Okay, I think we'll get started. It's great to see everyone. We are nearing the end of the morning of the second day of the Cantor Global Healthcare Conference, and I've had five in a row, and you know, they say you should save the best for last. And frankly, we're doing that this morning in many ways with a company that I've known for a long time, several years, Intra-Cellular Therapies. And it's been fun to watch this one go from absolutely an early, you know, out of the university lab idea development stage company to a company that is now a fully integrated revenue generator, high growth, top line, impactful with a drug for patients, and then a pipeline. So it's great to introduce, Dr. Sharon Mates, who's the company's CEO, has been the company's CEO for this entire time, and Dr. Suresh Durgam, the company's Chief Medical Officer. Sharon and Suresh, thanks for joining me today. Thanks for having us. Thank Thank you. Great to see you. Sharon was just vaccinated. Happily, she's here. Been flying all around. So we'll take it easy at the beginning and ask you seemingly a softball question, which is actually not so soft, because we want just one answer, and that is, if you look back over the last year, what are you most proud of having accomplished as a team at Intra-Cellular? So first, thanks, Charles, for having us here. Secondly, yes, I've been flying all over the place, and I think my ears are still somewhere in the air. So I hope I can hear everything and that everyone here can hear me. I should also say that today we will be making forward-looking statements within the Private Securities Litigation Reform Act of nineteen ninety-five, and I refer you to our website and to our SEC filings, as actual results may differ. So having said that, as I said, I'm flying all over the place. We have, you know, we do have a larger company than when you and I first met. Yeah. I think we did meet when we were a private company. Mm-hmm ... and, we had just taken the technology out of, Dr. Greengard's lab- Mm ... which we use to be able to interrogate cells in the brain, and help us create our platform of CNS profile. So I'll fast-forward that to Caplyta's approval in two thousand nineteen, which was for the treatment of schizophrenia, was our first approval, and two years later, in twenty twenty-one, we received an approval for bipolar depression. So you asked me what I'm so proud of, and I'm sure we'll get into all the questions about MDD. Yeah. And now we've had just spectacular results in MDD, and I think I'm very proud of our organization. I think our team. In fact, I'm just coming from our primary care expansion- Yeah ... meeting. Okay. Where was that? That was in Orlando. Yeah. That's where I was, the last couple of days. So, I think I'm extremely proud of all that. For those who don't know us, last year, we, with Caplyta, had $462 million in revenues, which was an 86% increase from the year before. And the first half of this year, we had a 50% increase, over first half of last year, and we've projected for $650 million-$680 million in revenues this year. So I think- Wow ... we're very proud of that. We're very proud that we are helping patients and that we think that we will continue to help patients both in bipolar depression and schizophrenia and hopefully, as we progress, in major depressive disorder as well. Yeah, so a real drug with real impact with patients and a potential TAM expansion on the horizon, which we will talk about. But not a ton of antipsychotic drugs become billion-dollar molecules. There are a few, but this is one that could do, it seems, even on the back of just schizophrenia and bipolar. Right. I think, just to frame the market, so schizophrenia has about 2.6 million adults. Bipolar disorder has four to five times- Yeah ... that population, which is why we saw this hockey stick- Yeah ... upon approval for bipolar disorder. So it's about eleven million patients with bipolar disorder, and MDD is an even larger population of about twenty-one million, but the addressable population is about the size or a little larger than bipolar because some patients are treated effectively on their SSRIs or SNRIs. So this would be adjunctive therapy and- Yes. So, so we are looking at adjunctive therapy in major depressive disorder for those patients who are being helped by their current antidepressants, but not maximally, so they still need something else. To bring the audience up to speed, to bring me up to speed, and to remind us of the inherent properties of Caplyta (lumateperone) that you believe are getting traction in the market, I'm gonna ask you a question. But I also wanna bring Suresh into the- Mm-hmm ... conversation because he used to be at a company that has one of those billion-dollar molecules, and so what is it that really you think attracts prescribers and patients to Caplyta lumateperone, not only in schizophrenia, but bipolar and maybe an eye towards what will happen in MDD? And you were at AbbVie. Yes, I was started with. I'll say AbbVie. With Forest Laboratories. With the drug Vraylar. Different iterations of Forest Laboratories. Yes, yes. In terms of your question regarding lumateperone, what we are hearing from our key opinion leaders and prescribers, and also when going to conferences, that if you look at the compound itself, we have shown that in terms of the efficacy, it was shown efficacy in schizophrenia, bipolar depression, both in one and two, as monotherapy and adjunctive therapy. And recently we have announced results of adjunctive MDD in patients who don't respond to had inadequate response to SSRIs or SNRIs or other antidepressants. So in terms of the profile itself, one of the reasons patients usually switch medications is due to the side effect profile. Looking at the side effect profile that is most commonly considered liabilities for antipsychotics are metabolic issues, that is both increase in glucose, insulin resistance, as well as triglycerides and cholesterol. And then EPS, that is extrapyramidal symptoms, is another big major burden. Yeah. And weight gain- Mm ... as well as increase in prolactin. These are the common ones that people look at- Mm ... thinking about antipsychotics. And we have shown that in the data that was generated, in all indications, starting from schizophrenia to recently announced MDD indications, we have seen that in all these, the metabolic parameters, prolactin, and weight, they were all, and EPS, they were all similar to placebo, and it has shown over and over again in every indication. I think that that resonates, and also the efficacy is strong. If you have seen the results we have announced for MDD, adjunctive MDD, the effect sizes were very robust. Quite, quite nice. Um- Point six. For an adjunctive treatment, yes. Yeah. Point, point six. Point six, yeah. Very nice. Very nice. So we'll talk about MDD in a second, but one, you know, last commercial question, and I promise not to ask too many. But I wondered if this profile is gaining traction in the market with regard to adoption, but also more importantly, or as importantly, with regard to prescription refills, persistence, maybe less so in the schizophrenia population, but certainly in the bipolar depression population. In both schizophrenia as well as bipolar- Okay ... we've had very good patient retention. Mm-hmm. We also have very good coverage. So in the Medicare and Medicaid, which schizophrenia is primarily covered by the public markets- Yeah ... you know, 80-plus% in public markets. Medi- Medicaid. We have virtually, you know, you never have 100%, so we'll say greater than 99% coverage in the public markets. Then in the commercial markets, where we also have very robust coverage, and it's about 90%, which is on par with the other branded antipsychotics that have been around longer than us. So we're very pleased with our coverage, and we're very pleased with the retention rate on drug, and you'll see in our MDD studies, where we do, you know, you do these open label safety study- Yeah ... that you allow patients to roll over. We also had a very large percentage of patients roll over, and they also stay, have stayed on the drug. So, typically, you have very large numbers of dropouts on these. Mm-hmm. We've not had such large numbers of dropouts. Mm-hmm. So we're very pleased to see, and which is why you see in our refill rates, they're quite robust. That's nice, new incremental information with regard to the open label extension, experience. I think that's Study 503, if I recall- You're absolutely right. Yeah. That's right. Yeah. When do you think you'll be able to publish that information? Because like you said, you have very nice efficacy data that you've released from two Phase IIIs. Yeah. It'll be next year sometime. Right. So Suresh, Yeah ... as I recall, your experience with this other drug at the other company, you had to run several studies to get a couple work out. Were you surprised to see how robust the data was and how consistent it was across studies? In terms of the mechanism- With MDD? Again, when we designed the trials, we based on, again, we have shown in our very first trials with schizophrenia also, we included patients who had depressive symptoms. Mm-hmm. That was our first indication. Mechanistically, we thought it could work. Okay. But looking at including patients, schizophrenia with depressive symptoms, in that small subset of patients, we also saw improvement in symptoms of depression. That led to our bipolar, and also we have seen replicated the same thing, and the results for the bipolar mood space was very robust. And then, with the same knowledge, we have taken into adjunctive MDD, and we were able to replicate that, too. And we, again, typically, you would expect a two- to four-point difference between drug and placebo in MDD trials toward the lower end for the adjunctive. But in this particular case, maybe with the mechanism, you know, contributions from different aspects of the drug with the SSRI action, the 5-HT2A antagonism, contribution from the glutamate, indirect D1 indirectly acting on the NMDA and AMPA, all those might have contributed to the superior, maybe the strong efficacy we have seen. Yeah, I was actually quite surprised by the effect size and the, you know, frankly, the absolute change. I... On top of standard of care, I thought you'd get a few points- Mm-hmm ... three-ish, right? Maybe four. But very, very good on that. Do you think that the patient sample that you enrolled in the adjunctive MDD study is representative of the broader population? Does this translate into potentially a broad use of the drug in MDD, should it be approved? Yes, it is. You know, because, again, looking at patients who had inadequate response to treatments, and that's exactly the population we have looked at, and similar to other, you know, what are approved products, that that will translate into patients who don't respond to one or two drugs, you know, in the initial phases. When prescribers are now much more comfortable, as they have been used to seeing the antipsychotics over now several years, they're comfortable switching to adding on an antipsychotic early on in the treatment. So, and we have shown that population that this is working well. There's also the side effect. If you are adding on top of another compounds, we also showed that the side effects are not increasing. Yeah. So we'll talk a little bit in a few minutes about the future of psychosis treatment, specifically with insight, schizophrenia. But before we do, let's talk about the adjunctive treatment of depression and what you're doing from a strategy standpoint to enable that. You said you just came back from Orlando, so you have a commercial infrastructure. You're going to perhaps expand a little bit. But what are next steps for you in terms of seeking that label expansion? Right, so currently, we have a sales force of about 370 sales reps. Okay. Or had, I should say. We've now just finished an expansion, adding another hundred and fifty- Mm ... sales reps. Now, the 370 covered 43,000 targets, and these are all of the caregivers who treat schizophrenia, bipolar depression. Mm-hmm. Some of them treat MDD, or the psychiatrists all treat MDD as well. Yeah. However, we also address those high-prescribing primary care docs and nurse practitioners, PAs, who, while don't cover schizophrenia at all- Mm-hmm ... they do cover bipolar depression, and now we're adding those primary care targets who also address major depressive disorder. Okay. So we already have the psychiatry world, and we're going into the primary care in a much deeper way now because they are comfortable prescribing for MDD, and more and more. That's what I heard. ... they're seeing for bipolar. In fact, they're up to 25% of the scripts for bipolar now. Yeah. I mean, with our healthcare today, it's going more and more to a primary care world. So we now, with our expansion, have about 530 reps, and we'll account for we've gone from 43,000 targets to 70,000 targets. So I think we're covering the United States very effectively. Wow, that's a competitive field force, that's for sure. It is. It is. Impressive. Uh-huh. From the days of old, right? Right. Big, big company, but big opportunity. Right. So, should you see a label expansion, which I entirely believe will happen, my opinion, would this sales force be prepared to hit the ground running, it sounds like, and make an impact, you know, within the first or second half of the year next year? I think you should look to the second half of the year- Okay ... next year. Okay. Um- That was sufficient. We first have to file for our approval- That was sufficient. ... which will be this half of the year. Okay. I think yes, so we will. And so right now, these representatives will be going to be educating on bipolar disorder, and then, but they'll have experience with the drug for when we launch it. And the calling. Mm-hmm. But, so I was fishing. You're gonna file this half of the year, but it's a label expansion for a drug that's well-known from a safety and efficacy standpoint in the market. Couldn't it be a rapid review? I think we would guide you to a standard review. Okay. This agency really is accustomed to standard reviews, and that's 10 months. Okay. But there's no data or anything that you intend to file later on that- No, our- But beyond what- ... our filing is very straightforward. We did have our pre-SNDA meeting. Everything's agreed upon, everything... I mean, it's putting everything, the whole package together. There's always a big package, even though it's an SNDA- Sure ... filing. And if you're sitting here talking to me, you're not- Oh, believe me, he doesn't get out very much anymore. So the indication that you would request, I assume, is adjunctive MDD? Right. That's correct. Would you seek to include or call out on the label anything about mixed features? It seems to me like that's not necessary. It would be obvious to a prescriber that the drug should work, but there was once a debate on that, and so how do you... where do you come down on that debate right now? In terms of the current, what we're filing would be, focus is on adjunctive MDD. Mm-hmm. Of course, any positive data in indications, including mixed features, is going to be helpful in the overall package. And in terms of the current indications, of course, it'll be adjunctive treatment for major depressive disorder. And in terms of your question regarding mixed features, we are presenting the data at conferences. We are going to be soon publishing it and talking about this at conferences. And future, how we progress, that's the next step, but for right now, our focus is adjunctive MDD. And also, I want to remind that in the current label for the bipolar- Right ... we are covered for the overall population. For the mixed features in bipolar. Okay. Correct. You don't have to seek a special label on that? No, our... The indication is a broad label for- Yeah ... adjunctive treatment of major depressive disorder that we're seeking. So I haven't done this math. I should do it quickly in my head, but I'm not going to. I'm gonna ask you, and that is that if you took $600 million in revenue and split it between schizophrenia and bipolar, what would be the rough contribution of the two? Right. So presently, obviously, it's all a numerator-denominator story, right? Yeah. Because of the patient number. So when we started out, schizophrenia was our total revenues. Then bipolar came... And, and by the way, I should remind everybody, we launched just as the world was shutting down. December, yeah. 2019, right? In March. Well, we got approval in December of twenty nineteen, and we launched in March- Oh, right, right. ... of 2020. Right. Yeah. How quickly you forget. We launched- Yeah ... right as things were being shut down. Crazy. We had to cancel our in-person national sales meeting, and we went fully virtual. Yeah. Even in the face of that, we did quite well in schizophrenia, and then in December 2021, we received approval for bipolar depression, and we were able to immediately launch for that indication, and we did have this hockey stick-like projection. That has continued. We now have gone from total schizophrenia when we first launched to right now. We're under 20% of our scripts are in schizophrenia. I think that is what, if you look at, the other antipsychotics that have had an approval. It is purely. It doesn't mean that schizophrenia is not an important indication. It means just the sheer patient size. Yeah. So, you look at Vraylar, that we were discussing before. AbbVie says they're under 10%. So I think as our numbers go up, you'll see our percentage in schizophrenia decrease as well. It's patient size, so it's prevalence, but it's also perhaps incidence with versus bipolar, but it's also compliance and persistence and sticking with the drug, and- Right ... and so as the world of, treating psychosis, specifically schizophrenia, may change here shortly, you know, I'm gonna ask you how much of a change that is. I guess that's probably the smaller piece of the pie, and what is really interesting or important to you is that you continue to differentiate Caplyta in the marketplace with regard to its depressive properties, not, certainly for bipolar and MDD and adjunctive MDD, but not necessarily its antipsychotic properties, correct? We think that Caplyta should be the drug of choice for mood disorders. Okay. So, you're correct in all of the depressive disorders. One thing you should remember, too, while the numbers change, the diseases don't. Correct, right? So, and in schizophrenia, it's the patient journey, and, you know, for instance, their lack of insight. Yeah ... which causes them to believe that, you know, "I'm cured. I don't need a drug," which is why those patients cycle more than in any other indication. Mm. So regardless of the drug, they continuously cycle from drug to drug. Also, for schizophrenia, there are 20-plus generics- Yeah ... approved, and bipolar, there's many fewer. So we're at, you know, very few drugs, less than a handful. And they're primarily branded drugs. As well as in adjunctive treatment in MDD, the same thing. Yeah. Less than a handful. Yeah. Yeah, so very different situations. So they're... Schizophrenia, they feel like they're better. They don't have insight, and then the side effect profile starts to raise its- That's right ... its head. Very. With bipolar, maybe there's more insight, and, oh, by the way, the side effect profile, the differentiation, very different for Caplyta than some of the other drugs, perhaps. That's right. Very good. You think that that plays out in MDD as well? Even more so maybe. I would think so because again, if you take the profile we have, in terms of the side effect profile, for example, first, with the efficacy, it was robust efficacy. And then if you look at the side effect profile, we have consistently shown that even in MDD population, the profile has not changed. What we have shown with schizophrenia and bipolar is still the same profile with respect to, again, the metabolic parameters, the prolactin, and weight gain. They were all similar to placebo, so there's no changes there. So I would expect that the same thing will continue for adjunctive MDD also. The same thing with the movement disturbances. So our safety profile has persisted across each indication, which is really rewarding for us to see in our clinical development. So last question on this, and then I want to talk about pipeline for the next half an hour. Last question: Will the world change on September 26, I believe it is, with KarXT perhaps being approved, with regard to the competitive environment and what you face in terms of treating schizophrenia, and then the other indications? There are no other indications- Right ... right now, okay? Right. So for schizophrenia, these patients, as we said, they constantly cycle through these drugs. Mm-hmm. So we think that any option is great for patients, so we look forward to any new entrant for schizophrenia because they will continue to cycle through these drugs. Again, we think that, I mean, again, we think schizophrenia is an important patient population- Yeah ... but it is of nowhere near the magnitude that these mood disorders show. Sure. And so far, we're the only new entrant, and I don't even see anybody on the horizon there. Yeah. I think that we continue to pursue. We have many clinical studies ongoing in pediatric populations, in autism spectrum disorder, and irritability and agitation in autism, in the pediatric population as well. I think that we have a lot of expansion still with Caplyta. With just Caplyta, and irrespective of the impact that the muscarinic modulators, the agonists, may have on the treatment of psychosis, they can't get to depression. They can't get to some of these other indications that are really the growth engine for Caplyta. I'm not gonna speak for anybody else's molecule, what they can possibly do, but I can tell you, certain- As an analyst, I believe they can't get there. Okay. Oh, all right. So fine, I can- You know I'm always right. I can agree with you. Okay. Right. So let's talk briefly about 1284, an oral dissolving tablet. Mm-hmm ... sublingual for lumateperone, basically. What are the next steps with that? We're in a clinical trial for GAD. Yeah. You wanna talk about GAD a little bit? Sure. Yeah, for the 1284, we are progressing several studies. We have already started the adjunctive generalized anxiety disorder study. That is the first study we have started. We also have started our psychosis in Alzheimer's patients- Okay ... and looking at the behavioral psychosis. We are just. Also, soon we'll be starting agitation in Alzheimer's and also a monotherapy study in adjunctive generalized anxiety disorder, GAD. So all these studies, two have already started. One, other two will start pretty soon. So we are in three indications, and these are all studies that even though they are Phase II studies, they are powered as Phase III, and if successful, can be used as a registration study. I look forward to seeing those outcomes. Unfortunately, we are pretty much out of time, and I do have another half an hour worth of questions for you sometime. So please join me again. Sure ... on a Fireside Chat. I appreciate the- I will ... time that you've spent with us. Thank you. Sharon and Suresh- Thank you … Thank you to the audience for your interest in this.