Good morning, everyone. Welcome to another session at the Goldman Sachs Global Healthcare Conference. We're very pleased today to be joined by Intra-Cellular Therapies. Thanks so much for joining us here this morning. Maybe we'll just start with an overview. I know most people probably know the story, but I think it's helpful to get started there. So focus on maybe some of the key value drivers you see over the next, let's call it, 12-24 months. I'll hand it to you, Sharon. Thanks. Should I start with, or maybe I'll start with a little bit of the history of the company and then. Sure. Whatever you think is most relevant. Well, what's relevant is Intra-Cellular Therapies. We started it in 2002 to commercialize technology from Dr. Greengard's laboratory, looking not just on the surface of the cells, but downstream intracellularly. I think we're very pleased that we started in 2002. We have our first product approval, and that's for CAPLYTA, that I'm sure will be the bulk of the discussion today. Our first product was approved in 2019 for the treatment of schizophrenia. We launched at very challenging times, just as the pandemic was occurring, but we were very successful. Then in December of 2021, we received our label expansion for the treatment of bipolar I and bipolar II depression. The trajectory of CAPLYTA has been very rewarding, very pleasing to see since that time, such that last year we grew revenues by 86% to $462 million. We are on a trajectory this year where we've guided you higher between $645 -675 million. So we're very pleased with the trajectory of CAPLYTA. I'm sure we'll talk a lot about our continued quest for label expansion in MDD. But just to give you a little summary, we have a very robust phase three program, registrational program in MDD. Our first study read out very, very positively, and we are very anxiously awaiting the second readout, which will happen later this quarter. So we also have other label expansion studies for CAPLYTA that we can go into. And then we have a very robust pipeline with 1284. I don't know, do you want to say that or. We can get to it in a minute, but if you want to provide an overview, that's fine. Okay. Overview is we have a very robust pipeline, 1284, which is a deuterated lumateperone that is. And then we have also studies for agitation in Alzheimer's disease and psychosis in Alzheimer's disease. And all of these studies are phase 2 studies, but they're powered as phase 3 studies. So, and their size, which means they're also sized as phase 3 studies. So we're very much looking forward to that. And then our newest research program still is our what are called non-hallucinogenic psychedelics or neuroplastogens, which are for rapid treatment of depression and other mood disorders that we hope to bring into the clinic next year. Great. So much to go over, but appreciate the overview there. As you said, CAPLYTA has seen pretty strong growth over the past several years. This year, guidance $645 -675 million. Let's talk about some of the drivers of that growth, particularly as we look forward, where do you see kind of sustained growth coming from? Yeah. So as Sharon mentioned, we have been very pleased with the continuing, really robust prescription growth that we've been seeing unabated. And I think the growth is coming from a broad range of areas as CAPLYTA is not really being niched in any particular area. So when I say that, we're seeing very strong use both in bipolar I and bipolar II. We're seeing use across the various lines of therapy. So we see new patients, first-time patients being put on CAPLYTA, as well as switch patients coming from other antipsychotics, both generic as well as branded products. And so we see it being used as both monotherapy and adjunctive therapy. So it really is getting a good broad use. And I think the growth is coming from two metrics that we look at very carefully, is the breadth of our prescriber base. So how many unique prescribers of CAPLYTA have there been? We're now up over 40,000 unique prescribers. We're adding 3,000-4,000 new first-time prescribers of CAPLYTA every quarter. We continue to grow the depth of their writing as well. Each of those physicians are writing more and more prescriptions. As a physician gets more and more comfortable with CAPLYTA in their practice, they find additional patients to put CAPLYTA on. That's really where the growth is coming from. We see that strong growth continuing into the future. Before you go on, I would like to just interject, please. I think that I neglected to open with the fact that we're going to be making forward-looking statements. I would refer you to our, that actual results may differ, and I would refer you to our website and to SEC filings for continuous updates on the company. Absolutely. I do that with our disclosures as well sometimes. Okay. So you talked about some of the growth and where you're getting it from. I guess you've also put some metrics in terms of quantifying the breadth as well as the depth. Maybe you could just provide us an update and kind of how you think that could continue to build from here. Yeah. We really, since the launch of bipolar depression a little over two years ago, which is where the majority of the growth is coming. Our schizophrenia business is growing. It's growing solidly. We're seeing good growth there. But the real explosive growth that you've seen with CAPLYTA is coming from bipolar depression. And that's coming both from, as I mentioned, increasing the breadth of our prescriber base, so 3,000-4,000 every quarter. And that's been very consistent. So we see that continuing into the future for some time, as well as the depth of prescribing across that prescriber base of over 40,000 physicians now, the depth of prescribing is getting deeper and deeper. So that's really where the growth is coming from, from both of those areas. We continue to put promotional effort against finding both new prescribers of CAPLYTA as well as the existing prescribers prescribing for more patients that they find appropriate in their practice. What have you seen with respect to both the compliance and adherence to CAPLYTA? Can you just contextualize that for us relative to the broader antipsychotic landscape? Yeah. You know, back when we first launched CAPLYTA, we had a hypothesis that we would see very strong compliance and persistency, mostly because of the very favorable safety and tolerability profile that the product has. Now, there's a lot of reasons why patients don't comply or persist with their medicine. Safety and tolerability is a big one. So as we got out in time from the schizophrenia launch and we look back at persistency, because you follow these cohorts of patients over time, so it takes a little while to gather the data. And when we compared CAPLYTA to other recently launched antipsychotics, we found that CAPLYTA was indeed outpacing the other antipsychotics in terms of the persistency. So that wasn't a surprise to us. It was more confirmation of the hypothesis that we had. Now, we're getting close to having enough on bipolar depression. We don't have quite enough data yet to be able to look at that fully. But from anecdotally, what we hear and what we see from physicians and from patients, we don't see there being any real difference in bipolar depression in terms of any issues with persistency with CAPLYTA. Okay. You've spoken to gross-to-ne t in the mid-30s over the course of the year. I guess, is it right to expect that over the longer term as well as we look forward? I know maybe we add in the MDD launch that's coming as you talk about kind of the growth tonight on the forward. Yeah. So we guide on an annual basis the net growth. And as you pointed out for this year, we've guided to the mid-30s% for the year. Our Q1 came in in the mid-30s%, and we expect the remaining quarters of the year to come in at the mid-30s% as well. Without providing guidance longer term than that, what I would say from a net growth perspective in this category of antipsychotics, unlike some other categories, payers don't manage these products at the indication level. They manage it at the brand level. So in other words, they don't have specific criteria for each of the indications. They have them the same across the board. So just as when we went from schizophrenia to bipolar, we didn't see a rise in our rebates. We don't expect to see that in MDD either. Without providing you long-term guidance on growth tonight, we also don't expect that to rise with the addition of a new indication. This might be sort of a tricky question to answer, so I'll ask it two ways. I guess, as you think about where we are relative to sort of like the peak opportunity for CAPLYTA in maybe these two first indications, or like what inning are we in is a great sports analogy everyone likes to use. So where do you think we are relative to kind of the peak opportunity set here? Yeah. We think we're still in the relatively early innings of this game, you know, especially bipolar depression. It's a large patient population, large group of prescribers, significant unmet need, and fewer approved products to treat bipolar depression. So for all those reasons, the kind of growth that we've seen early on with CAPLYTA, we expect to see for years to come. Okay. And then as you think forward, and perhaps this is a little tricky, and I'm going to make some assumptions here that the MDD trial looks as good as the first or almost as good as the first and it gets approved. But as you look at the antipsychotic market and the CAPLYTA sales, you know, five or six years from now, what portion would you expect to come from each of the major indications? Yeah. No, good question. I think what we always do in cases like this is we look at historical preference, right? So there's some good ones. The most recent one, honestly, being Vraylar, because if we go on to get an approval on MDD, we'll have a very similar indication set as Vraylar. So if you look at their data currently, the vast majority of their prescriptions come from the mood disorders, either MDD or bipolar depression. And the last time I looked, I think their schizophrenia business was less than 10%. So over time, and that makes sense, right? Because schizophrenia is 2.4 million U.S. adults. Bipolar depression is four to five times the size of that at 11 million. MDD is 2x bigger than that at 21 million. So these are very large patient populations in the mood disorders. And that's where the antipsychotics really begin to grow and really become blockbuster products. And the schizophrenia portion, while important and certainly important to patients and important to the company, becomes less and less a portion of the overall business. Sure. The breakdown between bipolar and major depressive disorders, it's harder to know? I wouldn't say it's hard to know. It's probably about the same. MDD, I think if you look at the antipsychotic prescriptions in the marketplace, it's the largest indication. Bipolar depression isn't far behind. They're both very large populations, very large indications in terms of antipsychotic prescribing. The addressable population is pretty similar. Even though there are many more patients with MDD, there are patients who are treated sufficiently with their SSRIs and SNRIs. Population size is fairly similar. There's probably a little more with MDD, but they're not far off. Okay. That's helpful. I got the cart slightly before the horse. So let's go back to the data in MDD. You recently reported the phase 3 results. We expect another one reported by the end of the quarter, end of the month or so. Maybe you could review the data to start and just level set us on what you showed in that first phase 3 trial. So what we showed in the first phase 3 study was that patients were extremely robustly treated for their major depressive episode and adjunctive treatment. In adjunctive treatment, you typically look for a change in the MADRS of two to four points. And what we saw was over that. It was almost five points. And consequently, the effect size was extremely robust, no matter what you looked at. If you looked at the primary endpoint, which is change from baseline on the MADRS, or if you looked at CGI, or if you looked at whatever metric you looked at, the effect size was between 0.6-0.7. So it's very, very robust. So we're very, very pleased with that. It is much more difficult to treat patients adjunctively. And it makes sense, right? Because these are patients who are already being helped with their antidepressant, but just not sufficiently. So that's why typically, and we power the studies to be for a two-point change, because typically that is what you see between, you know, two and 3+ points. And so we were extremely pleased in the results that we got. And it does track along what we saw in patients in monotherapy with mixed features, where again, it's mixed features. So maybe you'd say you'd go to the higher change in points. However, these are very, very difficult to treat patients. And there too, we had a very large effect size. So we're seeing this over different studies. So we're really, really pleased with what we're seeing in treatment of all of these mood disorders. To your point, it was like the best ever placebo-adjusted response in this kind of setting. So as you think about what you'd attribute that to, and it may be difficult to do this, how much of that do you think is CAPLYTA being a great drug versus the trial execution that you guys have run? Well, of course, you can never dissect out all of the above. But I do think that, you know, our vision is to establish CAPLYTA as the drug of choice across these mood disorders. And we've been showing it across, you know, the depressive disorders, across even in our schizophrenia studies where patients came in with comorbid depression, we were very robustly able to treat them. So, and these have been different trials over different countries, over different time frames. So I do think the drug is definitely having an effect. Now, having said that, I think our clinical team is terrific. And I think they know how to execute clinical studies. Yeah. With that in mind, how should we think about read across from the success you had here, the success you had in mixed features to the upcoming phase 3 readout? Yeah. Well, I am very superstitious, and I don't want to count my chickens before they hatch. I'm hopeful. I think the study is designed the same way as the first one. It's powered the same way. The only way it differs is there are different clinical sites, meaning there are some different countries. But that's because you don't want to be competing with yourself and enrolling in the same clinical sites simultaneously. And these studies had a large overlap when they were conducted. But I think the important things, like the powering, like the number of sites, like the oversight, et cetera, are the same. So we're very hopeful for the study. Assuming that both end up being positive, you've commented that you could file for approval by year-end, I guess pending that it gets approved and on market, where do you think the most natural case or fit is in terms of adoption for CAPLYTA in this patient population? You want to take that or you want? Yeah. So in MDD, the antipsychotics are very well established being used adjunctively. That's where our indication would be. So these would be for patients who have had some response on their SSRI or SNRI, but not an optimal response. And so you add the antipsychotic. The results of the first trial, as Sharon said, were even better than we expected. The efficacy was extremely robust. We saw the same safety and tolerability favorable profile that we've seen in the schizophrenia population, in the mixed features population. So that was replicated. And we have a dosing regimen that is simple, convenient, one dose once a day. The physician can start the patient at the effective dose and maintain them on that dose. That is a very compelling product profile in any indication, but certainly in MDD. So as Sharon said, I think our vision, I know our vision is over time to become the drug of choice in the mood disorders. We think with a profile like is emerging from the clinical trials that that is achievable. We should not minimize the ease of use. Just for those who may not be familiar traditionally with the antipsychotics, the theory was that you keep increasing the dose until you get all these movement disturbances and akathisia, and then you back off. Here with CAPLYTA, we've shown that that's not necessary. You can start and stay on an effective dose. And I have to say, prior to an approval, we did get some pushback on that. But maybe COVID actually helped us because docs were extremely thankful that they weren't being called in the middle of the night. What do I do here? You know, these patients, they're either not being helped. We need to titrate them up. We need to titrate them down. But now it's just everybody just says, yeah, start and stay on the single dose. So I think that parents like it, patients like it, caregivers like it. So we think that that has really turned out to be very important for the product. Sure. As you look at the success you've had here in the phase 3 study, I guess, do you have any consideration for further study in a monotherapy setting? In a monotherapy in MDD? In MDD. Yeah. So we're thinking about it. It wouldn't be your standard study, but we are thinking about it. We've had some discussions with the agency about it, and we're weighing our options here. We'll see how we go forward there. Okay. And as you think about other kind of indications that you could go through, you've referenced a few, but maybe you could run through the list of the expansion indications that you are actively considering and sort of talk about why, like what the mechanistic rationale is for CAPLYTA in those patient populations. So certainly we have a very robust pediatric program. That's first. In the pediatric program, of course, there's in bipolar disorder, as well as in autism and irritability and agitation and autism. We're also looking at, you know, well, most antipsychotics that are approved, they can be used and they are used off-label in mania. We think there may be some utility, especially for pediatrics in mania. Maybe adults in mania might be one indication then and pediatrics. Then we have a few others that you'll be hearing about from us. Great. What should we anticipate with respect to sales force expansion ahead of this MDD launch, assuming it comes? Yeah, we've said before that we do expect to have a significant expansion. That significant expansion would allow us to optimize the launch, particularly in the primary care community. In our current indications, schizophrenia certainly, even bipolar depression. In bipolar depression, primary care plays an important role, but probably a lesser role than, obviously, psychiatry and the nurse practitioners that support them. As you get into MDD, primary care becomes increasingly important and they see more and more of these patients. So an expansion for us would take us deeper into primary care. We cover today virtually all of the psychiatrists and the nurse practitioners that support them for schizophrenia and bipolar depression indications. There wouldn't be much more there. I think as we think about the launch too, and potential launch in MDD, we currently target about 43,000 physicians, again, mostly psychiatrists and the nurse practitioners that support them, some primary care. Those physicians, by the time we get to an MDD launch, perhaps later next year, would have had four or five years of experience with CAPLYTA. So we would expect a very rapid uptake for those, because virtually all 43,000, they're high-volume prescribers for bipolar depression. They will be high-volume prescribers for MDD as well. So we would expect a rapid uptake there. And then the expansion, as I mentioned, would come by going deeper into brand new targets for us in primary care. Yeah. As we think about the competitive landscape in major depressive disorder versus some of the approved indications, I guess, are there any other nuances that you would highlight as you think about preparing for a launch in MDD? I think in some regards, it's a lot like bipolar depression. Schizophrenia is different. All antipsychotics get their start in schizophrenia. Every single one of them has an indication in schizophrenia. When you get to bipolar depression, there's only a handful of approved agents. I think there's five. When you talk about the adjunctive use of an antipsychotic in MDD, again, there's only four or five antipsychotics approved. So the competitive set is much less than it is in schizophrenia, and in some ways is very similar to bipolar depression. So I think that dynamic will be similar in the MDD indication. So beyond lumateperone and/or CAPLYTA, you do have a deuterated version known as ITI-1284. I guess, talk to us about the target product profile there and why this form makes sense for the indications you're pursuing. So we were looking for a target product profile that would be that we thought CAPLYTA was a great TPP, but then we wanted to be able to express more of the parent and have a drug that can be also used very robustly in the elderly patient population as well as other populations. So our chemists did, they deuterated all around the molecule, and they did find one site of deuteration that they thought was really the most appropriate to be bringing forward for several indications. So 1284 has been through phase one studies and where we've shown that in the phase one studies, it was generally safe and well tolerated, as well as we found that we did express more parent. So the metabolites are qualitatively the same, but quantitatively they're very different, with the parent being expressed the most and then the other metabolites at much lower levels. You know, the phase 1 studies, each patient population, we had one elderly patient population, but it was a very small cohort. And so while there were advantages, that's why we're going into the next studies, because we think that we want to see that these hold up in these studies. I guess, what are those advantages as it translates into the clinic of having something that expresses more parent over the metabolites? Well, one thing was that there was less somnolence, which could be important in an elderly patient population. Now, I should tell you that can be somewhat mitigated by the time of day that you give the drug. But we think that there are a few things, but I'd rather not say them until we show that, until we demonstrate that they're real. Okay. Understood. You've disclosed plans to evaluate this in studies of Alzheimer's disease, agitation and psychosis, and in generalized anxiety disorder. I guess, could you talk about the kind of rationale for this indication selection? Yeah. So first of all, there are large patient populations with large unmet medical needs. So that's the first thing. We're starting these studies, these phase two studies in succession, the first one being GAD, and there we're doing it as an adjunctive treatment to the presently approved drugs that are primarily SSRIs and SNRIs. And then there's one other one, buspirone. So we think there, again, it's like an MDD. It's a large patient population, around 10 million patients with GAD, half of whom at least are not optimally treated. We think that it, and we have seen that we think that the product profile of the molecule is such that we should very effectively be able to treat their anxiety. So that's why the GAD, psychosis in patients with Alzheimer's disease, again, it is the product profile of Luma through its 5-HT2A mechanism, through very importantly, its D1 activity as a partial agonist, and then also SSRI activity. So we think for both psychosis as well as agitation, this drug should be very well suited. Great. And can we get like a status update on these phase 2 proof of concept studies? Where are you in terms of entering the clinic and enrolling patients? And at what point will we get some guidance on timelines for data? We're going to be putting them on clinicaltrials.gov very shortly. The first one will be GAD that we've told you the first half of this year, which is on track of being put on there very soon. Then just a couple of weeks later, the psychosis in Alzheimer's, and a couple of weeks after that, the agitation in patients with Alzheimer's. They're all happening in very close proximity to each other. I imagine it's too early to say like on these trials timelines for data, but as you look at precedent, maybe like how long do these trials typically take for a large robust phase 2 in each of the indications? Yeah. So there aren't no, well, successful studies, there's no indication for adjunctive treatment in GAD. So that one, when we put it on ClinicalTrials.gov, we'll give you our best estimate of the enrollment. Psychosis in Alzheimer's and agitation in Alzheimer's, those studies are long studies. They are difficult to enroll patients. And so those are each, I would tell you, a couple of years. Okay. You mentioned earlier one of the early stage programs for non-hallucinogenic, basically psychedelics. I guess, talk about the target product profile as you think about a product in that space. Yeah. So we're really proud, I'm really proud of our chemists and what they've done here. So this is an area that has typically been looking at 5-HT2A agonists that go down a pathway of both beta-arrestin and G-coupled proteins. And the hypothesis is that the G-coupled protein pathway is what causes these hallucinations. So we have what are called biased agonists. So they go down the beta-arrestin pathway. In animals, they don't cause the hallucinations and the delusions. And we do know that in our animal models, they are rapid acting. We can give them daily or we can give them intermittently. So we're very excited about this program. And we think that not having the hallucinations is important from a safety standpoint. And it also, well, we don't have the equivalent so far of the cardiac toxicities that you see with the psychedelics that do cause hallucinations and delusions. We are really, really excited about this program. It's very early, but we think that there's a lot of promise here in the mood disorder space. And we'll be looking at both acute use and chronic use, which we think can be important in these patient populations. Okay. Maybe a couple of miscellaneous questions with our last few minutes here. How are you thinking about ex-US expansion for CAPLYTA? Is that something that would be of interest for you, particularly on the back of the MDD success? Yes. I think ex-US, I mean, patient populations are important patient populations. We do look to expand ex-US. I think we're being very deliberate in how we look at these countries. And we do expect us to be there. It will just be in a very thoughtful way. Okay. Does that, I guess, think about partnership versus going it alone, is that something you would be considering doing on your own? Or is that something that you think a partner would be really helpful for? I think at the moment we're looking at it in partnership with others, not going it alone. Okay. I think one of the things that came up on the last quarterly call was like business development as an area of interest. I know you've been talking about it for a while, but it was a focus there. I guess, as you think about capital allocation priorities, where does BD rank? Yeah. I was a little bit surprised that that quarterly call got so much attention that it did, because I said nothing I haven't been saying for almost two years now. And that is that, you know, a company our size, of course you're always looking at business development. Optimally, we would be bringing in something that Mark and his group, an approved product that they could add to their bag and that they could be out there selling. To date, we have not been successful finding that opportunity, because I think they just don't exist, quite honestly. You know, if they're so successful, they're in a larger company who wants to keep it. Or I think we just haven't found that opportunity yet. We continue to look. We are hopeful there is something there. So we've gone earlier and we look earlier at these opportunities as well. Then we also look at very, at much earlier opportunities. But this is, again, it's nothing new. It's nothing we just started doing, haven't done. Yes, we are very well capitalized, $475 million in the bank. And now with the raise, $75 million, we have over $1 billion, we have about $1 billion on our balance sheet and we have no debt. So we're very happy with the position that we're in. And we will be very prudent in our spend of that capital. And we are very, very focused on CAPLYTA, the expansion of CAPLYTA, and what makes best sense for CAPLYTA. Okay. Then in terms of round out that conversation, as you think about like sources of capital for it, is it something where you would consider taking on some leverage, obviously noting you don't have any at this time in order to do a deal that was attractive in your view? I think, you know, I don't think we'll cross that bridge when we come to it. We don't, we have no need for taking on any leverage right now. Perfect. This was a great conversation. Really appreciate the time this morning. Great. Thanks to everyone who joined us here and on the webcast. Thank you so much. Great. Great.