Good morning, ladies and gentlemen, and welcome to Intra-Cellular Therapies Conference Call announcing top-line results from Study 403. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automatic message advising your hand is raised. As a reminder, today's conference call is being recorded. I would now like to turn the conference over to Dr. Juan Sanchez, Vice President of Corporate Communications and Investor Relations. Please go ahead. Good morning. Thank you all for joining us on today's conference call to discuss the positive top-line results from Study 403. I was personally describing the results across the world earlier this morning. The slides for today's call are available on the Events and Presentation section in the Investor section of our corporate website. Joining me on the call today are Dr. Sharon Mates, our Chairman and Chief Executive Officer, and Dr. Suresh Durgam, our Chief Medical Officer. Following the remarks, we will open the call for Q&A. As a reminder, during today's call, we will be making certain forward-looking statements. These forward-looking statements are based on current information, assumptions, and expectations. These are subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements. The company disclaims any obligation to update such statements. I will now turn the call over to Sharon. Thanks, Juan. Good morning, everyone, and welcome to today's call. We are excited to be here today to share the robust top-line results from Study 403, our clinical study evaluating lumateperone in patients with major depressive disorder with mixed features and in patients with bipolar depression with mixed features. We are particularly pleased with the magnitude and consistency of lumateperone's effect across the primary and key secondary endpoints in both patients with MDD and in patients with bipolar depression exhibiting mixed features. This further validates lumateperone's broad potential in mood disorders and provides an important contribution to the field of neuropsychopharmacology. I will now turn the call over to Suresh, who will present the results of Study 403. Suresh? Thank you, Sharon. Good morning. Today, I will be presenting the top-line results for Study 403. That is our lumateperone study for mixed features in major depressive disorder and mixed features in bipolar depression. If you are reviewing the slide deck, I am on slide three. Before I go through the results, I would like to take a minute to talk about what mixed features are. Mixed features is a specifier in DSM-5 that is included for both major depressive disorder and bipolar disorder. It refers to the presence of subsyndromal manic, hypomanic symptoms occurring nearly every day during the majority of days of a major depressive episode. That means a patient must have a major depressive episode and should also have at least three manic or hypomanic symptoms at the same time. This is the focus of our study, which affects about a third of patients experiencing major depressive disorder or bipolar depression. The reason we are studying this patient population is because these patients with mixed features respond poorly to antidepressants, have greater symptom severity, higher risk of suicide attempts, more comorbidities, and higher healthcare costs than depressed patients who do not exhibit mixed features. This is a significant area of unmet need. Coming to the study design of Study 403 on slide four. The objective was to evaluate lumateperone 42 milligrams as monotherapy in patients with bipolar depression with mixed features and in patients with MDD with mixed features. The duration of the study was up to 10 weeks. There was up to two weeks screening period, followed by a six-week double-blind treatment period and then a two-week safety follow-up period. The key inclusion criteria were patients had to meet DSM-5 criteria for MDD with mixed features or bipolar depression with mixed features. Patients were required to have a MADRS total score of 24 or above, a CGIS score of four or above, and a YMRS score between four and 16. The primary endpoint was change from baseline in MADRS total score at week six. We evaluated MADRS total score for, one, the combined population of MDD with mixed features and bipolar depression with mixed features. Two, the individual population of MDD with mixed features. Three, the individual population of bipolar depression with mixed features. The key secondary endpoint was the mean change from baseline on Clinician's Global Impression Scale of CGIS at week six. We measured the CGIS for the combined population of MDD with mixed features and bipolar depression with mixed features, as well as the individual population of MDD with mixed features and bipolar depression with mixed features. Coming to the demographics and baseline characteristics on slide five. The average age is 43 years. The mean baseline MADRS score is about 31. The mean baseline CGIS score is about 4.5, and the mean baseline YMRS score is about nine. Coming to the primary endpoint on slide six. This is looking at MADRS total score for the combined patient population of MDD with mixed features and bipolar depression with mixed features. Lumateperone demonstrated statistically significant and clinically meaningful reductions on the MADRS total score compared to placebo at week six. You can see on the graph we saw statistical separation as early as two weeks, and it continued through the end of the trial. The drug placebo LS mean difference was 5.7, with a P value of less than 0.0001 and an effect size of 0.64. Now moving to slide seven. Let us look at the individual populations of MDD with mixed features and bipolar depression with mixed features on the MADRS total score. This is very similar to what we saw in the combined patient population. We see statistical separation starting at week twi and continuing through the end of the trial. For the MDD population with mixed features, the LS mean difference was 5.9, with a P value of less than 0.0001, with an effect size of 0.67. For the bipolar depression patient population with mixed features, the LS mean difference was 5.7 with a P value of less than 0.0001 with an effect size of 0.64. Moving to next slide. For the key secondary endpoints, which is CGIS, lumateperone demonstrated a statistically significant and clinically meaningful reductions on the CGIS score compared to placebo at week six. There was a separation by week two continuing through week six. Here the effect size was 0.59 with a P value of less than 0.0001. Next slide. Looking at the individual populations of MDD with mixed features and bipolar depression with mixed features, we see the same trend on CGIS again, which was statistically significant and clinically meaningful. The effect size was 0.57 for MDD with mixed features population, the effect size was 0.61 for the bipolar depression with mixed features population. Moving on to slide 10, the safety information. lumateperone was generally safe and well-tolerated, consistent with our prior clinical trials. The overall discontinuation rate in the study was 11%, with lumateperone was 12.1% versus 10% for placebo. The overall adverse event rate for lumateperone was 52.5%, and for placebo it was 36.5%. The discontinuation rates due to adverse events were 4.2% for lumateperone and 2.1% for placebo. The common adverse events, defined as greater than or equal to 5% of lumateperone and twice placebo, were somnolence, dizziness, and nausea. The adverse events were mostly mild to moderate and similar to those seen in prior clinical trials in bipolar depression and schizophrenia. There were no serious adverse events reported in the lumateperone group. There was one in the placebo group. Next slide. In conclusion, lumateperone 42 milligrams demonstrated robust efficacy or placebo with respect to change from baseline to week six in MADRS total score and in CGIS score in all patient populations evaluated. Lumateperone 42 milligrams continued to exhibit a favorable safety and tolerability profile consistent with our prior studies. Thank you. I will now turn over the call to Sharon. Thanks, Suresh. We're excited about today's robust results in our mixed features program. These results provide important data about the efficacy, tolerability, and safety profile of lumateperone for these difficult to treat patients. Our lumateperone program extends across multiple major neuropsychiatric conditions, including MDD, for which we have an ongoing registration program. We are pleased with the commercial uptake of Caplyta for the treatment of bipolar depression and schizophrenia, and we are excited about the potential for further label expansion of Caplyta in other mood disorders. We look forward to updating you on our progress. This concludes our prepared remarks. Operator, can you please open the line for questions? Thank you. Certainly. Ladies and gentlemen, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. In order to accommodate all participants in the question queue, please limit yourself to one question, one follow-up. Please stand by while we compile the Q&A roster. Our first question coming from the line of Brian Abrahams with RBC. Your line is open. Hi, this is Leo on for Brian. Well, first of all, congratulations on the strong data. I guess my first question is, can you talk about what you envision the regulatory path is now that you have the data in hand and it looks favorable? Do Do you have a date scheduled to speak with the FDA? Are you guys planning a submission? Do you have a sense of what the feedback might be? Do you have a sense of how the regulators might handle the trial design changes given that this was originally a bipolar study? Hi, Leo. Thanks for the comments. Let me start with an overall comment is, we just got this data. What we've said is that once we get the data, we will go to the FDA and discuss our results. We'll let you know the next steps following those discussions. As to whether or not you already have a date, first you have to put your data together, and you have to send, you know, a request to the FDA, et cetera. We will do that as soon as possible. But at the moment, there's no date set up yet. We're looking forward to that date, and we'll let you know how things progress. Operator, next question. Thank you. One moment for our next question. Our next question coming from the line of Jessica Fye with J.P. Morgan. Your line is open. Great. Good morning. Congrats on the data. Thanks for taking my questions. I am sure another successful trial for Caplyta and mood disorders is making people think about the adjunctive depression studies that you've got coming up. Any update on the timing for when we could hear those results? You're right. We think these are great data and it makes us even more optimistic on the future and on the ability of lumateperone to treat patients across a broad spectrum of mood disorders. What we have said, as you know, is that we are on track for filing in 2024 for MDD, for adjunctive treatment in MDD. We'll update you as we get into this year. We'll update you on the progress and hone down on the timelines a bit. Thank you. Thank you. Our next question coming from the line of Andrew Tsai with Jefferies. Your line is now open. Hi, team. thanks and congrats on the robust data. I mean, you are seeing a strong effect size in both the BPD and MDD subgroups. The question is, what would be your base case inception in terms of the number of additional studies needed to get mixed features approved? Secondly, what would be your upside case? Could it make sense to discuss with the FDA whether an eventual sNDA could combine this mixed feature study along with the positive MDD study so that you can obtain indications for both mixed features and MDD together in a single sNDA, for instance? Thanks. Yeah. Thanks for the congratulatory note, and thanks for your questions, Andrew. Again, I think, you know, as you know, we have never wanted to put words into the mouths of the FDA. What we continue to say is we're gonna put this data together, we're going to go to the FDA, and we're gonna talk to them about the next steps. I think that we can ask the question in any way we like, and the answer is still the same. We need to go to the FDA and talk to the FDA, and determine the next steps for the program. We are very pleased with the fact that we have shown that lumateperone has a very broad breadth associated with it that we believe that it's, it is, you know, possible to treat across many of the mood spectrum disorders. That really pleases us. That's, that's the going theme here. We're very pleased with the data today. We think that it does demonstrate the effect of lumateperone across a broad population and that with major depressive episodes. We think that lumateperone has demonstrated the ability to be successful across these different indications. Very clear. Thank you. We'll just remain patient. Thanks. Yeah. I'm sorry. That's I guess what I should hope for is patience. We all want to know all the answers. Okay? Understood. Thanks. Thank you. Our next question coming from the line of Charles Duncan from Cantor Fitzgerald. Your line is open. Yes. Good morning, Sharon and Suresh. Congratulations on a very nice result. I had a couple of quick questions. One is, I note the age range was pretty broad. There were a lot more females than males. I guess I'm wondering, were there any correlates of activity that you saw or efficacy that you saw in terms of severity or gender or even age? My second question is a different flavor of the next steps question. I'm wondering when you anticipate being able to present this. Would it be in the second quarter at ACNP or APA, or would it be later on this year? Thanks. I'll ask Suresh to take the questions. I would remind you, this is, today we are presenting the top line. We just literally just got the data and wanted to get it out as quickly as we could. I'm actually not sure Suresh will be able to give you any more color on your questions. On when we're gonna present the data, you said ACNP. That's not, that isn't in the second quarter. ACNP is towards the end of the year. You know, we are racing to get all the data together, and then we will certainly publish the data, and we will present the data as soon as it's all put into presentable fashion. Suresh, did you have anything you wanted to add or not? Only in terms of the demographics you asked, I think the question was about more females than males. That is typical for mood disorders, about 60/40 split. That is pretty common in mood disorders across but depression trials and bipolar trials. Again, regarding individual data, we will again announce as we progress. Okay. I look forward to, for the presentation of, the, data at components. Thank you. Our next question coming from the line of Sumant Kulkarni with Canaccord Genuity. Your line is open. Good morning. Thanks for taking my questions. It doesn't look like there's anything mixed about this data, so it's nice to see all the progress you're making on behalf of patients and other stakeholders. Two questions, quick ones. We know there's some good prevalence data on mixed features, which is about a third of the patients with MDD and bipolar depression. Specifically in your study, what fraction of patients screened in because they met the criteria for mixed features relative to those that had regular MDD or bipolar depression? The second question is, what was the main driver of your decision to pursue an adjunct treatment indication for MDD versus Caplyta as monotherapy? Okay, I'll ask, Suresh. Did you wanna take that? Yes. Regarding the first question regarding, I think the question you asked was regarding what percentage of patients are mixed population patients. The answer to that is, as you know, that initially the study was designed as a bipolar depression study, and the patients are studied as monotherapy for bipolar depression. Since we completed the successful completion of bipolar therapy, depression as monotherapy and adjunctive treatment, Study 403 was amended to evaluate lumateperone as a treatment for patients with MDD with mixed features and bipolar depression with mixed features. All patients in the amended protocol met the criteria for mixed features. Patients were diagnostically verified. All of them who entered into the amended protocol should have a diagnostically verified DSM-5 diagnosis of mixed features, both for MDD and for bipolar depression. Oh, right. I meant, a screening fraction. Yeah. Like how many patients active screening? Right. Yeah. That, again, patients who come for screening, all of those patients we will screen patients, if they don't meet criteria for mixed features, they will not enter the study into this, into the protocol. Right. We may have further data for you once we have all of the data analyzed, not just the top-line data, Sumant. We may have that broken down for you. Okay, thank you. As to exactly how many were screened in that. You asked the second question about adjunctive treatment. Why did we pursue adjunctive treatment and not just a monotherapy? The answer is because there are many patients who are treated just not optimally treated on their antidepressant. We felt that the adjunctive treatment was an important market, an important patient population, to be treating. Thank you. Thank you. One moment for our next question. Our next question coming from the line of Jason Gerberry from Bank of America. Your line is open. Hi, this is Perry on the line for Jason. Thanks for taking our question and congratulations on the data. First, I'm curious about the strategy to educate prescribers moving forward ahead of any label expansion opportunities. Would reps be dropping off published manuscripts to healthcare providers? Just wondering about any initiatives moving forward. Second, I'm curious, are there any specific analogs or prior studies done in mixed features that can help us understand the types of studies that fell short of securing a label in this indication? Thanks. Yeah. For the initiatives, we will publish this data. We will present the data at meetings. Additionally, as I said, we will go to the FDA to determine the next steps for the program. As to, you asked a second question. Can you repeat it again, please? Hello? Can anybody hear me? Yes, I can hear you. Your line is open. Hi. Yeah, I'm wondering if there are. Oh, I'm sorry. -specific analogs. Yes. That's right, yes, specific analogs. Yeah. Mm-hmm. First of all, in bipolar depression, there have only been retrospective analyses done. We're the first to my knowledge of us doing a prospective study. In MDD, there was one prospective study done. However, that was prior to a DSM definition, and it wasn't mixed features even. It was mixed episodes. It's slightly different. But the answer is that sponsor did not go forward after their results, and we can't speak for another sponsor as to why not. There's very little precedent in this arena, which is exactly why we have taken all the precautions we have and that we are saying that we're very pleased with the data today and that we're going to pursue a path of going to the FDA with the data and discussing it with them. As well as I said, publishing the data as quickly as we can and putting the data out there at meetings, et cetera, as quickly as feasible. Got it. Thank you. That's very helpful. Congratulations again on the data. Thank you. Thank you. As a reminder, ladies and gentlemen, at this time, please limit yourself to only one question. Our next question coming from the line of Marc Goodman from SVB Securities. Your line is open. Hey, thanks for taking my question. This is Rudy on the line for Mark. Congrats on the strong data. A question regarding the ongoing Phase III study in adjunctive MDD. I know studies four there is in monotherapy setting, but ongoing study in adjunctive setting, how should we think about the difference here? Also, are there any other key differences versus the ongoing Phase III study that you wanna point to? Thanks. I think you said it correctly, that Study 403 is a monotherapy study, whereas the adjunctive study in patients with major depressive disorder is an adjunctive study because it's adding on lumateperone to those patients who have seen some benefit with their antidepressants, but it's not optimal, so you're adding it on. What I would ask you to remember is that while these are different paradigms and different indications, one's adjunctive treatment in MDD and one's monotherapy in mixed features, what they have in common is that they are treating major depressive disorders. What we have shown in our studies to date is that lumateperone has been successful in treating a major depressive episode in across these different indications. Got it. Thank you very much. One moment for our next question. Our next question coming from the line of Graig Suvannavej h from Mizuho. Your line is open. Hey, good morning. Thanks so much for taking my question. Congratulations, Suresh and Sharon, on the great result. I was wondering if you could comment on whether with this study you have a better assessment of your potential impact on the mania side of mixed features or if that's of any interest or relevance as it relates to how you think about the drug and efficacy in this patient population. Just currently your overall current assessment of the lack of the level, excuse me, of the level of recognition of mixed features or patients who have mixed features by the prescribing community, or in other words, how much education do you think that you will need to fully penetrate the mixed features market opportunity? Thank you. Okay. Thanks, Graig, for the questions. I'll start, and then I'll ask Suresh if he wants to comment. As Suresh mentioned, we did measure the YMRS as part of the entry criteria into the trial. They had to have a YMRS score that was indicative of them having mixed features. It wasn't a full-blown mania. It wasn't nothing. It was in between. Hence we set the YMRS score, which, as Suresh mentioned, was between four and 16 as part of the entry criteria. We went ahead and we analyzed the YMRS score every week, time point. I don't wanna take Suresh's data from him. He can tell you the results of the data 'cause he's very proud of this data. We are all very proud of this data. We think that it does go to demonstrating the benefit in treating this patient population, as far as YMRS score goes. Suresh, do you wanna fill in what you saw? Sure. Yes. The mixed features, again, as we just discussed that the YMRS score was between four-16. The average baseline score was about nine. That represents very well the mixed features component of it. Analyzing the YMRS data, it was also statistically significant compared to placebo in the combined patient population as well as in the individual populations of MDD with mixed features and bipolar depression with mixed features. Great. Second, your second question was, Do physicians understand what mixed features are? I think, the answer is more and more they do. I think there's still room for, patient, for, physician education here. I think with the publication of the DSM-5, I think that, the answer is more and more physicians are now aware. I think what this study does is prove the concept, again, of the ability to treat these patient populations. Okay, thanks, Sharon. Congrats again. Thank you. Our next question coming from the line of Umer Raffat from Evercore. Sir, your line is open. Hi, guys. Congrats on the data and thanks for taking my question. This is Mike on for Umer. A lot of my question's been answered, but I just wanna follow up with regard to your prior comments. You seem to be optimistic on lumateperone potential across the spectrum of mood disorders. I guess, do the mixed features data today make you more optimistic about the probability of success in adjunctive MDD? To what extent can we use the performance in mixed features as a proxy for trials? Okay. Hi. Thanks, Mike, for the question. Again, as we've said, while each of these patient populations may be different patient populations, what they all have in common is a major depressive episode. Where bipolar depression is different from mixed features, and bipolar depression is different from mixed features and major depressive disorder and MDD, what everything has in common along with the adjunctive treatment for MDD is a major depressive episode. This gives us confidence that across this spectrum, lumateperone may have activity in treating all of these depressive episodes across the mood disorder spectrum. Suresh, do you wanna add anything to that? Sure. First, we are excited of the data we have shown today that lumateperone can treat different populations across the spectrum of mood disorders, as we have shown today, both in MDD population and also in bipolar depression with mixed features versus MDD with mixed features. While these are different patient populations, as Sharon was just mentioning, treatment of adjunctive MDD and patients with mixed features, all they have common is the major depressive episode. Data presented today shows the ability to treat in both these populations. Also we have been incrementally establishing evidence in the mood disorder spectrum, one different lines of evidence. One is the mechanism of action with our SERT inhibition, and also on the indirect effects of D1 on AMPA and NMDA from a mechanistic point of view. Second, we also have shown that in our schizophrenia studies where patients had comorbid depression, both treating patients who were on antidepressants in that trial and also with as monotherapy, that it did show efficacy there. The major depressive episodes in bipolar depression program also showed efficacy, and we demonstrated that it works in that population. In the 404 study post-hoc analysis, we have shown that it worked in the mixed population. Now this is a prospective study in 403. This gives us more confidence in this mood disorder spectrum. We have a very robust program for adjunctive MDD. Great. Thanks very much. Thank you. Our next question coming from the line of David Amsellem from Piper Sandler. Your line is open. Hey, thanks. Just a couple. One is, do you start thinking about a program in mania specifically now that you have some data in mixed features? What's the utility of doing that? Secondly, just a minus, I might have missed this, is what portion of the unipolar depression population actually has mixed features? Thank you. I'll start with the second question of what portion of the MDD population has mixed features. It's around a third of the patients in both the bipolar and MDD population have mixed features. The numbers range anywhere from 25%-40% in each of them. The most common numbers that one sees is about a third of the patient population. Then do we start thinking about a program in mania? You know, we think about programs across a variety of different arenas, so we'll see as we go forward. I think we were very pleased in showing in this study that those patients who came in with a YMRS score that was elevated, that we were able to statistically significantly treat those patients. Thank you. One moment for our next question. Our next question coming from the line of Ashish Verma from UBS. Your line is open. I, thanks for routing my question. Congrats on the data. Just two from my side. I think, you said you'll go to the FDA. I guess I'm curious, like, is there any precedent where this division of the FDA, the Neuropsych, has accepted a regulatory application based on just a single clinical trial? Then the second one, for this mixed features population, like how long can these patients be in mixed features state? Do you think this would require chronic treatment or is it more of a short to medium-term therapy? Thanks. I'll ask Suresh to take the second part of the statement, and I'll just very quickly dispense with the first part of the statement. Again, you know, again, the FDA has a wide latitude of what they can and cannot do. We do not speak for the FDA. We will go to the FDA, and we'll talk to them about our data. That's the first part. Suresh, do you wanna take the second part of the question? Yes. In terms of the mixed features, in general, for bipolar depression, mood disorders, these are chronic diseases. These require long-term treatments, and that depends on patient to patient, but usually they are chronic long-term diseases and that requires chronic treatment for these diseases. Operator, are there any more questions? Yes. One moment for our next question. Our next question coming from the line of Corinne Jenkins with Goldman Sachs. Your line is open. Hey, this is Palak on for Corinne. Just two questions. One is, what is your appetite and financial capacity to run additional studies as you continue to think about mixed features? The next is, do you expect to see any change in prescribing behavior on the back of these results, particularly within the BPD indication? Thank you. Our appetite to run further studies, et cetera, is gonna be dependent in part on what we get from the FDA. Again, our plan is to put all the data together and go to the FDA and speak to them and discuss the regulatory path forward. Okay? The second question, I guess I would just add to that, though, that you know, that we are looking at our lumateperone program across multiple major neuropsychiatric conditions, which includes adjunctive treatment in MDD, for which we right now have an ongoing registration program. With that, you asked the question again about bipolar. Again, the answer is the same, that we will race to publish the data, we will race to go to the FDA and talk to them. We think this is very good data. We think that it can be helpful for bipolar patients. One moment for our next question. Our next question coming from the line of Ami Fadia with Needham & Company. Your line is open. Hi. Thanks for taking my question. Can you comment on kind of the consistency of efficacy across the three different subpopulations that you highlighted? To what extent does the FDA need to see a difference in efficacy in the mixed features subpopulations to be able to grant a separate indication for those subsets? Thank you. First, we're really pleased with the effect sizes that we saw in these patient populations. I'm not sure I really understand your question, other than, you know, we're pleased that we saw that lumateperone was successful in treating different patient populations with mixed features very robustly. I'm not sure I really understand the question any more than that. Does Suresh, do you have anything you want to say or are you good? I'm good. Yeah. Thank you. I will now turn the call back to Dr. Sharon Mates for any closing remarks. Thank you, everybody, for joining us today, and thank you for the congratulatory remarks and for all of your very good questions. You know, we are really pleased with the data that we showed you today. As you know, it's now, it's on our website, under events and presentations. At your leisure, please have a look at the data. We will keep you informed as we go forward. We're very excited to take this data to the FDA and talk to them about it. Thank you for joining us on today's call, and have a good day. Operator, you can now disconnect. Ladies and gentlemen, that does end our conference for today. Thank you for your participation. You may now disconnect.