Good morning, and welcome to the BioXcel Therapeutics' SERENITY III Part One Top Line Results Conference Call. At this time, all participants are in listen-only mode. If during the conference you require operator assistance, please press star zero on your telephone keypad. After the presentation, there'll be a question and answer session. If you'd like to register a question, you may press star one on your telephone keypad. To remind everyone, certain matters discussed in today's conference call and/or answers that may be given to questions asked are forward-looking statements that are subject to risks and uncertainties related to future events and/or the future financial or business performance of the company. Actual results could differ materially from those anticipated in these forward-looking statements. Risk factors that may affect future results are detailed in the company's quarterly report on Form 10-Q for the quarterly period ended March 31st, 2023, which can be found at bioxceltherapeutics.com or on www.sec.gov. As a reminder, today's conference is being recorded. Joining us on today's call are Dr. Vimal Mehta, Chief Executive Officer, Dr. Rob Risinger, Chief Medical Officer of Neuroscience, and Matt Wiley, Chief Commercial Officer. Richard Steinhart, Chief Financial Officer, Dr. Frank Janka, Chief Scientific Officer, Dr. Robert Berman, Adjunct Professor of Psychiatry, Yale University School of Medicine, and Dr. Scott Zeller, Assistant Clinical Professor of Psychiatry, University of California, Riverside School of Medicine, will also join us for Q&A. It is now my pleasure to turn the call over to Dr. Mehta, the CEO and founder of BioXcel Therapeutics. Please go ahead. Thank you, operator. Welcome, everyone, and thank you for joining our call today to discuss the exciting journey of BXCL501 for potential use in at-home setting for agitation associated with bipolar disorders and schizophrenia. Just to remind you, IGALMI's two strengths of 120 microgram and 180 microgram are approved by FDA. IGALMI is already benefiting patients in the real world when they arrive for treatment of agitation episodes in an institutional setting, where rapid onset of action is of utmost importance. The company has evaluated half dose strength, 60 microgram, of the approved 120 microgram dose for moving from institutional setting to home setting, where earlier intervention is needed. I will provide an overview of results and their potential importance in advancing our goal of addressing the 39 million annual episodes, representing a $4 billion addressable market for agitation associated with schizophrenia and bipolar disorders. Robert Risinger will then highlight the data for further evaluation in the at-home setting and our plans for part two of the study. Next, Matt Wiley will discuss key market insights about patients who experience this type of agitation in the at-home setting. We are also pleased to welcome Dr. Robert Berman and Dr. Scott Zeller, who will be joining us for the Q&A session. This is an exciting day for BioXcel Therapeutics. We are incredibly pleased with the results from SERENITY III part one, as we believe they represent a key advancement in our lead BXCL501 program. The results attained in this study allow us to confidently move forward with the second part of SERENITY-III. In particular, the most promising findings were the wide therapeutic window suggested with the half of the approved 120 microgram dose of IGALMI and the safety signal in line with our placebo arm. This is an extremely positive and important finding to enable us to pursue BXCL501 administration and evaluation for the first time in the at-home setting in part two of the SERENITY-III trial. This is also a significant milestone in advancing our land and expand strategy. This includes addressing the estimated 23 million annual bipolar and schizophrenia-related agitation episodes occurring in the at-home setting in the U.S. Reaching patients as their agitation begins with safe and effective treatment is critical. Our aim is to arrest agitation in early stages, reduce patient suffering, and potentially obviate the need for emergency room visit. This would clearly benefit patients and caregivers as there is no FDA-approved drug for home setting for this debilitating condition, while also helping to relieve a large economic burden to our healthcare system. SERENITY III was designed with the at-home patient in mind. The first component of the two-part study was incorporated to enable a mid-study evaluation to optimize part two. Keep in mind, this study investigates a new setting for an approved drug at a lower dose to evaluate safety for at-home use. We are pleased with the outcome, and the opportunity to test in the at-home setting is a positive development for the agitation program. We believe the results presented today strongly support the potential use of BXCL501 beyond the institutional setting. Beyond SERENITY III, we are very excited about BXCL501's recent and upcoming data readout, which we believe showcases its pipeline within a product potential. These include the positive top-line data we announced for the major depressive disorder program last week and our TRANQUILITY II trial examining 501 in Alzheimer's-related agitation expected in June. As a reminder, our Alzheimer's-related agitation program is evaluating 40 and 60 microgram doses of BXCL501 in TRANQUILITY II and III. In elderly patients, the exposure levels of the 60 microgram dose are almost double and equivalent to the 120 microgram dose in adults. Additionally, the 60 microgram dose met all five efficacy endpoints in the TRANQUILITY I study. We are confident in the TRANQUILITY II design and plan. These catalysts support BXCL501's potential in multiple neuropsychiatric conditions of significant unmet medical need and reinforce the breadth and depth of our innovative neuroscience portfolio. With that, I would now like to turn the call over to Rob to walk us through the data from SERENITY III, part one in more detail. Rob? Thank you, Vimal. I'd like to start by echoing Vimal's comment that this is a very exciting moment for the company and an exciting potential opportunity to help an additional millions of patients. Let me give you a brief review and orientation to what we have and where we're going. I will review the trial design, the study rationale, and dive into these data results. We're incredibly pleased with the results from part one. Our goal is to treat agitation at home, and therefore, the overall goal of SERENITY III is to maximize the potential margin of safety of BXCL501 for broader use, while maintaining a proportional level of efficacy consistent with the approved doses, all of which we believe are supported by the data discussed today. We found clinically meaningful efficacy results, with one-half of patients responding to this dose. The response was consistent with dose response observed in prior trials. The dose was well-tolerated, consistent with our overall objective to gain approval for use at home. Part two of the trial is advancing, with FDA agreement to initiate testing doses of 60 microgram or greater, such as 80 microgram, in the adaptive design, where we will examine safety and efficacy of use in a non-medically supervised setting. Slide four is the schematic. SERENITY III is a 2-part, double-blind, placebo-controlled pivotal trial designed to evaluate a 60 microgram dose of BXCL 501 in acutely agitated patients with bipolar disorder or schizophrenia for at-home use. Part one of the study was similar to SERENITY I and II. It was designed to assess the efficacy and safety using the same inclusion and exclusion criteria, and similar primary and secondary endpoints of a 60 microgram dose in bipolar disorders or patients with schizophrenia in a monitored setting. The primary efficacy endpoint was a group mean reduction in the PANSS excitatory component, or PEC, total score at two hours post-dose versus placebo. Important secondary measures included response rates by the Clinical Global Impression of Improvement scale, or CGI-I, as well as the PEC. CGI-I response is defined as the assessment of very much or much improved, whereas a 40% decrease in PEC score defines a clear response using the primary measure. Part two of the study is conducted in an outpatient trial, where patients take BXCL501 films home, when they become agitated, take the film or are prompted by a reliable informant who is a family member, spouse, friend, or potentially caregiver. The patients in SERENITY I, II, and SERENITY III, part one, were treated in a highly medically monitored setting, just like patients who are evaluated in an emergency room. SERENITY III, part one, these patients were serving as surrogates for agitation in the at-home setting. We expect that these patients may have relatively greater levels of agitation compared to home-based patient populations. Perspective, let me describe the spectrum of agitation, the experience of agitation, and where patients may come into contact with healthcare along the spectrum. We know that patients' agitation escalates, sometimes to the point of requiring emergency medical treatment. However, they seek or are taken for urgent or emergency evaluation from home. Home is where the agitation experience tends to originate from onset, often through escalation. In fact, patients may recognize an onset even before behavior is objectively manifest. Some patients describe a sort of aura, somewhat like what described by patients who suffer migraines. Individuals may experience this disquiet before and during what family, friends, or spouses observe and describe as harbinger behaviors. For example, patients may initially isolate themselves, limit social contact in order to quell the growing inner discomfort. Family, friends, spouses, having become familiar with these episodes, are attuned to these behavioral patterns, which typically trigger their attempts to de-escalate, provide support or other assistance. In part two, we will be studying BXCL501 for potential treatment at home as the agitation escalates. We believe this is a window of opportunity to intervene at an earlier time with potentially lesser agitation prior to requiring emergency medical treatment. Contrast this, however, with the results I will now describe. Like SERENITY I and II, patients in this SERENITY III part one trial were selected, having reached a level of agitation typically seen in emergency evaluations. Despite the potential difference in baseline agitation, the data generated in part one provide us a rigorous evaluation of safety and tolerability, similar to that conducted in the pivotal SERENITY I and II trials. While assessing efficacy of a dose of BXCL501, selected as one half of the approved 120 microgram dose of IGALMI. We powered part one specifically based on our phase I dose-ranging study, where we observed a reduction in PEC score of one point or greater at multiple time points prior to the 2-hour endpoint. The purpose of part one was to evaluate potential adverse events under similar monitoring conditions that were present for SERENITY I and II participants, and to evaluate results in order to inform the design of part two outpatient at home study using this 60 microgram dose or an alternate dose and dosing regimen. This describes the demographics and baseline characteristics of this study. Notably, the baseline PANSS-EC score was 17, a moderate level of agitation comparable to SERENITY I and II trials. This level is readily apparent even to an untrained layperson. If you're sitting on a park bench next to a person with this level of agitation, you would likely feel compelled to get up and move away. Let's start with safety and tolerability, which is critical for advancing any therapeutic to the home setting. In SERENITY-III, part one, BXCL501 showed remarkable tolerability results, with the number and type of reported events virtually no different than those reported or observed with placebo. No serious adverse events were observed, and none of the adverse events reported required medical supervision, intervention, or monitoring. Adverse events were mild to moderate and none observed to be severe. Adverse events were limited, with the most common being somnolence, defined as feeling drowsy, sleepy, fatigued, or sluggish, occurring in 13% of patients versus 7% in the placebo group. Only one incident of orthostatic hypotension and one hypotension occurred in the 60 microgram dose group, and no bradycardia or other cardiovascular events were reported in the active arm. Except for somnolence, the incidence of adverse events were in the single digits, with the most common reported being oral paresthesia or mouth numbness, dry mouth, dizziness, and finally, nausea in 2%. Each was reported with a somewhat lower or smaller incidence by the placebo group. Turning to efficacy results on slide nine. In part one, a 60 microgram dose of BXCL501 demonstrated clinically meaningful results against pre-specified secondary measures. At two hours post-dosing with BXCL501, the primary time point for the trial, the group mean change from baseline in PEC total score differed from placebo with a p-value of 0.077. At four hours post-dose, BXCL501 separated from placebo with a p-value of 0.049 on the primary measure. 52% of patients treated with 501 responded at two hours based upon PEC response criterion, which was significantly more compared with those treated with placebo for a p-value of 0.039. We observed a significantly greater proportion improved by PEC and CGI response over the course of time. A simple majority responded by two hours with a 40% or greater reduction in PEC total score. This is greater than placebo with a p-value of 0.019. Response by PEC continues, reaching a total of 56%, responding by four hours with a p-value of 0.038 versus placebo. At the pre-specified 2-hour time point, a significantly greater proportion were judged by investigators as very much or much improved by CGI. We believe these data in aggregate indicate that at this dose, a significant proportion of patients experienced substantial and meaningful clinical benefit, as evidenced by clinical response. For example, the 60 microgram dose produced measurable, directional and clinically meaningful effects across three different measures: a PEC change, the proportion achieving a PEC response, and response based on CGI-I versus placebo at time points as early as one hour through four hours. The data suggests a substantial safety margin relative to currently approved doses of IGALMI. Taken together, we believe these results are compelling and support further investigating dosing of BXCL501 in the at-home, non-medically supervised setting. This information allows us to proceed with part two of the study, where we're using an adaptive design to evaluate doses of 60 microgram or greater, such as the 80 microgram dose, which has demonstrated statistically significant clinical effects in the prior phase I-B dose ranging study, as well as the potential to repeat dosing as may be required to treat home-based patients. Of the measures shown, the CGI improvement scale is closest to an efficacy measure in part two of the study. One reason for the adaptive design in part two is that caregivers or informants, as well as patients, are using a number of measures, including a modified CGI improvement scale, to report their response at home. As we collect the psychometric properties of the scale, we will formally power the study to demonstrate efficacy of one or more doses in part two. This will also provide confirmatory measures in support of efficacy as secondary objectives. It's important to note, treat an agitation episode closer to the onset in the at-home setting is expected to be different than this study conducted in an institutional setting, where agitation had already escalated and was established. As a result, a lower dose, which may result in fewer adverse events, may also provide sufficient activity to demonstrate an acceptable benefit-risk profile. The adaptive design of part two will allow us to precisely investigate this in a quantitative manner. The results of part one of this study enable us to dial in efficacy in a manner of speaking. The generally well-behaved, proportional population response data in each successive clinical trial to date, along with the reliable dose exposure data from this formulation, enables projections of efficacy and tolerability based upon population PK and PD modeling in order to determine the best treatment paradigm. Finally, a reminder that assessing multiple doses across various neuropsychiatric diseases in different settings is a critical component of our long-term growth strategy. As the exposure to drug differs depending on the patient population, the optimal dosing is not expected to be the same in all patient groups. In particular, when using the same doses, the exposure in elderly patients is predictably higher than that in younger ones, and therefore, the effects of treatment are expected to be greater in accordance with greater exposure. Specifically, a 60 microgram dose in the elderly produces exposure equivalent to approximately 120 micrograms in adults and not a 60 microgram dose in adults. For this reason, the IGALMI package label indicates the recommendation for physicians to use one half the dose in elderly by reason of this well-known increased exposure. Confirming this effect, results of the previous phase I-B two study in agitation of Alzheimer's dementia. In our TRANQUILITY I trial, a single 60 microgram dose met all the efficacy endpoints in all of five different measures as early as one hour after dosing, with a 70% PEC response rate at two hours, compared to 0% with placebo. To summarize, we are extremely pleased that our part one results support our approach to part two trial design, which includes evaluating BXCL501's potential safety and efficacy for multiple episodes in an at-home setting over three months. We look forward to further unlocking BXCL501's full therapeutic potential to treat agitation in additional settings and via additional or alternative doses. As a reminder, FDA discussions are ongoing and will occur following the conclusion of SERENITY III, part two. At that time, we plan to discuss potential label expansion for IGALMI into the home setting. Let me now turn the call over to Matt to discuss important market insights about patients who experience bipolar or schizophrenia-associated agitation at home. Matt? Thank you, Rob. Good morning, everyone. The market need for BXCL501 in the at-home setting is palpable and urgent. Agitated adult bipolar and schizophrenia patients have few options, and their healthcare providers are both under-diagnosing and under-treating it. These patients are typically aware when they're having episodes, don't like it, and try to do things to make the episodes stop. We have seen in previous market research that these patients will use exercise, meditation, alcohol, illicit drugs, and other means in an attempt to arrest these events. While our current commercial efforts are focused on the treatment of agitation in the emergency department and psychiatry settings of the hospital, the majority of these episodes occur for these patients outside an institutional setting. Patients report having approximately three episodes per month and rate the severity of the episodes as moderate to severe. Approximately one-quarter of these patients have a prodromal event, which predicts an episode is about to occur, and this increases with episodic severity. This phenomenon was, prior to our research, not well understood or appreciated. For patients, agitation episodes are characterized as something beyond their control, and they differentiate it from ordinary fear and anger. Looking at slides four and 19 of our presentation posted on our corporate website this morning, these are just two real-world examples to show how powerless these agitated patients feel trying to control their own emotions and psyche during an episode. Despite this, only 41% of the patients reported having a diagnosis of agitation, and only 35% were receiving any therapeutic treatment for their episodes. When patients were provided a target product profile for BXCL501, they found the product to be unique and felt a high likelihood to try it for their episodes. Most importantly, we found in this research that patients expressed they would likely use BXCL501 in 80% of their episodes. Patients also intended to take it during the previously mentioned prodromal stage or at the onset of the episode. This market condition may be favorable as patients have expressed their desire and intent to intercept the agitation before it has significant time to escalate. In summary, there is a large unmet need and desire to self-address this need. When considering the significant positive feedback we have received for our approved drug, IGALMI, by real-world patients to date, we see this as an enormously important opportunity, which our investigational BXCL501 product is strongly positioned to address. With that, we would now like to open the call for questions. Operator? Thank you. We'll now be conducting a question and answer session. If you'd like to ask a question today, please press star one from your telephone keypad, and a confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants who are using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment please, while we poll for questions. Thank you. Thank you. Our first question is from the line of Colin Bristow with UBS. Please proceed with your questions. Hey, good morning, and thanks for all the this useful color and clarity that you've just given so far. I guess the primary question we've been getting this morning, I think is at the top of people's minds, is just around getting comfort around the exposure you'll see in TRANQUILITY II. You know, you've addressed some of this already, but how confident are you that the sort of the baseline population enrolled is going to see this 120 microgram exposure? Then how should we think about this in terms of interpatient variability? Yeah, another thing that I'm not sure if you could provide is the potential powering for TRANQUILITY II. Just finally, one last thing, as we think about future studies at this lower dose, we consider switching to longer time points for PEC, et cetera. Thank you. Let's see. Let me take those questions in sort of sequence. The exposure levels of the elderly are well known and described, not just in our hands, but multiple independent publications describe much greater exposure in the elderly, given the same dose. FDA has agreed, and it's literally in our current package label, that the recommended dose in the elderly is one half of the dose in younger adults. And the proof in the pudding, if you will, in our TRANQUILITY I study, was demonstrating effects using the same primary measure, for example, the PEC. Those effects were quite robust and very much similar to higher doses in younger adults. With respect to the variability of exposure in the elderly as compared with younger adults, I don't believe there's a substantial difference in the variability. Although it's proportionate, I think the, as I've always said, this film formulation is quite robust and gives us reliable, proportionate increases in exposure across the dose range. In the elderly, thus far, we've seen very consistent pharmacokinetic exposures. Maybe I'll turn this over to Dr. Lathia, our Head of Clinical Pharmacology. Regulatory Affairs. Yeah, this is Chetan Lathia, Head of Clinical Pharmacology and Regulatory Affairs. We have done some robust pharmacokinetic assessments in our first trial, TRANQUILITY I, and we have data demonstrating that the exposures in TRANQUILITY I are approximately 2-fold higher than those in healthy subjects and in schizophrenia and bipolar disorder patients, as Dr. Mehta mentioned at the beginning of the discussion in the introduction. There was a question about interpatient variability in exposures, and we have information that indicates that the interpatient variability in elderly patients is consistent with what we have observed in the healthy volunteer and the schizophrenia bipolar setting. More importantly, when we looked at the exposure response evaluations in the first trial, TRANQUILITY I, as Dr. Risinger mentioned, we have very robust efficacy data across the entire range of patients that we evaluated in five separate measures, including PEC score, which is the primary measure in TRANQUILITY II and TRANQUILITY III trials. Let me answer your last portion of your question. We are, in fact, conservatively powered in TRANQUILITY II with regard to the effect on the primary endpoint, which is the change from baseline in PEC total score at two hours. We demonstrated robust statistical significance on this measure in TRANQUILITY I, and we expect the same or in fact greater powering because we now have 50 patients per arm versus 50 patients on placebo in TRANQUILITY II. Great, thank you. Our next question is from the line of Greg Harrison with Bank of America. Please assist you with your questions. Hey, good morning. Thanks for taking the update, or for the update and for taking the question. At this point, what determines your ability to increase the dose in part two to 80 micrograms? What's the process in general as far as making adaptations to part two of the trial? We have FDA agreement for a 60 microgram dose, which can be repeated, if necessary, at home. The agreement with the FDA includes the overall design of the adaptation. We're using the data that we're announcing today in simulations from PK/PD modeling in order to project, alternate doses between 60 and 120, for example. We really are looking to, as I said, dial in efficacy, where we can optimize the effect of the drug at home and still maintain a safe exposure and safe, well-tolerated, dosing to treat agitation at home. In terms of how we're doing this in the adaptive design, we literally take the primary measure, which is not a PEC at home. We're using a modified CGI-I. This is clinical improvement that is rated by the patient and by the informant. We believe the reliable informant, being independent of the agitated state, is likely to give us a better discrimination of improvement. Therefore, as we're collecting the psychometric properties, the standard deviation, and the capacity to identify an improvement, we'll be able to accommodate that and then power up or down the second part of the trial. Let me turn it over to Chetan Lathia in order to describe this in a little bit more detail. This is Chetan Lathia. We have a large amount of PK/PD data, over 1,000 patients worth of data in schizophrenia, bipolar population, and we had already done exposure response or PK/PD modeling based on previous data. As Dr. Risinger points out, we have initiated PK/PD modeling to add the new data that we have obtained from this study to perform, to revise our modeling effort and to perform simulations to estimate, based on this, the appropriate dose that would give us a very good benefit with an appropriate safety tolerability. We believe that it is targeted towards 80 microgram, but it could be a dose between 60 and 120, as Dr. Risinger has pointed out. Very helpful. Thanks for taking the question. The next question is from the line of Robyn Karnauskas with Truist Securities. Please proceed with your question. Hi, good morning. This is Nicole onto Robyn. How do you think the at-home setting could impact the separation from placebo on the efficacy scores, given that the at-home setting might be less agitated than the institutional setting? Thank you, Nicole. Please relay to Robyn. We appreciate the question. The adaptation in part two is literally to accommodate whatever the variance may be, or fidelity, call it, of observing agitation at home. Lesser agitation may have a more subtle effect. In fact, we are collecting more than a single measure of efficacy at home. We have behaviors that are emitted. They're tracking behaviors. They're also tracking the timing of resolution of these behaviors. We have a time for the resolution of the agitation. We have a time for specific behaviors. We have specific range of behaviors that are typically manifest at home. We don't just have this modified CGI, we have a whole range of information to provide. We know that the FDA likes to approve drugs both on patient, or in this case, caregiver-rated outcomes, as well as a wealth of data that supports and confirms whatever p-value you may come up with. They really like to see that it works from a variety of perspectives, and so we have a large amount of data. Great. Just a quick follow-up. Can you clarify what the timelines to proceed for part two are and what the filing timelines will be? In terms of proceeding for part two, we are proceeding directly to part two. We're initiating that study shortly. If you don't mind, let me revert and ask maybe Dr. Zeller to describe agitation as it is manifest and rises to the level of an emergency or requiring emergency room treatment. We know the patients try to treat themselves, and maybe he can describe a little better what they do and what options they have. Yeah, I'm happy to join in on this. There's a real, natural kind of situation that when patients start to feel agitated, you usually go through a kind of a mild to moderate agitation that will, could at any time escalate into severe agitation, which could include aggression and violence. Certainly something that we want to avoid. The patients often know that they're starting to feel agitated, starting to feel restless, that are those early stages where you're perhaps, you know, not able to sit still, starting to get irritable, then up into moderate agitation, where you're starting to get angry, maybe clenching fists, maybe starting to yell or respond to different stimuli in a negative way, all the way up to that severe agitation, which is, of course, what we want to avoid. When we talk to, you know, family members, when they're coming in with their family member for a visit, for example, they'll say, "What can we do when we start feeling agitated, when we start feeling the need for... We need something more? Should we go to the emergency room? Should we call you up? Is there, can we take an extra dose of the medication? You know, there might be an inclination in some folks to say, "Well, maybe just take an extra one of your antipsychotic." That's really something that we want to avoid because, we know that, as you go up in the dose of antipsychotics, you tend to hit a plateau in responsiveness for symptoms, but you greatly increase the risk of bad side effects, such as extrapyramidal symptoms or, you know, dystonic reactions or akathisia. We really want to avoid, increasing an antipsychotic or using anything else. There hasn't been anything that we can recommend to families that they could use when they start to have that prodrome of mild to moderate agitation and knowing that there might be something really bad on the horizon. It's really exciting to think that we could have something that we could confidently tell family members, "You know, have this in the house. You start seeing agitation," or telling patients directly, "If you start feeling that agitation come on," boy, wouldn't that be a great thing to be able to have and know that you're not gonna end up having to go to the emergency room. You're not gonna break anything or get some bad outcome at home. There's definitely this whole situation that's this vast need that we see as clinicians all the time. Great. Thank you. The next questions are from the line of Sumant Kulkarni with Canaccord Genuity. Please proceed with your questions. Morning. Thanks for taking my questions. I have three. The first one, what percentage of patients, if any, in Part one of SERE-III, were aged 65 and older, and how did IGALMI perform at the 60 microgram dose in those patients? We had a relatively small proportion of 65 and older. The exact number, I can't provide you at this moment, but it was small enough that I have really no confidence in projecting, with, you know, numbers under 10. M y second question actually does not involve a read-through to TRANQUILITY II; rather, it's a potential read-through from TRANQUILITY II to at-home use. Based on your comments, we know exposure levels are different in older patients, but given TRANQUILITY II already involves a 60 microgram dose and also involves residential care facilities, would that data set be good enough to de-risk at-home use of IGALMI, especially given the burden of proof for safety in older patients is typically higher versus younger ones? I believe you're making a quite a valid point. We know that the FDA considers special populations from the standpoint of safety, exposure, and PK parameters, and this is a population that has much greater exposure than otherwise younger adults. Having the safety at a 60 microgram dose in this, call them vulnerable population, should provide, you know, robust safety data and tolerability that the FDA may well find persuasive. My last question for now is, given part two of SERENITY III does not include PEC scores, is there any precedent for a product being approved for at-home use on safety data alone or on different endpoints? Maybe I'll turn that over to our KOLs. I'm not aware of agents that were approved simply based on safety data for at-home use. This is Rob Berman, adjunct professor at Yale. I can't think of a precedent on that per se, but I would say this, that you know, what we're looking at here through TRANQUILITY and SERENITY is a very robust package showing exceptional efficacy on agitation and at the same time, exceptional tolerability. I think the perspective the FDA will look at is risk-benefit, and I think this clearly stands out in that regard. Got it. Thanks. Our next question is from the line of Yatin Suneja with Guggenheim. Please proceed with your questions. Hi, this is Delma for Yatin. Thanks for taking our question. Do you need to discuss with the FDA on known PEC score as approvable endpoint before starting the part two of the trial? What level of placebo just delta do you need to show on CGI score to get the FDA approval for at-home use? Finally, how long do you expect the part two will take to complete? Thank you. I'm sorry, we didn't get your third part of that question. Could you repeat the third question? Yes, I was just asking, how long do you expect it will take to complete part two, to have the top line results for part two? Let me answer both your first and second question. We're describing the psychometric properties, meaning the sensitivity of the modified CGI-I scale and the variance in an adaptive manner. Once we have quantified those, we are then able to numerically power appropriately part two of the study. The total number may go up or down based on that variance. We do know that the most sensitive rater for each individual patient is someone who knows them well. It's not a cold, independent rater who really doesn't understand the patient or their typical progression of behaviors. I think that gives us, in a sense, superior sensitivity using this scale in the hands of someone who knows each individual patient. We'll be very interested to see the sensitivity of this measure, describe that, and be able to power, part two appropriately based literally on the data that's coming in from part two. In terms of how long it will take, that depends on the total number and also the accrual rates, which we don't like to project until we're literally accruing patients. Once we have that, we're happy to share our projections for when that trial will conclude. Great. Thank you. Thank you. Our next question is from the line of Corinne Jenkins with Goldman Sachs. Please proceed with your questions. Good morning. I noticed that both the drug and the placebo cohort achieved a change in PEC score that was almost a full point lower than what we've seen in the prior SERENITY studies and in the phase I-B. Is there anything you would attribute this overall lower difference in benefit, given the dose response till now has always been pretty consistent? Maybe I can describe the fact that this has been remarkably well-behaved in terms of dose response. This is very consistent, the findings that we're demonstrating here with a dose response in terms of efficacy and separation from placebo. We've always accounted for a placebo effect, and if you don't do that, you are suspect to greater variance in the response and separating from placebo. We knew that we took literally one half of the approved dose. We expected much lower response rates. We did not expect a three or five or six-point change as what we get with the 120 or 180 microgram dose. Our effect size remains over one, very much like 1.2. Maybe, I don't know, Dr. Berman, you could comment on, you know, the range of efficacy across doses and consistency. Yeah. I mean, effect sizes of 0.3 to 0.4 are what you see in most psychiatric blockbuster drugs. This is remarkably higher and along the lines of drugs like ketamine and such. I think this is still consistent with what I said before, exceptional efficacy. You know, this study also, as you point out, was without patients, and it was very importantly demonstrated or will be demonstrating the safety in this outpatient setting. Overall, I think it's consistent with all the studies that have come before. Just to bear in mind, the efficacy really is a game changer in the context of its exquisite safety and tolerability. Patients really don't like taking extra doses of their antipsychotic or benzodiazepines. They cause sedation. This is a drug that has potential appeal to the patients, and so allows them to engage in the treatment. I think, you know, they'll experience it as different and will, I think, also quite effective, so. Okay. Well, is CGI-I, like, do we know if that's an acceptable and approvable efficacy endpoint for regulators, or have you talked to them at all about that particular endpoint? Or are we just, you know, kind of assuming at this point? We have an agreement with the FDA for the measure. Again, we're providing the explicit properties of that measure in that home setting, with these caregivers and with patients. Yeah, this is Chetan Lathia, Head of Regulatory and Clinical Pharmacology. We have explicit agreement with the FDA on the parameters by which the entire program, with part two supporting part one, would be approved. Modified CGI-I is a clearly agreed upon tool that we will use to demonstrate efficacy in addition to safety, which is the primary endpoint for part two. Okay, thanks. Thank you. Our next question is from the line of Graig Suvannavejh with Mizuho Securities. Please just hear with your questions. Good morning. Thanks for taking my questions. I'm just curious, you know, you were looking for a one point placebo-adjusted delta. You did not technically hit statistical significance at a 2-hour time point, I'm just wondering if there was something around the trial design assumptions, whether there was an opportunity to perhaps make different assumptions to be able to achieve statistical significance. I just wanted to kind of get your perspective around that. Second, this might be a question for Dr. Berman, who's on the line. There was stat sig that was seen at a 4-hour time point, and I'm just wondering if you could provide, for context, whether having a drug that works hour hours versus four hours, if that makes a difference. Perhaps, you know, in relation to other drugs that you're using, is that four hours or two hours meaningfully different, such that, you know, this would be, from a speed-of-onset perspective, an ideal treatment? Thanks. I think there are a number of assumptions that we made. We're exploring if there were factors that contributed to sort of missing a 0.05 at a 2-hour time point. The most obvious accommodation would be to sort of shift our time of primary endpoint at home to four hours. It appears, by all of the data, that the response to this lower dose takes a little bit longer to evolve. That certainly is... Well, maybe Dr. Zeller could comment. I don't know that that's an issue at home. We know providers in the emergency room want fast, now effects, and that's not exactly what we're seeing with the 60 microgram dose in this study. There are some take-home messages, and there may be factors in the study that we can adjust in part two. The most obvious way is to increase the dose to, say, 80 micrograms or better. Again, I just want to- Yeah, I can jump in on that. Oh, I'm sorry. Yeah. What I was about to say in terms of... Okay. In terms of the two hours versus four hours, I think you've had this kind of standard of the 2-hour endpoint with all the other treatments for agitation that went through the FDA historically. Everybody's kind of looked to that, and it makes more sense when you're talking about the institutional side, where you're in the emergency department, you're in the psychiatric facility, where that, you know, more rapid onset is really key. When you're at home, you know, agitation tends to have this waxing and waning, where it's almost like a stairstep or a sine wave that's kind of climbing up. What you really wanna do is to be able to intervene and help a person modulate that agitation, that's not gonna just be, you know, a five-minute episode, and then it goes away. It's gonna be something that's kind of ruminating there in the background, if you will. What we wanna be able to do, if you can have something that's working great two hours to four hours, that's really going to be extremely useful at home because you don't know what's gonna be happening next over those next few hours. You know, it might be something disturbing that happens to that individual. There might be something frustrating that comes up, and when that does, we're gonna have a longer effect, which I think is gonna be more useful at home than we would necessarily be looking at in the clinical setting. Those are great points. I'd just like to point out that, again, the totality of the data here shows a very consistent efficacy, even at two hours, even though the P value is 0.07. I think the FDA will appreciate that, as they did with other drugs that, you know, had two studies, one with a P value under 0.05 and one with slightly a smidgen above it, like brexpiprazole. I don't see there being regulatory concern about that number. What was the effect size of the most recent approval? I don't recall. Nothing close to one, even? I'd have to say, my guess is 0.4. Yeah. I shouldn't be quoted on that. Yeah. Thank you. At this time, I turn the floor back over to Dr. Mehta for closing remarks. Thank you, everyone, for joining us today on short notice. Have a great day. This will conclude today's conference. You may disconnect your lines at this time, log off your webcast, and have a wonderful day.