainwright. Please go ahead, Doug. Hi, good morning, and congrats on the data. Maybe starting for the Praxis team, you know, the PPR model is known to be very good for generalized epilepsy, and I think, you know, 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. Thank you. Yes, thanks, Doug. Our original idea here, once we're planning this study before the results, right, today, was to, I would say, take a steady course from focal, running one or two studies in focal, and then expanding to generalized. That, I think, is the more throttled path. As we now sit back and look into what we are seeing, and you probably heard, as I'm sure you did, Steve, talking about 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 gonna 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 actual financial part of this, right? There are about 30% excess patients there when you account for focal, too. So you're growing the available pool by at least 30%. That is a fair bit of upsides, 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, you want to comment a little bit on the second part of the question? Yeah, I mean, I think there is a tremendous unmet need in generalized epilepsy. You know, 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, you know, equally disruptive, they tend to be tonic-clonic seizures. These patients have increased risk of mortality as well. And the treatment options are not ideal. You know, while valproate is probably the most effective treatment arm, and obviously, it has a lot of problems, not just in women of childbearing 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've only have had tonic-clonic seizures. They may not have EEG abnormalities to confirm their epilepsy syndromes, so you need to, you know, you 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. You know, I applaud all the companies that are engaging in studies in this population, even before their compound is on the market. Great. Thank you so much. Thank you. Thanks for the questions, Doug. Our next question comes from Asim Rana at Truist. Please go ahead, Asim. Good morning. Congrats on the data. This is Asim on for Joon. Just one quick question. Marcio, you mentioned going forward with a 20 mg dose for the efficacy study. Just curious, given today's data, why not go with the 45 mg dose or possibly higher, given the tolerability of this PPR study? Thank you. Yeah, no, absolutely, and thanks for the question there. The, when, when you look into our previously published phase I results for PRAX-628, right? At 20 mg daily, considering about a 1.3 accumulation to a steady state, we're actually gonna be reaching therapeutic exposures that are actually higher than what we've seen with 45 mg here. So since we're looking for the chronic treatments 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 mg by giving 20 mg every day. So we're not giving in or giving up on the potential efficacy there. We're just actually surpassing that. We're more than comfortable with 20 mg and 30 mg, and the levels that we are achieving there to an average of 10 to 15-fold what is expected to be therapeutic. So we're really well covered. Thank you. Of course. Thank you for the questions. Our next question comes from Kambiz Yazdi at Jefferies. Please go ahead, Kambiz. Good morning, Marcio and team, and congratulations on the result. Maybe, Dr. Friedman, one question for you. What is the importance of therapeutic margins and speed of achieving therapeutic concentration for an anti-epilepsy medications? And then maybe for the team, investors I've spoke to, who 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're exposed to, that they would not have a PPR? Thank you. Sure. So maybe I'll just going to start with the second part there, and then hand over to Dan. So what we see, we simulate the patients, right, upwards from 0 hertz and then downwards from 60, and we define a range at baseline. What you're seeing on the sole partial response here on that 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 zero. In all the other instance, including on that same patient at 45, that went to zero. So very consistent, very clear. Our previous bar that we discussed with all of you, once you have two partial response at the as the go-aheads in either cohort. So I think we're well past what would be a necessary range here to move this program successfully forward. Dan? Yeah, 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 one. 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, you know, 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 of those things that a molecule can have that makes the primary frontline caregivers for people with epilepsy, doctors and other clinicians treating people with epilepsy, comfortable with its use are gonna be important for its adoption. Thank you so much. Yeah. Thanks for the questions, Kambiz. Our final questions come from Laura Chico at Wedbush. Please go ahead, Laura. Good morning. Thank you for taking the questions. I have one clarification on the 15 mg patients moving into the 45 mg cohort. But first, wanted to ask a little on the AE with respect to sleep paralysis. There's any additional commentary there, and for some of the sleep paralysis? Yeah, no, absolutely. Thanks, Laura. So that 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 you are trying to understand there, if you don't mind repeating? Yeah. Thank you. So if I'm reading correctly, there were three evaluable patients in the 45 mg cohort that came from the 15 mg cohort. So I'm just trying to understand the three patients from the 15 mg cohort that moved into the 45 cohort, what were their responses in the 15 mg? Oh, yeah. No, no, perfect. Perfect. So- Thank you. Thank you so much for repeating. So one of them was actually the very first patient enrolled in the study. Came at 15 mg, and she had like a very pronounced PPR. It's actually an adult woman that's been avoiding any light and 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 mg. Actually had a very benign safety profile. Came back about three months later, a little bit over 100 days later for the 45 mg and had a complete suppression. For all the others, they all have complete suppression, so they were the same. But that 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. Thanks for the questions, Laura. So this concludes today's question and answer session. I'll now turn the call back over to Marcio for closing remarks. Yeah, thank you very much, and thanks, everyone, for joining again. Most importantly, thank you for all the patients who participated on the trial, got dosed, but also the ones that didn't participate, but went through the screening and really dedicated their time and efforts here to science. They're the real winners today. As a reminder, we have a very, what I'm gonna call, eventful year. We're happy to start with these results for PRAX- 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 PRAX-562 are coming soon. We're equally excited about the potential there. On two DEs, initially, that really don't have any other treatment options right now. They're incredibly refractory, and nothing that is in development or right now in the market can help this patient. So excited for that result soon. Quite importantly as well, you might have seen on our most recent 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 wanna thank everyone at Praxis involved in all these programs, and looking forward to have those two 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.