BioXcel Therapeutics, Inc. Stock

Greetings, and welcome to the BioXcel Therapeutics webcast. [Operator Instructions] It is now my pleasure to introduce Vimal Mehta, Chief Executive Officer and Founder of BioXcel Therapeutics. Thank you. You may begin.

Thank you, operator. Good afternoon, everyone, and thank you for joining us today. We appreciate your time and interest as we share an update on the commercial strategy and launch plan for IGALMI, ahead of its potential approval for the treatment of acute agitation episodes associated with bipolar disorders and schizophrenia in the home setting. As you all know, these episodes represent a frequent and challenging reality for patients and caregivers, often occurring outside of clinical settings where there are currently no FDA-approved therapies.

We are entering a key period for BioXcel Therapeutics as we prepare for the upcoming November 14 PDUFA target action day for IGALMI. At this time, our focus remains on executing our launch readiness, activities to ensure we are well positioned to bring this treatment to patients and caregivers as efficiently as possible if approved.

Finally, I would like to thank our Interim Chief Commercial Officer, Mark Pavao, who has been instrumental in developing the launch plan and commercial strategy for IGALMI and our moderator, Michael King, for leading today's event.

With that, I will turn it over to Michael King.

Thanks, Vimal, and good afternoon, everybody. It's nice to join you today. I'm delighted to have been asked to moderate the Q&A session of this event, which I hope will illuminate the significant opportunity for IGALMI at home and in conjunction with that, of course, with BioXcel stock.

In the interest of disclosure, before I introduce Mark Pavao, I would like to just read the following disclosures. First, BioXcel is an investment banking client of Rodman and Renshaw. Number two, we cover the stock, which is rated buy and we've established a $17 price target for the shares. And finally, neither I nor any member of my household own shares in the company.

So with that, let me introduce Mark Pavao. Mark Pavao has more than 30 years of U.S. and global commercial leadership experience across the biopharma industry, including extensive prelaunch planning and on-market commercialization in CNS and additional therapeutic areas. He has contributed to the commercialization of multiple CNS therapies, including Abilify for schizophrenia, bipolar disorder and depression; Paxil for depression; Risperdal for schizophrenia; and Nurtec ODT for migraines. And I would just add editorially that the parallels here are very strong.

So without further ado, let me let Mark launch into his presentation, and we will come back at the end with a Q&A. Mark, over to you.

Okay. Michael, thank you very much, and I'm excited about the opportunity to share the IGALMI at home opportunity from a commercial perspective and talk about what we've learned from our market research as well as how we're thinking about the go-to-market plans for IGALMI.

Let me start off by setting the stage by reminding us where IGALMI has come from and where we're going. IGALMI was approved back in '22 for use specifically in the institutional setting with administration under health care supervision. Fast forward to last year, the SERENITY At-Home study demonstrated that IGALMI can be used successfully at home by patients administering it to themselves without medical supervision. That data has now been filed through an sNDA. SNDA was accepted for review. We have a PDUFA date of November 14 and are looking forward to launching in first quarter of '27.

So as you will see, as we go through the story, the market opportunity expands significantly from the institutional setting to the at-home setting. But more importantly than that, the value proposition completely changes. In the institutional setting, there are other medicines indicated for the treatment of acute agitation. In the at-home setting, nothing is indicated. Further, the goal in the institutional setting is to calm patients down who have presented to the ER. The goal in the at-home setting is to help patients deescalate, so they don't end up in the ER. So very, very different value proposition in the at-home setting.

So let me -- I'm going to walk through a couple of slides that summarize what we've learned in the market research that we've done. First, we've talked to physicians, we've talked to patients, we've talked to payers and what's come through about the condition itself, acute agitation in the at-home setting, it happens frequently, it happens often. 36% of bipolar patients who are well controlled on their underlying mood stabilizers, 50% of schizophrenia patients who are well controlled on their underlying antipsychotics experience breakthrough agitation, which can be distressing, disabling and if it escalates can lead to those hospitalizations or worse.

The symptoms span a range of areas from emotional symptoms like tension and irritability, behavioral symptoms like restlessness and overactivity, cognitive symptoms like impulsivity. And despite all of this, nothing is indicated to treat acute agitation in the at-home setting. The market opportunity is very large. And the IGALMI profile is very, very strongly fit with the unmet need. So as we talk about the opportunity itself, agitation at home is under-recognized and undertreated. And I say that it's -- the analogy is the tree that falls in the woods. If you're not there, you don't hear it.

So physicians know that patients get agitated. They're very aware of the patients who are agitated at home would end up in the ER. They are less aware of how frequently and how often patients are agitated on their own, but they do know that it happens. When they do treat patients at home, they're basically doubling down on typical or atypical antipsychotics, oral antipsychotics, which are slow to act or benzos, which are controlled substances and have other issues.

So physicians recognize that the current treatments are not optimal. And when they see the IGALMI profile for at-home use, they're very excited, and they project that IGALMI will be used in 70% of their appropriate schizophrenia bipolar patients who experience agitation in the at-home setting. We've talked to patients. Patients, all of whom have experienced what it's like to be in the ER, be treated in the ER and be calmed down with either injectable antipsychotic or an injectable benzo, that -- those experiences are not pleasant. And when we talk to patients and we present them with a TPP, the target product profile for IGALMI At-Home, very, very high interest. And they project that they would use this in 80% of their future episodes.

We also talked to payers in our market research to understand how they would think about placing IGALMI on formulary. And the consensus was -- we talked to 5 payers, these were payers that represented very large health plans. The consensus was that because nothing is indicated because this is an unmet need, because appropriate treatment that avoids the escalation and an ER visit or hospitalization that IGALMI will be covered on formulary with common restrictions such as prior authorization to label, so making sure that only patients who have an indication for schizophrenia bipolar get the medicine and potentially quantity limits as well since this is not a medicine indicated for chronic use, but it's a medicine indicated for episodic use.

So moving along in the research, we also were able to dimensionalize the size of the opportunity. And in our research, we were able to calculate that there's 2.3 million treated bipolar schizophrenia patients who have frequent acute agitation. Frequent in the research was defined as 10 to 15 episodes per year. And of those treated patients who have episodes, when you map out the number of episodes they have, which is about 4 per month, that adds up to an addressable population of about 86 million episodes per year. When you think about this in the context of the 16 million episodes per year that are seen in the institutional setting, you understand that this represents a significant expansion of the addressable market for -- available to IGALMI as we move forward and secure this indication and take it to market.

Mark, can I just ask a quick question on this slide?

Sure. Of course.

Why do you think the hospital setting is so much smaller? Those numbers are significant as far as the number of episodes. Is it because patients never get to the ER, are they reluctant to go to the ER, are they treated elsewhere? What explains that dichotomy?

Yes. I think it's a couple of things. First, we know the patients are reluctant to go to the ER. Either they've been there before, it's not a pleasant experience. So they will avoid it if possible. And secondly, I think patients are largely -- they're suffering in place. They're experiencing distress. It's ruining their day. They're becoming uncooperative or perhaps belligerent in whatever work setting or home setting that they're in. But it doesn't get to the point to require hospitalization.

In our research, both in the clinical study, but in the market research we did, we learned from both physicians and patients that the agitation episodes come in different levels of intensity. And we found that about 1/3 of the episodes are mild, 1/3 are moderate and 1/3 are severe. And often an episode a mild episode can escalate to moderate, which can escalate to severe. So the goal here is going to be when you have a medicine that is uniquely designed and specifically indicated for this condition in the at-home setting, you help patients avoid the escalation that can lead to the hospitalization.

Okay. That's super helpful.

Yes. You bet. So moving on to the next slide.

Here, we'll begin to talk about how we're thinking about bringing IGALMI to market and the impact that we're trying -- that we think we can make on the market. And basically, we have an opportunity to redefine the standards of care. Now that we have a medicine that is specifically studied for specifically indicated to treat patients in outpatient at-home setting for the first time because nothing is indicated today, we have an opportunity to help patients treat themselves. And this was very, very motivating to patients.

What do we need to do to make this happen? One is to elevate the recognition of agitation in the at-home setting as being a real condition that happens frequently and can be treated with IGALMI. As we do that, we'll want to -- we'll then look to establish that the right way to treat is as early as possible. So as symptoms are coming on, have IGALMI on hand, treat it, don't let the episode escalate, which may lead to hospitalization or worse.

And as we're successful in establishing the practice of medicine and the pattern of care and IGALMI as a new standard, we can then work with the guidelines agencies, the path lines agencies to hardcode IGALMI into the pathways into the guidelines. So at a 30,000-foot view, this is the opportunity that we have. And I'll say that for people with agitation who experience this at home, schizophrenia and bipolar patients experience this at home, this is kind of like having the EpiPen. That's -- it's a great analogy. So patients who are at risk for allergy, severe allergy, they have an EpiPen on hand, and that's what IGALMI is going to present to our patients.

Moving forward, as we think through the different audiences, the kind of work that we'll be looking to do in the period leading up to launch, it's all scientific communication. We've got great data. So we want to get that data out. We want to be presenting the data and elevating awareness about the unmet need that exists in helping patients with schizophrenia and bipolar who experience agitation at home. So it's elevating the awareness of the unmet need and making sure that physicians are -- have been exposed to the SERENITY At-Home data.

So there are many scientific congresses that we can get to present the data. We'll be engaging with physicians and some physicians in the context of advisory boards to get their advice on how we can best bring the message to the market and then obviously leverage those insights in the finalization of our go-to-market plan.

Mark, I just wanted to jump in real quick. If you just spin back 1 slide, if you don't mind, I don't want to get too granular with this question. But as far as these congresses are concerned, can you talk about what you're permitted -- you as a company are permitted to do and say at these conferences under the regs? And from -- who from the company is allowed to participate in these congresses. Are they medical affairs people? What can you say about these...

Yes, absolutely. So all of this is done under scientific exchange. We have great data. The data gets written up in the context of abstracts and posters and publications and we have obviously medical people within the company, and we'll be adding to our medical affairs leader who's within the company at this point, eventually a team of MSLs. So all this will be done in the context of scientific disclosure.

So moving on to an important part of the building blocks for the launch plan and getting ready for launch is preparing the value proposition, the data that goes into building out the economic justification to the payers to make sure that IGALMI is broadly available as quickly as possible. This is not a flipping-the-light-switch exercise. It will involve significant conversation with payers over time, understanding their needs, understanding their level of awareness of the situation. And probably in many cases, I expect we're going to have to do some education here because when you enter a situation where nothing is specifically indicated, there's going to be the need to educate payers on why a fast-acting sublingual pill or sublingual film that is calming without being sedating that the patient can administer on their own at home is better than an oral atypical, which is being used now in the case of the at-home setting, which does not work fast and exposes the patient to atypical side effects or a benzo, which is a controlled substance and exposes the patients to other side effects.

So there will be the need to educate. But the point here is that with the payers there's a value proposition to be built. There are pricing and contracting strategies to be developed with the goal being that we get to launch and through the launch year with the opportunity to establish formulary presence with as little friction to patients as possible.

Moving on to the prescribers. Mission-critical for the launch of IGALMI at-home study is going to be educating prescribers. The prescribers in this particular case are basically doctors who treat schizophrenia and bipolar. This is a market that I know well. We've talked to these doctors over many years. It's a very concentrated group of physicians. So approximately 65% of the opportunity in schizophrenia and bipolar is covered by less than 10,000 doctors. So it doesn't take a very large sales force.

If you figure -- I think on the order of magnitude, we're talking somewhere in the 80 rep range to cover this kind of opportunity. So with a relatively small sales force, we're able to cover 65% of the opportunity from an education perspective. And then over time, obviously, we can expand as we gain traction or as we move further and have additional indications for IGALMI.

Mark, you anticipated my question about the size of the sales force, so I'll leave that alone. But in terms of the physicians, is this an 80-20 type of situation? Or where 80% of the scripts are written by 20% of the docs? Or is it more evenly distributed?

No, it's definitely 80-20. It's probably a bit more concentrated than that. I mean we're covering 65% with less than 10,000 doctors. And it doesn't take that many more doctors to get to 80%, very concentrated footprint. So thanks for that, Michael.

So moving on to the patients. Once we have physicians educated and we've got really good access through the payers. And importantly, the payers, we're talking not only Medicaid and Medicare, which are important for schizophrenia, but the commercial payers are going to be important for us. So once we have really good access across the payers, messaging the patients is going to be important. So this is not something we'll do at the beginning, but I think in the fullness of time, there's an opportunity to help patients recognize that there is a new medicine that can help them manage their agitation on their own at home, help them understand how easy it is to use, give them the confidence to know when and how to treat themselves.

And in some cases, help educate the caregivers to support their family member with schizophrenia and bipolar to treat appropriately when they feel the agitation coming on. So in the fullness of time, there's definitely an opportunity for consumer messaging, not -- I'm not talking big DTC from day 1, I'm not even talking big DTC in the second year; it's a very, very targeted messaging opportunity. At launch, though, what will be important for patients is making samples available to patients through doctors' offices and in those samples, having patient starter kits that make it very clear what this medicine is and how to use it, how to administer the dose to yourself. And of course, we'll have those dosing instructions available on online as well.

So wrapping up, and then, Michael, we can get to whatever questions you and others have. IGALMI, it's a great story. The clinical data that was completed in last September came through very, very nicely, studied 250 patients. Those 250 patients had over 2,500 episodes of agitation that were successfully treated. And largely, what that study showed is that patients can dose themselves successfully at home with IGALMI. That data has been packaged. It's been submitted to the FDA. We've got a PDUFA date, November 14. We have a really good work plan for the next 9 months to get I ready to launch with -- assuming success on November 14, we'll be ready to launch in the first quarter of '27.

So I'll wrap up there, and happy to take any questions.

Thanks, Mark. That was brilliant. Yes, and I have to commend the company for having done an extremely thorough job of not only conducting the trial, but some of these -- the comparator trial for sort of basically operating the patient's ability to treat themselves is outstanding. So I think that, in my opinion, reduces regulatory risk pretty significantly.

Mark, let's start off with kind of the patient vignette. What does it look like to live with bipolar or schizophrenia and being someone who gets these fairly frequent bouts of agitation? Walk us through what that experience may look like? What happens and what is the patient's options when there's no options available and it escalates into a crisis. So maybe you can talk a little bit about that.

Sure. So I'll take that one. Thank you, Michael.

So look, schizophrenia, bipolar, these are serious mental illnesses. These are distressing, debilitating, very serious medical conditions. They are controlled with strong medicine, typical and atypical antipsychotics. They're great medicines. They help patients significantly, but they have a lot of side effect burden. So -- and bipolar, the mood stabilizer is the same. So first, you have to think about this in the context of the underlying medical situation that these people are already working through.

And then on top of that, a patient who is diligent with their medicines, they're well controlled, they're living in the at-home setting. They then have -- and we know from the research, many of them will have breakthrough symptoms of agitation. And this is -- these are just stressing symptoms. As I said earlier, it's -- the symptoms exist, you've got emotional symptoms where there's -- it's -- they get anxious, they feel kind of uncomfortable. It can escalate to behavioral where they get -- there's ferocity in escalating situations, progression. We've had -- we've heard from patients who experience this at work where they basically become not only dysfunctional at work, but they potentially are exposed to losing their job.

So it's a very distressing situation for patients. And up until now, without anything specifically studied for an indicated, they're left to use off-label medicines. Right now, the -- what is used are the atypicals, which I said earlier, expose us to even more side effect burden or the benzos, which have different side effect issues and also are controlled or in the case of escalation, they end up back in -- if they're lucky, they end up back in the ER. If they are so out of -- so agitated, so out of control, so belligerent, it's not -- some patients end up in handcuffs.

So it's just a terrible case from a patient perspective. So the ability -- and I'm going to go back to the EpiPen analogy because I love the idea that for the first time, these patients are going to have something that they can carry with them, whether they're at home, whether they're out in the park, whether they're at their job and if they feel this coming on, they can control themselves. They can dose themselves. And as I said earlier, the nice thing about IGALMI, the profile at the highest level, it calms the patient without knocking them out. And that's what's very attractive here.

And your comment about they feel comment. So there is a prodromal effect in many cases.

Yes. I wouldn't describe it as prodromal. It's not like a migraine prodrome, but they do -- before someone is moderately or severely agitated, they're mildly agitated. So they do feel kind of an internal disquiet and internal anxiety that if not addressed -- and people have different coping mechanisms, but if not addressed, it can't escalate, and that's what we're trying to get to.

Got it. Got it. Okay. I think you also answered one of the questions that was in the question queue about the benefits or downsides of benzos and the other agents that are used off the table. Also, just with regard to what -- now this sort of bridges into what changes now that there is an option where something could be used, a substance could be used earlier in the home instead of waiting and calling either 911 or the ambulance comes. What is it about the mechanism and formulation of IGALMI, the speed of onset, tolerability, all the -- as you mentioned in your formal comments, the TPP that makes it well suited into that moment in a way that the existing off-label options do not?

Well, you -- I think you just said it yourself. It's fast acting, right? So onset of action as quickly as 20 minutes. That is really, really important. In the ER setting, the -- what is used, what is indicated and used are often the IM, so the injectable atypical antipsychotics or IM or IV benzo. And the reason that they're administered intramuscularly or intravenously is for speed of onset. So now you have an opportunity to get speed of onset in the at-home setting with a medicine that patients can administer themselves.

So when I -- as I think about IGALMI, if there's one attribute that at its highest on the priority list of attributes, it's absolutely that. It's -- patient can administer it themselves and speed of onset. But beyond that, next, it's -- this is not an antipsychotic. This is not a benzo. This is a novel mechanism that calms the patient without sedating them. And we saw this in the clinical studies that the patients were -- as part of the clinical work, they had to respond to questions every 10 minutes, and there was no patient that couldn't respond to questions.

And that's very valuable because in the ER setting, often patients are knocked out. In fact, when I was -- I'm going back many years when we're developing aripiprazole, Abilify, for IM injection, one of the issues was and what we thought Abilify would hopefully overcome was patients that get an IM Zyprexa, they're knocked out. And when the patient is knocked out, they're taking up space in the ER, the doctor can't intervene until the patient is aroused. That's not the case with IGALMI.

Yes. And then they can't go back to work if they work or...

That's exactly right.

There is productivity -- all right. I'm going to ask a couple more questions. We're getting a bunch of questions in the queue, which is nice. I'm going to -- the ones that have been addressed, I will not bring up, but the ones that have not, I'll hope to get to. Just a couple more questions, Mark, before we get to the online questions. And again, the size of the opportunity, how does that -- I kind of asked this before when we talked about the 86 versus the 16. But in sort of again, in the real-world setting, how does that funnel down? Are there patients that are not so severe that they just sort of ride it out? Or are there others that self-medicate with other things, alcohol or substance of abuse or whatever, but how does that funnel down?

Yes, that's a great question, Michael. So the funnel -- I'll just talk through the funnel first, and then I'll talk about what we heard from physicians and patients around how patients within the funnel would be treated. So at the top of the funnel, you have about 8 million people with -- diagnosed people with schizophrenia and bipolar. Of those, about 6.5 million are treated. Of those, we then took cuts based on are they living at home because our population of those living at home. And what share of those patients have frequent agitation?

And we got this by asking doctors, okay, think of your population, what percent of your schizophrenia and bipolar patients experience frequent agitation defined as 10 to 15 episodes per year. So that got us from the 6.5 million down to 2.3 million. We then took one more haircut, which was based on of these 2.3 million, let's make sure that we are screening out patients that did not fit the SERENITY At-Home entry criteria. So for example, if a patient was abusing illicit drugs in the last 6 months, they were excluded.

So we excluded about 20% of the patients. So that got us to about 1.8 million addressable patients. And in the study, we saw that on average, 4 episodes per month, that's 48 per year, 48 x 1.8 million gives you the 86 million episodes per year. In our research and very consistently, whether we talk to patients, whether we talk to doctors, those episodes appear to be 1/3 mild, 1/3 moderate and 1/3 severe.

First, I'll say that in the clinical study, in the SERENITY At-Home study, the product works regardless of the level of severity. So we saw reduction in agitation, whether the patients were mild in severity, moderate in severity or severe in severity. So from a clinical perspective, we know that it works across the spectrum. And then we asked physicians and we asked patients, "Well, would you reserve this just for severe cases or would you want to use it in mild cases to prevent the escalation?" And the general consensus was, "You know what, we're going to use it across the board," because if you're mild and moderate, you obviously want to avoid escalation to severe.

And if you're severe, you want to manage that. So I think that broadly, there's going to be broad interest in this. And now once we get out in the real world and patients have experience with it, I suspect that patients -- doctors and patients will develop their own strategy around when is my agitation the kind of agitation that I'm going to jump on and I'm going to take my IGALMI for. But right now, based on what we know today, it works well across all 3 disease spectrums, and there's no reason to think that it wouldn't be used in all 3.

Okay. Great. I just wanted to ask one more question on reimbursement, and then I'll take the questions that came in online, and if there's time left, I can come back. But as far as the payers are concerned, a couple of questions on that. Have you -- has BioXcel undertaken any kind of pharmacoeconomic study to demonstrate to the payers avoided costs of hospitalization, lost productivity, risk to ER personnel, et cetera? Have you done any studies like that? And then in the case of Medicare, Medicaid dual eligibles, how does that situation look? Because I know there's a fair number or a fair proportion of patients with schizophrenia that are unfortunately indigent. How do they get covered? And do you have to go sort of state by state with that population to get your approvals?

Yes. Both good questions. On the economic model, so we've done no HEOR works yet. That's in the plans. And -- but -- and let me just point out an obvious point of practicality. Before the drug is on the market and has broad use, the models we'll be building will be hypothetical theoretical models, right? Post approval, once we actually have use, we can then reinforce those models with real-world data and bring really robust economic justification models to payers.

So in the launch period, we'll have a nice model that will project the opportunity to offset cost of an ER visit or hospitalization based on using IGALMI. Although I'll tell you -- and that's going to be important for the payers. At the same time, we're not going to shy away from painting the picture of patients today that are in distress because the drugs that are available to treat acute agitation at home are not great. And this is a new paradigm and having the freedom to carry a medicine around that can help abort a case of agitation quickly, whether the patient is at home, in the park, at work is very valuable. So that's the case from the health economic perspective.

To the Medicaid, yes, Medicaid and dual eligibles, Medicaid is a state-by-state thing. So we will have to go state by state and and do what's necessary to get this on the state Medicaid formularies.

And as it is -- I mean, how difficult or straightforward is it to access those patients...

No. We're talking patients with severe mental illness. There are protections in place for this category of patients, this category -- these medicines. So nothing is ever easy, but there will be willingness to hear the story. I'm fully sure of that.

Okay. Wonderful. All right. Let me take these questions in order of the -- of which they came in because I think that's the only fair way to do it. So the question is, how do you think about preventing overdosing in the real-world setting?

Yes. Nice question. We know from the payers that they will -- this is a medicine that will be used episodically, not chronically. And one of the criteria from the payers will be quantity limits. So first, patients will not have a large number of film strips on hand. It's too soon to say what the limit will be. But if you extrapolate from the fact that on average, we see 4 episodes per month per patient, you need to think about more than 4 per month because you don't just do for the average patient, you need to make sure you're covering most of your patients under your quantity limit.

Plus, the medicine is designed to be redosed within 12 hours, so 1 episode could get 2 doses. So I would expect maybe patients have 10 on hand at any given time. But the second thing to realize is that the underlying medicine, dexmedetomidine, is used in the ICU setting as a sedative anesthetic. So this is not the kind of medicine that's going to get overdosed from a, hey, I like this medicine, I want to take more of it. And if someone does take 2 or 3, the primary thing that will happen is they'll get tired. So we've had -- I know the company has had those discussions with the FDA. That was an important part of doing the at-home study and demonstrating that it could be safely administered by patients in the at-home setting. And the clinical data stands for itself, 250 patients over 3 months, we were able to identify when to treat themselves and how to treat themselves and to treat themselves on their own without medical supervision.

And I would add to your comment, Mark, that about the opioid withdrawal studies used doses of 240 micrograms. So we know that if you get approval for the high dose at 180, you have clinical experience with a dose that's at 240. So that's one -- if the question is concerned about safety. The other point I would make from your -- the question about sort of the maximum amount of drugs that someone could have. If you look at lofexidine, which is marketed under Lucemyra, that is typically given 3 tablets 4 times a day, maximum 16 a day and up to a maximum of 14 days. So there may be some constraints put on IGALMI at home as well. Would you -- is that fair to say?

Yes. I think the -- yes. I think the primary constraints will come from, look, this is a medicine that's designed to be used episodically. So let's estimate how many episodes should we reasonably expect to treat over the course of a month and make a prescription based on that.

Perfect. I think this is a bit -- this is a question that's related to that, which is based on the payer feedback. What do you think the pack size will be? Sorry, what the pack size will be that they will accept per prescription? And I think we've talked about that. I don't know if you want to -- if there's anything to add there?

Yes, not really. I mean, right now, it's packaged in units of 10s and 30s. I think the 10-pack sets up nicely for a monthly prescription. But what's interesting about IGALMI, the film strip itself is actually individually packaged in a sealed package that has its own NDC code. So whether we put 5 films in the box or 15 films in the box, those changes can be made pretty quickly. But right now, we've got a 10-pack and that feels like a good number.

Okay. Perfect. This has to do with TRANQUILITY. I think I'm going to skip over that and come back to it. Let me just say I want to stick with some of the -- yes, let me ask this -- I know I'm going out of order now, but there's a question about, again, a clinical presentation of agitation. It says how long does an agitation episode typically last if untreated and will IGALMI simply shut it down?

How long does it last?

Yes. How long does it last?

Yes, it varies. It varies. And what we know from the experience is that IGALMI works quickly, as quickly as 20 minutes.

Right. Okay. Here's another question in here about the number of units in a pack, so I think I can skip that. These others have to do with strategic questions. So maybe, Vimal, I can get you involved here. There's a couple of questions. Company in talks with any major pharmaceutical company, potentially partner or assist in the marketing. Are you looking at partnerships to help with the launch? Yes, those are the 2 questions that are related.

Those are very relevant and good questions. We are exploring all opportunities. And part of the exercise, Mark is working on, we are evaluating what is required to launch this product, and he -- some of the work has been done and some of the work is in progress. And we are looking at all options to make sure we can bring this medicine to as many patients and caregivers we can, which could involve established footprint with a partner to commercialization to other opportunities. So we are quite open, and we are working on it, and we want to get to that by the time we get to the PDUFA date.

Terrific. I know what the answer to this question is, but I think you should at least address it, Vimal, which is with 80 reps, what are your -- you're estimating your cost of launch in '27?

I think that work Mark and team are doing what the total cost will be. It's just not the rep cost. It's additional things that you require to launch the product. And having a strategy, what strategy we are adopting in terms of what we discussed previously, what options we're going to use, then we will be able to provide more guidance what the cost will be for the launch in 2027.

I like that answer. Also, do you think the product is appropriately priced at $105 per film given the value it brings to the table, especially at the in-home setting? How much you think a patient co-pay would be for that? I think it's kind of tough to say, but I'll ask it anyway. And how many films do you think would be in an average initial Rx? And we already talked about that. So maybe the first 2 questions of $105 per unit and then I don't know if you can speculate on the co-pay. I don't know how you would do that, but go ahead.

Sure. So when we did the research with the payers, and again, this was, I would say, preliminary research to get a sense for how they would think about covering this on formulary, and we got positive feedback there. We were transparent that right now, the product is available, it's priced at $105 per film and really had no pushback there. I think where their head went was, okay, in the neuro-psych market, a new branded drug is typically priced $1,500 to $2,000 per month. And here, we have a medicine that is -- works in the same space, but it's about $100 a dose and how many doses per month?

Well, it's not going to be 15 or 20 doses per month. So I think they felt, okay, this seems reasonable. As far as co-pays go, once we get to Medicaid, the Medicaid co-pays are low. So it's just a matter of getting on the Medicaid formularies. The commercial co-pays will vary. And obviously, our strategy will be to work with the payers to very clearly elucidate the value proposition to the payers, to physicians and importantly, to the patients so that they don't put extreme hurdles in place for these. Patients are suffering enough. Let's let them get access to important medicines at a reasonable out-of-pocket. But quite frankly, with the commercial patients, if we find that the out-of-pockets are too high, there are things we can do to help lower those in the commercial world and...

Yes, you can do co-pay assistance.

That's right.

Yes, you do co-pay assistance, you can do couponing, you can do sampling. I mean there's a lot of a lot of strategies you can...

That's right. Yes.

I think it is a bit redundant, but just in order to make sure everyone is happy on the asking questions online, do you currently feel like you have the -- I think the better way to ask it is, do you feel like your sales and infrastructure capabilities can support a full U.S. launch or would that require additional partnerships? And I'll let you address that as you see fit.

Yes. So I'll take a stab, and Vimal, you might want to jump in. I mean at this point, we have a great launch plan. So the work that we will do between now and launch. And we have a very, very -- we have an emerging finely tuned view of what a successful launch infrastructure needs to look like. All that is to be built over time. As Vimal alluded to, he's talking to a lot of folks and what exactly the launch, the go-to-market infrastructure looks like will really depend on that. Vimal, anything you want to add there?

No. I think that's pretty much. Currently, we have some advantage because we did do the launch in the institutional setting, if they are helpful. But for home setting, we will have to build the infrastructure that Mark mentioned.

Okay. Terrific. Let's talk about -- I'm going to come back with some questions of my own in the closing minutes, but let me just put up 2 more, which is what are the key milestones investors should watch between now and the PDUFA date that could meaningfully change your trajectory?

So I think approval is the major catalyst right now. We are in the review process for our sNDA and preparing for a launch, which is the commercialization activities ongoing with Mark coming on board. In addition, we have already have alignment with the FDA to initiate a second confirmatory Phase III trial for our Alzheimer's agitation program. So initiation of that program would be a key to expand market from schizophrenia bipolar-related agitation to another indication in Alzheimer's. I think those are the key value drivers for our 501 program.

Okay. Great. And then I'm going to piggyback on this question, which is the -- well, this question is asking about TRANQUILITY. We know you have breakthrough therapy designation for Alzheimer's agitation, but studies are currently paused. So Vimal, you just mentioned TRANQUILITY. I guess what are the obstacles to getting those started? And would you -- the question is, would you convert TRANQUILITY trials to at-home trials?

So TRANQULITY plan will be that we have done one Phase III trial in ALF, assisted living facility, and we have demonstrated 60-microgram dose shows positive results both from an efficacy and safety perspective. Now we need to do a second confirmatory trial, which is covering broader population, ALF memory care as well as nursing home. So we are covering full spectrum of Alzheimer's and then the patient who get maybe mild, moderate or severe agitation mild, moderate and severe. That's the second confirmatory study that is required to expand into the Alzheimer's agitation. And in that, as I mentioned, we have alignment with the FDA on the protocol as well as we have selected a CRO, and we are geared to initiate that trial, and we will announce when we can initiate that trial.

Okay. Maybe talk a bit about -- because I think the exciting part of the story from my perspective as an analyst who tries as hard as he can to make money for his clients, just how large the opportunity is, Alzheimer's agitation, opioid withdrawal, how do these add the layers of addressable patient populations?

So good news is that 501 has a potential pipeline in a product potential. Conceding is very unique mechanism and it can apply to various conditions, which you mentioned. Currently, company has focused on schizophrenia, bipolar agitation and now institutional and home setting with potential approval with the sNDA. And Alzheimer's agitation expand into that indication. Both of them are extremely large opportunity from a company perspective. What potential is more, as you have seen, we are conducting investigator initiated trials, and this is a clinical and scientific community who gets funded from the outside, and they are running these trials in opioid withdrawal as well as recently, we announced that acute stress reactions or acute stress syndrome that happened prior to the PTSD.

There is a trial that is being done funded by DoD by University of North Carolina and opioid withdrawal by Columbia University. So we continue to supply the drug. We continue to get clinical signal that can expand. But company is currently focused on those 3 indications, schizophrenia, bipolar and Alzheimer's because these are really large opportunities and 501 can have a lot of potential once we succeed in these 3 indications.

Great. All right. There's 1 more question in the queue. I might ask it a little differently, but the question is about now that you've got a PDUFA date, have the discussions with potential strategic partners changed at all? Has that moved the needle, I guess, I would say, in terms of the partnership interest?

What we observed that as you do the derisking of the opportunity, which was first Phase III data that came in last fall, then it was submission of the sNDA and now acceptance of the sNDA. All these things result in increasing the interest. That's what I would say.

Yes. Yes. I'm sure it's a cumulative effect. Okay. Well, look, we're just about at the top of the hour. I just wanted to close out or at least Vimal we'll have your closing comments, I'll make some brief remarks, and then we'll wrap things up. So anything you want to say in closing before we go?

No, I think this is great that we were able to hold this session, and I would like to thank you, Mark; and thank you, Michael. As we have highlighted, we believe IGALMI represents a significant opportunity to have a real impact on the lives of patients and caregivers managing acute agitation in home setting. In the next several months, we will continue to advance our commercial launch preparation, and we will get the potential approval announcement. We appreciate everyone joining us today and your continued interest in our progress. We look forward to keeping you updated as we move ahead.

Great. Thank you, Vimal, and thanks, everybody, for joining us here today. Again, it's been my pleasure to moderate this event. When we first heard about the BioXcel story, we got very excited about it, and I'm old enough to remember a company called Avenir many years ago that had a drug that there were a lot of skeptics about, turned out to be a terrific drug, a terrific launch and a wonderful exit for the company about 10, 12 years ago. I would -- I see lots of parallels between the BioXcel story and Avenir from my past as an analyst. And again, we appreciate the company and management team taking the time to do this for everybody, and we wish you an enjoyable rest of your day. So thanks, everyone.

Greetings, and welcome to the BioXcel Therapeutics KOL Virtual Roundtable Day. It is now my pleasure to introduce Vimal Mehta, CEO. Thank you. You may begin.

I'd like to start by welcoming our participants. We are thankful for your leadership and expertise in the Alzheimer's agitation space, particularly as we focus on the significant and underaddressed challenge of acute agitation episodes in Alzheimer's dementia.

Next, I would like to thank our moderator, Anjalee Khemlani, an award-winning journalist who moderated our last panel in December. We are thankful to have her experienced voice be the guide for today's conversation among our distinguished KOLs.

There are currently no FDA approved treatments specifically for acute episodes leaving a critical gap for patients, caregivers and clinicians managing these episodes. The need for a treatment specific to acute agitation episodes remain urgent.

At BioXcel Therapeutics, we are steadfast in our commitment to advance meaningful innovation in areas of unmet need such as this one. Our mission is to advance BXCL501 to reach patients and caregivers who currently face limited treatment options. In the previously announced results from a Phase III pivotal study of BXCL501 for the acute treatment of agitation in Alzheimer's dementia BXCL501 was well tolerated and met its primary efficacy endpoint.

Anjalee, I will turn it over to you for the panel.

Thank you so much, Vimal. Hello to everyone. And let me take a minute to introduce this wonderful panel. We've got Dr. George Grossberg, Dr. Anton Porsteinsson and Dr. Angela Sanford, I'm going to give you all a minute to quickly introduce yourselves. Let's start off with Dr. Sanford.

Hi. My name is Dr. Angela Sanford. I'm a Professor of Geriatric Medicine at Saint Louis University, and I'm also serving as the Interim Division Director of the Division of Geriatric Medicine. Thank you for having me today.

Of course, welcome aboard. Dr. Porsteinsson.

Yes. Good afternoon, good morning, depending on where you are. Anton Porsteinsson, by training, a geriatric neuro psychiatrist that I specifically focus on the current study of older individuals with dementia, such as Alzheimer's disease. And I'm a professor at the University of Rochester School of Medicine. Pleasure to be here.

Welcome. And then finally, last but not least, Dr. Grossberg.

Thank you. George Grossberg, I'm an academic geriatric psychiatrist at Saint Louis University School of Medicine, and I have a new endowed Professor ship, which is the Dr. Henry and Amelia Nasrallah Professorship. But I've been in this space Alzheimer's disease and specifically developing new treatments for neuropsychiatric symptoms of Alzheimer's disease, like Dr. Porsteinsson for a number of years. I am speaking to you now from one of our teaching nursing homes which is an environment where obviously new treatments for particularly acute behaviors are sorely needed. Happy to be here.

And my goodness, you talk about being on the ground level to understand this very important subject.

Well, thank you all for joining us. And I want to start out with getting our hands wrapped around the acute agitation issue. So as we understand it, episodes in Alzheimer's dementia remain significantly under addressed. It is an issue that affects so many millions of people and their caregivers and to your point, Dr. Grossberg as well in care facility. So this is an issue that is really something that we need to look at. It's something that has no real solution other than basically sedating patients as far as they understand.

And so I'd love to start off with Dr. Grossberg, we're going to kind of get our handle around why this conversation is important. What do we need to understand about acute agitation and it's sort of a debilitating impact on care and caregiving.

Yes. No. I think that's a great question. I think most of us, when we think about agitation in disorders like Alzheimer's disease, think of it as kind of a chronic persistent problem. And currently the only FDA-approved medication for agitation in Alzheimer's disease as well as almost every other drug in the pipeline, except for the one we're going to be talking about today, focuses on more persistent or chronic agitation. In fact, the International Psychogeriatric Association, the IPA, who have developed the diagnostic criteria for agitation. Those criteria call for pretty much persistent day-to-day agitated behaviors that are impacting quality of life for at least 2 weeks or longer. So they don't really address acute agitation which can occur intermittently, which can occur even during the course of more persistent kind of chronic agitation.

And of course, when it happens in the nursing home like where I'm at right now, often it's a reason why patients are sent to the hospital to the emergency room. If it happens at home or the family is taking care of someone who has an acute aggressive or agitated behavior, Often, they're also rushing off to the emergency room. So it's a reason for heavy utilization of health care resources and we do not have anything currently that's FDA approved for the acute agitated episodes.

Maybe if you can tell us a little bit about what is currently out there? Why it's looked at in terms of a chronic management situation and how we can think about what defines chronic versus acute?

There are not many FDA-approved medications, really only the one that I know of for even chronic agitation. And acutely, we will try anything in the acute setting, not anything, but we have not very good medications, medications that aren't very safe to use in older adults, but we use as last resorts. And that's sort of what we're stuck with in the acute settings.

Like Dr. Grossberg, I work in the nursing home. And yesterday, I had a patient that was acutely agitated and the nurse was saying, I don't know what to do. What can we give her? This is not going to work out today for us to deal with this. So it's a very chronic problem with acute flares and it can really impact quality of life for patients and caregivers.

Portion maybe explain to us what -- how it presents in the acute form and then how it presents maybe more in the product form?

Absolutely. So I want to make sure we understand that episodic agitation or acute agitation, those are the 2 terms that we use pretty interchangeably, it can happen in any setting, it that can happen in long-term care. So a skilled nursing facility. It can happen in an assisted living facility, and it certainly happens at home in the community.

So you heard George talk about the diagnostic criteria for agitation according to the IPA criteria. And there, you require at least 2 weeks of relatively frequent occurrence of agitation, and you also want a certain intensity of that agitation. And agitation is one of the most distressing behavioral disruption in Alzheimer's disease as well as other dementias. The episodic agitation is, on the other hand, it happens sporadically. It happens episodically. It can happen in someone who doesn't have chronic agitation but it can also happen for someone who has chronic agitation.

But now whether you use nonpharmacological interventions or medicines like the one that is approved for that brexpiprazole, you still can have these kind of breakthrough episodic agitated behaviors. They often are associated with the patient not understanding what's going on, getting overwhelmed and just kind of boiling over, becoming restless, there can also be verbal aggressiveness, even physical aggressiveness. It can be because someone is uncomfortable. They've got pain, they cannot communicate what's going on. It can be very simply that someone wants to be left alone all the time.

And you can't do that. You have to provide care. You have to provide attention. It can be personal hygiene. It can be attending to urinary or bowel needs, et cetera, and it creates this blow up.

And I can give you another example. One of my patients lived with her husband, their kids, grandkids, lived one city over 45-minute drive. Every time that they thought about visiting the grandkids, the family, just the right over, she would get so agitated, so restless. Yet whenever he was there, she was happy. It gave her husband reprieve, allowed them to connect with family. But that -- those are the types of situations where we can have this bubble up.

And what often will happen is that you stop going out, you stop socializing. You stop seeing family, you stop seeing friends. You don't get the care that you need or should be entitled to because people, be it family caregivers, professional caregivers have to deal with the intensity of these behaviors.

Yes. It seems like it could be really disruptive to daily life. And so having a solution and one that would be easy for caregivers in addition to be able to use is really necessary. I also have started thinking a lot more about how we're sort of in a phase of having more care needed for an increasingly elderly population. And so not only are these treatments needed because of the ongoing need, but also because volume-wise, there is an opportunity there.

So let's break that down a little bit, right? In terms of looking at the population and understanding who benefits the most, what does a treatment like BXCL501 have what opportunity does it have to help the market help caregivers help in facilities, but also to help maybe bring down the cost of emergency care as well. Maybe Dr. Grossberg, you can start there. Dr. Grossberg?

I didn't know you were calling on me. I'm sorry. Yes. So I alluded to some of the issues that you brought up a whole lot of different things. But obviously, we know the demographic imperative that the population is aging and that the most rapidly growing segment of our population are older adults. We know that the Alzheimer's population is expected to double or more in the next couple of decades. We have already over 7 million individuals.

And I think Anton, as you pointed out, these people are living with Alzheimer's disease in different locations. They may be living at home with family. They may be in memory care, assisted living, they may be in skilled nursing or long-term care retirement communities. And as the numbers of Alzheimer's patients increases, obviously, we're seeing more and more of the neuropsychiatric or behavioral problems and the most disturbing and common behavioral problem is what I call the spectrum of agitated behaviors. Everything from irritability to anxiety to more overtly agitated behavior to even more overtly aggressive behaviors. And when you see the most overt behaviors, including aggressive kind of behaviors, no matter what setting one is in, then you need to take that patient usually to the hospital to find out what's going on.

And once they get to the hospital, we use off-label treatments that can make things worse. We use antipsychotic medications, like quetiapine and drugs like olanzapine and so on, which can sedate the patient, increase the risk of falls, making it really hard to figure out what's going on. I think Anton, you pointed out so many of the good triggers of agitation, whether it's pain or infections or environmental changes. There are quite a few things that we need to look at. But first, you need to get the patient under control, and you need something that's going to not make them a zombie. It's not going to sedate them, it's not going to make them more confused. It's not going to increase their risk of falls. And that's where a compound like dexmedetomidine, a BXCL501. That's where it comes in, where it can get the patient under control relatively quickly. Unlike some of the things in the pipeline and the currently approved drug, which you need 2 weeks to even titrate an effective dose, it gets them under control in minutes rather than days or weeks. And that's what you need, especially in acute agitation situations, whether in the hospital, the emergency room, whether in long-term care, whether at home, whether in memory care, it can be useful in all of those arenas.

To emphasize that point from earlier, this is the acute episodes can happen in those who do experience chronic agitation, but also in those that don't, correct if I'm understanding that correctly. And so the idea that this could help a very large percentage of the population is imperative how often do you see breakthrough agitation episodes in patients? That's a question coming from the audience. And by the way, audience, you are allowed to send in questions, I will be reading them, periodically, continue.

I don't know if it's for any of us, but I'm not sure that we have really good data on -- relative to that question. I can tell you from an experiential standpoint and all of us are coming from a little different kind of arena, as we can all comment about that is that it's not rare. It's actually quite common. Whether it's occurring in isolation in someone who hasn't had the chronic agitated behavior, or whether it's episodic, like you pointed out, Anton, it is very common and even individuals who may be already on treatment for more chronic, we'll call it, or persistent agitation. There can be this breakthrough kind of agitated or aggressive, whether physical or a verbal episode that makes it very hard for the staff or for the family to take care of the individual, and that's when they go to the hospital or reach out for help.

I think one of the difficulties is the unpredictability. And we shared examples of that. Sometimes maybe that patient on the car ride would do okay. And once she got to the family's house was okay. But sometimes it just was very difficult, and you never know the family members and the caregivers and the patients never know sort of when it's going to come on. And so I think the unpredictability makes it so difficult for quality of life.

And let me give an example and kind of put it more into maybe the results that we see in clinical trials. So for chronic agitation, if we see about a 30% improvement in frequency and intensity of behaviors. We often say that that's a responder. 50%, we're very happy. So that tells you that there remain about 50% to 70% of the symptoms that are kind of boiling underneath. This can take chronic agitation from being unmanageable to manageable. But the medications that we're looking at 4 chronic agitation. None of them by the way they work, none of them, it doesn't help to give another pill. Okay. He's having a bad day today.

How about if I give another pill? It doesn't work. That's not the way that the currently available medication works or the ones that are currently in development. So therefore, we have to have other options. A lot of the medications that are used in the community right now are sedatives. And they may have hours worth of sedation associated with them. Many of them are specifically kind of advised against in terms of don't overuse these medications for this population. So finding something that works predictably with a relatively rapid onset of action that doesn't kind of -- that more makes people tranquil and somnolence, sleepy, sedated. That's appealing. That's appealing to clinicians.

The other thing I'll just say, Anton. The other thing that's appealing is not having the box warning. Because this is not an antipsychotic, and it's not -- doesn't have the box warning relative to increased mortality. And one of the things I find, for example, in the nursing home I'm at right now, the primary care doctors who admit here and follow patients here often don't want to deal with antipsychotics. They want to prescribe them because of the box warning, they'll refer those people immediately to us. So having a potential treatment that doesn't have that liability, in addition to all the pluses you mentioned, Anton, I think, is a good thing.

It's important, too, when compared to what's on the market because we do have that concern of overmedicating of not being able to treat people correctly. And to your point, Dr. Grossberg, about the quality of life, I think that's a key part of this conversation, right? We haven't able to, at a point in time where there are so many folks that are entering the space we have been able to find a solution that is going to help maintain some kind of independent living, quality of life. It really does hamper individuals in their ability and puts extra burden on caregivers who aren't able to then put their lives in active mode. They have to constantly be watching out for episodes to your point, even hiding and staying away.

So is it -- the first part of the question is this eases the burden for caregivers and caretakers and clinicians. Is there any possibility in this situation for self-administration -- or is it not an option because individuals who are going through the episodes can't really -- don't really realize they're in the middle of it?

Let me just kind of give a quick perspective from my end. So clearly, we're using oral medications in most of these situations. There are occasionally in the hospital or even possibly in the nursing home that we may have behaviors that are so intense. That you need to -- and people are so unwilling to or unable to kind of help with taking medication, et cetera. that you might need to use an IM or a melt away or something like that. But in most situations, people aren't distressed, they're upset, but they often seek some sort of solution to this as well. This is not just distressing to family caregivers or professional caregivers. These are behaviors and actions that are very distressing to the patients. And they seek some sort of a solution, some sort of a solace.

But you do need to kind of work with people if you have someone who has moderate or more advanced dementia, how do you take a thin film. So it's a medication where the active compound is kind of built into this thin film that you put on the mucosa in the mouth. And with that, you have a pretty quick and reliable absorption.

So that is an issue. Clearly, there's not going to be 100% success rate with that. But targeting people in the earlier clinical trials, there was a pretty good success rate even with patients that had moderate to advanced the dementia living and skilled nursing facilities. So it's doable. It's absolutely doable. And so I still see it as a viable delivery system.

I interpreted your question differently. I interpreted your question as asking about whether this population could self-medicate. And generally, the answer is no. It's really almost unheard of that I would have an Alzheimer's patient come to me when they come to clinic or in the nursing home saying, Doc, I need help with my agitation, what do you recommend? So we're almost always depending on the family, on the professional caregivers, in the long-term care environment to really tune us into what the problem is and that there is a problem. And we're making a decision for the patient about what's best.

Yes, I agree, Anton that it's easier when you have a film, you could put it anywhere in the mouth. A lot of these patients might spit out a pill if you put a pill in their mouth, if you don't have that rapid absorption. But generally, the format that this drug is available in, I think, would have pretty high adherence.

That's good to know because one of the incoming questions is thinking about safety. We mentioned or we were discussing earlier that it's not going to be like other medications where you have maybe an overdosing problem or not overutilizing. Does this also have that concern? Or how do you think about that in terms of an at-home setting, the use of in at-home setting?

Well, I think there are plans to do an at-home study, and I think that will be useful and very important I think in some data that the company that I've seen has previously, it seems like the compound can be administered, maybe 3 or more times even during the day, spaced out over time without additional deleterious side effects. But I think we need probably more information about specifically about -- we know about the half-life, but how often it can be given within a 24-hour or any given kind of time frame. I think that's going to be very important, particularly in the home where a nonprofessional person who is making the judgment about when to give and how often to give.

Yes. Do you think that there is any concern about general dosing safety considering what we see with sedatives and the like. Is this the type of medication because it's an episodic situation, do you think that there needs to be or based on any of the data that you've already seen that there's any discussion that needs to be had around what -- if there is potential of overdosing?

So if you look at the data for dexmedetomidine, I think it is important to understand that this is a medicine that has been used particularly in ICU settings and for multiple years. Then it's given via injection. So this is a way to use the same medication that doctors in those settings are actually quite comfortable with using without injecting someone.

So if we look at the side effects in the TRANQUILITY II study, then basically, slight somnolence, so in the kind of mild to moderate range was the most common in about 15% of participants. Lethargy was extremely rare. So you had kind of some somnolence, but the highest state of that, which we would refer to as lethargy, that was very rare. That was in kind of the low single digits. You kind of be thoughtful about anything that kind of sedates people. And if you think about how this drug works, it then does that by kind of tuning down the norepinephrine system. And with that, there are going to be some people that might have a slight drop in their blood pressure.

But that was also kind of seen at about 15% and also usually in the mild range of severity. So we're not seeing in the clinical trials, a lot of incidents where someone had to be attended to or taken to the hospital or something like that because they had a significant reaction to a single dose.

I agree with that. I think the example you cited, Anton, of this drug having been used and being used even currently, in its intravenous form in the ICU in older people with multiple major cardiovascular and other serious medical problems. And having confidence in this drug that it's not going to snow the patient, it's not going to exacerbate other acute serious medical problems that are serious enough to have them wind up in intensive care gives you a great deal of comfort. It gives us a great deal of comfort. And it's not a new drug. It's something that we know, albeit in a little bit of a different form.

The administration of this. Is it something that would be needed just as needed? I know we mentioned there's a difference in the patient population between those that already have chronic and those that don't in the chronic population, is it seen as sort of in tandem? You can give a patient who's on chronic meds also this? Or will that need additional studies?

It's used that way in the intensive care unit in its intravenous form. But I do think that we might need additional data, let's say, for example, someone is on brexpiprazole which is the FDA-approved drug for chronic agitation, and they have breakthrough anxiety. I wouldn't have any hesitation in recommending the oral film version of this drug for those acute episodes because there's no indication there would be any adverse interaction or significant side effects when both are on board, although that hasn't been specifically studied as far as I know.

What do you see as sort of the biggest challenge in addressing this population in being able to identify the right moments to administer and the like. How do -- how should we be thinking about how to think about this drug once it reaches commercialization and is on the market?

Anyone, any takers? We can skip over that one.

Go ahead, Anton.

Sorry, George, you take that one.

Maybe you can put your question in more of a nutshell. I mean I hear you asking about, let's say, this drug does get FDA approval and becomes commercialized how it's going to be utilized? Is that what you're asking?

How it's going to be utilized and are there any challenges you're foreseeing?

Well, I mean, cost is always a challenge, any new medication and trying to get insurance reimbursement. But otherwise, I think with its really good profile, ease of administration, not having to worry about the patient kind of spitting pills up and so on. I think it would be relatively easy to use and would have high adherence. So I don't see any particular problems.

So a few of the things for me would be basically it's novel. It's different. So anything that's different is has a little bit of you have to kind of explain to people, okay, this medication doesn't come in a pill. It comes in this film. You have to explain to people why the film can be appealing. You have actually basically placebo films that you can work with teaching people to use. So they get a sense of comfort. I saw one of the questions in the list of questions sent in. How quickly does this bring about the benefit. And I think that it's important to understand that you see behavior start to kind of drop in 30 minutes and 60 minutes, it's considerably lower and a split between drug and placebo.

The big issue is that events where we have someone go completely off the rocker. Those happen, but they're relatively rare. And when you have something that is that intense, be it at home or in a skilled nursing facility or assisted living. Those are in the situations where someone appropriately might need to go to the emergency room if they can't be safely managed at all. But there are so many kind of incidents that are somewhere kind of in the middle. You can't just work with them nonpharmacologically, distract them, offer them ice cream, whatever you do. It's not enough.

And that's -- those kind of rightsized events are pretty common. They are often situational. Like I said, you can kind of have a sense when they are more likely to happen. Around personal care, around you needing to go to the doctor or maybe a right to visit family. So you work around that. And I saw another question.

What about if someone is so angry, so agitated would you stick a finger in their mouth? I mean there are going to be situations where you hopefully will use good judgment. But it is remarkable what we ask of professional and family caregivers and what they can manage. These are not wallflowers. They handle situations that I would not want to be in on a day-to-day basis. And here, we offer them an additional tool that may help with kind of keeping someone out of the most intense settings. It's really hard to take someone to the emergency room to urgent care.

It's disruptive for everyone involved. The professional setting as well as the home setting. We want to avoid that. nobody benefits really from going to the emergency room. That's really just a safety issue or a last resort because you can't handle it better.

In terms of the sublingual administration, I also worry about when staff members have to use an injection. When the person is acutely agitated and you're coming at someone with the needle, that doesn't seem very safe. So I almost would prefer the sublingual route than here, take a needle and go inject this in this person who's filing about. I think we're asking a lot when we ask people to do that.

It's a really good point. It does help with the safety.

And there's other -- we have other products that have been on the market for a long time that are commonly utilized. We have olanzapine comes in an oral film, where risperidone comes in an oral film and those have often been used.

I was going to ask how does it compare delivering this oral route versus some of the other drugs that are on the market, to your point of having to teach individuals that this is a film. It seems like that is a fairly novel but not hard to do necessarily at all. Dr. Grossberg, do you ready to this?

It's an easy sell we talk -- I use -- one of the medications I use for this indication is a transdermal patch and I think that's a lot more complicated than this as to where it goes, where it shouldn't go, how you change it, make sure there isn't too much air underneath it. That's much more complicated. And people are okay with that. I think this is a really easy sell.

Or dealing with -- the skin irritation from the topical patches and then how much you need to kind of teach people to wipe off any adhesive residue, et cetera, et cetera. So we work with this.

It seems like this is going to be able to answer a lot of questions and save a lot of folks' time. You've also clearly defined kind of who this potential market is I'll give it back to you guys to kind of share any final thoughts on sort of what you see as the potential market, the sort of benefit of this drug in its form and its oral form, and we'll just go a round-robin, Dr. Sanford, we can start with you.

I work across the geriatric care continuum. So in the outpatient setting in my clinic setting, I see it as a way for caregivers to keep people in the home longer before institutionalization and I also work in assisted living and memory care, the same with that care setting. Everyone's dreaded thing in life is going to the nursing home. No one wants to go to the nursing home. And so I see this as a way to be able to help people live independently with their caregivers in the less restrictive care settings for as long as possible.

So for me, I think the big issue is that the medications that I'm kind of forced to use currently. Those could be the atypical antipsychotics, the more sedating ones or benzodiazepines. They often have an impact of -- it could be short to 6 hours, but it could be a 12-hour tranquilization, a pretty high side effect burden. And I'd like something that is less likely to cause a problem where the kind of onset of action is, fairly well prescribed. The absorption is reliable and the duration of effect is reasonable.

So for the situations that I mentioned before, where there are episodic agitated events that you can't deal with otherwise. This is going to be helpful. That's where I want to use this for, for example, the rights, the flights, the oppositional behaviors around personal care. That doesn't necessarily have to happen every day, but you also can't do that every 2 weeks. I mean you will need to kind of make sure that you're meeting the needs of the patients. And ultimately, that's going to reduce caregiver burden. And I think Angela put it very well, reduce the need to kind of push up to a higher level of care.

Yes. So it occurred to me that there are other arenas where a drug such as this in its current format may be useful. And just this past week, I got a call from one of our residents who was seeing patients on the consult service of our big teaching hospital. It was an older woman in her 80s, who was on internal medicine, who was clearly delirious. Delirium is an acute confusional episode. I think she maybe had some baseline dementia, but I'm not sure. But now she was very confused, very disoriented and very agitated and they needed to find out what the cause of this acute confusion and disorientation, which was triggering the physical agitation and aggressive behaviors was all about and they wanted to give her something that wasn't going to knock out, wasn't going to be heavily sedating, was not going to even further maybe impair her cognition and so on.

So BXCL501 or dexmedetomidine becomes a really good choice because it can give you relatively quickly, not in hours or days or weeks but usually within, let's say, 60 minutes or 90 minutes, pretty good control of the patient without really contaminating things with sedation or other impacts on the cardiovascular system without making them more foggy or more confused cognitively, giving us an opportunity to evaluate them and see what the trigger might be for this delirium the acute confusion and disorientation. So I think it has a major role there, it might be used off-label, but that's okay as long as we know that it's safe and well tolerated.

Yes, that's a really good point. Well, thank you so much for your insights really helpful in sort of explaining what we're dealing with here and the market potential for this. Thank you so much for your thoughts.

Thank you.

So back to you, Vimal.

Thank you, Anjalee, for guiding today's discussion, and thank you to Dr. Sanford, Dr. Grossberg and Dr. Porsteinsson for sharing your expertise and perspective. We are also grateful to everyone who joined us and contributed their attention to this important topic.

Today's conversation confirm the importance of acute agitation in Alzheimer's dementia and the clear gap that persists in treating these sudden episodic events. Patients, caregivers and clinicians are still without an FDA-approved option, specifically designed for acute episodes. Advancing solution that is specific for these episodes remain an essential priority for us at BioXcel Therapeutics.

We appreciate your participation and look forward to continued progress in addressing this critical area of need. Thank you again.

Thank you.

Good morning, everyone, and thank you for joining us today. I would like to start by welcoming our distinguished participants. We are grateful to each of you for bringing your deep experience in the agitation space to help us shape this important discussion. Your insights are essential as we continue working to improve care for the millions of patients and families managing acute agitation associated with schizophrenia and bipolar disorders in the home setting.

I would also like to thank our moderator, Anjalee Khemlani, an award-winning journalist known for our thoughtful and in-depth reporting on health care. We are delighted to have her guide today's conversation and introduce the clinical experts who will be sharing their perspective.

An episodes of acute agitation remain a significant challenge, especially for those navigating them outside clinical environment, the need for practical patient-centered innovation has never been clearer. Today's roundtable reflects our commitment to advancing solutions that can help reduce the burden on patients, caregivers and the health care system as a whole. Our mission at BioXcel Therapeutics is to transform patient care and conversations like the one we are about to have play a meaningful role in shaping the future of how agitation is recognized and managed in real-world setting. With that, I would like to turn it over to Anjalee to begin the discussion.

Thank you so much for that introduction, Vimal, and a pleasure to be here with you all today. As noted, I am a health care journalist and have been so for about a decade. So that doesn't necessarily mean that I know everything, but always willing to learn more and certainly learned a lot in preparing for this discussion. So I would like to open the floor for our distinguished guests, starting off with Dr. Leon Ravin, who is a Psychiatrist and Statewide Psychiatric Medical Director for the Division of Public and Behavioral Health at the State of Nevada as well as Dr. Marc Milano, who is the Chair of Emergency Medicine at RWJ Barnabas Health, and then Dr. Leslie Citrome at the -- who's a Clinical Professor of Psychiatry and Behavioral Sciences at the New York Medical College School of Medicine. Hello all. Thank you for joining us so early in the morning, and I hope our guests are awake and paying attention.

So I'd love to start off with taking a look first of all, at defining what we're going to be talking about today because agitation sounds like something simple to understand, but it does have 3 different sort of layers or levels, if you will, as well as it does present across different diseases. So could we just open the floor by setting the tone on what we're focusing on today when it comes to the state of agitation. And I'd love for Dr. Citrome to start off.

Well, agitation is a behavior that's marked by increased activation, both mentally and physically. And it's very uncomfortable for the patient. They don't like to be agitated. And as a clinician, I'm worried about the agitation escalating to aggression. So I'd like to nip agitation into the bud. When someone is starting to ramp up, it's really important to offer something to dial it down in the hospitals, inpatient unit or in the ED, we observe this. At home, they observe themselves or maybe a caregiver observes somewhat ramping up. And the earlier you intervene, the better off everybody is. As I'm going to repeat, it's very uncomfortable for the individual who has agitated.

Dr. Ravin, could you sort of lay out how this is or what the need sort of is to treat and sort of what we see presented when folks show up at the hospital, but also how this presents at home.

Yes, absolutely. I want to expand first to say that agitation has a double layer in a sense that, first, it's an emotional state. When people experience agitation, they may start feeling uneasy nervous stent. We all have had it. If you ever were too close to miss a connection on a flight and you were trying to figure out if you're going to make it or not, you had that emotional experience. And frequently, if that becomes a result, that's when the physical symptoms of agitation may become more apparent with anything from pacing, talking too much or even become angry, irritable and hostile.

So for us for health care professionals, we often observe agitation in the clinical settings when it gets to that physiological -- physical response of the patient. Unfortunately, a lot of times, patients experience that agitation and we don't see it and it escalates, escalates until somebody calls a doctor. And at that point, the amount of information that is clinically required more than what the patient needs at the beginning of escalation. And if we have instruments where the patients could use to help them before it gets to that physical response of agitation, it's really helpful. In clinical settings at home everywhere, we recognize times when it's nice to take the edge off. And it's always nice when we have an instrument that is [indiscernible] and clinically proven to help.

Dr. Milano, I'm going to come to you in a second. But Dr. Ravin, just to go back to that for a quick second. As someone who is charged with public health, do we also see this present maybe in those who are less fortunate? Are these the types of episodes we see maybe on the street with homeless individuals?

Yes, absolutely. As I said, agitation is not specifically to [indiscernible] symptom. Everybody can experience it. However, in people with mental illness, particularly with severe mental illness, you may appreciate how they have less ability to cope with stress, they have fewer resources. They already may be responding to voices. They may be already feeling that somebody is watching and trying to harm them or have the irritability from being in a manic state. And they are much more susceptible to that agitation. And again, the agitation is not hospital specific it happened in any settings, including when people are on the streets and unfortunately, that often leads to confrontations or involvement of the law enforcement.

Absolutely. Dr. Milano, I'm going to bring you in now. Dr. Ravin did bring up the example of, if you nearly missed your flight, I'm thinking also road rage probably counts as part of this. So let's talk about that. As someone who is the Chair of an emergency department, I'm sure you see this all the time in the ED. And of course, Jersey is known for its angry people, joke, joke. So let's talk about that. Let's -- can you just sort of maybe describe the different levels and sort of how treatments do exist in the hospital setting right now and why this pivot to at home is so interesting?

Sure, absolutely. From a functional perspective, you can look at agitation in many ways. There are well-articulated scales that our distinguished colleagues use quite frequently. But in the ED, our classification is pretty simple. It's mild, moderate, severe, and maybe there's even a fourth degree of combated and dangerous. So for us, our armamentarium around those patients first involves identifying them and addressing their needs appropriately. There are medications we currently use, most of which require some type of restraint of the patient and administering the medication via a needle and syringe, which presents risks to patient and staff.

So we moved toward medications that are less invasive, less dangerous to administer, although then they require participation from the patient, a patient who is cooperative in order to do that. I've often thought to myself, if we had a tool that could pre-escalate, right? Because we've talked a lot about escalation and when the patient is already on that escalator, it becomes extremely hard to ramp them down. So what I've always wished for in my -- sort of my magic toolbox was, is there a tool? Is there a medication that the patient could have at home when they're starting to experience the symptoms of agitation before they get to me.

And it's not very self-serving for any doctor to say, I want to decrease emergency room visits, right? I mean my business is based on lots of people coming in, but these patients are so distressed. There's such a great risk to themselves and to others that I prayed often for something that could get to that patient and get into that patient before they even arrived. And even if they had to come to the ED after all, wouldn't it be great if they received a medication or a therapy that could get them in a better place. Again, I love to use the word pre-escalation around that.

Can you delve into that just a little bit more and explain to me how having an at-home treatment wouldn't necessarily erase the need for them to come to an ED? Why would that still be part of their needed treatment?

Well, I think it could go down 2 different streets, right? One street is that they administered a therapy at home and didn't have the efficacy and realize they still needed to come to ED for further care. But yet by the time they got to the ED, they were in such a better place that their treatment was safer and more efficient and more effective.

However, I think in many cases, with the appropriate reescalation, that patient might not need to come to the emergency department at all. And that's a very scary, uncomfortable place. I always say coming to an ED is feeling out of control for whatever reason. I've had too much pain. I've had too much anxiety. I've had too much agitation. And then we do things in the emergency department to take even more control away. Sit down, I'm going to put a thermometer in your mouth. I'm going to probe you with an IV.

I'm going to put a blood pressure. I'm going to make you dress take your belongings and make you wear a fitting down maybe leave you in a hallway, right? So really, the whole idea would be avoiding getting into that stage to begin with.

Thank you for clarifying that. Dr. Citrome, did you have anything that you wanted to add to that? I don't know, it seemed like you wanted to jump in.

Yes, I want to emphasize the need to avoid the escalation. That's really critical here. If we can nip this in the bud, we can avoid the escalation of simple agitation to aggressive behavior, and we certainly don't want anyone hurt. So I reflect back on my years running a psychiatric intensive care unit, as well as a research unit for people who are persistently aggressive.

And we instituted a structured program where we could identify people as they were starting to become agitated. And our whole goal was to dial that down. And part of our research was actually looking at aggression, but we didn't see very much because we were able to have a structure and intervene early, and we were successful in doing that.

That's very insightful. Yes, Dr. Ravin?

Yes. I would like to focus to the settings that are outside of the hospital. And let me walk you through a worst-case scenario. You have an individual with severe mental illness, let's say, schizophrenia in the group home. They are doing fairly well. The medications mostly control their symptoms, but they still have bugging thoughts, let's say, roommate is stealing their cigarettes and messes their belongings. They go to the group home provider, discuss the concerns. They say, no, it's really not true. We talk to the roommate, everything is fine, but the person still has those [indiscernible], they're getting agitated. They get in angry.

At some point, they start shouting without much of resources in the group home, what are the options? Call 911, get the ambulance. If you like, they take the person to the hospital where they spend time in emergency department, taking a lot of resources going through expensive workup. If they're not very lucky, the cops show up. And there is a confrontation with the police department. And then if the person starts making any threats, they get arrested, they go to jail, they find it obviously incompetent to stand trial for many other reasons, usually in small charges.

They still may spend weeks in jail and then transfer to psychiatric facility until they are back to the group home. All of that could be over an episode of a single escalation at home when they get agitated. So if you think of the resources from a public health perspective, having something that could take the edge off, be available to the patient when they need it, when they requested is a much easy interaction. It's easier on the patient. It's easier on the health care providers, and it's definitely a lot less costly to us as a society.

Yes. It sort of reminds me of the story of naloxone and having to really reduce the burden on law enforcement to intervene in some of these episodes. So it seems like more and more of the focus -- as we get more and more focused on behavioral health, this opens up that conversation to sort of how can we treat in different places.

As a reminder, also to the audience, you can start submitting your questions, we will take them in the middle of in the middle of the conversation.

So one of the things that I wanted to ask is looking at this as a behavioral health issue, there are clearly certain diseases that are impacted by this. There's also the opportunity for Alzheimer's, which is an even bigger market down the road. And so I know the company is focusing on that. But talk to me about what kind of a market this is. Dr. Milano, I'd love to hear from you as operating in an easy, what kind of financial burden this is you have to stay stocked, and when you are out of stock, what that looks like in terms of alternate interventions? How does this present itself?

Well, I think we heard from one of my distinguished colleagues that once the snowball starts rolling downhill, it becomes very, very difficult to stop it in its course. So again, the earlier the intervention, the more efficient and effective the intervention, the less staff will be needed to manage the patient, the less time in the emergency department, the length of stay in the ED will be shortened, but also if the patient requires admission to a psychiatric inpatient facility, that time will likely be shorter, too.

So given the fact that we're dealing in a DRG payment environment and if a patient is in the hospital for 3 days or 7 days for the same episode of care essentially, the facility gets the same reimbursement. So if I have to use 7 days of a bed, versus 5 or 3 days of a bed because we started an intervention sooner, it's clearly going to offload the system and again, make the care more efficient and allow the facilities to be more prosperous financially or to be more viable. So I think that's a big pitch from a perspective of why would a facility be interested in a novel intervention, we'll call it, that gets people better faster.

I think from the patient level perspective, it's back to life, back to home, back to family, back to work, and all of the economic burdens that are engendered by family has to take off time to be with them in the hospital or take care of them when they get out, the cost to employers when the patient is unable to provide services. So there are many socioeconomic and sort of bi-psychosocial correlates to this. So again, framing the problem for me, I have an emergency department that sees about 300 patients a day in total.

But almost 10% of them are behavioral health patients. So up to 30 patients a day that we see come in with some form of behavioral health crisis. And again, that stay could be as short as a few hours in the ED to 24 hours, 36 hours in the ED, and then cascading into many days in the hospital. Some of these patients are in the hospital, and we have psychiatrists on the call, but these days can be 4 to 7 days or longer.

So again, thinking about the financial constraints of a DRG payment, meaning no matter what you did in those days, you're getting paid the same amount, a shorter length of stay with a less intensive therapeutic environment will certainly, again, help the facilities to be more healthy and help my ED to be more healthy and have the cascading -- have the bandwidth to care for all those 300 patients that come in every day.

Dr. Citrome I saw you raise your hand but I'm going to get you in a second. But Dr. Milano, just to dig down a little bit deeper into that, just you provided a set of about 310%. Of that, do you have any further sort of understanding of how -- what percentage of the payments you're getting and the reimbursement you're getting comes from, say, government pay versus private and how that then sort of gives you the story of why an at-home treatment might be more palatable?

Well, that is going to be very regionally specific and almost micro environmentally specific. So for my hospital, which is in an intercity, we refer to something called the payer mix. That is what percentage of patients have Medicaid, what percentage of patients have Medicare, which percentage of patients have commercial insurance and then, of course, self-pay or charity care, right?

So if you're in an environment that is enriched in patients who have, let's say, less insurance, right? And that's a real thing is under insurance or no insurance, obviously, that financial pressure on the hospital will be much more intense. We have to provide the same level of care regardless. And in fact, we pride ourselves on that.

However, the reimbursement for those episodes of care is substantially less when you're talking about a government payer. That's just the nature of the way things work.

Dr. Citrome?

So I was serving as a consultant to an assertive community treatment team, and the goal of the ACT team is to avoid hospitalizations. And the only way to do that is to keep an overall good sense of where the patient is at. You usually are in a group home, we talked about group homes. The issue here is, group homes cannot always handle a patient who is becoming agitated. They can offer a PRN or as needed oral medication that usually a standard, but it takes time for that to work. And during that time, the person continued to be agitated. And really, everybody wants something that works quickly and effectively. And then you can actually avoid an ED visit and certainly avoid hospitalization. So the key here is the swiftness of response in an outpatient setting, preventing the cascade of events that ordinarily would occur with ED visit, inpatient hospitalization and you're kind of stuck.

Yes, Dr. Ravin?

So I would also would like to add the patient aspect. We really want our patients to be engaged in treatment and the best way to do so is give them the treatment option that they feel that is helpful, well tolerated, quickly acting and not causing any substantial problems in the long run. Currently, in outpatient settings, there is a great unmet need for that.

Usually, the medications like Dr. Citrome mentioned, benzodiazepine groups that may cause substantial problems in the long run, they have potential [indiscernible] symptom, withdrawal, even life-threatening withdrawal. And unfortunately, many other medications are not nearly as fast when the patients need help. And the goal, of course, is to patient when the patient feels they need it, not when the need becomes apparent to everybody around them. And right now, having a medication that could be quickly absorbed to the bloodstream, could quickly provide relief, it's really a tool that we desperately need to be added to our portfolio in outpatient settings.

No, I was just going to jump in on Dr. Ravin's comment. A big part of this is patient and staff safety, too. Because, again, if the oral medicines don't work, what's the next step? It's a parenteral medicine. It's an injection, which again is not the safest thing to administer to a patient who is fulminently agitated or potentially even combative in fighting with you. So if there was some bridge between, let's say, a traditional oral medication and a parenteral aka injected medication that was absorbed quickly and reliably and worked fast, you'd have a magic bullet there.

I'm curious about this also in context of the reference to naloxone. I'm seeing a question from the audience that I remember hearing a lot about at the time. Looking at overuse of an at-home option, is that a concern? And do you think that there should be any kind of safe bars, what kind of labeling would you like to see for any kind of at-home use? Who wants to go first on that one?

I can go first. So obviously, with any pharmaceutical product, there's always concern what's going to happen if it's not used according to the standards of care. There is -- anything over the counter. You buy Tylenol, if you don't take it as prescribed it may cause problems. It is understood patient and caregiver education is extremely important. What we know from safety and efficacy, when you have a tool that can provide relief and the patients are the driving individual in care, the risk of abuse or misuse rather is lower.

For the patients, they get their relief when they take the medication. They are the ones actually who admin the medication to themselves. So it's not like an emergency room or in health care settings where staff may reach out for injectable intramuscular medications for quick control of behaviors does not exist therefore, having that option that is currently not available is extremely important.

I think the data will speak for itself with any intervention when used repeatedly. And part of the concern is, is someone going to abuse it? Well, if it doesn't have any hedonic quality to it, I don't think so. Are they going to rely on it too much? Well, that's a minority of patients as well. And we have to make sure that for that minority, whatever they receive is safe.

And so that's going to be a very important outcome when assessing any intervention that's used repeatedly over time. I want to get back to the issue of speed of onset. I keep on harping on it, but it's really important. I have had patients who've asked me for an injection on an inpatient unit, not because they want the injection per se, but it works quickly and they want relief of their agitation quickly.

It's what we call ego-dystonic. They really don't like that feeling and they want something that works rapidly. So I had people ask for injections. I mean I thought it was quite remarkable that they would want this. I think they would rather have something by mouth that works very quickly. But at the time, all we had were the injections.

That's a really good point. Would you say that this is beneficial to patients who experience consistent agitation? Or is this more for sporadic episodes to have the at-home solution, whoever wants to take that?

So I'm going to jump in on that one. That's been an area of research that I've been spending decades on. The issue here is we can treat an acute episode with a number of different interventions. And some have pluses and some have minuses. We want the easiest thing to administer that works the fastest and so on. But once that's done, we have to have a strategy to decrease the frequency and intensity of these episodes moving forward. That's a whole different question requiring different considerations.

I'd like to pivot to now looking at the at-home treatment, the at-home setting. We know that across different disease states, access to medicines is always an issue, whether it be for financial reasons or transportation reasons. There's just always some barriers for some folks. Considering this as an option, firstly, to include one of the audience questions, is this -- would this be considered preventative care?

And then secondly, with the access part of it, maybe I'll start with you on this, Dr. Milano. But looking at the access part of it, do you have concerns that if more at-home options are available or even just a single at-home option in this case is available, does that change maybe the reliability and consistency of treatment that a patient can get?

So I think it does go back to Dr. Citrome's point about what's known and what's well studied, and what may be fought for further study. So what we know about certain agents like, let's say, for instance, dexmedetomidine, which is a medication which we have used in the emergency department for acute agitation. It hasn't really been studied to my knowledge as a chronic medication. It has really been studied in most detail when a patient is agitated.

And patients are very, very familiar with their own experience of agitation. They know when they are so-called ramping up. So my current thinking on this is we need to really look at how this medicine would perform in an outpatient setting with patients with very clear guardrails about when to use it and when to call for help. But I truly believe that when administered judiciously, appropriately and at the right time, this medication would be incredibly effective again at maybe a boarding that ED visit or if the patient did wind up in ED, they would be in a much, much more calm, much more tractable state.

From an access perspective, I think that's the question with every medication in terms of like who can get it, how is it compensated. So I think that's really a question for the folks on the sort of pharmaco business and more than the clinical end. But from my perspective, it should be made available to the patients who need it most. And often, those are the most economically disadvantaged patients.

To answer the -- yes, Dr. Ravin, if you could jump in, but also answer the part of whether or not you think it should be considered preventative care.

Certainly. So first of all, let me touch on the pharmacoeconomics of that and insurance coverage. As any new medication comes to market for those questions are evaluated by managed care organizations on the cost care. And for me, the vision is pretty clear. You have a medication with unique mechanism of action. There is nothing else that is consistent with other mechanism of action or delivery of the medication to the patient. They care if this intervention is not provided, it's much more expensive.

And 911 call may easily be in tens of thousands of dollars of cost. anything from expense on law enforcement, paramedics, trip to the emergency room and potentially even short hospitalization stays. So even if insurance companies may initially look reluctantly and add another medication to the formulary, the benefit seems to be pretty clear on that.

And as far as prevention, it is prevention. I would say it's a secondary prevention when you're not preventing a disease, but you're definitely preventing the severity of symptoms from needing high levels of care. And if the person at the comfort of their home, that's something that may avert much higher demand for services. It is definitely a preventative measure.

There's a really good question from the audience. I was wondering this myself. How much awareness do you think there is in the physician community about the availability of an at-home treatment? And then I'd like to tie that into what I was thinking about when it comes to the physician community, sorry, which is also the availability and access in sort of D2C spaces, right?

We've seen that increasingly become popular in behavioral health. How do you each think about access when it comes to online prescribing and the like, as well as physician awareness of that area, as well as in general available options. I don't know who wants to go first on that? Dr. Citrome?

So access is really important to emergency interventions at home. And we have several examples we talked about naloxone, also the EpiPen. In case of emergency brake glass type of intervention is very, very helpful. I think there will be people who want to do that, who want to make that available for their patient.

Right now, we're kind of stuck. All I can prescribe to my outpatients is an extra dose of their antipsychotic or perhaps benzodiazepine, and I tell them like use this when you need to, but not every day, if you find yourself using it too often, I need to know about it. But keep in mind, it will take a little while before it starts to work. And sometimes it doesn't work fast enough and you need something that works faster. So having something available like that, I think, would be very desirable and many clinicians would want that for their patients.

Do you think so that that's also true in sort of like the online space? I'm thinking the conversations that have come up because of the GLP-1s and sort of the way the patient population has shifted to wanting to gain access quickly and on their own to potential treatments.

Well, if you're asking me, you're asking the wrong guy because I'm not a fan of telemedicine, especially in the types of patients that I've managed over the years. But let's say you are remote, let's say you are in an isolated community. And let's say there is no specialty provider available, then yes, okay, you can make a case that you can bring someone in remotely or you're in the ED and you don't have a psychiatrist available on site. Can you connect with someone? Yes. But for a person, let's say, they're on Google and they're asking we need something for agitation, contact this or that person. I'm not sure I'm comfortable with that. In fact, I know I'm not comfortable with that.

Yes. Dr. Milano will come to you next.

No, I fully agree. I think we've seen a lot of [indiscernible] that occurs in the telemedicine space due to the lack of that true patient-physician interaction. And this is delicate population. This is -- can be a volatile population. So I would not immediately advocate for access on that level because I do think that there has to be certain, again, guardrails in place and measures in place to make sure any medication is being administered safely, particularly when it's being self-administered in case of emergency.

And Dr. Citrome gave a brilliant example of an EpiPen, right? It is a life-saving intervention when used properly. It can be a not-so-safe intervention when used improperly. So I think it's all about getting good patient education. And sure, if you've had a visit or 2 in person with Dr. Citrome, you have a plan in place and then he may need to see you, although he probably wouldn't, from a telemedicine perspective. But let's say, you've gone on a trip 2,000 miles away and you can't get into his office, then obviously, I think you use that, but that would not be the way to initially access this medication in my book.

Yes. I would like to offer somewhat more alternative point of view because I guess I don't have a luxury of working in the state where a lot of population lives exclusively in urban centers. So we have millions of people in the same communities. Yes, we have some counties like that, but we also have rural frontier counties where the only way to get help is with telehealth.

And those individuals deserve the same access to care as those who live in large communities. We have to engage those individuals who have to provide proper education to patients, families and health care providers. With this in mind, we -- I would have a whole lot more concern prescribing somebody medication with addiction potential like benzodiazepines than a medication that doesn't have this formula. So in my mind, with proper education with guard rails as discussed, the access can be offered to individuals, both in rural communities and in urban centers.

And I was thinking of you actually when I was asking about that because I know that, that has been a much bigger route of access or at least hopes pinned on telehealth and sort of remote options. And I've personally had over the years, as a health care reporter people telling me their problems. I'm not a doctor, but they seem to think that sometimes so they ask me for an advice or share their stories.

And I've heard a lot about people who increasingly are frustrated with the maybe slower pace of in-person treatment. And so they are more willing to find that online avenue, especially if they've been on something for several years. They're like I already know what I need. I just need a place to give it to me fast, easy, quick and it's sort of that e-commerce mindset, that Amazon mindset, right, that we all have as -- or we all see in patients nowadays. And also I'm curious, maybe, Dr. Ravin, you can sort of expand a little bit more on what might be the pitfalls of having a treatment or a home treatment like this available on an online space, but also maybe the benefits and sort of where you see that balance sitting especially in the context of cash pay because that's also what I'm envisioning.

Absolutely. So first of all, I don't want to equate telehealth provided consistent with the standards of care to some of the shady practices where people just first learn on Instagram, what they want and then shop around in the nation, trying to see where they could get a prescription of it. When we provide care, be that in person or via telehealth, we follow the same standards. We have ability now to look at patients' history of getting prescriptions. And if there are any red flags about doctor shopping or getting controlled substances from multiple locations, it pops up.

So we already have the ability to know what and when the patient is prescribed and what habit they have. We don't have any evidence at least to the best of my knowledge, that medications like we discussed today have the same potential for addiction or diversion because diversion is another component that we always worry and even with benzodiazepine that earlier today.

If we follow safe practices, if we follow professional treatment guidelines, it is a treatment option that could become available to individuals where the alternative is either to take the medication at home or drive for 2 hours to the nearest hospital to be seen. And when you're already in acute agitated state, I guess we can all agree that taking a drive on the rural highway for 2 hours is not always the best option.

And I want to also dig into something that you all brought up earlier, and this is related to one of the audience questions to about a label update, noting that withdrawal symptoms may occur if the drug is used for longer than 24 hours. And I know that you talked about patient safety and patient education. I wonder if that plays into any concerns that you might have for an at-home?

I know we've talked about other different like EpiPen as well. I think increasingly, there's been a discussion, especially in a world of GLP-1s around what does treatment at home look like and what does dependence look like, and whether or not maybe the need for guardrails as well as what patients might consider a forever treatment looks like versus what the clinical requirement and need is.

I don't know if you can answer that, Dr. Milano, in terms of thinking through all of these and just sort of reiterating maybe how to think through what a shift to at-home might look like?

Well, I think patient selection is always key when contemplating any therapeutic intervention. So again, establishing that physician-patient relationship, understanding what the patient's predilections risks are, their previous history of abuse or, let's say, irresponsible medication use is all germane and critical to being successful with any therapeutic intervention, whether it be intermittent or long term.

So I would sort of talk to Dr. Citrome more just because he's in the outpatient space, he's seeing patients quite a lot on a chronic basis, whereas my care is really on a more intermittent basis. But I think the main things are safety guardrails in place, excellent, impeccable patient education and again, an understanding that we're using this medication for one purpose or another and that the patient clearly understands what those utilization guidelines are going to be.

Yes. Dr. Citrome, go ahead.

So when treating someone, let's say schizophrenia or bipolar disorder, over the long haul, you're going to want to have a patient on a foundational treatment. That foundational treatment will hopefully decrease the intensity and frequency of agitated behaviors. But sometimes they're -- it won't prevent them all, and you'll have some events that are not controlled and you have to have something in place, a plan to deal with that.

And generally, that's been a PRN of something. Sometimes the foundational antipsychotic is the PRN and sometimes it's a benzodiazepine, that's a PRN. The problem is for at-home use today, they're oral, and they take time for them to work and they don't always work. So if we had something that is a different chemical entity, a different mechanism of action that actually works quickly and easily and well accepted by patients, that can go a long way in taking care of these events that occur intermittently in outpatients despite being on a foundational treatment.

If you don't mind, I would like to add too as a clinician, if the patient tells me that they need that as needed treatment on a frequent basis. It's a signal. It's a signal that whatever the foundational treatment that Dr. Citrome is talking about is not working as intended. So there would be the first red flag to start the conversation. How we can optimize the rest of the treatment to make sure that we are providing the patients the care they need and the relief of the symptoms that they are seeking.

And I think finally, as we wrap up, the prospects we're talking about something that is still sort of in the works, right? The idea of an at-home treatment, the filing with the FDA is yet to happen.

In terms of it becoming a reality, so far with the data generated from clinical trials, what would you say is -- what could be any kind of concerns that the FDA might have? Obviously, we talked about patient abuse. Do you have any other thoughts in mind on what could stand in the way of something like this getting approved?

So BioXcel was very careful in the conduct of the at-home study, and they examined 2 very important points. One is, is it safe with repeated administration? And there were several subjects where there were repeated administrations self-administered. And the other is, does it continue to work? And so that was also examined as well. So those are the 2 key things I think the FDA will be interested in.

Thank you for that. Anyone else? Okay. Well, I would love to thank you all for the wonderful insightful conversation. I certainly learned a lot. Any final thoughts before we turn it back to our host?

All right. Thank you to the audience for the amazing questions. I know we can't see you, but round of applause for our 3 panelists here, Dr. Citrome, Dr. Ravin, Dr. Milano. Thank you for your time. Back to you, folks at BTI.

Thank you, Anjalee, for coordinating this great conversation. And thank you as well to Dr. Citrome, Dr. Milano and Dr. Ravin for your contributions. Most importantly, I want to thank everyone who joined us today for your time and engagement.

As we conclude today's discussion, one thing is abundantly clear, the need for safe, reliable and accessible at-home treatment options for acute agitation has never been greater. Patients and families continue to navigate these episodes with limited tools often under stressful and unpredictable circumstances. We appreciate your time and engagement today, and we look forward to continuing these important conversations as the field moves closer to meeting this critical unmet need. Thank you all.

Greetings, and welcome to the BioXcel Therapeutics. [Operator Instructions] Please note that this call is being recorded. I will now turn the conference over to our host, Vimal Mehta. Thank you. You may begin.

Thank you, operator. Good afternoon, everyone, and thank you for joining us today. I'd like to start by welcoming our distinguished participants. First, Dr. Leslie Citrome, Clinical Professor of Psychiatry and Behavioral Sciences at New York Medical College. We are grateful to have your deep expertise to help frame today's discussion. I would like -- also like to welcome Sumant Kulkarni, analyst at Canaccord Genuity. And finally, my colleague, Dusan Kostic, our Senior Vice President of Clinical and Medical Affairs here at BioXcel Therapeutics, who has been instrumental in advancing this program.

With today's top line exploratory efficacy results, together with the positive primary safety data we shared previously, we believe we are taking an important step toward expanding into the home setting, bringing forward a new treatment option for the management of acute agitation. Our mission has always been to transform patient care and today's progress brings us closer to easing the burden patients and families face when managing episodes of acute agitation at home. With that, I will turn it over to Dr. Citrome to share more about the data and importantly, about the real-world challenges faced by patients and their families. Dr. Citrome?

Well, thanks very much. Welcome, everybody, and thank you for the opportunity to talk about something that has been part of my career for several decades. So just to put this in context, I used to work for the New York State Office of Mental Health. I ran an inpatient unit dedicated to research and evaluation and included a research program for those who are persistently aggressive. At the same time, I also did on call at a variety of emergency departments. I did leave that position in 2010 and became an outpatient psychiatrist essentially continuing research and evaluation as a consultant and also served as a voluntary consultant to our assertive community treatment team in the county where I resided.

And the goal of that assertive community treatment team is to keep people out of the hospital. What gets them in the hospital is getting agitated, getting aggressive and brought into the ED and ultimately admitted. So this is something that I've looked at in research and in clinical care and very interested in this. I'm going to talk about agitation associated with bipolar disorders or schizophrenia in the at-home setting and describe to you the SERENITY At-Home Pivotal Phase III safety trial top line results, also placing it into context regarding what we think about clinically as what is important.

Here are the forward-looking statements. So what is agitation? Well, it's a huge burden with no clear solution here and debilitating not only for patients, but also for health care providers and family members. People who are agitated with these disorders have recurring episodes. Although the symptoms vary from person to person and range from mild to moderate to severe, we do know that they generally escalate, if not addressed as soon as possible. If it's not addressed, then it can escalate, lead to an emergency department visit and ultimately hospitalization. Once someone is in an ED and/or hospitalized, the price of care or the cost of care is tremendous compared to what could have been beforehand if we only prevented that progression.

Best practices tell us to use behavioral calming techniques. So we've learned that in inpatient units and best practices in outpatient clinics to use verbal de-escalation techniques. But very often, that is not going to be sufficient, and we need to offer some medication assistance. Now in an ED and inpatient unit, we've resorted to intramuscular injections when we had to, but we never really had until very recently oral alternatives that allow us to avoid injections. And we never really had anything at home that would be the strength of an intramuscular injection but given orally. We want something that the patient voluntarily agrees to, and that is often not voluntarily agreeing to an injection. It's voluntarily agreeing to take something by mouth.

Now it also has to be calming and not unduly sedating. Our goal is not to put someone to sleep, but to calm someone down so they can go on with their day and recover from their agitation episode. Now ultimately, if this does not happen, people end up in the ED, end up in the hospital, end up in physical restraints, end up being over sedated with other means of addressing agitation such as giving more antipsychotic or using benzodiazepines.

So there's got to be a better way in order to address this at home in the clinic, not necessarily under supervision of a medical provider. And right now, we're going to talk about the use of IGALMI, dexmedetomidine sublingual film currently only available under a health care provider supervision, unfortunately, because this is an ideal way of addressing agitation early. Our goal is to address it early. So when someone becomes distressed, and that's the beginning of agitation, it occurs on a continuum, but invariably, for many people, it leads to an escalation and ultimately loss of control. Now we measure agitation and research by actually quantifying the degree of poor impulse control, tension, hostility, uncooperativeness and excitement that forms the key to a rating scale used for pivotal trials in the inpatient unit.

In the outpatient unit, we know it when we see it, someone is visibly agitated, pacing about, making maybe some verbal threats, but we don't want that to escalate to actually physical aggressiveness. So at-home intervention may actually allow a patient to really avoid de-escalation, and this requires early intervention with something efficacious. So pre-agitation, someone knows that something is up, and they will ask for what can I do now and maybe they have self-soothing things that they do, maybe listen to music, maybe go into a room that's more quiet, maybe someone talking to them about other things besides what they're kind of obsessing about. But unfortunately, that can often escalate to actual frank agitation. The idea here is to intervene here while it's still in the mild range before it becomes moderate or severe.

It's been estimated that about 60 million to 80 million episodes of agitation occur amongst 23 million patients that we're talking about at -- in the at-home setting. Ultimately, in a hospital, we'll see close to 20 million episodes. It's hard to quantify precisely. This is not something that's always coded as such. But in my experience, it's the most common reason why people get admitted to the hospital or at least brought to the ED. The SERENITY program evaluated IGALMI initially through SERENITY I, SERENITY II through the pivotal trials leading to approval under health care provider supervision by the FDA in April 2022. Based on studies that I'll show you the highlights of, very interesting studies, I have to say, in terms of the effect size. Now what I mean by effect size is the degree of improvement of agitation in a quantifiable term, not just probability of being better than placebo, but actually the difference from placebo.

And up to now, and there have been no FDA-approved therapies for agitation associated with bipolar disorder or schizophrenia in the at-home setting. That may change if IGALMI is successful in achieving approval for at-home. And the SERENITY At-Home clinical trial gives us information about how this is possible. It was initiated in September 2024, and the top line data readout was very recently, as you already know. And what was used here was a dose that was not the top dose. 120 micrograms is not the top dose, but it is an efficacious dose and is a reasonable dose to take at home. And the idea here in SERENITY At-Home is to make sure that it is tolerated and actually safe. So people had to understand how to use it and understand what to expect.

There's a planned supplementary sNDA submission for the first quarter of 2026. So IGALMI, dexmedetomidine sublingual film is approved currently for the acute treatment of agitation associated with schizophrenia or bipolar I or bipolar II disorder in adults under health care provider supervision. Now the bipolar I or II disorder indication is broad, whether you're depressed, whether you're manic, whether you're in the maintenance phase of the illness. That's unique amongst all agents approved for agitation associated with that disorder. 120 micrograms is the lower dose, and we're going to take a look on how successfully it was used at home.

But first, I'd like to go over the 2 trials that led to its approval by the FDA. They're very impressive in terms of the degree of response here. On the left-hand side of this slide, you have the usual response over time graph where the PANSS Excited Component total score is used as the outcome measure. It is reduced over time over a period of 2 hours, of which the study was conducted primarily. And the primary outcome measure was, of course, the decrease in the PANSS Excited Component at the end of 120 minutes, but a difference was noted as early as 20 minutes in the schizophrenia sublingual dexmedetomidine versus placebo study, at basically the doses of 120 and 180 micrograms per dose.

Now that's interesting of itself, but look at the difference in size between the gray line and the blue and orange lines, that represents the effect size and the difference from placebo is actually large. It's not just statistically significant, it's also clinically relevant. When we look at PEC response, that tells the whole story. That's the responder rate. So it's the number of patients who have at least a 40% reduction from baseline at 2 hours on their PEC total score.

Now this is important because every other study for almost all of them have used this as the outcome measure in terms of measuring responder rate. And the rate on placebo, the response is 40%. I'm not surprised. Patients expect some degree of effect. They're blinded. They don't know what they're getting. They're getting reassurance and support for sure, and they expect to get better, but they're on placebo. So you would think that someone randomized to real drug would have a higher response rate, and they do, double.

And if we look in absolute terms, it's a huge difference. Now why do I say that? Well, before I do that, just a brief mention here about the bipolar disorder study. I just want to mention the same degree of response and maybe even a little bit faster in the bipolar population. This was published in JAMA, the JAMA, not JAMA Psychiatry, the actual parent journal. And they don't generally publish psychiatric trials unless they're innovative, they're different, and they talk about an intervention that is new. So the question asked here, of course, is sublingual dexmedetomidine effective in treating acute agitation associated with bipolar disorder. The answer is yes, at both doses that were tested.

But here is how I like to look at data. I'd like to look at number needed to treat. How many patients needed to be randomized to the drug instead of placebo before you expect one additional responder. And we define responder here as the 40% decrease from the PANSS Excited Component from baseline. And the number needed to treat of 3 is actually rounded up from a little less than 3, where for every 3 patients randomized to drug versus placebo, you expect one additional responder. Now this is actually a very actually impressive effect size. When you look at the effect sizes for inhaled loxapine it's a 3, ziprasidone IM it's a 3, olanzapine IM is a 3. So we can say the oral sublingual film of dexmedetomidine has an effect size that is equal to intramuscular administration.

Aripiprazole IM is no longer commercially available as a fast-acting anti-agitation agent in the U.S., but it is available in Europe. Now on the right-hand side of this slide, I have a notation here, not shown are data for haloperidol or lorazepam that is typically used in the treatment of agitation. And these were the active controls in some of the studies, particularly the olanzapine IM and aripiprazole IM series of studies. And I was able to pull together the responder rates for each of those agents. And they turn out to have a number needed to treat values of 4, actually weaker than the effect size for dexmedetomidine sublingual film as well as weaker for inhaled loxapine, ziprasidone, olanzapine.

Now I want to take -- bring your attention to the vertical lines that you see on this slide. You know those lines that go up and down around the number, that's the number needed to treat estimate. You'll see that there's no vertical line for dexmedetomidine. That's because the 95% confidence interval lower bound is 3, upper bound is 3. So the estimate is very precise. If you like Cohens d as the effect size measured, that's used for continuous measures. Some of you may be familiar with this. And this is traditionally used in research to calculate, for example, how many patients would you need in a clinical trial and helps you with sample size estimates.

Nevertheless, the Cohens d in standard deviation units is one standard deviation unit. That is a large effect size comparable to what we would see with very few treatments in psychiatry. So let's go over the top line results for SERENITY At-Home and dig down a little deeper with some of the details. So data was collected in 2,500 treated episodes in about 200 patients who self-administered the film. It was well tolerated with no drug-related serious adverse events. So that was the primary goal of the study to make sure it is safe and usable. There were no syncope, no falls reported in the dexmedetomidine arm, adverse event profile consistent with what we have seen in the IGALMI label and multiple clinical trials in an institutional setting, and I'll show you that.

Tolerability with re-dosing remains similar throughout the trial. This is new information because the actual limitation of use for this agent is one dose, okay? And under a health care provider supervision, repeated dosing was not actually studied in the pivotal studies done inpatient, but it was necessary to look at an at-home use because typically, people will repeat dosing. So one of the questions is, is it tolerable? And does it continue to be efficacious. Patients experienced similar benefits throughout the study with repeated administrations.

So let's go over the trial design and dig a little deeper into the data. So basically, agitation was assessed in people identified with bipolar disorder or schizophrenia residing at-home. In a certain proportion of patients, people had a co-resident family member or informant with them. In others, they did not. It was double-blind, placebo-controlled. And the primary goal is to evaluate the safety of the 120-microgram dose of dexmedetomidine in that at-home setting. After screening, patients were randomized 1:1 to receive either dexmedetomidine or placebo.

And there was a maximum of 1 dose of study medication within 12 hours, but it could be repeated. The alternative interventions were permitted. Patients could do whatever they like, essentially, meditation, alcohol or cannabis or other medications to reflect real-world coping strategies. There were no restrictions based on that. So it's a pragmatic at-home trial. Even though it's randomized, double-blind and placebo-controlled, it is pragmatic in terms of the real-world patients that were enrolled in the study. Primary objective was safety. And as exploratory objectives, we have a measure of efficacy by a modified clinical global impression 2 hours after dosing to evaluate the patient's impression, I'm going to show you, of their experience with dexmedetomidine in that outpatient setting.

So the included patients were men and women with a wide age range of 18 to 75 with the disorders in question here that we see essentially approval for bipolar I or II disorders, schizophrenia, schizoaffective disorder or schizophreniform disorder. Now it's sometimes difficult to distinguish schizophrenia from schizoaffective disorders. It's based on a history of mood episodes during the lifetime of the disorder. This is kind of tricky, but they're included. Schizophreniform disorder, if someone has symptoms for longer than 6 months, they graduate to having schizophrenia. They needed to be on a stable psychotropic regimen for at least 30 days. So these were essentially stable outpatients, but with a history of agitation.

There was a certain requirement that they have a history of at least 3 agitation episodes in the past 3 months. This is not unusual in day-to-day clinical practice. And discharging patients from the hospital my experience, I needed to keep in mind a strategy, what happens if someone gets agitated at home. Excluded were patients with serious medical illness that would prevent the safe use or not under supervision, of course, so congestive heart failure, recent myocardial infarction, hepatic disease that is clinically relevant. Also excluded were patients with comorbidities that predate the schizophrenia or bipolar disorder diagnosis because it would interfere with the evaluation of efficacy within the population of interest here.

Also excluded were those with moderate to severe substance use disorder in the past 6 months because that would also interfere the assessment of safety and tolerability and also efficacy. Agitation due primarily to acute intoxication or substance use was also an exclusionary criterion because this study was not intended to look at that kind of agitation. So top line results in more detail. Here are the baseline demographics and disease characteristics, well balanced across the treatment arms, median -- well, mean age here, close to 50, about 50-50 men, women, about 50-50 white versus other race or ethnicities. And the primary diagnosis, about 50-50 schizophrenia, bipolar disorder. About close to 1/4 of the patients had an informant. This was by design and the time since diagnosis, at least a decade. So these are typical outpatients with schizophrenia or bipolar disorder.

In total, I mentioned close to 2,500 agitation episodes about -- in about 200 patients, about 80% of treated patients completed the full 12-week study. There was an average of about 12 agitation episodes recorded per treated patient, reflective of the repeated nature of agitation. And we're going to show data collected for the episodes of in total of what was collected here. A total of 246 patients were randomized. And importantly, all patients were able to successfully self-administer the film. Now when used in clinical practice inpatient, patients also self-administer the film under supervision. Now no one places this under anyone's tongue. It is not safe to put one 's fingers in someone's mouth when they're agitated. Dentists don't like to do that, too instantly. So this is actually a very important point. Can the patient put it under their tongue successfully to gain actually the benefit of this drug? And the answer is yes, they can. Well tolerated. So the primary objective of the pivotal study trial was met and no patients discontinued due to a treatment-emergent adverse event in the dexmedetomidine arm.

The adverse event profile, as I mentioned earlier, was consistent with the approved IGALMI label and other clinical trials that were conducted in the institutional setting. There was no drug-related SAEs, no falls, no syncopes, no new or unexpected treatment-emergent adverse events either and no severe treatment-emergent adverse events associated with the dexmedetomidine treatment and most treatment-emergent adverse events were mild.

Tolerability remained consistent across multiple repeated dosing throughout the trial. So why do I say it's comparable to the institutional setting data? Well, let's take a look at somnolence, single dose, the rate of somnolence with IGALMI was 22%. That with placebo was 6%. And that was in the single-dose SERENITY I or II pivotal trials done in institutions. What about at-home? Well, at the first dose, the rate of somnolence was 22%. And with placebo, a little higher 17% than what we saw in patient, not to be unexpected here in this kind of trial.

In terms of all doses, when we look at that, the rate of somnolence as an AE was down to 14% versus 8% for placebo. The remainder adverse events in the SERENITY At-Home trial were low in percentages, so single digits and the difference from placebo reasonably small. So overall, well tolerated. And as I mentioned before, generally rated as mild. When we look at repeated dosing after doses 1 to 3, after doses 4 to 12 and after doses 13 and beyond, we see no signal that there are problems that are a surprise later on with somnolence, oral paresthesias, dizziness, dry mouth, nausea or headache. So well tolerated. And when used once, used again and again, no surprises.

In terms of the incidents, they did not increase over time. So exploratory assessments of treatment benefit, let's take a look here. Now this was exploratory. This was not the main intent of the study. Study was not actually passed but they're very interesting in terms of descriptive information. Similar reductions in symptom severity with repeat dosing over the 12-week period. The efficacy of the 120 microgram dose for single-dose administration was proven and is as approved in the inpatient studies, the safety and exploratory objective was to assess continued benefit with repeat dosing, and that was found. There was a demonstrated mean reduction in the mCGI-S score as measured by the patient from baseline compared to placebo at 2 hours across close to 2,500 treated episodes and was statistically significant.

Complete resolution of agitation, that is a 0 was significantly higher with dexmedetomidine compared to placebo across agitation episode severity. And there was a similar reduction in agitation symptoms in both the duration of -- over the duration of the trial and number of treated episodes. So no matter how you look at it, it continued to work. Let's take a look graphically at the percent of fully resolved episodes by baseline severity. A difference was noted between drug and placebo across severe, moderate, mild and overall. Now in the chat, I noticed there was a question regarding, well, what about moderate? Why does that -- those 2 bars look closer together. I think statistically, it is a dead heat. The study was not really intended to actually go to some such fine granularity. And I wouldn't say this is altogether something that I would worry about clinically. I am pleased that, of course, severe has the biggest droplet. But again, I'm not surprised there because they had a lot of ways to go and the expectation there is that they would get better.

Now nice to know severe, moderate or mild. Overall, the difference is still better for dexmedetomidine sublingual film in terms of fully resolved episodes versus placebo. Now remember, placebo is not no treatment here. Placebo is given double blind to someone who doesn't know they're getting placebo, who actually repeat the doses of placebo over time with the expectation that they're getting something out of it. So they're getting the placebo effect. Now the drug effect would be over and above the placebo effect. So let me summarize. We have a drug that is well tolerated with repeat dosing across the trial duration. The safety profile was consistent with what we know with the prior inpatient SERENITY trials. No discontinuations due to treatment emergent adverse events in the dexmedetomidine arm, no serious drug-related adverse events at all, no falls or syncopes and all patients, importantly, successfully self-administered the film.

Benefit was maintained over time, no attenuation of effect or agitation symptoms -- on agitation symptoms across multiple episodes so continue to work and no loss of efficacy there. Results are supportive of this new indication. And hopefully, the FDA will look favorably upon this. So I want to thank you for your attention here. I'm going to be more than happy to address any of your questions.

Thank you, Dr. Citrome, for your very insightful presentation. We will now move to our Q&A session, which will be moderated by Sumant Kulkarni with Dr. Leslie Citrome. Sumant?

Thanks, Vimal, and thank you, Dr. Citrome, for your time and perspective. We'll jump right into Q&A. So you went through all the data that the company has presented so far in the SERENITY At-Home trial, which showed consistent rates of adverse events so far in this trial versus its performance in earlier trial than [Technical Difficulty]...

You're breaking up a little bit.

Yes. So your microphone is not sounding great right now.

Let me try to fix that really quickly here. Is this better?

Is there some way to type it in...

I don't think there is, but let me check.

It's better now. Go ahead, sir.

It is Okay. Great. So I'll start again. So you went through some of the data that the company presented in its SERENITY At-Home Phase III trial. What do you think really stood out in this data to you? And if you had to pick [Technical Difficulty]...

I'm sorry, the sound has deteriorated again. You sounded good at the beginning and then it's kind of choppy. Does everyone else notice that?

Yes, it was. It was chopping again.

Is this better? Sorry about that this is the same mic I've always used. I'm not sure what's going on. But the question is, what do you think really stood out in the data to you? And if you had to pick, was there anything that you thought that could have been better in the dataset?

So I -- sorry, I couldn't understand maybe what people can do is type it in the chat. That would work. And there are several questions in the chat that possibly would be of interest to others. So let's go by that. Meanwhile, if you can have a headset or another microphone, that would be helpful. So I answered the question, why do you think mild or severe episodes are treated better than moderate severity? I think it's a dead heat statistically. It's an exploratory measure and not powered to look at that. I'm happy to see that across the board, we have descriptively at least we can say it was statistically separating.

Do you think the totality of the 215 patients included in the efficacy analysis will be included in the FDA's assessment of the sNDA? Or is it possible some patients could be screened based on length of follow-up given 168 completed the full 12-week trial on something or something else? So the FDA will look at completers. They will do last observation carried forward. They will do all sorts of things. But you got to remember, this is a safety study. So the efficacy analysis is there supportive. It reassures us that we're not wasting time here or wasting effort here, but it's a safety thing. I think they'll look primarily on that. But of course, I don't have a crystal ball, and I don't quite know exactly what they are going to decide. But I would go by what is the primary intent of the study and also maybe the company can provide additional detail regarding that.

Next question, Dr. Citrome, what is your opinion about inhaled loxapine as an episodic treatment alternative? Yes, not bad. However, it requires something a bit more difficult than putting something under one's tongue. It also must be administered under health care supervision, basically because you have to assess the lung function before making sure there is -- they're cleared medically regarding that because of some concerns there. It also is very expensive. So that's an issue, too, with inhaled loxapine. But it's a good drug. When I looked at the effect sizes there, it was on par. The 95% confidence interval was a little wider. But I say it's a reasonable option regarding a noninvasive way of treating agitation. But again, under health care supervision, and there's -- I don't think any way that would be approved outside that setting.

Is there a way to compare the efficacy demonstrated in the institutional setting with the at-home data reported today? Well, indirectly, we can say it's all in the same direction that there is improvement. There may be efforts underway looking at this outcome measure. I'll leave that to the company to describe further information regarding that. But again, this study was a safety and tolerability study. The efficacy is there to make sure that we're not spinning our wheels here.

Okay. What is the percentage use in the at-home setting does he expect or would predict to see in mildly agitated patients, moderately agitated patients, severely agitated patients? So if someone has this at-home and knows that it works to treat their agitation, I would think that they would use it. Now they -- in the past, people have used their antipsychotic, which is actually not always optimal because if they're already on the antipsychotic, what is more oral antipsychotic going to do for them. The pharmacokinetics are not favorable in terms of leveraging the sedative part of that antipsychotic. They may have a benzodiazepine on hand, but that's a problem. Benzos are scheduled. They can be easily diverted and it's known that taking a high dose of a benzodiazepine gets someone high.

So it's not something I like to prescribe. I do when I know the patient is going to be not using that excessively. And basically, what I do there is I give a prescription. It needs to last a very long time. If it doesn't, then I worry about them either diverting it or misusing it. So I like the idea of dexmedetomidine sublingual film there because it's not going to be used in that manner. Now there's always the risk that it will be used in case of emergency break glass, but that's okay if someone needs that, if the self-soothing or calming doesn't work, then that would be a logical next step.

So what sort of evaluation do you need to make as a physician before you would write an at-home prescription for IGALMI? Well, I want to make sure they understand what it is and how to take it. So what I would do is, for example, take a placebo IGALMI product, have them put it underneath their tongue as instructed and make sure they can actually do it, follow those instructions. Beyond that, I want to make sure that they understand that this is for emergency use, at-home use emergencies. And the idea here is to nip things in the bud if you feel you're going in the wrong direction.

Now patients often know when they're revving up and they ask for something. And I know this from my inpatient work and outpatient work. Inpatient, it is not unusual for someone to come up to me and says, I need a PRN. And it is not unusual to ask, I want the injection of ziprasidone or olanzapine. This was quite a surprise to me, but they had expected olanzapine or ziprasidone IM to work faster. And that's what they wanted. I never had anyone ask me for a shot of haloperidol, which was the standard of care in my institution before the availability of olanzapine, ziprasidone IM. No one asked for that because it was unpleasant. But they do ask for things that are easier to tolerate that they know will work relatively quickly.

Okay. What -- how long is this therapeutic effect? So I think the best measure of that would be to look at finer detail about repeated episodes and all of that, that is to come. And if we can look at the pivotal studies, we have some degree of information there over a course of time. I don't have this at my fingertips, but it is readily available. Let's see. We already addressed the proportion who would be compliant. I would assess the compliance ahead of time to make sure they understand that.

Usually, people are more adherent to medicines that they take for something that is acute because they know something is wrong. They feel bad, and so they'll take something for that. Something sort of like pain, someone will not tolerate the pain will take something for. This is different than adherence of something that's on a maintenance use. So someone being maintained for their stability may feel good one day and may not be adherent that day. By the way, this is not only the problem with bipolar disorder and schizophrenia, but also for diabetes, hypertension and asthma. You feel good, you may not feel the need to take your regular medicine.

Dr. Citrome, Sumant Kulkarni is connected again.

Okay. Great.

Thanks. I hope this is better, Dr. Citrome? Let me know you can hear me better now?

Much better. Much better.

Okay. Great. Great. Thank you. Sorry about that. So I was asking, you went through some of the Phase III SERENITY At-Home trial data that the company presented. What do you think really stood out in that data set to you? And if you had to pick, was there anything you thought could have been better?

So the thing I was looking at -- so I'm going to make full disclosure. I was the Chair of the Data Safety Management Board or Drug Monitoring Committee for this study, and our charge was to assess the safety and tolerability primarily. So I think we were encouraged at the lack of a safety or tolerability signal. There was no worry there. And at the end, when the blind was broken and for all to see, I think that struck me here. What also struck me is the persistence of effect when repeated use. So this was an unknown going into the study. So that really struck me. What can we do differently? So if only we had other measures to look at, so we're going to -- the company intends to look at all the data that's collected and fully understand what goes on in terms of the efficacy side of the story as best they can. The study was not powered or intended to look at that specifically. We know the drug works based on its initial approval for inpatient use. We know that people endorsed its efficacy. We know people had resolution of their agitation superior to that seen with placebo, but those were exploratory.

In the recent safety dataset, and you alluded to this just recently, we saw the rate of somnolence go down with repeated dosing. But why do you think efficacy also did not go down? What sort of reasons would you ascribe to that?

Yes. So efficacy does not equate with sedation. So when you have an adverse event or somnolence or sedation, it represents something untoward, something that someone complains about. And it's not something they want. So that's how it would come to be that it would be an adverse event. Someone taking a medicine for calming purposes, it's ideally they should not feel sedated. They should feel calm. Now over time, they may be more used to thinking about what the medicine is doing for them, and they'll be better able to identify the calming effect than the sedating effect. The other possibility, and this is purely conjecture on my part is that with repeated use, there wouldn't be as much sedation. Now I don't know that for a fact, but this is how it was reported.

But I want to disabuse anyone of the idea that sedation equals efficacy here. That's not the case. In the old days, that's all we can do. And so essentially, we would put people to sleep. We don't want to do that today. So if I could just go off on a tangent for a moment here. In the ED, what we want is people to calm down, cooperate with tests and procedures, cooperate with admission procedures if they're being admitted. We don't want them sleeping because if they're sleeping, they cannot be medically cleared, and they'll need assistance with their activities of daily living with toileting and so on. So our goal is calming not sedation.

Right. So with the caveat that you do not have access to the full set of interactions between the company and the FDA, given the at-home data we have seen so far, how would you handicap the chances of a supplemental new drug application for BXCL501 being approved for at-home use?

Well, I'm always asked this question, no matter what I'm consulting about and who I'm consulting with. Now I usually hedge and say, well, 50-50. I would go higher than that with this based on the data and how it looks. How much higher? Well, anyone's guess. In a normal world, I would say yes, but we're maybe not in a normal world right now. So -- but I would think so.

And I'm going to tap into your expertise here on your past examples of any psychiatric products that were primarily used in institutional settings initially that went on to become hits when used at home and what led to that successful transition?

So very often, it's a seat of the pants. If you get upset at home, just take more of your regular medicine, make sure you tell me about it. And it may be an issue that we have to adjust their dose of their foundational antipsychotic. But they may have had breakthrough episodes of agitation despite their stability, in which case you need another strategy. It's not going to work, giving more of the antipsychotic. So in the past, we've tried our best to train patients to take benzodiazepines sparingly and use that. But there's always the problem of diversion or taking more than what you want. And I've heard countless times of people coming to ED and saying, I ran out of my Ativan or I dropped it down the toilet or something like that. And basically, this is a problem because I don't want to prescribe Ativan for them to take home. So this is an issue here. And if I had something that I'm fairly comfortable that they wouldn't divert or abuse, then I'd be happy with that.

In your real-world experience, do you have any estimates for the number of agitation episodes your typical patient may experience in a month?

Yes. So my clinical experience may be different from someone else's because remember, I ran an inpatient unit dedicated to patients who are persistently aggressive. So when we discharge them, we fully expect them to run into problems. Also, when I consulted for the assertive community treatment team, that too was a problematic patient population. In that case, when they became agitated, they would end up in the ED and potentially hospitalized. And our goal was to keep people out of the hospital. So it was fairly frequent that I would consider something for at home or something at least that they can call and say, well, time to take this medicine that we prescribed for you to take now.

And having that available is useful. Also, if someone is living in a communal care setting, there's a caregiver, some staff available, then they can be also very helpful to give something. Now staff importantly, want to give something that works, and they will be very unhappy if they're giving something that just doesn't do the job because they feel perhaps in danger. So something that works, predict is comfortable with will go a long way. So in my case, lots of patients. Now if you have a suburban private practice and treat only patients with depression, that's a different story.

Right. Is there any type of patient who presents themselves with an agitation episode that you would not prescribe this product to? And why would that be?

Yes. So someone who is incapable of sitting down, calming down and taking something by mouth despite my best efforts with verbal de-escalation, despite everything I have in terms of past relationship with the patient, the therapeutic alliance with the institution and so on, they're still going to -- not going to sit down for you and take something. I have no choice there than to give something parenterally. I don't like to do it, but I have no choice. And when I do that, I need 5 staff, one for each limb, and one to give the injection. So it's something I really try to avoid.

I'm going to flip the script a little bit. And if you were to place yourself in a sales rep's shoes detailing the at-home use product to a psychiatrist, what features or data of this product would you call out to convince a doctor like yourself to prescribe the product?

So I would describe -- I would -- the foundation is the efficacy profile done with the pivotal placebo-controlled trials. So that gives me the ammunition necessary to say this is as good as intramuscular olanzapine, intramuscular ziprasidone and the effect size at least is nominally greater than intramuscular haloperidol or intramuscular olanzapine. Yet it's not an injection. It's given by mouth, it's under the tongue and patients can go home with it. How does that sound to you? It's not going to be like a benzo where they don't work as well, I think, and you have the risk of diversion and perhaps misuse. So I think it's a compelling argument to have something like this on hand.

And in your view, what do you think the typical psychiatrists would need to see to start prescribing this product relatively quickly? And would that happen or not?

Yes. So basically, you need an educational effort, right? So you need to teach about what agitation is, how it can escalate and how we can manage it outside the institution to prevent someone from actually coming to the institution. And I think for those who work in community mental health who have a cadre of patients with schizophrenia or bipolar disorder know exactly what I'd be talking about. So that would be the target practitioner that I would contemplate. Nurse practitioners as well deal a lot with community mental health centers, also on ACT teams and so on, maybe even to a greater extent. So I want to make sure that they're included in these educational efforts.

So if you fast forward to an eventual labels that might be published for this product, assuming at-home use is approved, would you see any potential safety issues that might make it on the label ability to drive those kinds of things that may limit real-world use even if the product is approved for outpatient use?

So whatever is in the label now about warnings and precautions, that would apply to at-home use. So there are some caveats to the general use of dexmedetomidine sublingual film that would need to be followed.

All right. Now in the real world, and you had a slide on this, but at what point in the, I guess, spectrum of the agitation episode do you expect to see patients using this product?

So I would expect it that patients have ability to detect when they're becoming agitated and when they think they've reached -- they're going to reach the point of no return. And patients generally have that degree of insight. Even amongst my most agitated patients on the inpatient unit, they kind of knew. I mean, they would ask me, I need my PRN. And they knew the consequences of their agitation going out of control. It's not pleasant. So they know. And by having something on hand, maybe they could actually be better managed over time. So I think there's a huge opportunity here to help patients along and keep them out of the hospital.

You mentioned the price and cost initially in some of your remarks. How price sensitive do you think reimbursers could be to this product? And do you think that prescribing physicians will think of cost or price as a variable in real-world usage?

Yes. So the only people who are stymied by cost as a practical obstacle that is actually quite substantial, are inpatient providers who need to prescribe something for inpatient use where the hospital has to pay for each drug as it's in their per diem. So they're often restricted by the formulary. However, preventing escalation of agitation can save a lot of money. It could save hospital days, it could save time in the ED. So there is still that use of dexmedetomidine sublingual film in the ED and the outpatient setting despite the cost because ultimately, you save money.

In terms of outpatient use, I find that providers are generally insensitive to price as long as they can access the drug. So if there's a prior authorization process, they'll do it. If there's a failed first process, that gets more tricky because who wants to fail first before giving something that actually works. But in any case, it depends on the plan. Those receiving Medicaid benefits actually have better access than lots of people on commercial insurance. So I'm not terribly worried about outpatient access provided that the providers are understanding the value of this intervention and willing to do the prior auth, which they have done for branded antidepressants, branded antipsychotics quite regularly.

Got it. And I apologize if you already addressed this question because I think it's part of the audience questions as well. But do you think patients will be compliant with using this product at home in a real-world setting?

Yes. So it all boils down to does it work for them? If it works for them, they'll be adherent to it. If it doesn't work for them, they won't. In reality, someone who is in the maintenance phase of a psychotic disorder or a mood disorder feels okay, and they may not be adherent with their foundational treatment. This is true, as I mentioned, for all chronic illnesses, including asthma, hypertension, diabetes and so on. But when someone is in crisis, it's different.

Right. Now we have 2 patient populations here, one in schizophrenia, one with bipolar disorder. Do you have any reason to believe the product may work differentially better in any of those patient populations?

Then what?

Then let's say, it works better in agitation in schizophrenia versus agitation in bipolar disorders, type I or type II if it...

Yes. No, I'd see no difference there between the 2 diagnoses. It's transdiagnostic, this anti-agitation effect. The company only studied it in those broad disease states. They didn't look at it in others. I would think it would work in the others because of the nature of what this does. But it's been studied in schizophrenia and bipolar disorder, hence, the approval.

Got it. And on background atypical antipsychotic use, do you expect this product to work better with any background molecule? Is there any reason to expect that or not?

No, I don't expect it to have any differential effect. It's very hard to tell with combinations because patients who are agitated are receiving all sorts of things and the sample size is so small to be able to know if there's any advantage of one combination or another. But I can't think of any that would be -- makes sense pharmacodynamically or pharmacokinetically. It's much the same thing as when someone asked me, well, which antidepressant does this second-generation antipsychotic work best with for adjunctive use in MDD, and I have no answer for that either.

That's what I have, Dr. Citrome. I think you probably went through several of the questions already that we have from the audience. But if there's any that you'd like to pick, please go ahead because I was out for some time.

Okay. Let me scroll down here and make sure I covered. Yes. Yes, I think I basically covered most of these questions. What is the -- yes, what is the NNT for the CGI? Well, I can't wait to get my hands on that. I need categorical data and then calculate it. And maybe I'll do that if the data is provided to me.

Thank you, Dr. Citrome. I'll turn it back to Vimal now for some closing comments.

Thank you, Dr. Citrome, for sharing your perspective, and thank you as well to Sumant for your valuable contributions. Most importantly, I want to thank everyone who joined us today for your time and engagement. We are excited about the progress we have made with the SERENITY At-Home program and remain committed to advancing this potential new treatment option for patients and families who face the daily challenges of agitation as we move toward our planned sNDA submission in the first quarter of 2026. We look forward to keeping you updated on our progress. Have a great day.

Good morning, and welcome to the BioXcel Therapeutics SERENITY At-Home Phase III top line results conference call. [Operator Instructions]

Just 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 June 30, 2025, which can be found at www.bioxceltherapeutics.com or on www.sec.gov. As a reminder, today's conference is being recorded.

Joining us today on today's call are Dr. Vimal Mehta, Chief Executive Officer; Richard Steinhart, Senior Vice President and Chief Financial Officer; Frank Yocca, Chief Scientific Officer; Dusan Kostic, Vice President of Medical Affairs Strategy; and Dr. Matt Mandel, Vice President of Clinical Development. We will also be joined for Q&A by Dr. John Krystal, Robert L. McNeil, Jr. Professor of Translational Research and Professor of Psychiatry of Neuroscience and of Psychology at the Yale School of Medicine.

It is now my pleasure to turn the call over to Dr. Mehta, the CEO and Founder of BioXcel Therapeutics.

Thank you, operator. Welcome, everyone, and thank you for joining our call today to discuss the results of our SERENITY At-Home Pivotal Phase III Safety Trial. The 120-microgram dose of BXCL501 was well tolerated in patients with episodes of agitation in the outpatient setting and met the primary objective. This outcome was observed across repeat dosing and through the duration of the trial. We are extremely pleased to share our trial outcome, which we believe represents a significant milestone in bringing a new treatment option for home setting in the bipolar disorders or schizophrenia-related agitation.

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Agitation associated with bipolar disorders or schizophrenia is a debilitating condition for patients and threatening for health care providers. Current treatment approaches are suboptimal, and there is no FDA approved therapy in the home setting. Most episodes of agitation occur at-home and may escalate to the severity that requires emergency room visits. The early intervention in the home setting may potentially prevent escalation of symptoms, reducing the year with its hospitalizations and use of emergency interventions.

Our initial estimate of 23 million agitation episodes at-home was driven by claims data, which we believe are likely under reporting the incident. Our market research as well as a published patients survey suggest an average frequency of 3 to 4 episodes per month, representing a larger market opportunity. We believe patients experienced an estimated 57 million to 77 million agitation episodes in the home setting annually in the United States. The number of episodes observed in our At-Home trial is in line with the frequency of agitation efforts.

With today's positive data, I want to take a step back and look at our holistic SERENITY program. We observed favorable and consistent efficacy and safety data across 2 SERENITY trials, SERENITY I and II, which resulted in approval of IGALMI at the 120- and 180-microgram dose in medically supervise setting. To support the potential label expansion for home use, we conducted the SERENITY At-Home Pivotal Phase III trial. We are pleased with the results obtained today and preparing for the sNDA package for planned submission in Q1 2026.

As a reminder, the focus for expansion of the IGALMI label is on the 120-microgram dose, the lowest approved and marketed dose.

With that, I will now like to turn the call over to Matt.

Thank you, Vimal. Good morning, everybody. There are no FDA-approved therapies for agitation associated with bipolar disorders or schizophrenia in the at-home setting, and the SERENITY At-Home trial is a pivotal step on the journey to bring new treatments to an unmet need with a label expansion of IGALMI. As a reminder, IGALMI is FDA approved at 120 and 180 micrograms for the acute treatment of agitation in these populations, sublingual or buccal, with use today occurring under health care supervision.

Our At-Home study evaluated the approved 120-microgram dose. Across the study, we acquired data on 2,628 agitation events with more than 2,400 treated episodes. On average, patients treated 11.6 episodes. Patients self-administered all doses successfully, indicating that though they were experiencing agitation, they can reliably administer the film. Agitation is unpleasant for patients, and they're motivated to treat it.

BXCL501 was well tolerated across multiple administrations throughout the duration of the trial, with no drug-related serious adverse events, no excessive sedation and no fall. The overall adverse event profile was remarkably consistent with the approved IGALMI label. Additionally, patients experienced consistent benefits with repeat dosing throughout the study.

Adults with schizophrenia or bipolar disorder living at-home were randomized 1:1 to take BXCL501 120 micrograms or matching placebo. The primary objective was to describe the safety and tolerability of use when needed over a period of 12 weeks with an exploratory assessment of continued benefit. Patients with and without reliable informants like family members were enrolled. By design, the study captured safety data in the context of outpatient use to reflect common strategies that patients use to treat their agitation.

Patients were allowed to employ alternative interventions, which commonly include other medications, meditation, exercise, alcohol or cannabis. This was a rigorous outpatient study, which required multiple contacts every week for investigators to monitor patient safety and record episodes. Enrollment included eligibility reviews to ensure each patient met all inclusion and no exclusion of criteria.

Adults aged 18 to 75 were enrolled with schizophrenia or schizo effective disorder or bipolar I or II. All were on stable psychotropic regimens for at least 30 days and experienced 3 or more agitation episodes in the prior 3 months. Patients were excluded if they had unstable medical illness, had moderate or greater substance abuse or agitation driven primarily by acute intoxication.

Baseline characteristics were balanced between treatment and placebo. The mean age was approximately 47 years old in both groups, with sex, race and ethnicity evenly matched. Diagnoses were evenly split between schizophrenia and bipolar disorder. About 20% of patients had an informant or caregiver. The average time since diagnosis was approximately 17 years, which reflects the fact that these patients are familiar with agitation and how they treat it.

This study captured 2,437 agitation episodes experienced by 208 patients, 81% of those patients completed the full 12 weeks. On average, patients experienced 11.7 treated episodes each, and each patient was able to successfully self-administer the film.

Overall, BXCL501 was well tolerated in the at-home setting. Importantly, there were no discontinuations due to drug-related adverse events or tolerability. The adverse event profile was consistent with the approved IGALMI label, with no new or unexpected treatment-emergent adverse events identified. There were no drug-related serious adverse events, with no falls or syncopy events in the BXCL501 arm. All treatment-emergent adverse events were mild to moderate in severity. The drug was well tolerated across the 12-week period.

Somnolence was the most common adverse event at 22% overall incidents in the single-dose Pivotal SERENITY I and II trials, which form the basis of our label. As predicted in this outpatient study, somnolence was once again the most common adverse event, with overall incidence of 22%, which matches the incidence in SERENITY I and II. With repeated dosing, as shown in the last 2 columns, it was an even lower incidence of somnolence.

This held true for the incidence of other TEAEs as incidents for first dose was comparable to the single-dose SERENITY I and II trials. The adverse event incidents remained low with repeated dosing.

So this table shows treatment-emergent adverse events broken out by a number of doses. The columns show adverse events overdoses 1 to 3, 4 to 12 and 13 or greater. The incidence of adverse events does not increase with increasing use. For example, somnolence, being the most common adverse event, does not increase, but actually appears to decrease with repeat use. In fact, most treatment-emergent adverse events, the incidence of those tends to decrease over repeated dosing.

As you can see, when broken down by study week, from the first 4 to the last 4 weeks, and as reflected in this table, the incidence of TEAEs did not increase over the 3-month trial period. Somnolence, paresthesia, dizziness and dry mouth, all showed a similar pattern of reduced incidents over time.

Data from more than 2,400 episodes includes patient and informant assessments of agitation. Our exploration of this data demonstrate that BXCL501 was well tolerated and provided continued effect and consistent benefit across repeat dosing over the 12-week trial. Complete announces of the full data set are ongoing.

In summary, BXCL501 was well tolerated with multiple repeated dosing across the trial. Outpatients successfully self-administered the film as needed for agitation at-home. There were no discontinuations for tolerability and the incidence of AEs were remarkably consistent with the current label. While we are focused on analyzing this large safety database, we look forward to presenting the full data set, including exploratory endpoints in the near future.

Now I'll turn it back to Vimal.

Thank you, Matt. As our next steps, we will share our data. It's a lot of data on over 2,400 episode that we have collected that were treated in multiple scientific presentations. We have already started combining the sNDA for -- it's a work in progress, and we plan to submit it in Q1 of 2026. And at the -- in parallel, we are developing our commercial strategy if this drug is approved, that how we're going to bring this medicine to millions of patients who are in high unmet need in the home setting.

Thank you all for joining us today and for your continued interest. The results we have shared mark an important step forward in our commitment to patients, family members and advancing a label expansion for IGALMI in the home setting. We remain focused on the path to the sNDA submission and look forward to keeping you updated as we move ahead. Thank you again.

[Operator Instructions] Our first questions come from the line of Elemer Piros with Lucid Capital Markets.

Congratulations. My first question is regarding your observation of the number of episodes per month. I think the previous reference of 1 to 2 episodes came from Symphony claims. And how reliable those estimates were in your view? And the current observation of 3 to 4 episodes per month, is that congruent with your previous post-marketing study that you conducted?

Yes, thank you for the question. So we do feel that the estimate based on the claims data is actually underestimating the number of episodes, mainly because there is nothing approved by the FDA. So the claim -- for something to be in the claim, there needs to be either prescription or a contact with a health care provider. So we thought that the more appropriate and more accurate measurement was done in market research. So we did a market research with about 80 patients, and they indicated that they are experiencing about 3 episodes per month. There is also survey, patient survey published in a medical journal that looked at about 500 or 600 patients, and they also indicated that their average number of episodes per month is actually closer to 4, somewhere between 3 and 4, but closer to 4. So the number of episodes that we are seeing in our study is fully in line with that 3 to 4 number.

And so the second question is about your preliminary assessment of the efficacy of the drug. I think you used the modified CGI or global impression of severity scale. If you could tell us a little bit more of how it's done. What does the scale look like? And how does it compare to when a physician assesses the efficacy [indiscernible]?

Yes, sure. So we couldn't really send the trained raters to patients' homes when they had episodes. So we couldn't really use the same instrument that we used in our original SERENITY trials, which does require a trained rater, health care professional. So we were looking at what to do. We did some qualitative interviews and in -- also in discussions with the FDA and with the patient groups, we realized that a simple scale from 0 to 3 would be most appropriate for use in this patient population. So we are talking about 0 being no agitation, then 1 being mild to moderate, and 3 severe.

So patients will basically just evaluate and assess and say, well, my agitation was, let's say, severe or moderate at the beginning of the episode and 2 hours later, it was -- it either stayed the same, got worse or it became mild or there was no more agitation. So that was the scale. How it compares, obviously, it is -- it's not a trained rater. Trained rater would probably give a better assessment and what's also very important, the scale, the PEC scale that was used for initial approval goes from 5 to 35. So it's very granular. It's very -- it has 5 items. So it's much more precise for assessment than this scale, which is not that granular.

And my last question here is, there were discontinuations, and you mentioned that those were not due to treatment-related or adverse events. What were some of the examples for discontinuation?

Well, as usual, in this patient population, and by the way, this rate of discontinuation is really good for this patient population over 3 months. But as I said, as usual, the most common reason for discontinuation from the trial is lack of follow-up. The patient moved, did not show up at the site and so on. So that's the most common reason. Then there was a number of reasons where -- which encompass 1 or 2 patients only or 3, like 3 patients got pregnant, some patients didn't follow the protocol and so on. But really, there were no discontinuations for any drug-related events, be tolerability or efficacy.

And I get back onto the queue, but maybe a follow-up if we have time, to the physicians on the call. What are some of the off-label alternatives? Obviously, there is nothing approved at the end of your at-home setting. If they could explain or explore that topic.

Yes. So essentially, the options out there are antipsychotics or benzodiazepines, both of which have their downsides, if you will, but nothing approved as we have previously stated.

Our next questions come from the line of Ram Selvaraju with H.C. Wainwright.

Congratulations on this data, very important landmark development for the company. Just wanted to ask about what your current thinking is regarding the FDA stance with respect to the at-home setting, particularly as the agency looks at ease of use in the at-home context? And if you can highlight for us any practicable differences with respect to at-home administration of this product versus the institutional setting.

So we announced very recently, I believe, on August 16, that we got alignment with the FDA. We had a planned meeting with the FDA for August 20. We received our preliminary meeting comments. And when we looked at that and our goal was to get alignment on content and format, what is needed to submit an sNDA. So we ultimately decided to -- that this meeting is not required anymore. And the meeting minutes we received becomes the official record.

So in terms of what is needed for the sNDA, this Phase III trial, which we announced the results at-home, is paramount and critical. And we are very pleased the results we have received in terms of the tolerability for the drug that we announced, and we will submit -- analyze all these data and submit to the FDA.

In addition to that, CMC package, there is one difference between the in-care setting and the home setting in terms of the pouch, which holds the film. It has -- it's childproof, so patients have to cut it in the home setting, and you saw that we recorded more than 2,400 episodes where patient self-administered the drug. So that's very encouraging.

And then third is nonclinical section, which we have already written up in for the sNDA. And once CSR is ready and some of the data for the CMC that we will put together, we will submit the sNDA package to the FDA.

And then maybe can you comment at this juncture on -- based on the strength of the data so far, based on existing familiarity with 120-microgram dose, how are you thinking about commercialization options at this point in time? And have there been any developments in your thinking on that front as you look at the U.S. market, in particular in the context of the previous commercial history with BXCL501?

We have been focused on completing this Phase III trial. Now this trial has been completed, and we are very pleased with the results we have received. Our next focus is sNDA submission, as I mentioned, and then develop our commercialization strategy, which can be a multipronged strategy, which could include working with some strategic partners who may have established footprint to 50-50 relationship, to self, like we doing the commercialization.

So at this point in time, we are keeping all options open. And as we progress, we will update that, which is the most optimal option. As you saw, the number of episodes in the home setting is large, plus we have a drug already approved in the institutional setting. We want to make sure we have right kind of a footprint to bring this medicine to as many number of patients as efficiently we can.

Great. And then lastly, I just wanted to ask about, as you're thinking about future indications for 501 beyond the schizophrenia and bipolar disorder context, and especially within the context of treatment of acute agitation episodes in patients with dementia, maybe you can comment for us on not only the ramifications for future developments coming from the SERENITY At-Home study and being able to define safety in this at-home population and what implications that might have for the future clinical development path of this asset in the dementia population with acute agitation, but also the FDA stance as it has pertained so far to IGALMI/BXCL501 in the neuropsychiatric setting and how that provides a potential template for the cost-effective development of 501 in the future in dementia patients.

Alzheimer's agitation, as we all know, is a very large unmet medical need. Our estimate there is even bigger than the schizophrenia, bipolar, almost more 100 million episodes, what we know today, our estimates. So -- and already in that program, we have one positive Phase III trial, demonstrating the safety and efficacy for 60-microgram dose. So that's extremely encouraging.

We have alignment with the FDA to initiate second confirmatory Phase III trial using the 60-microgram dose. We have a protocol agreed. We -- it will be a 150-patient trial with 75 patients in each arm. And the only difference compared to our previous TRANQUILITY Phase III trial is that we will be using all kinds of Alzheimer's patients. So in our previous TRANQUILITY trial, II trial, we had patients who live in the assisted living facility. Now it will encompass assisted living facilities, memory care centers as well as nursing homes. And this will -- and all kinds of spectrum of agitation, whether it's mild, moderate or severe.

So since we have demonstrated one positive Phase III study, we are like ready to go and start our second Phase III study. We are currently evaluating our CRO choice, and we have the protocol in alignment and now having completed the SERENITY At-Home Trial, we will have internal resources available to be able to initiate the trial.

So it's a very exciting program. It's a large opportunity. And considering that we have already demonstrated, now safety in a home setting for the first time until now, all our trials, which are over 10 trials were conducted in the institutional setting. So it's a very major milestone for a drug that was in a -- sitting in an ICU unit and then we brought it to the institutional care and now it's going in the home setting. So it's a very major step, and safety data is extremely encouraging. We are very much encouraged.

So initial next Phase III trial will be in the in-care setting, like as I mentioned, ALF, nursing home or memory care. And once we demonstrate the Phase III data, then we will conduct similar kind of a home setting trial in Alzheimer's agitation, which will be, again, we'll get alignment with the FDA, it will be a safety trial, so that we can cover patients who live in the home setting and patients who live in the in-care. And all of us know, most of the biggest reason for Alzheimer's patient to go in the nursing home or ALF is agitation or their underlying disease, Alzheimer's. So it's a very major step, the data we received today, to have conversations with FDA.

Congratulations again.

Our next questions come from the line of Graig Suvannavejh with Mizuho Securities.

Congratulations on the data for this At-Home study. My question really has to do more about the company and where it currently stands with regards -- now having the data in hand, what kind of options the data open up for the company, especially in light of where the company is currently with respect to its cash balance, current OpEx spend.

Could you give us a sense of what kind of financial options or opportunities this might open up for the company, given -- I believe your cash levels may currently be supportive of a runway through maybe the balance of the year, but maybe not beyond. And if you're looking at a filing in terms of first quarter of next year and on the assumption there's a 10-month review for that sNDA. Just can you give us a sense, Vimal, of kind of the strategy around financing the company.

Graig, that's a very good question, and we continue to evaluate various options. Having this data -- positive data opens a multiple optionality for the company in terms of bringing this medication to the patients. So that could include strategic partnering, that could include royalty deals, that could include financing. All options open up. We are very pleased that we have multiple options, and we will work in the interest of our shareholders to maximize the value, the option that will deliver the value.

But today, we are very excited that we have this data, and we are on the journey to bring our current drug, IGALMI, like an expanded label in the home setting. So I would say that it's a very exciting day for the company to have all these options opened up, and we will provide the street update as we move along. And we will be very pragmatic about it, what makes sense to maximize the value for our shareholders.

Just as a follow-up, if I could, just on this topic. You've got the data in hand. It seems to me that the next key event for the company will be the submission of the sNDA, and I don't recall of any other data events throughout the balance of this year. And with that in mind, third quarter results typically get announced by the company in November. I'm wondering if we should be expecting or planning an update from the company before you next announce third quarter results?

I don't think, Graig, I will be in a position today to announce what updates we can provide, but we will be working and have been working on multiple options, and they are in front of us, and we will decide what makes more sense.

Congratulations again on the data.

Our next questions come from the line of Sumant Satchidanand with Canaccord Genuity.

I have 3 questions, 2 for the company and 1 for Dr. Krystal. I'll start with the one for Dr. Krystal first. In real-world use cases, at what point in an agitation episode do you think it would be optimal for a patient to use this product? And what percentage of agitated patients that present themselves to you, would you prescribe this product for?

Sumant, I'm just -- we are just checking if there is any technical difficulty. I want to see that if Dr. Krystal is on the call.

Sure.

You can hear me now?

John, your line is now live, yes.

Okay. Okay. Great. Sorry. All right. So I apologize for the technical glitch there. First, I think it's important to take a step back and say that agitated behavior is among the most disruptive kinds of behaviors that can happen in home. It not only motivates patients to seek higher levels of care, such as emergency rooms and inpatient hospitalization, but it can profoundly undermine the relationship of patients and their caregivers and actually destabilize home living situations as caregivers become -- feel threatened or frightened about managing these challenging clinical situations.

And sometimes, this can lead patients to have to leave their current living session and find other places to live. So it's a very high priority issue.

So the question about the optimal timing of dosing in episodes of agitation is an important one because, obviously, the goal is to prevent these blowups from occurring at home, which can have such negative consequences. And so as patients are experiencing rising distress and feeling themselves become agitated at the early stage is when you want people to be intervening to stave off these episodes of agitation if possible. And it's my sense that patients can monitor themselves and caregivers can provide constructive feedback.

And one of the nice things about IGALMI, given its tolerability and safety profile, is that it's an intervention that's likely to be used. And adjunctive antipsychotics, when used for agitation and sometimes even the benzodiazepines, carry with them certain side effects that patients sometimes find unpleasant, and making them less interested in taking these extra pills when they're experiencing an episode of agitation. And I think that's really an opportunity for IGALMI to be utilized in these episodes of agitation.

The question about what percentage of patients would it be prescribed for, I think it's really a difficult to answer -- a question to answer precisely. But clearly, those patients who are having meaningful -- clinically meaningful episodes of agitation at home would be great candidates for it. And I think it's very promising and something I would consider for my patients that are experiencing those episodes.

So now for the company, how closely do these data confirm to the alignment that you reached with the FDA? And what do they mean for your confidence to get supplemental new drug application for At-Home use approved by the FDA?

And second, we see the percentage of adverse events involving somnolence go down over repeat dosing. Why do you think that happens? And do you have any initial thoughts on how efficacy might trend with repeat dosing?

Yes. Thank you. So we had an agreement with the FDA about the protocol. I mean, any comments that they made on the protocol be incorporated before starting the study. So we are fairly comfortable that we are answering all the questions that FDA has asked, and that the results of this trial will, as planned, form the backbone of our sNDA preparation and submission.

Regarding the question of the loss of efficacy because the tolerability got better. We -- one of the questions that we asked for this study was to look at the exploratory analysis regarding the effectiveness of BXCL501. So certainly an important question was, does the benefit that patients are experiencing continue over time and with repeat dosing? As we said before, FDA was very comfortable with the efficacy of 120 micrograms, but that was determined with a single dose. And we wanted to follow how this benefit behaves with repeat dosing. And as we announced in the press release, the benefit, the reduction in symptoms that we see with BXCL501 persistent throughout the studies, throughout the repeat dosing. We do not see any attenuation of benefit with higher number of doses. So you can say we don't really see any tachyphylaxis.

So this pretty much is similar to our post-marketing commitment study that we did with a higher dose in inpatient setting, where we administered up to 7 doses, and where we saw no tachyphylaxis or tolerance over 7 days [ that we end ] up to 7 doses. We now extended this to a much higher number of doses and to a much longer time period. So definitely, we feel that we have answered that question. At this point, of course, we will be doing an additional analysis, but the data are pretty clear at this point.

Our next questions come from the line of Samir Devani with Rx Securities.

Congratulations on the strong safety data set. I guess I've got maybe 3 questions. Just we've given us the average number of episodes. I'm just wondering what was the maximum number of repeat doses that occurred? And is there any concern about potential misuse or abuse? That's the first question.

Yes. So we don't -- I mean there was a wide number, but we don't really -- we haven't really looked at the number and the density of doses. I mean, as its 2,400 doses. Our primary objective was to look at the safety and be able to provide everybody and to announce the top line data for the primary objective. So these additional measures of the distribution of dosing, the density, whether people were taking it day by day or over a longer time period, we haven't really analyzed those data. The patients were allowed to take one dose in 12 hours, no more than that.

And to date, we don't really have any evidence of any abuse potential. The drug is not scheduled. Patients were taking it as needed. So we don't really have any indication of any abuse potential. But at the same time, we don't also have any information on the distribution of dosing at this point. This data will be coming up shortly when our statisticians have had some time to catch a breath.

Did any patient try to cut the dose in half?

Not that we are aware of. We have -- we don't know.

Okay. And then maybe a question for Dr. Krystal. Just in terms of trying to assess the sort of real-world uptake. I'm just wondering -- think about factors that may influence that uptake. And I guess things like driving restrictions, would that be a potential factor that would influence uptake? And what other factors could you consider?

Sure. Well, obviously, in terms of driving restrictions, the major issue there is the sedating effects of the drug. On the other hand, the data that we've reviewed are for patients with psychotic disorders who are agitated, who I would suggest are not a group of people we want driving anyway.

So I think my guess is that the sedation, to the extent that it occurs, is probably contributing to some of the benefit that some of these patients are getting from IGALMI. And so that I think in terms of real-world impact, I think when you are in an agitated state and need to calm down quickly, safely and tolerably, I think IGALMI can be a real value there to fill that need. And because it's relatively short acting and it's relatively well tolerated, I don't see it as having a negative impact on lifestyle, generally speaking.

Okay. That's great. And then just one final question for the company. Obviously, I appreciate that you're assessing your options, commercial options from here. But just maybe to give us a flavor of what might be required, what sort of infrastructure do you perceive being required to market this in the U.S?

So we have done initial assessment, as everyone knows that -- we had a commercial group. We launched IGALMI in the institutional setting. So we have a lot of inherent knowledge. While we were preparing what would be required for a home setting, our initial estimate and it's in our deck that we posted about the commercial opportunity, sometimes in mid-August, it will be about initial 50 to 70 sales rep that will be required to go to the market to initiate and launch the drug. And as we learn more, then we will expand.

But initially, that would have provided a good coverage to get this product out. And there is some benefit of product being in the marketplace. Our brand is there, patients have the experience as well as the physicians and the family members. So sometimes, we have seen currently, patients come back and say to the year and say, "I want IGALMI." So I think brand is building. And with this data and then upon getting approval when we get that from this FDA, between now and then, we'll develop a strong commercialization strategy. Unmet need is so huge, much larger than we originally thought, and it will make perfect sense to have a strong commercialization strategy that can bring this medicine to those patients.

Our next questions come from the line of Alec Stranahan with Bank of America.

Great to see the data. Just a couple from me. I guess, first, looking to the efficacy readouts later this year. I know you looked at CGI-I and SERENITY III Part 1, which actually showed us that significant improvement over placebo. Curious whether you'd expect an even larger separation here in SERENITY At-Home given the higher dose? And any I guess, similarities? Or is SERENITY III, maybe not the best comparator for what we should expect in the next readout?

Yes. Thank you for the question. Yes, definitely, I think SERENITY III Part 1 is not a good comparator, not only because it used a lower dose, but also because it was done in the in-care setting. So all the ratings were done by trained clinicians. So even though clinical global impression, CGI is sort of sounds the same. It should be noted that the one that we are using in this trial at home is -- has M in front of it for modified. So it has only basically 3 intervals for anchor points, from 0 to 3, while the clinician-rated scale has 7.

And in addition to that, the clinician-rated scale is basically based on the observations and the experience of trained health care professionals, while the modified CGI that was used in this trial is being assessed by patients themselves. So it's more sort of a patient-reported outcome. So it would be very, very difficult to compare across the trials for that reason.

And I would like to add in this trial, there is a 20% cohort of informants also. So we had agreed with the FDA, that patient alone as well as patients who live with their caregivers, so about 20% patients have the informant. So they also made the assessment. So when we have done full analysis, Alec, we will have the data from patient assessment as well as from the informant, and that was designed so that we can get data from both sources for this MCGI scale.

Okay. Okay. That's helpful. And then one more on somnolence. It looks like the placebo rate was actually meaningfully higher than in SERENITY I and II, in SERENITY At-Home. Do you think this is a difference in how it was reported between the 2 studies or maybe more due to patient characteristics in the at-home versus institutional setting?

Yes. Thanks. So I don't think that's because of the way it was important, I think -- reported. I think it's more because this was a pragmatic study. And as Matt mentioned in the design section. So the patients were really allowed to use all sorts of other coping mechanisms, including alcohol, cannabis, meditation and so on. So that's probably one of the reasons why you see a higher rate of somnolence in the patient group.

Also, we talked to some of the experts in the field, and they say that the fact that as somnolence is mentioned as a potential adverse event on the case report form may have contributed to that because patients may have expected it. And then it goes down quite a bit with repeated dosing when probably they realize they are not experiencing anymore. So those are the 2 factors that are possible. But of course, it's all the matter of speculation at this point. But it's really not -- we don't feel it's the matter of how the adverse events are reported.

Our next questions come from the line of Elemer Piros with Lucid Capital Markets.

Yes. Just a quick follow-up, please. In the exclusion criteria, I didn't see that you listed anything regarding cardiovascular background or limitation. Is that the case? And if you could comment on that, please?

Yes. So there were, I mean, so there was an exclusion for patients with any unstable medical illnesses. I mean, among those would include the cardiovascular as well.

Our next questions come from the line of Sumant Kulkarni with Canaccord Genuity.

I have 2. So in your latest 10-Q, you reviewed that you're running a 30-patient informant trial to evaluate correlation between patient information measures and the PEC score. Is there a way you could handicap the chance of seeing what might be considered an intuitive result on that trial?

So that trial is done. It's an open-label trial. We have already recruited more than 80% of the patients. And in that trial, design is very simple. That these patients are recruited with the informant, and then patient reports, trained rater reports, PEC measurement before and after taking IGALMI. Then a patient reports how they feel like with MCGI and informant.

And we have done -- it's an open-label trial, 80% recruitment, and we are trying to look for the correlation between the PEC and MCGIs because, as you know, MCGI is an exploratory endpoint, FDA agreed that 120-microgram has a well-established efficacy and safety, and we demonstrated the safety in our home trial today.

And also initial data is quite encouraging what we have seen, using the patient reported how they feel benefit from this drug. So this is a kind of saying the correlation study that we are performing for the measurements we have done in the current trial.

And my last one is actually a bit of a bigger picture, almost strategy like question. Given how much artificial intelligence appears to be intertwined in the company's DNA. With this data set, do you expect to use your engine to generate any maybe counterintuitive results or anything like that or anything that might generate new intellectual property?

Great question. So once our team, while this trial was going on, our AI team helped us identify various sites where the patient flow can happen. So AI was used there, and they've been building models using what unblinded data, what we were collecting. And now data has been unblinded. So they will be in a position to look for and do some analysis, which normally is outside the current method normally use. We'll continue to do that. Plus we will try to see if AI provides us any additional insight, both from a understanding the patient population, our safety results, our efficacy results, and we will update once we had a chance to do those analyses.

I'm showing no further questions at this time. I would now like to hand the call back over to management for any closing comments.

Thank you very much for joining us today. It's a very exciting day. We are very excited to move forward this drug, for submission of our sNDA, and have a great day.

Thank you. This does conclude today's teleconference. We appreciate your participation. You may disconnect your lines at this time. Enjoy the rest of your day.