Okay. Good morning to everyone here in person and those listening via webcast. Welcome to the BioXcel Therapeutics Commercial Day. My name is Matt Wiley. I'm the Chief Commercial Officer here at BioXcel. On behalf of everyone in our organization, thanks for joining. Today we're very excited to share our progress on the IGALMI launch and to share with you some early key performance indicators. We've also assembled a great panel for you today to share information on the evolving market dynamics as well as the value proposition for IGALMI. We hope that you find the presentation today to be both relevant and elucidating. As a reminder, during today's presentation, certain matters discussed may be 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. Today's presentation will focus on IGALMI, which was approved by the FDA in April 2022 for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. IGALMI has not been studied for use beyond 24 hours after the first dose. For detailed information about the risks and side effects, please see the full prescribing information and important safety information, which can be found at igalmihcp.com. Joining me today are Vimal Mehta, our Founder and Chief Executive Officer of BioXcel, who will provide an overview of the company and our disruptive approach to the agitation market. Brendan Schulte, our Vice President of Sales, who will share our progress on sales force deployment and the evolution of the sales organization. I will be providing several key updates on our IGALMI commercial progress, including strategic review and a summary of our activities since the trade launch in July. Today, I will also disclose some key performance indicators for the first time. In addition to our BioXcel speakers, we also welcome distinguished healthcare professionals to our event who will provide various unique real-life perspectives on the agitation market and their views on the unmet need for patients, caregivers, and the healthcare system. These include Dr. Sheldon Preskorn, who is President and CEO, World-Wide Clinical Psychopharmacology Consultation, and brings over 25 years of direct experience in neuropsychiatric drug development, spanning from principal investigator in clinical trials to clinical administrative experience as a supervising physician. Karen Sands, Adult Nurse Practitioner and Faculty Preceptor at Duke University School of Nursing, who will share her perspectives from over 32 years of experience in medical and surgical critical care. Dr. Jacob Hanley, who is an Advanced Practice Prescribing Pharmacist, Director of Pharmacy, and distinguished Chairman of the P&T or Pharmacy and Therapeutics Committee at Kedren Acute Psychiatric Hospital and Community Mental Health Center in Los Angeles, who will share his in-depth knowledge of complex health systems and how the pharmacy and therapeutics process works. Let's get started this morning by turning things over to Vimal Mehta, Founder and CEO of BioXcel Therapeutics. Vimal. Thank you, Matt. Good morning, everyone, and thanks for coming in person to join us and anybody who has joined us virtually. It's a very, very exciting time for the company as we transition from an innovation company to a commercial stage company. IGALMI is our first product that just got approved in April. Today we will be showing our approach to getting a leadership position in the agitation space, how we are progressing strategically, both on the commercial front as well as on our innovation front as we have multiple Phase 3 trials ongoing. In addition to that, our team, as Matt said, will show almost less than 4 months of progress since our trade launch when the drug became available in commercial channels. Exciting, what I call as a proof of concept, what we wanted to establish, considering there is no commercial precedent, there is no analog for a product in neuropsychiatric space that is episodic in nature and to treat agitation. There have been no innovation for over a decade in this space. This is extremely exciting and, I will give you a quick overview of the company, and then I'm going to pass it on to our speakers as well as our team to share the progress. IGALMI, as I said, it's been a decade since any product for acute treatment of agitation was approved. In four months, we continue to learn that agitation is a underserved and under-diagnosed market, and it's just not well-recognized. As you can all imagine that there is an innovation that can change the indication, and I couldn't think of any other indication better than depression. If you start thinking of depression market in 1980s, like depression market was not what it is today. Today, you have TN and 38 million prescriptions written for depression. What changed that? Innovation. The Prozac launch, other drugs that got launched that started changing the landscape. We believe that IGALMI is at that intersection currently. Also, we get put into the bucket that it's a hospital-based launch and all that. I think that is true, because these patients end up in the ER, and they need to be treated there. But this product obviously has a much bigger potential. We're just getting started and targeting the 16 million episodes that happen in the ER with IGALMI. What has been our journey, if you're not familiar with the company? We were set up to deliver innovation, and I truly believe we are the first public AI company that focused on neuroscience and immuno-oncology. BXCL501, which was our lead product, got approved in first two indications, and BXCL701, which is our immuno-oncology product, we already have done proof of concept. We're really proving why we were set up to take advantage of the data, you can bring drugs rapidly to the marketplace. What are we trying to disrupt here? Three parameters: R&D economics, probability of success, and timelines. That's exactly what we will be demonstrating, that IND to commercial launch in 4 years today. That's what our journey is. In addition, this is very important that this is the first oral film for treatment of episodic events. If you think about FDA history or you think of the neuropsychiatric space, episodic drugs have not been approved. Most of the time, neuropsychiatry has chronic drugs. We're shifting the paradigm, and we are working with our partner, FDA, to help achieve that because they also see there is a need for acute or episodic drugs to treat these patients as and when the event happens. We have built an integrated commercial team, which Matt and Brendan will talk about, and they chose a very dynamic model, a two-step approach. They said, "We're going to cover. We have 70 geographies to cover. We're going to cover 26 geographies in the beginning, develop the market experience, gain the market access. As we do that, in tandem, we will expand our team. That's what they will show that now they are going to cover all 1,700 hospitals, 70 geographies in 2023. 2022 was an approval year, as well as learn the market as much we can, as fast we can, and that's the progress you will see today. We executed on a strategic financing of $260 million with our partners Oaktree and QIA. That gave us the capital to capture our opportunity that is on the right side. There are 139 million episodes of agitation between these three indications that are listed, bipolar, one in two is schizophrenia, and Alzheimer's-related agitation. Opportunity is very large, and we believe we are very well poised to capture that opportunity. How are we going to do that? This 16 million episodes, we already have IGALMI approved. It's already commercially launched. There are 23 million episodes which are at home for bipolar and schizophrenia patients, and that is our next focus. What is new here? We starting the SERENITY III pivotal program once we got an alignment with the FDA, and I'm announcing today that top-line data readout will be expected in first half of 2023. We will have the data readout to show how we can move this drug from an institutional setting to at-home setting. That expands our market. It provides drug to broader set of patients. The next bigger opportunity, which is humongous, which is 2.5x 100 million episodes, is huge, and we are already on our way. We have two ongoing trial, TRANQUILITY-2 and 3. TRANQUILITY-2 is enrolling, and TRANQUILITY-3 will start soon. As we have said, the top-line data readout is expected in first half of 2023. Besides commercialization of IGALMI, which is extremely exciting, we will have two readouts from our pivotal trials which will expand our commercial opportunity to 139 million episodes. Just to give you a quick snapshot, our strategy in Alzheimer's-related agitation, we are focusing on acute agitation and intermittent chronic agitation, which is also a acute situation. It just happens more often. 501 is placed in that. There are two treatment settings, primarily assisted living and nursing homes, as well as at home, where these patients stay. One of the primary reasons for Alzheimer's patient to go to the ALF or nursing homes is because their agitation cannot be managed at home. If the agitation is not managed here, some of these patients end up in the hospitals also, like bipolar and schizophrenia patients. We are developing a wearable device to combine with BXCL501, so we can capture pre-agitation state, so IGALMI can be given in early stages. We have our BXCL502 program that will help us capture the chronic agitation. It's a completely novel mechanism. It was AI was used to identify. We haven't disclosed the mechanism because of the other people are developing drug. Once it goes through the clinic, we will share the mechanism for BXCL502. It just summarizes what are the key milestones we have been able to achieve from 2018 to approval in April, and our commercial success that you will see today will be less than 4 months since the launch. I just wanted to show that our team has been very executing on various milestones in a very timely manner, and it's been a great progress that a drug has gone to the marketplace, which already is helping the patients and the healthcare providers. A couple of words about IGALMI. You already know we have a very broad label. I want to make sure everybody knows it covers mild, moderate, and severe agitation. FDA granted us that label, and we truly believe, based on all the market research we have done as well as all the field intelligence that has come, it has a significant game-changing potential, which I already said that depression market did not evolve until in 1980s. I think this is a time for agitation. What have we achieved? I think we are well-positioned to maximize IGALMI's potential. We have received very positive market reception, which our team will share. Highly favorable market dynamics. Two reasons, the safety to the frontline workers, which you will hear from our KOLs. Physical restraining costs a lot of money. It costs legal liabilities. There are a lot of issues related to that. We are already gaining market access, and Matt will provide you what we have done in terms of our P&T reviews and where we are. In addition, as I said, we had a successful proof of concept with first wave of the sales team, and we are expanding into 70 geographies to cover all our 1,700 target hospitals. Thank you. With that, I will invite Dr. Sheldon Preskorn, who doesn't need any introduction. He's well known in the neuropsychiatric space. He's been associated with this drug from the preclinical development, translational work to clinical development, and he's first author for our JAMA publication. Welcome, Sheldon. Thank you, Vimal. Thank you so much. Thank you all for being here. I know that this presentation. First of all, I'm on a timer, so I'm going to endeavor to be finished in 20 minutes. I'm gonna be talking about psychomotor agitation. As Vimal mentioned and Matt mentioned, I've spent 45 years in psychiatry. I've spent about half of my time in the delivery of care through residents in residency programs. I've been in ERs, I've been in acute psychosis wards, I've been in outpatient clinics, which is what I primarily do now. The other half of my time was in drug development research. As a result of my first activities, I've literally been in 2 firefights in ERs. I wasn't the active shooter in either one. Unfortunately, two people died in the first one. I was held hostage at gunpoint by a veteran when I was a chief of psychiatry at a university-affiliated VA. I tore my anterior cruciate on the left side trying to restrain a patient who was trying to attack another physician. I personally know 10 people who have died as a result of attacks by agitated patients. In two recent experiences, I've had agitated patients in the last month in the outpatient clinic in which the patient was not doing well in terms of their psychotic illness. They came in somewhat agitated. I ended up with the resident talking to the patient, and we ended up saying, you know, "You're either gonna go into the hospital voluntarily or you're gonna go into the hospital involuntary. The question is not whether you're going into the hospital, the question is how." We talked through, and I won't belabor that 'cause I don't have the time, but this would've been a perfect situation to give IGALMI. In addition, it would have been a no-brainer from economic standpoint because the cost of the IGALMI was much less than having to call an ambulance, which cost over $1,000, and would have been less of a burden for everyone. Well, with that said, psychomotor agitation is associated with poor outcomes in patients with schizophrenia or bipolar disorder. As Karen will tell you, it's also poor outcomes for the healthcare providers who treat them. This shows you the prevalence of agitation, psychomotor agitation, and this shows you what the consequences are. Since you can read faster than I can speak, and since I'm going to try to get through this quickly, I'm not going to read every word to you. Next slide. Next slide. It's not working. Well, I could read every word for you. No. If somebody will advance the slides, that'd be great. Okay, the algorithm. When you're looking, like I was, looking at this patient who's agitated, the question is determine the need for pharmacologic intervention. By golly, slides went out. Once you've determined that, then you end up determining are they voluntary or are they involuntary. If they're voluntary, you may use up until the time of IGALMI a number of oral medications. The downside to those medications is that they can take time to act because it has to travel from your mouth to your GI tract. Depending upon the drug, it can, ironically, in the case of a benzodiazepine, disinhibit you. In the case of an antipsychotic, it can cause extrapyramidal side effects, some of which can look like worsening of your agitation. Now you're gonna need to back up two slides or so. The existing medicines have some limitations. What I was going to do is to describe the reason why IGALMI works in agitation. What I would show you here is I would show you the brain, and I would show you an area of the brain, which is the locus coeruleus. The locus coeruleus is a cluster of neurons, about 100,000, that exist under the floor of the fourth ventricle. This is your smoke alarm in your brain. Now, I'm not going to go into a long-winded discussion, but the brain actually is five brains. It evolved over 3 billion years, and when you got a brain stem, you had the locus coeruleus. The locus coeruleus regulated your respiratory drive and your cardiovascular output, and it sensed, it actually monitored your acid-base balance because if you were becoming hypoxic, then that would fire off. It would increase your respiratory drive. It would increase your cardiovascular system. As the brain evolved further and more brain came on top of that, it innervated up into those regions. Then when it fired, it increased arousal. That's what causes you to wake up in the morning. Your locus coeruleus, one of several things that cause you to wake up in the morning that changes you from sleep to consciousness. This is a real test of my remembering all the slides, but essentially what you will see is the locus coeruleus regulates everything from when you're asleep, the locus coeruleus shuts down, to when you start transitioning into wakefulness, the locus coeruleus starts firing, to when you become hyperaroused or hypervigilant, then the locus fires further. When you have a panic attack, if you think about the symptoms, you're thinking you're suffocating. You think that you're going to die. Your cardiovascular system goes up. You vasoconstrict, and your heart increases its firing rate. At that point, if we could go back one slide, we may not need to. Oh, we'll forget it in the interest of time. You shift from phasic pulsing of the locus coeruleus to tonic. You're continuously firing your locus coeruleus, and that's why you're in this panic attack. It regulates everything from going to sleep when it shuts down, to gradually waking up, to a normal level of alertness, to increased anxiety and hypervigilance, to episodic panic attacks. Then in the condition we're talking about, you're now in tonic firing, and you are in a flight or flight mode of action, and aggression can occur. This is the locus coeruleus. I've just described it. Here it is, cellular representation, the synapses. Normally this is a system in which it is carefully regulated because you see these little blue dots, that's norepinephrine. You see right here a receptor, which is what's called the alpha-2 adrenergic receptor, and that receptor responds to norepinephrine by decreasing its firing rate. It's a tightly regulated system in which it's got a governor on it, and the governor is the neurotransmitter that you have, and that's the reason why you aren't having panic attacks all the time or in a fight or flight mode. Dexmedetomidine acts like an artificial norepinephrine at that receptor and allows you to drive down the firing of the locus coeruleus. Very slick. This shows you normally you're in phasic. That means it's pulse firing. This is tonic firing. This is what happens when you get into a fight or flight reaction. The tonic firing causes anxiety-related symptoms. People are pacing. You have likely passed these people on the streets, and some of them, you might not move too far away because they're maybe talking to themselves a little bit. Maybe they're fidgeting a little bit. Now there are others, you're gonna move to the other side of the street because they're yelling out, they're marching up and down, they're making loud statements. You've encountered psychomotor agitation. Next slide. This simply shows you this system is a critical. By the way, it's in your brainstem because it's a very fundamental system to mammalian brain function. Deep sleep, drowsiness is all low to absent locus firing. Relaxed alertness, the firing rate's going up. The further you go to the right, the more your locus coeruleus is firing. We nicely know the physiology, and we can target the physiology underlying the psychomotor agitation. Now, in the interest of time, not going to belabor all the points of this, but in looking at dexmedetomidine, there were several characteristics. Why pick it? Good question. Well, one is this shows you maximal activity. This is. Norepinephrine will cause 100%. At the alpha-2 receptor, this causes 90%, or it's almost a full agonist at that receptor. Actually at the 2B receptor, it's even higher than norepinephrine, and it's as high or slightly higher at the 2C. This is a full agonist at the alpha-2 adrenergic three receptor subtypes. In addition, there is another receptor called I1 imidazoline, which is a receptor in the periphery that can lower blood pressure. We want something that decreases the firing of the locus coeruleus without dropping your blood pressure. If we look at clonidine and lofexidine, two other alpha-2 adrenergic agonists, you see that they're more potent. The smaller the number, the less the concentration of the drug you need to occupy the receptor. You can see that you hit that receptor before you hit the alpha-2. If you look at dexmedetomidine, this is the racemic mixture. It hits. The selectivity is 5,000 times. That means you would have to go up 5,000 times on the concentration before you hit that receptor, which is a direct flip-flop of what happens with clonidine and lofexidine, and that's the reason why they're more associated with or certainly consistent with why they're more associated with decreasing your blood pressure. Now, as has already been described, the delivery system is via a film. The nice aspect about this is you don't have to have somebody swallow a pill and then take the time that you have with gastric transit. Two, you don't have to come up to an agitated patient with a syringe and say, "Would you like me to give you a shot?" Because that, if anything, tends to elevate them. This is a measure of the degree of agitation. Anytime you do a study, you have to have a measure, obviously. Mild, you're nervous, you're tense, you're grumpy, you're anxious. You probably have felt that way in the last week or two, but not to a dysfunctional level. Insulting, frightening, in danger. That's the person that you may give a several feet pathway to when you walk past them on the street. Here, aggressive, violent, desperate, confused, you're going to cross over to the next side of the street. This shows you the PEC scores that are associated with that. In the case of the studies with IGALMI in agitation, they had to score a 14 as a minimum to be in the study. They're right at the edge of the distinction between mild and moderate. This is the person that I was seeing in the outpatient clinic. He, at this point, you know, was certainly trying to drive home a point. "No, I don't need to go in the hospital. Yes, I was up all night. Yes, I was disturbing the neighbors, but I don't need to be in the hospital." I'm going to tell this person they need to go into the hospital, which I did. It would've been at that point I could say to them, "So, Joe, we're gonna get an ambulance. They're on the way. We didn't have to get the police department because you agreed to go voluntarily into the hospital. I know you're feeling anxious. Would you like me to give you something you can place on your tongue and experience relief?" The reason why you do that is to prevent this. At this point, you've missed out. That's the reason why what you wanna do is treat early when you begin to see that person escalating, because as Karen will describe, this person who's now at severe agitation is the person who can inflict damage. One of the people that I know was a psychiatrist, was stabbed 178 times by his agitated patient, and then the patient ran over him with his car. That was severe agitation. It is a buccal adhesive film, and it doesn't matter whether it goes under your tongue or goes on your buccal mucosa, you're going to get 72%-82% absorption. It's very simple. By the way, if you swallow it, you don't absorb it. The half-life of the drug or maximum time to peak concentrations with that film is about 2 hours. That works very nicely because the drug is getting into your system quickly. It's gonna take about an hour for an oral medicine to hit your duodenum, where you can start absorbing it. This is already moving towards maximum absorption. The half-life of the drug in plasma is about 3 hours. Now, the biological half-life from the brain is about double that. That gives you a nice period of coverage. The two things you want, you want something. Well, actually three things. You want the patient to be able to administer it themselves, that way they have some sense of control. Two, you want it to get into the system quickly, so you begin to have effects. And three, you don't want it to persist for an excessive period of time. The results were highly statistically significant. BioXcel wouldn't have me here, you wouldn't be here if that wasn't the case, but it met its criteria. There were two studies done. They were exactly the same design. One was a group of patients with schizophrenia who were agitated. The other was a group of patients with bipolar disorder who was agitated. They were screened to ensure they met the inclusion/exclusion criteria, and then they were randomly assigned to either 120 micrograms, 180 or placebo. Exactly the same design. Again, the primary outcome was the change in the PEC score, which is the PANSS, Positive and Negative Symptoms of Schizophrenia, the excitatory component. This shows you the results. This is reducing agitation. This is time. This is the placebo group. This is the 120 micrograms. This is the 180. Notice that it became statistically significant at 20 minutes. We were already seeing separation. Didn't take 2 hours to reach maximum concentration. We were already seeing an effect. I'm gonna point out down here is your response rates. This is the reduction in scores. This is whether it's meaningful, and that means that you actually have responded. It was 34% for placebo. Why 34% for placebo? Because in those mild patients, you talk calmly to them, you put them in a quiet environment, you give reassuring statements, and that will work for some people. You don't engage them in an argument. That would be the opposite direction. A hundred and twenty, sixty-seven percent, a hundred and eighty-seven percent. To translate that into meaningful numbers, it means you need, in the case of the 182 people to get one additional person better. In the case of the 120, it means you need three patients to get one patient better. Oftentimes, we think about placebo meaning nothing. In point of fact, placebo means everything except the investigational product. This shows you, and I'm gonna go through this quickly. This is the clinical global. This tells you that the investigator, without using a rating scale, could pick up that the person was getting better. It's completely consistent with what you saw with the PEC scale. This is the side effects. As you might expect, it's decreasing locus coeruleus firing going downward, so you can get some somnolence, hypotension, and orthostatic hypotension. Notice that a small percentage, it was moderate. Somehow they left out the other curve. We had the curves for bipolar and schizophrenia. They probably left them out because you would think you were looking at exactly the same curve because they're exactly the same. All right. Summary. There is a significant unmet medical need. We now have a treatment that meets the criteria that consensus leaders before IGALMI came around, which was non-invasive. You don't have to stick a needle in somebody. Calmness without unarousable sedation, easy to administer, which the patient administers to themselves. Rapid onset, non-traumatic, non-coercive, a good safety profile and patient preference. Oops. Go back one, if you don't mind. This simply summarizes what Vimal told you. I went two minutes over, but I blame it on the slides. At any rate, thank you so much. Now I turn it over to Karen, who will come up and say a few words about her background because she's truly on the front line, and she's the nursing staff, and she's had to deal with the injury of her colleagues. Thank you so much. Thank you. My name is Karen Sands, and I have 34 years in the nursing profession, and I have had patients across the entire agitation spectrum, from point of entry into the hospital to death. I have 30+ years of critical care ICU experience and the last 2 years of my practice have been I work as a nurse practitioner hospitalist in the organization where I work. I thought I knew agitation and delirious patients working in a critical care environment. When I moved to the emergency department, I really. My eyes were opened after working in healthcare for 30 years. The next 15 minutes, I want to take you into the life of what the nurse deals with on a daily basis. The nurses are the frontline defenders. Obviously, you need the providers to put the plan of care in place and to order the appropriate medication, but it's the nurse at the bedside that's carrying out the care. That kind of goes over my career there for the past 34 years, 35 coming up. When we've got a patient that's agitated, when we look at that agitation spectrum, it is so key that our nurses know and have in their toolbox the ability of a drug that's gonna be easy to administer and take quick effect and that you calm down a situation before it gets to a situation where violence and assaults occur. That is when the patient is starting to have that fluctuation and a change in their mental status. They're becoming very confused. They may have alternate levels of consciousness, being hyper or hypo. You know, you really have to determine, especially in this patient population, your bipolar and schizophrenic patients. They have many of them have a combination bipolar schizoaffective disorder. It's a combination of the two diagnoses. These patients are extremely difficult to manage. It's key. It's key to have a tool in your tool chest to be able to treat these patients appropriately so that we don't have to escalate care to a higher level of care. Now, I believe that a picture is worth a thousand words. Yes, we're dealing with humans, but I want you to think about that agitated patient that is on the verge of becoming violent. You talk about, you know, the patient walking down. You're walking down the street, and, you know, you're thinking about going to a different side of the street or giving them a little bit more room. Well, I'm talking about the nurse. I'm talking about the nurses at the bedside. We don't have an option to go to the opposite side of the street. Our option is we go to the bedside, you know, and this is our scenario. We're taking care of this patient. Our key that the nurses need is we need to stabilize the situation. We need to deescalate the agitation that's going on, and we need something that's gonna act rapidly and quickly. You take that patient that literally has the strength of Goliath, I mean, just roaring, raging mad, that becomes aggressive. Press Ganey just recently reported out, you know, how many assaults and violence are happening in the hospital on a daily basis. It's over 50. They looked at 400 and some hospitals out of 6,000. Out of those hospitals that were reviewed, over 60 assaults on a daily basis, over 1,500 on a monthly basis, and in just a quarter, over 5,000 staff people are being injured by these patients. What we wanna do is we wanna take this visual picture, and we've got the enraged patient that's agitated, and we want to be able to get them to a more calm, cooperative state, so that we can provide the care. When we're talking about the team, everybody on the healthcare team is important. even though I'm a provider at this point in time, I will always respect the nurse at the bedside the absolute most because they are the front line, and they do have a need. Their predominant need is you've got this wild, agitated patient, and what you want is you want a tool in their toolbox that they can pull out to utilize. To get that patient quickly under control. Because guess what? In the emergency room and in these different settings that we're talking about is having these patients, they don't come in for a social visit, guys. You know, they're sick. You know, many times, you know, when we're talking about the patients in the emergency room, they're coming in because they've got multiple health reasons. It's not just because they're agitated. Now, some patients coming into the ED are just because they're on that agitation spectrum, and they're just escalating, and they come in for just that management. As far as most of our patients, you know, they've got an additional acute illness. The nurse has the need to have a patient that's calm and cooperative so that they can carry out the plan of care that has been ordered. Then the pharmacy, as you'll hear here in just a few minutes, the pharmacy, you know, their goal predominantly is looking at the pharmacokinetics of the drug, getting it on the formulary, getting it on to the education to all the staff members in the hospital and everything, and ultimately doing a cost analysis to make sure that we're making a financial decision that will be good for the healthcare center arena. You know, the physician and us providers, essentially, we come in and we want to be able to quickly assess the patient and determine, can we move that patient to a lower level of care? Can we get this patient home? In an emergency department, what we're wanting to do is get that patient back out the door and not ever admit the patient. What I wanna talk to you about is using a medication like IGALMI to stop this kind of train that's headed for disaster. We want, you know, a drug that's easy to administer, has a rapid onset, it has very few side effects, it's cost-effective, and more than anything, we don't oversedate that patient. Because if there's anything that I have learned in the 30 years plus that I have been in the healthcare arena, oversedation is a real thing. It happens every day in many facilities all over the world, and it's because we did not implement the medication options in a timely fashion. We've now got a patient that's enraged, agitated. Think about that lion that's getting ready to just completely attack, and that is what these patients are. They are violent. What ends up happening is they get an IV injection or IM injection to the dosage of that they become oversedated. Now they're somnolent. Their lights are out, nobody's home kind of thing. That patient now has the potential to develop hypoxia. Because their level of consciousness is so impaired from the sedation agent that we've used, you know, maybe they're gonna aspirate their own saliva, so now you've got aspiration. That can ultimately lead to the fact that the patient needs to be intubated, placed on mechanical ventilation, and taking up an ICU bed. Well, boom, right there, you've just cha-chinged $7,000-$9,000 just for having a patient intubated in an ICU arena. Some goals that, you know, when you're talking about having tools in the tool chest for the nurse is, you know, you want a drug that's gonna deescalate that agitation. You want all that fight and flight response. You want something that's just gonna calm the patient down. But support the respiratory status. You wanna know that you've got a drug that's got an expected dose response, which I'm gonna talk about. Dexmedetomidine, IGALMI, is an awesome option for our future and our patients. When we look at the goals and considerations when we're managing agitation, one of the key things, you know, I've been in the healthcare arena long enough that I've been on multiple committees, and cost and length of stay is totally a real thing. Everything that you can put in place to prevent an additional cost or an additional charge to the system is so beneficial. Choosing that right drug is most beneficial because it's going to impact the whole. You can't just look at a piece of the pie and think, "Okay, I'm just gonna do this, and it's not gonna affect the rest of the hospitalization." It is. That's the reason why we want to relieve the patient's anxiety. We want to treat them. We want to get them compliant so that they can actually participate in the care. There's a lot of variables that come into play when you're trying to treat this agitated patient because they're confused, sometimes disoriented. You know, maybe they haven't slept for two or three days, and that's why, you know, they've gotten already to this agitated state. It's just a constantly changing environment. It's very, very hard to take care of this patient. When the patient is enraged, when he talks about locus coeruleus, you know, when those neurons are firing, this patient is in that fight or flight mode. We're talking about beads of sweat. You know, they're diaphoretic. Their heart rate's up. Their blood pressure's up. They're trembling. I mean, they may be pacing the floor in the room. You know, you may maybe see them start hitting the walls. I mean, these are things that aren't uncommon. I wish I could write a book because I'm telling you, it would be a bestseller in that I can't make this stuff up. This is real life. It's very challenging to take care of this patient that's having all these symptoms. They're very agitated. The nurse needs a medication in their toolbox like IGALMI. It's a very tightrope that we have to walk, and it's very much a balancing act. We want to decrease the potential of the patient needing to be transferred to a higher level of care. This medication, you know, is an option that could treat the agitated patient and not have to worry about going to a higher level of care. Today, today's time, many times the patients are dosed with IV sedatives or IM sedatives, and the patient becomes somnolent. They have to go to that higher level of care. You've got a patient that was wild crazy, kicking and everything, and now you've got a patient that just, that's just laying there in the bed. Now you've got the potential for developing blood clots, healthcare-acquired pneumonia, and the need for additional dosing. Because guess what? You've had to give them so much that now, you know, they're asleep, and they're not waking up. We're like, "Oh my gosh, has this patient had a stroke or a neurological event?" Now we have to send them down to the MRI scanner to scan their head just to make sure that that hasn't occurred. All of those things impact the whole. It's very much a challenge in the ED. The patients come into the ED for multiple medical reasons, and here's just a list. That agitated, delirious patient is the patient that, you know, has schizophrenia and bipolar disorder in addition to one of these things. Just put that in perspective. You, you've got a patient that's already has a disease process of agitation with the bipolar and schizophrenia. Now you've put an acute illness on top of it and you've got a huge problem. As far as the prevalence of this patient population, it's printed in the literature anywhere from 20,000-60,000 patients with a combination of the two groups of patients. But the problem is there's a huge potential of patients who have this disorder that have never been diagnosed because they use polysubstances to self-medicate and treat their selves. Would it not be awesome to have this as an option for them to have in the community? It really would. It's very challenging for the providers in the ED just because of the workload, the stress. The ED and the critical care units, these are areas in psychiatric wards that, you know, people don't come for social visits. I mean, they. You know, it is constant chaos and stress and crisis going on. You can only imagine that there, the providers that work in those areas, there comes a point where you're burnt out, like, you know, can we not do something different? For the nurses, you know, it's at a crisis level. We're at a very much of a nursing shortage, and the staffing is, you know, it's hard to staff for these patients because you've got a patient over here that has gone crazy. On that agitation spectrum that they go from 0 to 200 in two seconds. You know, every hospital system has a code that you call overhead. Essentially, what you do is, what that code means is that everybody that's available, come to this room now because we need your help. Essentially, all the safety guards, all the men, women, you know, that are available come, and we're having to physically restrain this patient that is actively trying to assault the staff. That is a live scenario that happens, I cannot tell you how many times a day. I'm not even being funny. It's so many times a day. You've got that patient. You don't have telemetry beds to monitor these patients, because once you oversedate them, you're gonna have to monitor them then. Because now you've got a patient that you question, can they protect their airway? You're gonna have to monitor those patients. You're having to escalate up to that higher level of care. The ED nurse is just like, "When can I move this patient? Please, God, can I please get this patient out of the ED?" Because they don't just have that one patient. They have five other patients. It's a huge challenge. I could give you 3,000 case scenarios, but I wanna give you three just to kind of give you a picture of what life is really like. First scenario, nurse I work with, I think she was about four and a half, five months pregnant. This patient was in with sepsis and had not really shown any agitation prior to the morning of the event. Patient did have bipolar disorder, was on the medications that they normally took at home, but just with the switch of a light, you know. I mean, this guy just attacked the nurse. He took her arm, and it was like the force of a jackhammer. I mean, it was so violent. He pulled her arm so hard that it literally dislocated the elbow from the arm. She lost all sensation and touch and all the fine motor skills in her hand. Was out of work for 3 months from her just being completely out of work. She came back to like a clerical job. She couldn't even use her hands for using the computer or anything. We have a nurse now that's out of work six months, in a workforce where we're already strained for nurses at the bedside. Craziness. Had we had IGALMI to use in that scenario when that patient started getting agitated earlier that day, the quick onset, that scenario probably never occurred. That nurse would not been taken out of that clinical situation. The second scenario is the nurse who went to get this patient up. This patient had bipolar schizoaffective disorder, and just she's going to get the patient up out of the bed, and this patient takes her fist, and she had shown no signs of aggression prior to this. Okay? This patient took her fist, beat the back of the nurse's head to the point that it tore all of her cervical and thoracic myofascia there. Permanently injured. She went back to school at 35 years old. She chose nursing as her profession. She wanted to help mankind, and now she has a result of a permanent injury, never able to go back into the workforce. The third one is a nurse that got bit. We had this patient that was enraged. You know, we'd given him all the sedation. It still wasn't taking effect. We ended up code 400. All the staff were there. The nurse was trying to hold the patient down, saying, "You know, we're getting you medication. We're trying to. You've got to calm down." This patient reaches up and bites her arm. Now, you know, like an animal will bite and release usually, right? Not a human that's enraged. Bit this huge chunk of her arm out, ended up developing severe cellulitis. Had to have grafting and just all those things could have been prevented if we'd had that in our toolbox. As far as IGALMI, what it provides for the nurse at the bedside, it's easy to administer. Got this patient that's getting agitated, implement it early, let the patient self-administer the drug themselves. That gives them participation in the care. Number two, the onset of action is gonna be within 20 minutes. What that means is that, you know, while you're doing all the things that we as nurses do, we decrease the stimulation in the room, we cut the lights down, we put warm blankets on them, do some touch therapy. You know, by the time that 20 minutes has arrived, you already see that patient that's wild, crazy, just calming down. The whole tension in the room improves. The cool thing is that you have a drug that you know the expected dose-response. The beauty of this whole thing is it doesn't depress their respiratory effort. What we need is this in our tool chest. We need it for these situations where the patient starts escalating on that agitation scale. We need education throughout the hospital system and the different provider units that will be utilizing this product so that we have it available. I think that if you ask any nurse that you work with, that you ever encounter, that you know, ask them, "How many agitated patients do you deal with on a weekly basis? How many of your staff have been injured or harmed?" I think that IGALMI is an awesome drug that has come on the market that's gonna do remarkable things, and I'm excited about it. Good morning. Welcome. Happy to be here. I wanna thank BioXcel for having me to have this discussion with you. We're gonna change gears a little bit. I think my colleagues did a wonderful job talking about the clinical aspects of what we see in the hospital systems in acute settings. Karen pointed out different settings you would be in, the pharmacy setting, the nursing, as well as the providers or prescribers. I wear two of those hats as a prescriber and being involved with the pharmacy department as a director of pharmacy. I'll tell you what the nurses do in that front line and see is something unbelievable, especially in a psychiatric facility where I am, where we see these at much higher volumes, if you will. It is unbelievable that for all these years, we still have not had something addressing the agitation until now within our tool belts. What I hope to do today is to give you a little more insight about the hospital systems, talk a little about the Pharmacy and Therapeutics responsibilities, and then that process in terms of formulary. Before we do that, I think it's important to understand of the different FDA-approved medications that come about. You have the ones in the retail setting, over-the-counter medications, or those that are in the community where prescriptions are written, and in that case, the education is delivered to the providers or the patients, in some cases. Medications are prescribed or picked up at a pharmacy to treat whatever symptoms might be. In the case of IGALMI, we're looking at a medication that's to be used in an acute setting. The process is a little bit different and complex, and I hope to shed some light on that because now you're kind of working backwards. You are approaching a pharmacy and therapeutics committee, creating the necessary documents for that medication to be presented to that P&T and then placed on a formulary for its usage. The complexity that I sort of wanna talk about is that of the system. We're not gonna go through all of them, non-integrated and multi-specialty, sorta self-explanatory. Accountability care organizations or ACOs, as you might have heard about them, groups of doctors, hospitals, and other healthcare providers that come together voluntarily to give coordinated high-quality care for the patients. After that, you would look at an IDN. This is more popular now and growing, and this is where all the attention is. Even hospitals that are not integrated yet, this is where they're looking to move towards. Health systems that aim to integrate the healthcare organizations to consolidate their mission. Some examples would be the NewYork-Presbyterian Healthcare System, Yale New Haven Health System, Henry Ford Health, and then you have the fully integrated delivery and financing system. One that most of us would be familiar with would be Kaiser Permanente, where they look at financials and that integrated health delivery under one roof. Purchasing groups, and why this is important to talk about in this conversation, because majority of the industries out there have for many, many years taken advantage of such thing. In the hotel industry, the restaurant industry, and many others. Believe it or not, in the healthcare industry, we were kind of behind in doing so. What do they do? GPOs or group purchasing organizations are entities created to really leverage and give some buying power to businesses, in this case, hospital systems and healthcare providers, in contracting either directly with the GPO, who has multiple contracts with other manufacturers or pharmaceutical companies or biotech companies, medical device companies, and so on, or directly with those companies. Now, to give you some examples of some of these in our industry, Vizient, Premier, and HealthTrust, these are three examples that make up three-quarters of those contracted beds. Those beds out there, staffed beds that are contracted through the GPOs, about 75% plus of those fall under these three. There are other smaller ones. MHA, MedAssets, these are actually quite significant in the long-term care setting. If you have such contracts, you probably have already had a head start in terms of getting out into the community in long-term care settings as well. I'll tell you, if you already have a contract with one or two of the main ones that make up 75%, you already have captured something that a lot of medications are trying to capture in the course of 9-12 months. Until this is in place, a lot of times when we're looking at formulary decisions, it is very difficult for a P&T committee to make decisions if the medication is not yet on a GPO contract, 'cause now you're paying full price for it. We'll come back to that in a second. What do those systems all have in common when it comes to drug usage or those policies and procedures that relate to medication or drug usage? That would be the Pharmacy and Therapeutics Committee. We've probably, in one way or another, been introduced to that or have heard about policies and procedures or other P&T committee responsibilities, some of those being reviewing newly available drug therapies. Some of the ones that would be relevant to our discussion. Staying abreast of developments in the pharmacy market. Managing the formulary. Of course, we're gonna talk about that as well. Being involved in quality and cost initiatives. We sort of heard about that earlier in earlier presentations. What's important to understand is that the P&T's responsibilities go beyond that. We're looking at a very small percentage of time spent on formulary management and deciding on medications that are to be placed on a formulary. Every single drug you could imagine goes through that process. There are some exceptions made in emergency situations. With COVID, for example, we saw a lot of red tape sort of being cut through when it came to some emergency usage of medications. Within systems, a lot of red tape are often cut through. When you have a medication. When you're looking at pharmacoeconomics, saving you a lot of money, but at the same time, when you look at the clinical benefits, the significance and what that medication is able to bring. In the case of agitation, we have not had much of a development that we could use in our tool belts. A medication like IGALMI is truly, suddenly, when we're using screwdrivers, a power tool that we could have in order to address some of the agitation that we're seeing that we've been using outdated medications that cause not only sedation but also cause length of stay. We refer to it as LOS. I think it's length of stay and loss of staff. You could lose staff based on agitation and some of the results that come of that. Policies and procedures, obviously, one of the things that the P&T is responsible for. We're not gonna go through them, but anything related to medication usage, safety, efficacy. That part, we already saw a lot of data on in terms of IGALMI's level of efficacy, what it has been able to do in clinical trials and separating from placebo, its safety and tolerability. We have known this molecule for some time. It's not new to us. I think that's a big plus. With regards to analyzing, studying, and reports. Pharmacoeconomics, of course, but drug procurement, how are we gonna get these medications eventually? What contracts are we going to have in place? The P&T advises the quality assurance department. It is part of the infection control committee, so on and so forth. The big meat of what the P&T committee does really is performance improvement. Looking at some of the key aspects of what goes on in a facility, and one of the reasons you don't hear much or know much about this is because this is not really talked about, read about, or published. These are in-house. These are data that is collected to be compared to benchmarks that are known nationally. We look at prescribing, dispensing, administration of medications, and monitoring. Within those, looking at medications that are relevant to our patient demographics, for example. You can imagine how each hospital, each system in a different location could have a different one. In terms of dispensing, looking at medication errors, looking at dispensing errors or medication distribution. What is our timeliness in terms of distribution of medication, procurement of medications, having the medications available, and the appropriateness of the medication. Administration. Stat and now, one that stands out here when we're talking about IGALMI, because this will be a medication. It is a medication that used in a more immediate case, where the timeliness of not only administration, but how fast or the onset of the medication, I think is key. If you think about injections, for example. We might think of them as a quick response, but the time it takes for preparation from the time that an order is put in, pharmacy preparing, and it actually being given to the patient, you could probably argue that having some sort of sublingual or something that quickly gets in the bloodstream might be just as fast, if not faster, in terms of availability and in terms of administration. Oral, obviously, if you're taking an oral medication, as it was alluded to earlier, the time it takes for that medication to actually start working, obviously longer. Monitoring. The P&T looks at medication errors, food and drug interactions, drug-drug interactions, adverse drug reactions, and all of the above. This is really to shed light on the fact that a lot goes on in that 1-2-hour P&T committee meeting that takes place maybe once a month, every other month, once a quarter, some facilities twice a year. Other broader responsibilities of the P&T. Reviewing and redeveloping drug monograph, coordinating drug recalls, looking at treatment guidelines. We talked about in previous presentations, when a medication is placed on a formulary or a change is made, even when there's an expansion on the indications of that particular molecule that's already out, treatment guidelines are reviewed and looked at for that paradigm or to looking at the algorithm of where that medication will be used in different scenarios and situations. We're gonna talk about some of them other committees that are important and involved in some of the decision-making, therapeutic assessment committee, value assessment committee, and so on. To shed light specifically on formulary medication management, medications that are FDA-approved, yes, are a part of that conversation, the P&T committee, about 50 a year FDA-approved medications. If you truly look at all the changes that are made within a formulary, it is beyond that. Indication expansions that I talked about earlier. For example, if and when IGALMI's indications after the trials do become approved for those other areas where it could be used, these will be reviewed again so that we could see appropriately where in an outpatient setting we could use this medication as well. Changes to package inserts, those are reviewed. There are about 1,300 drug recalls a year. Those are looked at for those that are relevant to that particular health system, that is reviewing them. Compounding medications, experimental drugs, clinical trials that are being done at the facility. These are all part of formulary decision-making and medication management. Now, this is not to overwhelm you. Kind of is. This is to really look at the process that medications go through, every single one. Every medication goes through this process, and I can tell you that medications that truly move up towards priority are those medications that are not what we call me-too drugs. In the psychiatric world, for example, in antipsychotic medications, one of the things we often say is, "Here's another me-too drug to treat schizophrenia." Because a lot of them work very similarly on particular receptors, dopamine and serotonin, in different manners with different side effects or different levels of efficacy. As it was alluded to earlier by Vimal, that in depression, we saw a quick shift suddenly and a change of something that was a game-changer. I think in terms of agitation, we are finally at that stage or step where we have finally had something come about that we have not had in our tool belt, where you could skip steps and you could really cut some red tapes in order to be added onto a formulary, even if not on formulary, to be used outside of a formulary. I'll talk about that in a second, how that is achieved. With all those performance improvements, the main purpose really is quality improvement. A lot of that information goes back, and we make changes as necessary. Any of these steps, by the way, can affect what we talked about earlier in terms of algorithms and treatment guidelines. You can imagine that once those decisions are made, we might need to go back to make changes in treatment guidelines. Really shedding light on the fact that we need to be patient for this process to take its course. It involves many different providers, as you would see in each of those boxes, physicians, nurse practitioners, pharmacists, technicians. In psychiatry, in particular, we always say it really takes a village to take care of each one particular patient. You might have some specialties out there where you have a physician, a nurse, and a few other staff. In psychiatry, you have social workers, case managers, technicians, those who give injections, those who are giving therapy, the groups, and so on and so forth. It does take a village to also review some of the changes that are made, but I think worthwhile when that finally happens, and that is when a new drug comes about. The formulary process really has a request. That request could be a one-time use or permanently being placed on a formulary. Something as simple as this request does have steps. Nine steps I've laid out for you here, starting from a formulary change request that you just saw, going all the way to a prescriber ordering a medication. It is important to note that some of these steps could be skipped. Sometimes you do go backwards in these steps, and sometimes there are steps within steps. What's important is that when you have a medication that has already checked off a lot of these things, it makes it easy on us to, for example, when we're looking at contracting or when we're looking at procurement of the medication, purchasing it. If a medication is already part of the GPO, where in our case, it's actually Vizient. If it's already part of a GPO contract, they have already checked that portion off for us, and we just jump right to number nine. What else goes on in between these steps is the involvement of the different committees within the committee, and that is the therapeutic assessment committee, truly focused on the clinical value of the medication, like the P&T would be, working in both, but probably more on the clinical side, and then the value assessment subcommittee that would look at really the clinical and the financial. What's important to point out here is that the financial. I know we talked a lot about the cost associated with agitation in terms of injuries, in terms of length of stay, the patient perhaps staying longer. One of the things we haven't talked about yet is the cost associated with damage to the structure of the hospital, cost of machinery. The medical equipment that is used in our facility today versus 20 years ago, the cost is unbelievable. I mean, some of these items, say, a Pyxis system that we use just to dispense medications. For that system to work properly in our hospital, you're talking somewhere between half a million to $1 million dollars. Now, there might be some warranties on the medication, but it is not covered when a patient throws a chair at the screen that system has, and it cracks in half. This is something we've seen. I could go on and on. A punch to the wall, yes, it will injure the patient. I don't wanna take the human aspect out of this, but I wanna shed light on the fact that that drywall that needs to be fixed, that just costs you $1,000. A medication that costs $100, $105. That's outside the GPO contract, by the way, for a facility like mine or others. I think it becomes a no-brainer for you to understand when you're looking at the pharmacoeconomics of what it will take to not treat the agitation and deal with the agitation when it's too late. When you compare costs there of thousands of dollars, each day stayed in the hospital longer than would normally, you're talking about $2,000-$3,000, depending on the type of hospital, the size of the hospital, and so on. A hundred and five dollars per dose. I think that's something very, very powerful in all the conversations that we have for us to have suddenly a power tool within our tool belt. That we have long been using this screwdriver, probably straining ourselves trying to hold the patient down. I can think of many cases, 6-foot-5, 6-foot-6 patients that took 8 to 10 of us to hold down, and yet still difficult to give an injection to. That's if the injection goes in the right place in that kind of chaos. Just to shed a little more light on where we are with things, imagine the complexity that we talked about, although doable. Yes, there are still steps, but now probably takes a little bit longer in some cases when you drizzle a little bit of COVID-19 on top of some of the things that we usually do in a P&T. You might be meeting quarterly, or you might not since then. This is more the conversation that was had in 2020. I think we've come a long way. Changes are made. Things are looking better. Actually, some opportunity has come about too, which I'll talk about. You might meet in person. You might not. A lot of us have gone virtual, not so much in the healthcare industry as in the supporting staff, but some have. Might have all the committee members present needed for quarantine. You might not. We have spent more time talking about COVID and monkeypox and all the infection control items you would imagine, more time than a lot of other things that goes on in the P&T. Budgets have changed and are shifted. Priorities have changed and are shifted. I think this is one area where it would be an opportunity for a medication like IGALMI because priorities have shifted in a manner where we are focusing more on cost. We are focused more on the whole patient care model rather than a specific disease state. We're definitely focused on freeing up beds and length of stay because there's a shortage of beds, at least where I am. There's a shortage of staff, and that's one of the other things we could have here. The last one, relationship with pharma that could have been changed, again, could have changed both ways. One where you want no more pharma perhaps knocking on your door until you're ready because you have a backup of all these medications you have to go through the P&T. Or others, perhaps like IGALMI, at least in a facility like ours, where we would probably have to pick up the phone and call them and say, "Come present this medication. Let's hear more about it," because this is an area that we really need to focus on where we've had no focus. To wrap it up, as I have already gone over by a minute or two, each country, each state, each county, and if you think about everything, the politics, the money, whether surplus or other ways, how it is managed and so on, each city and every hospital system is different. I hope I was able to shed some light onto what really goes on, but you cannot know one and know all. I'll end with this. One of the things I have tremendously appreciated about this company, at least where I am, I've not met most of their medical affairs team or sales team in other areas, but we've actually. I've chatted about this with Brendan and others, that some of the folks I've already met to try to move this forward a little quicker because of the need I think we have in terms of agitation has really impressed me in the amount of years that those folks have spent not just in CNS and psychiatry, but them understanding the complexity of the systems that I sort of alluded to or talked about here today. I appreciate that. I think you guys have done a wonderful job doing that. With that, I'll end and pass it to Matt. Thank you very much. Appreciate it. Thank you, Matt. All right. I want to thank all of our guest speakers for your time today. This is the slide that Vimal ended on. I'm not going to belabor this. We're going to go through all of this information. We're going to get to it. What I wanted to do is start with the voice of an agitated patient. It's a bipolar patient that was diagnosed over 5 years ago, 33-year-old female. She has multiple agitation symptoms per month and requires trips to the emergency department or urgent care 35 times a year on average. This patient has also required inpatient care due to her agitation twice in the last 2 years. Let's hear from her. Okay, maybe we won't hear from her. The quote is here for you to read. I think that part of the issue that these agitated patients have is that they feel desperate. They feel frustrated. They're not getting the relief that they need, and they really are at their wit's end. You know, when they go into the emergency department, this is what they're experiencing, both in and outside of the hospital setting. Let's talk about the evolving agitation market. Vimal had shared some numbers. He shared 139 total agitation episodes in those indications we're pursuing. I'm gonna talk about those in bipolar and schizophrenia. We have 16 million institutional episodes that we're focused on with this launch. And that's a really important number. We've also identified 23 million episodes for the at-home setting. I want to share with you very briefly how we got to these numbers. Those of you who've actually wanted to understand how we break down the market, this is how we do it. There is epidemiology-based information from general pop down to prevalence and diagnosis. That's the first part of the breakdown here. We go into the number of patients who have agitation. This is based on claims data. When we talk about self-managed episodes, that is predicated on primary market research that we've done, and then anything that's in the institution or other claims that we can assess, that comes from claims data. This is a breakdown. This will be in the deck for your review post-hoc, but this does give a fulsome view of how we get to those numbers. We're not making them up. Let's talk about how the market is evolving. This is the American College of Emergency Physicians poll that was just released about three weeks ago or so. I think it's instructive. The chart on the left-hand side shows that 55% of emergency room physicians have been physically assaulted, and they've witnessed roughly 80% have witnessed an assault in the emergency department. This is a big problem. Furthermore, in the same poll, 33% of emergency physicians have had an injury sustained due to an assault, and the assaults are growing. These injuries are growing rather. From 27% last time that this poll was done in 2018, up to 33% today. This is an issue that continues to evolve. We also know from the literature that Bipolar and schizophrenia patients are 28 times more likely to commit an assault in the emergency department than others. We are targeting the right patients with IGALMI. Now let's talk about the treatment paradigm in the emergency department. Eighty percent of the treatments used in the emergency department are intrusive, coercive. You have 10% that's IV, 70% IM, which means that you are coming at the patient with a needle, which creates a very unique paradigm for these patients who are elevating in their agitation. Patients acknowledge that their agitation escalates just due to being in the emergency care setting alone. That's part of it. Second thing is they acknowledge that they're typically needle phobic. They believe that being injected is invasive. They don't like being touched, feel like they're being euthanized or feel like a guinea pig when they're in the emergency department and they're being injected. Then of course, patients and caregivers alike report that there are negative emotions associated with either physical or chemical restraint. These are the issues that we have. These are a lot of the things that our faculty here has spoken about. We're dealing with, and we are entering a market at the nexus of increased agitation and injury, and then treatments that are escalatory in the agitation, not de-escalatory. That's where IGALMI is going to have a very nice set of wind at the back. Let's talk about our commercial infrastructure and progress. We have a fully integrated and experienced commercial team. We have marketing group that is responsible for driving market awareness and interest. When you think of the total addressable market, this is what marketing does, is it focuses on the broad market and making sure that there's broad awareness and broad education on the drug, so we can get to 100% of the market through their efforts. Market access, similar type of thing. They're focused on GPO contracting and so forth. I'll talk about that. Also the approach with the integrated delivery networks that can ensure that we will have reach and utilization beyond the hospitals that the sales team is targeting. Sales team is meant to drive hospital demand and pull-through. Then we have our support mechanisms and analytics training and distribution to support all of these efforts. This is a group that is effective for this launch and also will be effective for future indications. We can scale with this team in hand accretively. The core marketing messages that we have and I'm not gonna belabor these because I know that most of you have seen these, but mechanism of action and mechanism of disease are really important. What Dr. Preskorn talked about earlier this is really a drug that's bespoke for agitation. The time to agitation release, that CGI at 20 minutes, really important. The fact that IGALMI was studied across the spectrum is indicated for the spectrum of agitation severity is also important, especially when you're talking about the emergency department setting. Of course, the AE profile is favorable as well. Now, when we were getting ready for launch, we did market research with this message group. We wanted to see how it landed with physicians. At the beginning of the market research, they were given a product profile, and they were asked whether or not, or what percentage of patients they would potentially use this product for. The intent to use was about 20% or one in five patients. After we gave them the entire message platform that we're now out in the field with, we saw that the intent to use rise to two in five patients, so 40%. We basically doubled the intent just by telling the story. As we're getting out in the field and we're relaying the story to our key stakeholders, what we see is something very similar, is that the interest is high and the desire to at least have a deeper conversation about IGALMI with their P&T has grown. The marketing efforts transcend just what we say in the field. We certainly spend a lot of investment in going to conventions, doing peer influence programs. We've now had well over 1,000 HCPs that have had a fulsome conversation with us in these types of venues. We do digital marketing where we have reached over 100,000 unique individuals to our digital assets. Let's talk a little bit about the market access, and I don't want to restate these definitions, but I have this up here to show where the responsibilities between the market access team and the sales team reside. The market access team is squarely focused on negotiating with the group purchasing organizations, getting contracts in place, and unlocking that access in hospitals. Healthcare organizations or hospitals, that's where our sales team's focused. Any of our target hospitals are really in the line of sight for our field team. There are about 1,700 hospitals that we're focused on there. Then we have integrated delivery networks in the middle. Our market access team is really focused on a subset of these that are very large. Then where there are hospitals that are in our target universe, where they're part of an IDN, locally or regionally, that's where our sales team is also focused. That is a collaborative approach. Of course, even with the large IDNs, our sales team is driving the interest from the bottom up, and our market access team, our key account team, is working from top down. I'm not gonna belabor the timeline that Dr. Hani talked about. It does take a while. Typically, a GPO contract can take 6-9 months to negotiate, and the P&T process can take anywhere between 6-12 months on average, and that's when true demand and pull-through start. Here's where we are with our contracting. We are now contracted with nearly half of the beds in our target universe. We have signed the Vizient contract that was effective October first. That represents 46% of the beds that we target. Keep in mind that Vizient, Premier, and HealthTrust represent 77% of the staffed beds in the United States. They represent over 90% of the beds that we target. We're making good headway here. We're in negotiations with other GPOs, large and small, because we don't wanna leave anyone out. We just signed another with MHA on Friday. We are continuing to work through this process and get access with the GPOs, and we will continue to update this as we go. Now, I'm throwing this schematic up here just to make a point about the IDN. The IDNs have grandparent or corporate accounts, regional accounts, these are parents, and then you have child accounts, which are site of care. They have varying degrees of integration. At the very top, if you think about the Kaisers or the Ascensions of the world, they are highly integrated, which means that they have a lot of control downstream all the way down to the site of care. Then you have others that may not have as tight an integration, therefore do not have as much control. Where there's an IDN, there's not a lot of control, and they have their own individual P&Ts, that's where our sales team is gonna focus with the individual hospitals of interest. For our corporate account team, our corporate account directors that are focused on the IDNs, we will focus on those that are highly integrated and therefore have a lot of control. That way, when we're able to get on formulary with those IDNs, we can impact utilization all the way downstream to child accounts, even if our reps aren't there. This is a snapshot of those that have two or more hospitals, 'cause obviously we're focused where the agitation is most populous. That's gonna be in the hospital systems. These hospitals, these IDNs, 10% represent almost 60% of the total hospitals in the IDN systems. This is really where we can focus from a market access perspective. There are 59 total IDNs that we're focused in on. We have priority targets that are outlined here in red. These are gonna be at the very top of that pyramid. We have others that we'll focus on as a second tier. We deployed our corporate account director team in the third quarter, and there's good coordination between the sales team. There's a lot of synergy between all of the different disciplines in the organization to help these IDNs make their decision. The key metrics out of these IDNs is 33% of our targeted beds for our sales force are within these 59 IDNs, and about 40% of the agitation episodes and patients are also inside of these IDNs, which means that there is a lot of opportunity in those hospitals downstream where we're not actively making calls, but there are presumably gonna be agitated patients. If they have protocol and pathways developed, that can actually influence a lot of the opportunity where our sales team is not. Now, turning to sales, I wanna just spend a minute on this slide because we've done something that I think is fairly unique in this industry, is we have built out a database of 81 billion claims records, 5 years longitudinal. We've added to that hospital quality measures, other syndicated sales data, and we will continue to put our own data into this lake so we can examine it. Now, the first thing that we're gonna do with this data lake, the first thing that we have done, is look at our targeting methodology. What are the things that we think are most important in building our hierarchy for our hospital targets? It could be things like hospital beds, antipsychotic utilization. Certainly, we know where the agitation patients are. We know when they come into the hospital, where they go, where they leave the hospital, how many times they come back. We know where the frequent flyers are. That has gone into the methodology that we use for targeting. The model that we have today represents the majority of bipolar and schizophrenia agitation episodes and also takes into account almost 80% of the total psych beds in the US. Now I'm gonna invite Brendan Schulte to just give a brief summary of where we are in the deployment and also in the expansion of the sales team. All right. Thanks, Matt. Good afternoon, everybody. I get to talk about the deployment process and what we learned in 3.5-4 months of being out there. We started with a wave approach, right? To get a market assessment and response, but also in a post-COVID era, you had a lot of closed hospitals and reduced access. We wanted to get out into the market and see how we're gonna go ahead and penetrate these HCOs, these hospital accounts. As Matt said, we have 1,700 hospitals. We need 70 reps to go ahead and make that impact. We chose 26 selective territories to start. You'll see from the graphic on the left side here above me that those are predominantly major MSAs, but we also diversified the type of territories so we could see if the response is any different. Some are urban, some are rural, some are quite spread out, and some are condensed. It gave us a very good national feel for what the response was. Across the board, it was very positive across those target specialties: ED, psych, nursing, and emergency nursing specifically to that. Right now, we're into the coverage of wave two, and getting to 100% coverage with the 70 reps. We're gonna go ahead and get those folks on board in November. We'll be doing training in November and December, getting those initial HCP interactions for total execution with the field force for the entirety of 2023. Okay. The white space you see doesn't necessarily mean it's uncovered either. The CAD team Matt talked about definitely connects to IDNs in that space, but a lot of the covered areas have sister accounts that follow the same pathway and protocol from the mothership, and so we'll go ahead and make impact on those as well. What triggered some of this was not only the response but how much face-to-face time our reps got with practitioners. Close to 70% of all of our interactions were in-person, which beat my expectations of how we're gonna do this in a non-formulary world with a new brand, new company post-COVID, right? That's true across all those specialties, and specifically in the ED, where you often have to be on formulary before you even get in. It was a high response rate. We were invited in, and that was very positive. How we did some of that is the experience of a team. Hire some excellent people with intensive hospital experience, but also have a breadth of other specialties that raise the collective intelligence of the whole. That's how you go ahead and accomplish that. In our case, they have 22 years on average, 14.5 of those in the hospital, about 8.5 of that in the emergency department, which is definitely a unique trait among hospitals. It's not a big area for hospital field forces over the last decade, so the fact that we pulled them in with that experience is pretty critical. 6.5 years in the CNS market, and as I just mentioned, a diversity across other specialties, right? Cardiac cath labs, ICUs, oncology, ED, psych. When you bring a collective group in, you share those experiences. Typically a faster way to get to goal. is a preponderance of startup experience, which accumulates to over 250 product launches among these 26 individuals, about 8 per representative. We're extrapolating these numbers to the new folks coming on as well, and these will likely hold as far as experience numbers for the entire 70. Extremely experienced group who knows how to get into a hospital, has relationships built across a variety of specialties, and has launched a lot of drugs. Well, what kind of impact have they made? Out of 1,700 target accounts, there's 701 that roll up to these 26 territories. In just this short 3- to 4-month time period, we've made a significant impact, as evidenced by sales calls on these target providers, and in many cases, multiple sales calls with 510 of them. We've already reached 71% into that target universe, which beat my expectations of how many accounts we were gonna get to. One of the more predominant measures is in the kinda lighter blue color at the top of that right side, which is that our account depth and penetration has doubled within the last 2 months. What that means is not only is our field force getting into the hospital, but they're getting in now to meet secondary providers, and they're coming back in multiple times. That doesn't happen when you have a non-formulary drug if they don't want you to come in. One of the big mechanisms for driving that number is the amount of ED in-services we've been doing predominantly. To come into an emergency department, they typically do not let you in there to talk to their nursing staff unless you're on formulary. The fact that our field force is being invited in is an indicator that the message is well received and that there's a high unmet need. The fact that we're getting back in, and now you're seeing the depth build at target accounts, it's showing that message is now being shared from psych to ED to nursing and to pharmacy, and we're developing a multidisciplinary approach to push through that kinda 9-step formulary process we've seen before. We went out and found the territories. We got the response rate. It was positive. That compelled us to put the full 70 field force personnel in place and get them trained up, and we're seeing that response across the target specialties, and we've been to 71% of those targets already, of which 70% of those interactions were in person. A pretty nice significant achievement above expectations, from my perspective in that 3- to 4-month period of time. Now, I can fill this final slide for me with a lot of commentary and anecdotes. I just chose 2 that were recent, and they came to me personally, either from the field or for conferences. The first one about, "I could use this today," came from a nurse response to an in-service. What it shows you is that every single day in an emergency department, these patients are there. 1,700 accounts every single day are seeing multiple patients that could potentially be treated. The second one came up to me from a psychiatrist at Psych Congress who came over to our booth and sought me out, was quite emotional, and she's told me that, "Yes, I'm a psychiatrist. My mom's a schizophrenic, and she has post-traumatic stress from years of force and injections. I can't wait to get this." Why I chose this one is 'cause it gives you actually three perspectives. That of the provider, right? She's seen the patient side, right? She knows what it's like to be, in this case, taking care of a family member that's suffering. For her to see the need in an inpatient and outpatient was quite compelling, and she was going back to talk to her P&T committee members about it as well. It's an emotionally charged situation where there's a lot of people with high involvement, and these are just two of those particular cases. I really like what we've seen out of the first 3 and 4 months of getting out of the gate. Very excited to bring the full team up to 70 here in November and go ahead and execute in the hospital space in 2023. Matt's gonna take you through some more key performance metrics. Thanks, Brendan. We'll quickly get through these so we can leave some time for Q&A. But these are important. Let's talk about IDN key metrics first. Right now, we have 17% of the target IDN beds in process for voting in 2022. Thirty-five thousand, almost thirty-six thousand beds are scheduled to vote between now and the end of the year. We also have another fourteen thousand beds that are not in those target 59 that are also scheduled to vote. Now, keep in mind, we've done this with 26 territories filled. These are systems that are scheduled to vote because they see the value, and they wanna have a vote this year. We have over a dozen formulary wins already in hospitals. We have about 400 in process. 108 of those are in our target universe, and we have another 283 that are outside, that are going to be what we would call second-tier opportunities. These are hospitals that may be in very small IDNs, where once the drug is approved on formulary, they can also use it. We will hit these folks with marketing efforts to make sure that they have adequate knowledge about IGALMI. This team of 26 has effectively gotten to the formulary process for 2022 in 16% of their accounts. That's today. When we put these slides together a couple weeks ago, these numbers were lower. We would expect that there will be additional formulary reviews and potential formulary approvals this year in addition to what you see here. We'll continually update these on a quarterly basis. Now, what should uptake look like after formulary approval? This is from market research that we fielded last year and was read out in January of this year. Once formulary approval for IGALMI, we would expect that there will be trial in the majority of both emergency department HCPs and psychiatrists. Within that first year, certainly we'll see better than a third within the first six months. We're gonna see trial pretty early with this drug once on formulary. I'm gonna end on this slide, is that we have a lot of environmental factors that are favoring our growth as we head into 2023. We have an integrated commercial team that is already built, and we have the sales expansion underway that'll happen later this year. We will be poised and ready to execute in all 70 territories as we go into 2023. The market dynamics are evolving and favorable to this IGALMI launch. The wind is in our sails, so to speak. Sales interactions have been very positive, and we've had 71% reach, and early use is yielding the expected and anticipated results. Also, the good news here is 70% of the sales interactions are in person, so we're not being impeded because the drug is not on formulary, and we're not necessarily supposed to be on campus without that condition met. Market access momentum's building. We have almost half of the GPO beds now under contract and 17% of the target IDNs in process for 2022 voting. With that, I will stop, and I will ask our panel to reassemble up here. I believe that what I'll ask is, as you have questions, please direct your questions to me, and then I will share those with our panelists accordingly. Good to go? Good to go. Colin Bristow, UBS. Thanks for putting this on and taking the questions. Just three from my side, I guess. First, as a point of clarity, you said you've got just over a dozen formulary wins right now. Mm-hmm. That's the first thing. Second, from the clinical side, you described some sort of pretty extreme cases of agitation. I think the average PEC score on SERENITY I and II is around 17, 18. From your perspective, you know, what percentage of the patients you see on a daily basis are amenable to IGALMI, so they're not running people over or stabbing them? And then just finally, just, you know, a little bit out of the scope, but could you talk through just the broader opportunity that you see in dementia and how many of those agitated patients would fall into that category? Thank you. Okay. The first question was about formulary wins, and yes, it is over a dozen. I don't know if there's another question in there or not. Yes, it's. We will continue to update that metric. We want to get that out there, so we will give a quarterly update on the number of formulary wins. As it relates to the PEC score and whether or not a patient would be amenable to taking IGALMI, maybe Dr. Preskorn, you can talk about it first, and then Karen can add some thoughts. Well, I think right now, you know, the indications are for agitation and bipolar and schizophrenia. I think you saw the curve that I laid out about all the psychopathological states that people can have. I think certainly dementia is a prime target. I think the cost-effectiveness of this can be readily seen. You know, what leads healthcare providers or caregivers not being able to keep somebody at home is their agitation and their, you know, walking at night. The economics of that would be if that care provider can keep that person at home, their spouse, and not have to put them in a nursing home. You can just think about the cost-effectiveness of that versus the nursing home. When you get to the nursing home, what happens is when that person becomes agitated again is difficult for the staff to take care of, then they get hospitalized. I think again, you're talking about a very simple value aspect when you think about the cost of hospitalization versus the cost of nursing home. In terms of the number of patients, certainly, you know, agitation is very common in dementia, and it is often what leads to the need for nursing home and what leads from nursing home to hospitalization. If I answered your question. Now, I think if you go beyond that and you think about all the systems that are affected by agitation, obviously you would end up needing to get, you know, either indications for those other potentials or certainly physicians would need to feel comfortable in prescribing for them. I think the range of psychopathology that could be affected is substantial. I think just the percentage of patients that you see on an inpatient basis that fall within a sort of a PEC category that are amenable to being administered with IGALMI. Well, I think that's gonna depend upon the circumstances. I, for example, right now I'm in an outpatient clinic. My percentage of patients is relatively small, because there are people who come in for their outpatient, they're generally doing well, et cetera. On the other hand, another colleague of mine runs the psychiatric emergency room. They're about 17%-20% of all patients seen there have a psychiatric emergency, and probably you're talking about somewhere around 50% of those people could be a candidate for treatment with IGALMI. If you talk about the inpatient service, and I've certainly been on the inpatient service, it is not infrequent that you have patients who are quite agitated. I probably would say that that can range on the order of 5%-10%. It will vary depending upon what setting you're in. If you talk about ambulances, you know, ambulances frequently are bringing in people who are agitated. You know, right now, I know in my community, they gave up to 200 milligrams of ketamine, a dissociative anesthetic, IM to somebody, which is by far, not as kind and friendly as giving this agent. Thank you. To answer your question, I would say, first off, you know, in the healthcare arena, the nurses and the providers need to speak the same language. In our facility, we don't use the PEC scoring system. We use a Richmond Agitation-Sedation Scale scoring system. Because you can apply that to both everywhere within the hospital setting. When a nurse or, you know, calls me and asks me, you know, or tells me that the patient is a plus one or plus two, I know that that's the patient that needs to be treated. Since I've moved to the emergency room, I would say on average, and we see we have about a 140-150-bed ER, and we have an additional 20-bed behavioral health ER holding area. I would say on any day, 10%-20% of those patients are actively in need of treatment. It, you know, the thing that I'm excited about is that I think these patients can be treated, and many of those patients that are coming in just for the psychological illness alone and the agitation that that is just revving up, that we can stop that cycle and we can get them back home instead of now committing to a bed in the facility. I would say at least 10%-20%. Thank you. Okay. Bill, do you wanna speak to the Alzheimer's dimension questions? Sure. Alzheimer's and dementia is a very large opportunity. As you know that, we have two ongoing trials going on. We see that as very strategic to building our agitation franchise. Data readout from first Phase 3 trial, pivotal trial TRANQUILITY II, is expected in first half of 2023. It's kind of as Dr. Preskorn said, it's a huge problem because these patients will not be able to stay at home when their agitation cannot be managed. It's a huge healthcare burden, and there's no drug approved currently by FDA. Anything that is being used is black box warning, or there are some other issues with those drugs. This area is crying for help, and we are doing everything in our power to bring this medication to the patients. Chris. I think Greg right here. Okay. Greg. Hey, Greg Harrison, Bank of America. Thanks for hosting this event. Super helpful to our, you know, efforts to kinda model out the launch. Maybe one to start out for management. You know, as you get closer to data for at-home usage, how do you plan to evolve your commercial organization from where you're at with the initial launch? And what sort of challenges and opportunities do you see there? Just to be candid, we don't and we haven't presented a market entry strategy for the at-home use yet. I'll tell you one of the things that's gonna be critically important is that we get good utilization in the hospital, and the sites are familiar with it. Remember, a lot of these psychiatrists practice in multiple settings, so they may already be in a community setting where they have exposure to IGALMI when they're rotating into the hospital. That's gonna be important to establish both the knowledge and the credibility of the molecule there, and then that will help us accelerate the pace of growth as we go out in the community. The other thing I mentioned before is this 81 billion record data lake that we have. We can track the agitation patients wherever they are. We know where the concentrations are out in the community, and we can target around those. How we choose to deploy around that and what the market entry strategy necessarily looks like, we will bring that to light at a later date. We have a lot of the components in place necessary to give us the information to accelerate and capitalize on that market. Great. Then just to follow up, maybe Karen or Dr. Preskorn can give some input here, but just what is the sense that you have for patients' willingness to self-administer? I know that's, you know, one of the advantages here, but, you know, how is that challenge going to play out, actually getting people who are maybe highly agitated and not cooperative, getting them to actually administer the drug to themselves? Let's start with Dr. Preskorn, and maybe you can talk about the clinical trials and the experience there, and then Karen will go deeper. Yep. Well, certainly, you know, the clinical trials, you know, we did have a range of people. Minimum was 14 up to beyond 30, and these were all individuals who self-administered the medication. Now, these people's limitation is they were screened. One of the inclusion criteria was the agreement to take a sublingual tablet. So that's going to be, you know, a more favorable population obviously. But I think the real issue is getting the treatment to the patient earlier. I'll go to the tricyclic antidepressants, for example, that was mentioned. You know, in the days that I remember when we only had tricyclics available. What you were doing, why did that market explode? You know, it was $250-$300 million. In about 5 years, any single SSRI was 10 times that. Well, it did a flip on the cost-benefit analysis. When you gave a tricyclic antidepressant to someone, if they took a 2-week supply, they were at risk of dying from taking the drug. You were giving this to somebody who was suicidal, and as little as a 2-week supply could kill them. Under that situation, the seriousness of the illness had to be great enough to warrant prescribing the drug. As was said with the SSRIs, about the only way you could kill yourself was swallowing them in the bottle, so you choked on it. In other words, you couldn't kill yourself with the SSRI. Now you switch the benefit to cost ratio from the provider. I don't want to miss somebody who might have depression that is responsive to a medication as opposed to before the person has to be so ill that it's obvious, even though it's a potentially lethal drug. What I think is that's going to happen with the IGALMI when someone sees I've got a treatment that I can give, I can give it early, and I can prevent them going up to a thirty. The other thing I will say is this is an extremely predictable drug. I was involved from the very earliest stages of the development of the drug through the clinical trials. One thing that's clear is this drug is highly predictable. You know what you're going to get when you give this drug. The reason for that is because it targets that single mechanism. It doesn't have other off-targets. Its pharmacodynamics is limited to that mechanism, and it isn't converted to many other substances which many drugs are, so that you can have variability and response. Okay. To answer your question, I think that the fact that the patient can self-medicate themselves is one of the key benefits because these patients that are coming in that are agitated, they're begging for you to give them medication. I think that the fact that we can say, "Okay, here's this medication. You can put it in your mouth. I'd like for you to put it on your tongue, and you put it inside, you know, in the buccal area and mucosa. But in 15 minutes, you're gonna start feeling the effect of this. So just let's work with me. Give me a chance." And I'm telling you, the patients are gonna take it. That's the beauty of it because we, you know, we don't have to risk putting our fingers in their mouth, you know, and them possibly biting us or whatever. I think them being able to self-medicate gives them a sense of control, and I think that's a huge positive for this drug. We are at time, so we'll take 2 more questions and wrap. Greg? Hey, Graig Suvannavejh from Mizuho. Thank you very much for the presentation. I've got two questions, maybe one for Jacob so he can actually pitch in on this panel. First of all, thanks so much for shedding light on the hospital formulary process. That was really great for us. Maybe as we put IGALMI into perspective, could you give us maybe examples of drugs where the formulary process went really quickly and on the other side, where it didn't go very quickly? Yeah, absolutely. What were the attributes? Maybe if you can just comment on where you think IGALMI will fit in that range. Yeah. Obviously I would tell you very specific to, you know, my experiences rather than all the systems, but I could tell you generally speaking, and then I'll tell you what we have done. Generally speaking, in terms of priorities or how you look at medications, you look at a few things that I touched upon earlier. What is the need? We often refer to it as unmet need, but within patient populations or facilities. Then, what can this medication bring that we perhaps might not have not already had? I referred to the me-too drug saying, "Me too. I could do that as well." Those medications will probably move down a little in terms of priority versus a medication like IGALMI, where you truly, after decades, suddenly have a new treatment option that we didn't have before in an area that is very risky. Liability, costs associated, both direct and indirect, with agitation. To answer your question of medications that have moved quickly versus ones that have moved slowly. Ones that have moved quickly of most recent would have been COVID-related medications, so both, vaccinations as well as treatments of COVID-related symptoms. Those moving slowly have been those medications that fall into the me too category. Medications that do perhaps 80%-90% of the same of what we already have, with the exception of some percentage changes in terms of side effect profiles or pharmacodynamics in terms of some of the receptors they might bind to a little loosely or with higher affinity versus some of the other ones. To finish off your question in terms of where IGALMI will fall, I think I pointed to a few of them. The unmet need in this area, the fact that you don't just have providers like us that would care for a medication like this, but those in the executive office that would care for a medication like this and those that are not involved in the everyday, front lines per se, but see the associated cost of every agitation that takes place, whether it elevates to the point of stabbing and death or the milder versions of someone getting punched in the face or a drywall having a hole through it or a glass window coming down. I think you could see where I'm going with this as far as, how you would have that village I talked about, everyone being on board. Thank you. Then maybe one from Matt. You shared a slide that I thought was very powerful and where you had the market research and the TPP that was initially presented, and you had 20% of docs or healthcare professionals saying that they'd be interested, the intent to treat would be there. Then it moved up to 40%, so you saw a doubling. I guess the follow-up question is, does that mean that there's a lot more work that needs to be done to take that to maybe 60% or 80%? Kind of, how do we get a better sense of where you can take this product? Thanks. No. Market research is in a test tube. We have to presume that the way that our messages were communicated in that test tube environment are very different than a sales team that has copious amounts of experience, 21 years of experience, 14 in the hospital. These guys know how to deliver messages and can identify when they have an interested party. All the information that we're hearing back from the field has been quite positive to the message landing extremely well. Whether it's 40 or higher, we'll see. The interest is there. Certainly, just to dovetail on Jacob's earlier point about whether or not we should see an acceleration in formulary process and adoption for IGALMI. Keep in mind, we've been at this since the trade launch, since July. That's really when the clock starts for any P&T to even consider IGALMI. Through that 3.5 months, with 26 reps, we have 16% of their target hospitals already in process and almost 300 more that are in process beyond that. There seems to be a pretty good desire to move this along. 17% of the IDN beds already in process and expected to vote this year. It's pretty fast. I mean, I've been very clear over time that it takes 6-12 months trying to manage that timeline, effectively because that's what the process typically is. Yet we're seeing this pace which we feel is pretty good. Chris? Matt. Yes. I just had a couple of quick questions. One was just about the. It's Chris Harkins from Jefferies. How strict the label is the treating. Mm-hmm. Like how, you know, there could be agitation that presents in emergency rooms. Mm-hmm. -that maybe don't have a schizophrenia bipolar diagnosis. The other question I had- Obviously, there was some mention of polypharmacy, self-treating that some of these patients do. How worried are you about drug-drug interactions and like the broader applicability of IGALMI to your patients? Then the third one is maybe just a naive question, is there any risk to not getting reimbursed if IGALMI is dispensed in the hospital or the institute? These are all three great questions for Dr. Hani. Maybe we can start with the first one about strict to label utilization, how that might or might not happen. Yeah. in the hospital. Typically, newer medication when it is put on formulary, things will be strict and then as time goes, they might loosen up. That would be a quick answer there. One of the things I wanna talk about is drug-drug interactions, because that's actually one of the items that's looked at closely when you are deciding on a medication, particularly in the setting that we might be in with a lot of psychiatric medications that do have a lot of interactions. I can tell you, one of the things that we have learned of this medication through the clinical trials is that you could use it with majority of the medications that we actually use and treat. Some QT prolongations that I saw very short period of time in milliseconds that was changed. The only thing you would be mindful of is not using it with antipsychotic medications that truly have a high QT prolongation. Other than that, I think the fact that you could use this medication with other medications is one of the benefits. The other thing I'll say about that is, when it comes to drug interactions, there are a couple of things to keep in mind. A lot of times we're talking about cytochrome P450 enzymes through the liver and how a medication would be a substrate of that, and you take another medication, so it could cause accumulation or metabolism of the other medication. What you have to understand is this is a one-time dose, maybe 3. With 1, 2, 3, even if there was, I'm just giving you a hypothetical here, even if there was some drug-drug interaction where it would cause some increase or decrease in plasma concentration of another drug, those 1, 2, 3 dosages are not gonna be significant enough with the half-life that was shown to you earlier to have much of a significance. Okay. Sure. Just go ahead and give him the phone. I think Yatin had a question. Yeah. Thank you. Yatin Suneja from Guggenheim. Just a couple questions for me. With regard to the dozen of wins that you have achieved or you've been able to secure, what are the next steps? When you talk about the trial, what is a trial? What does it constitute? Do you start providing drugs to them? And how the revenue trickles in. That's one part. The second part is, you know, we know the price of IGALMI, you know, it's about $105. Can you put that in context relative to the reimbursement that the ER or the hospital gets? What part of that reimbursement, you think, the hospital will be willing to sort of give up to for IGALMI? Okay. If I understand the first question, it's about once IGALMI is approved through the formulary process, when does that trial begin or what does that trial look like? I can tell you about some of the hospitals that have had early P&T approvals of IGALMI. What typically happens is, you know, we ship the product in and then when there's an appropriate patient, it could be a week or two later. That's when the first trial, at least what we've seen. That's when that happens. And then it may be, you know, a couple, three days later, they may see another patient and then it starts to condense. As they see these patients and become more comfortable with how the drug reacts or acts in the patients, they feel more comfortable in dispensing and administering to more patients that they see with agitation in bipolar and schizophrenia. Second part of your question. Sorry. It was around the reimbursement that. The reimbursement is in a bundled payment. If they're ambulatory, it's gonna be in an ambulatory payment classification. For these patients, it could be anywhere between $300-$800, but that's based on our research. If it's in a DRG, it could be much higher than that. I will ask Dr. Hani maybe to weigh in on how the reimbursement works for these patients in the hospital and how the $105 WAC factors into those. Yeah. Those bundled payments. Typically, hospitals will have two different ways of having reimbursement. One would be flat rate. Patient's admitted, they occupy a bed, there's a flat rate paid that takes care of their food, medications, care. In a setting like that, the hospital would be paying for the medication. In another scenario, it would be where medications are billed as used. Depending on the coverage the patient might have, the medication will be used and then will be billed for coverage. That all depends on different insurance formularies that the medication would fall into and tiers and so on, depending on what that hospital might have in terms of affiliations with those coverages if they have them or not, depending on if it's a PPO or HMO, private or not. Thank you. All right. Sumant. Sumant Kulkarni from Canaccord Genuity. Thanks for taking my questions. I have three quick ones. First one's for Jacob Hanley. Can you think of any analogous products like this in the past when you wear your pharmacist hat, making it through the formulary process and how quickly uptake might have been at your organization? That's the first one. The second is for Dr. Preskorn. Given the mechanism of action of dex, are there any types of agitation that you think dexmedetomidine may not be able to be used for? The third is for the company. Vimal, you mentioned that agitation is somewhat like the depression market. Do you think BioXcel has to have Lilly-like resources to make this that type of market? I'll go first. Yeah. Again, not to get too specific with particular medications, you know, but again, I'll go back to sort of what I talked about earlier in different scenarios of medications. I'll give you an example of the antipsychotic world. I talked about ME-2 drugs coming out, but there was a time suddenly when we started seeing a wave of long-acting injections in that world. I would have to say that one of the things that quickly started getting a lot of attention at our facility, due to the compliance factor of those medications alone, wherein this particular case, the medication is given, it's gonna start working. A long-acting injection given will hold you over for one month to two months, depending on which medication you're using. Something innovative or as referred to earlier, that could be game changing, would normally move a little quicker or get more attention. the question. What was the second question? The question was, given the mechanism of action of dexmedetomidine, do you think there's any type of agitation that dex may not be able to be used for? Because this looks like a medication that could be used for anything. Um- in agitation. I don't know whether I would say there's any form of agitation. Is there any form of agitation? I do think you have to do a differential. You have to make sure you're not dealing with delirium as opposed to agitation, or you're not dealing with you know somebody who has a pneumothorax that can present with agitation. Those would be inappropriate treatments, certainly the pneumothorax. I think the other issue would be are there any specific patients who might be at increased risk? That may be a function really of changing the dosing rate. For example, if you had somebody who had acute myocardial infarction and had a very low cardiac output. I think there might be individuals that you would be more cautious about, simply because of their underlying medical status, but I think those would be far and few between. Sumant, I will answer your third question about the depression in IGALMI. I never meant that it will require Lilly type of resources, but that's a good thinking. What I meant was that whenever there is an innovation happen, that can help create a market. That's what happened in the depression market. Obviously, innovation is one thing, but you need to be able to market, sell, and get the market access, which our team is doing. In our case, we are totally focused on 16 million episodes that are very targeted and by, as, Brendan mentioned, that we will have the full 70 geographies covered in 4,170 hospitals. I think we are using a very laser-focused approach. Obviously, opportunity is to add on another 23 million episodes at home and then be able to capture the Alzheimer's related agitation. If all of this requires like getting to 300 million prescriptions and partnering, then we will consider that. As much we can do what we believe we can create the best value for our shareholders, we will go that path. We haven't even talked about the global opportunity. If you think about it, 130 million episode, similar size exists in Japan and Europe, basically for the opportunity. As we move along, as we have success, we will embellish our market entry strategy for home setting, for Alzheimer's related agitation and what kind of a partnerships or other things we may need to establish. I think just little early, but I think we're getting to that point. Thank you. Any others? Corinne. Corin. Sure. Yeah. Thanks, guys. This is Corinne Jenkins from Goldman Sachs. I guess one of the questions that I had is you think about that 80% that's currently IM and IV, what portion of those patients are getting that because they're not amenable to therapy? You talked about the treatment algorithm there versus they would be amenable to something like IGALMI. What% of patients, you mean with the IM? Like, if you're giving them an intramuscular injection now, is it because they're not amenable to other care or is it? Yes. because you don't have a good option otherwise? It would normally be where you need a rapid onset, and IM will give you somewhat more of a rapid onset, not 20 minutes, but over an oral medication. Usually that's where the person is already being combative, or close to combative. That's where you would end up using the intramuscular injection. Oftentimes those are people who are going to end up also on four-point restraints. Okay. However, I would like to add something to that. If in the process when that patient entered the healthcare door, you know, and they already were escalating on the agitation realm, initiating IGALMI early on would prevent that patient from escalating forward, which changes the whole dynamic of that patient's ED admission. Can I add to that? Not only it changes the dynamic of that patient, it changes the dynamic of the unit. I have referred to this before, that one patient being agitated and getting to that severe level will have a ripple effect. This is a domino effect, especially in a psychiatric facility, where suddenly you'll see two or more agitation. That's why we go into a lockdown. You have to, because other patients who are right at the edge of perhaps being shifted into becoming agitated will have now figured an opportunity to do so, inspired by another agitation. Mm-hmm. The other thing I'll say is in a psychiatric. IV would probably be the quickest way you could address something, right? We don't do any IV when it comes to agitation because we're not an emergency unit. The hospitals might. A psychiatric facility doesn't. For us, it's really, there is no choice. The IM is the quicker version of the two that we could give, oral or IM. Often controlled substance, something you wanna stay away from as much as you could in terms of treating these patients, especially if they've had a history of substance abuse of any kind. You don't wanna reintroduce that to the patients. They have often known injections as a punitive measure, so you're already starting off with bad rapport with this patient in terms of relationship. I think being able to not allow that escalation is key. That's where one of the questions I asked when I learned of the medication, IGALMI, through the sales rep that had visited me was, "When are we gonna hear more about this being used in our outpatient setting as well?" Because the tremendous opportunity, I think there, before they even escalate to getting into the hospital, that's where you're gonna have major prevention. So I'm excited to wait for that as well, just as excited as I think we all are in terms of using it in acute setting. Actually, that's what I meant when I talked about going from tricyclic antidepressants to SSRIs. You could see where, you know, IMs are where you know, absolutely cannot avoid treating. Here with a drug like IGALMI, you could actually initiate treatment much sooner. I think the critical thing is that, markets do not define drugs in psychiatry as much as drugs define markets. Because the better your drug, the more it meets an unmet need, the more people will be diagnosed and effectively treated. You will prevent things. Yeah. The oversedation component of that IM or IV injection is so surreal in the healthcare arena, and it consumes so much healthcare dollars. Because when the patient becomes a RASS score of -2, that patient has to be monitored in a monitored bed. You know, that just escalates the care right there in an environment where we don't have empty beds. Our critical care beds don't stay open 10 minutes. As soon as they're clean, there's another patient headed to it. You know, it stops that process. You're treating the patient that's agitated, and you're preventing them from escalating to that need for where they're oversedated. Yeah. I know we're out of time, so I'll leave it with that. We have such a backup in our emergency room that we have created psychiatric observation units where you're not actually admitted into the hospital. You're admitted into an observation ward where you may have somewhere around 30-35 people, basically in recliners in an open area, so nurses can go around and observe these people. Well, as was mentioned, you know, one of those people starts escalating and becomes agitated, and you're not able to effectively deal with it, you may have sort of a spread of that to the rest of the unit. It becomes a very problematic issue. We end up having to ship people 200 miles away to get treated. All right. Must have been a good question to get six or seven answers. First of all, I wanna thank our guest speakers for joining us today. Really appreciate your insights and your preparation. On behalf of BioXcel Therapeutics, I wanna thank all of you for your participation and thoughtful questions today, and being part of our 2022 commercial day. Thank you. Just a note of housekeeping. For those of you who are here live, there is lunch next door, and I look forward to further interaction.