Hi. Good morning, everyone, and thank you for joining us for this next session of Baird's Global Healthcare Conference. I'm Joel Beatty, one of Baird's biotech analysts, and I'm pleased to have us for this session with Intra-Cellular Therapies CEO, Sharon Mates, and Head of Investor Relations, Juan Sanchez. Thank you both for joining us today. Thanks for having us. Thank you, Joel. To begin, could you begin by providing an overview of Intra-Cellular for those who might not be familiar with the company? Sure. Thanks so much. It's a great pleasure to be here to tell you about Intra-Cellular Therapies, our past, our present, and our future. But before I do that, I do have to tell you that we will be making forward-looking statements today within the meaning of the Private Securities Litigation Reform Act of 1995, and actual results may differ, and we refer you to our website and to our SEC filings for continuous updates on the company. So having said that, we have been around since 2002. I'm one of the founders of the company, and we started the company in 2002, taking technology from the Greengard lab at Rockefeller, who had just received a Nobel Prize for his work on intracellular signaling pathways in the brain. And we took that technology to help us look at these pathways in the brain, to be able to compare different drugs and look at, as we made molecules, what might be helpful and what would be not helpful in developing new chemical entities. So we did that, and we set up a platform, and we call that platform CNS Profile, and it's a useful tool to look at different agents. So now fast-forward, though, and I'll tell you about some of our molecules, some of which we use CNS Profile to help elucidate these pathways in the brain. So our first product that's been approved is called CAPLYTA, and I'll tell you now, we talk about it as lumateperone when it is not approved in indication, and we call it CAPLYTA when it's approved and on the market. So our first approval for lumateperone, it's now CAPLYTA, and it's for the treatment of schizophrenia and bipolar depression. We first received approval for schizophrenia in 2019, and we launched in March of 2020. To remind everybody, what happened in March 2020 was the world shut down, and in particular, the U.S. shut down, and we were very adept at moving everything from in-person detailing, et cetera, to everything being done online, and we were successful in our launch. And then two years later, in December of 2021, we received an approval for our second indication for bipolar disorder. And those who have followed our trajectory, you see we've had, like, this hockey stick-like trajectory when we received approval for bipolar disorder. That is because schizophrenia, while a very important indication, has about 2.5-2.6 million adults, whereas bipolar disorder has 4-5 times the size population of over 11 million patients. Then I'll tell you about what is in the pipeline and what we are very excited as our next indication, MDD, or major depressive disorder, which is an even bigger patient market of about 21 million patients. So. And we expect to see another hockey stick-like trajectory with an approval in MDD. So our revenues last year, in 2023, were $462 million for CAPLYTA, and we've guided you to $650 million-$680 million this year. So we continue to have a very robust trajectory in bipolar depression, and we're very pleased. So we have also said, by the way, and I know we'll get into this later, that presently we have reps visiting primarily psychiatry offices. However, we do have a component of who visit both the primary care offices as well, and I think we'll talk later about increasing our reps to go deeper into primary care, first for bipolar disorder, and then for MDD upon approval in MDD. So I think that's CAPLYTA. In addition, we have a very rich pipeline, and we have that are in clinical studies. First of all, we have a very large pediatric program with lumateperone, which is very important because there are, it's a very large patient population there, too, about six million patients for the indications that we're looking at in bipolar disorder in this patient population, autism, irritability and autism patient population. We have our next development programs are 1284, which is deuterated lumateperone, for the treatment of generalized anxiety disorder. We also have a PDE1 program that is looking at movement disturbances in patients with Parkinson's disease, as well as a separate molecule within that platform for certain cancers. And we have another platform that's earlier in development that's still preclinical, called 1549, which is. We're very excited about it because they, they're called neuroplastogens now. They used to be called, non-hallucinogenic psychedelics, and we can talk more about that if there's time, too. So brief overview. Great. It's an excellent overview, a lot of points to jump into more. Maybe for CAPLYTA, you talked about a few different indications there, and that's caused some investors to point to Vraylar as something of a comparison for the launch. Would you agree it's a reasonable comparison? Can you point out any similarities or differences that would be good to keep in mind? Yeah. So while no two drugs are exactly alike, we do think that Vraylar is probably the most applicable comparator for us out there. They did launch in more indications than we launched in, and they did not launch during a pandemic. However, we are quickly catching up here, and we do think that we think lumateperone is best-in-class. We think the efficacy that we've demonstrated, the safety and tolerability, is unparalleled among the antipsychotics. And so we think, and from our studies that we've been doing in mood disorders, we think that lumateperone and CAPLYTA will be the go-to drug of choice for the treatment of all of these mood disorders. We just finished a few months ago, we released the data on our registration studies for major depressive disorder, and the results were unbelievable. These were adjunctive treatment in MDD, and we had incredibly robust effect sizes. And the safety and tolerability throughout the many, many thousands of patients that have been treated with CAPLYTA has been very consistent and very. We don't have increases in, we don't have weight gain, we don't have increases in prolactin, we don't have increases in cholesterol. All of the metabolic parameters, the key metabolic parameters, are similar to placebo, and we don't have those movement disturbances that other antipsychotics have. So we're very excited about launching, upon an approval for MDD, and we're very excited about the trajectory that we've seen, for CAPLYTA in both schizophrenia and bipolar disorder. Also important to highlight that you don't need to titrate CAPLYTA. Right. You can get to therapeutic dose with the first dose, which is a very important attribute for all doctors, and especially for primary cares. It's easier to manage patients with these attributes. Mm-hmm. Maybe kinda elaborating on that point, what type of mix of physicians are you seeing use CAPLYTA, you know, compared to, like, psychiatrists or primary care physicians, and how do you see that mix changing over time? Yeah. So presently, we call on about 43,000 targets, and these are primarily psychiatrists because that's who... So schizophrenia is really addressed by psychiatrists only, or 99%, whatever, from psychiatrists. Okay. Bipolar disorder, however, you do have a presence in the primary care world. And when I say primary care world, because more and more, we're seeing not only physicians prescribing, but nurse practitioners, PAs, et cetera, so which is why we're actually right now expanding our call list to address more primary care people. Right now, we call on those primary care physicians and NPs and PAs who are the very high prescribers for bipolar depression. But we are increasing our call list by adding 150 reps there, and so we are going to go broader within the bipolar space, which will also help have awareness for an approval in MDD. Good. For the CAPLYTA 2024 net sales guidance of $650 million-$680 million, are there seasonal factors that would be important to consider? There are seasonal factors. Let's take for the rest of this year, just looking back one quarter. Typically, summertime, there's a slowdown, and then starting now, you start seeing a ramp-up through the end of the year, and that would be typical for these drugs. Thinking about the bipolar setting, can you tell us more about how CAPLYTA is differentiated from other options? Yeah. So I started mentioning that before that CAPLYTA, first, we believe, is the drug of choice for these mood disorders, and as we keep demonstrating this through our clinical studies, those patients, we started very early in our schizophrenia studies, those patients who had comorbid depression when being treated for their schizophrenia were also helped with their comorbid depression. And we've seen this throughout all of our studies. We've done now, most recently, as I mentioned, these adjunctive treatment in major depressive disorder, and we're very, very pleased with the very robust results we've seen. And I mentioned about the it's not only, as Juan said, first of all, there's no dose titration needed for this drug. You give it once a day, and in fact, during COVID, that was extremely helpful. We would get comments from physicians all the time, "I'm not getting called at 10:00 P.M. What do I do? How do I titrate this drug?" They didn't have to worry about patients having these movement disturbances, et cetera. So it's once a day, no dose titration necessary, and no weight gain, no metabolic issues, no prolactin elevation, and so, and no, most importantly, no EPS, and no gut issues. It's really similar to placebo. It also has the broadest label. It's approved. Yeah For Bipolar I patients, for Bipolar II patients as an adjunctive therapy, and also as monotherapy. Mm-hmm. What type of payer access are you seeing in enabling CAPLYTA to be used as an earlier line therapy? We're very fortunate. We have very broad coverage, so it really. We do see first-line treatment, or we do see where the insurance requires it, that they've cycled through one or, in some cases, two other drugs first. But this is very typical in this class. These patients cycle through these drugs, so there is absolutely no issue. I mean, that is a hallmark of these diseases, that patients do cycle through these drugs. Good. For MDD, what's the status of the sNDA filing? Ah, glad you asked that. So we just recently had a pre-sNDA meeting, and with the FDA, and we're very pleased. It was a very good meeting, and that we are on track on our filing later this year, and all is a go. We're just putting it together. Great. And how do you see lumateperone comparing with other treatment options for MDD? Well, remember, this is for adjunctive treatment. So where we are treating patients is not where the SSRIs and the SNRIs are as their, you know, first-line treatment. This is for patients who are having some success on their antidepressants, but it's not optimal. And within that class of drugs for treating this, there are only a few drugs approved, and only the, I think there are four antipsychotics. And again, I mentioned all of the benefits that we believe lumateperone has in this class of drugs being very different in its safety profile, tolerability profile, no dose titration, and importantly, in the broad efficacy that we've seen. Got it. I believe Study 505 is still ongoing. Could you help put that study into context, and if there's something more that study could add? So, Study 505 was a study that we always have what are called backup studies to our program, and with our sNDA meeting, pre-sNDA filing meeting, we know we don't need that study for the filing. So, we're presently discussing how we might get some very useful information from that study, but it will not be part of our filing, so it's not a part of the package. Got it. I'm thinking you had to launch an MDD. Would a launch there be expected to impact the net price of lumateperone? No. So this is not a class of drugs that's, that is priced by the indication. It's really priced by the class. So, we expect the price to remain the same as it's been. And it is the same for schizophrenia and for bipolar depression, and it will be the same for MDD. And the insurance carriers, all. They don't start renegotiating and re-looking at you, and we have, in Medicare and Medicaid, virtually 100% coverage, so over 99% coverage. And in commercial, we have, 90% or a little bit higher coverage, and that's exactly what you would expect in the commercial coverage. And so we expect the coverage to remain stable or possibly go up a little bit, and in commercial side, and because MDD bipolar disorder is managed both by the public markets and the private markets. Schizophrenia is primarily 80+% in Medicare, Medicaid. Bipolar is closer to 50-50. And then you have MDD, which is skewed a little bit more towards the commercial side. So we would expect our commercial coverage to go up a bit. Great. Maybe moving beyond the U.S., could you tell us about the ex-U.S. opportunity for lumateperone? So we do believe there is opportunity ex-U.S. All countries, though, are not created equal, so we will be looking to be in other countries, but that's, that is still a work in progress. Got it. Let's jump to another agent in the pipeline. We can begin with 1284. There's a number of other indications for that drug, including generalized anxiety disorder, psychosis with Alzheimer's disease, and agitation with Alzheimer's disease. What gives you confidence in those settings for this agent? So what gives us confidence is the mechanism of action of the drug, and that's really where we start with the science, and this is deuterated lumateperone, so we know a lot about the molecule, and we've tested it in phase I studies, and we think that there are, from a PK profile, some benefits, especially in certain populations like the elderly for deuterated lumateperone. The mechanism of action, we know, has a real attraction in that, the way the drug's metabolized, we have more of the parent expressed, so should have more of the opportunity of both the 5-HT2A, the downstream processing, of the molecule through the glutamatergic signaling, and other. I know we don't have to get into the weeds here, but we do think that, there are some advantages here. What results from the phase II program could help support moving the drug ahead and support approval? Say that again? What results from the upcoming trials would. Oh. Support further. Oh, okay D evelopment and advancement? Great, thanks. So while these studies are called phase II studies, both the GAD studies as well as the psychosis studies, they're powered, and have the number of patients of a registration study. So if these studies are positive, they would serve as registration studies for us, so we would not need any other studies. Yeah, remember that for GAD, we just started an adjunctive study, and later this year, we'll initiate a monotherapy trial with 1284. Great. For 214, which is a PDE1 inhibitor, what's the rationale for using that drug in Parkinson's disease? Our early preclinical studies demonstrated that PDE1 inhibitors were very useful in helping with the movement disturbances and not causing these dyskinesias. That's where we started with the program. We also showed that there are benefits in cognition. That's early on with our preclinical studies. We then went into the clinic in Parkinson's disease, and we had a phase I/II study where we showed benefit here. Additionally, we have found, through time, that these PDE1 inhibitors. First of all, they're on demand. They're only active if there's a pathology. If there's no pathology, there's no action. We've looked at the cytokines, the chemokines. We found that these inhibitors are also very good at controlling neuroinflammation. That's how this program has started, and we're in our phase I/II study. We did monitor for this, and we did see some benefits in these cytokines, and we're monitoring that, and that will be important to look at in the phase II studies. And then we have a separate molecule that, along the same rationale, knowing the cells in the brain that called these microglia, that are important with this molecule. Some academic researchers who listened to a talk of ours actually said, "Well, you know, the macrophages of the periphery are the microglia of the brain," and that's how we started a collaboration with them, looking at cancers in the periphery. And we have one molecule that's in a phase I study, looking at that. Terrific. And for the, you mentioned the phase II trial for Parkinson's disease. Could you tell us more about the design there and what could be learned? So, the primary endpoint is using a Hauser diary, looking at movement disturbances and increases in on time. We are also looking at the MDS-UPDRS as a secondary endpoint. So I think. And we're looking at, very importantly, we're also looking at cognition. Biomarkers of neuroinflammation. Right. Yeah. And the biomarkers for neuroinflammation. Good. Moving on to another agent, 333. What's the status of clinical development of that agent? What do you hope to learn from the ongoing trials? So 333 is a mu-opioid partial agonist, and we think from our preclinical studies, there's utility in treating substance use disorder as well as pain. We are in a couple of different studies with 333. One is a PET study to look and see at the occupancy in the brain. It's a 5-HT2A antagonist and a mu-opioid partial agonist. So we're looking at a PET study to identify brain occupancy there. We're also. We've completed a single-ascending dose study, and we're in a multiple-ascending dose study, and based on the results from that multiple-ascending dose study, we'll determine how to move forward there. Great, and can you tell us more about the another agent, 1549, and the status of development there? So, 1549 is our newest platform, and as I mentioned in the opening remarks, these are non-hallucinogenic psychedelics or now called neuroplastogens. We think this is a very important class of drugs, we think because of the potential for a very rapid onset, for the treatment of depression, and also for other mood disorders. However, we think that having these hallucinations and delusions is not a favorable aspect, and hence we set about to develop non-hallucinogenic compounds. So we didn't take hallucinogens and try and modify them. These are new chemical entities, new structures based on our knowledge of 5-HT2A biology. So we've demonstrated the pathways they go down in the brain, primarily the beta-arrestin pathway, does not go down the G protein- coupled pathway, like the hallucinogens. And so we're very excited about this as a new class of drugs to treat mood disorders. What gives you confidence that you can kind of get these psychedelic or neuroplastic effects, or, you know, kind of the maybe good aspects of the psychedelic without some of the negatives, like the hallucinations and cardiovascular effects? Yeah. So, to date, we're basing that on our knowledge of 5-HT2A biology, the fact that we don't hit the 5-HT2B receptor in the way that causes the cardiovascular effects, and our preclinical studies, which demonstrate benefits without any of the untoward effects that you were mentioning. And that will be tested very early on. In our early studies, we will look to make sure that these are not drugs that cause abuse or dependence, and of course, that they're generally safe and well-tolerated. Yeah. We expect to enter the clinic next year with them. Great. Maybe moving to a bigger picture question, how do you think about business development for Intra-Cellular? Yes. You said bigger picture. We look at, so we started out looking at approved products only that, you know, our commercial group could put in their bag. We've since moved earlier in development. We do look at a lot of different opportunities, but they have to be, there has to be some synergy, either in the science or in the commercial aspects. So we continue to look, but we have a very, very robust pipeline of our own. So it would have to be something that had very compelling evidence for us to take and develop, or for us to commercialize, or if it's a commercial product already, to continue with it. But I should tell you, we're very well-financed. We have ended last quarter with a little over $1 billion on our balance sheet, and we have no debt. So we are well-financed to carry on all of our activities, to look at new opportunities. But to date, we have we're focused on our own opportunities and especially on the expansion of the opportunities for CAPLYTA. Good. Any projections on how long the existing cash could last for funding existing activities like CAPLYTA? So that's another way of asking us when we are going to be profitable? We have not given those numbers yet. But you guys are all very smart, and you look at our, you know, you look at our revenue numbers, and you look at our spend, and you can make your predictions. We will at some point start giving you that guidance as well, but right now, I think suffice it to say that we haven't given that. Put it this way, we're not in need of cash. Great. And with that, you know, I think we've reached our time, so thank you very much for joining us today. Great. Thank you so much.