BioXcel Therapeutics, Inc. (BTAI) Earnings Call Transcript & Summary

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.