Good morning, ladies and gentlemen, and welcome to the Intra-Cellular Therapies conference call announcing top-line results from Study 502. At this time, all participants are in a listen-only mode. 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 automated message advising that your hand is raised. To withdraw your question, please press star one one again. As a reminder, today's conference is being recorded. I would now like to turn the conference over to Dr. Juan Sanchez, Vice President, Corporate Communications and Investor Relations. Please go ahead. Thank you, and good morning, and thank you all for joining us on today's conference call to discuss the positive results from Study 502. Our press release describing the top-line results crossed the wire earlier this morning. The slides for today's call are available under the Events and Presentation sections in 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. I'm moving to slide 2. 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. Those 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, and the company disclaims any obligations to update such statements. I will now turn the call over to Sharon. Please move to slide three. Thanks, Juan. Good morning, everyone, and welcome to today's call. We're very excited to be here today to tell you the results of Study 502, which is our second phase III study evaluating lumateperone as an adjunctive therapy to antidepressants for the treatment of major depressive disorder, or MDD. Lumateperone has now demonstrated robust efficacy in two phase III registrational trials. We're very pleased with the magnitude and consistency of lumateperone's efficacy effects across both Study 501 and Study 502 on both the primary and key secondary endpoints in this difficult-to-treat patient population. Additionally, we continue to see a favorable safety and tolerability profile. These two studies form the basis of our supplemental NDA for the adjunctive treatment of MDD, which we anticipate submitting to the FDA in the second half of this year. We're excited about the possibility of providing a promising new treatment option to the large number of patients with major depressive disorder who have an inadequate response to antidepressant therapy. I'll now turn the call over to Suresh, who will present the detailed study results. Thank you. Juan? Thanks, Sharon. I'm on slide four. Let me start by saying we are very pleased with the data results. As Sharon said, Study 502 is our second positive pivotal trial in adjunctive MDD program. Study 502 is a global, multicenter, randomized, double-blind, placebo-controlled clinical trial in patients who have had inadequate response to 1-2 courses of prior antidepressant therapy. Patients were randomized 1:1 to receive lumateperone 42 milligrams plus ADT or placebo plus ADT. The study duration was up to 9 weeks. There was up to 2 weeks of screening period, followed by 6 weeks of double-blind treatment period, and then a 1-week safety follow-up period. The key inclusion criteria are: patients are between the ages of 18-65, who met DSM-5 criteria for major depressive disorder. Patients are required to have a major... A MADRS total score of 24 or above, a Clinical Global Impression Severity score, that is, CGIS, of 4 or above. Additionally, a score of 14 or higher on the Quick Inventory of Depressive Symptomatology Self-Report Scale, and inadequate response defined as less than 50% improvement to 1-2 courses of prior antidepressant therapy for at least 6 weeks of duration. These criteria represents patients who are either moderately severe or severely depressed. The primary endpoint was mean change from baseline in MADRS total score at week 6, and the key secondary endpoint was mean change from baseline on Clinical Global Impression Severity Scale at week 6. Next slide, on slide 5, you can see the demographics of the patients in this trial. Patients' average age was about 45 years. Most patients were female, in line with most other antidepressant trials. A total of 480 patients were randomized in this study. Now, going to slide 6. This is the primary endpoint, which is a change from baseline on MADRS total score to the end of week 6. The mean baseline MADRS total score was about 31. Lumateperone demonstrated a statistically significant and clinically meaningful reduction on MADRS total score compared to placebo at week 6. The least squares mean reduction from baseline for lumateperone 42 mg was 14.7 points, versus 10.2 points for placebo. That is a 4.5-point reduction with a P value of less than 0.0001, and you can see the actual P value on the slide, which is much larger. The effect size was robust at 0.56. As you can see, there was a numerical separate improvement on MADRS total score as early as week 1, just missing significance at a P value of 0.0504. The statistical significance separation separated at week 2 and was maintained throughout the study. Now I am on slide 7. Lumateperone also met the key secondary endpoint, that is the CGIS. The Clinical Global Impression Severity Scale provides the clinician overall assessment of the patient's depression severity based on clinician's interview. Lumateperone demonstrated a statistically significant and clinically meaningful reduction on CGIS score compared to placebo at week 6. The effect size again, was robust at 0.51, with a P value of less than 0.0001. Moving to the next slide, slide 8. Similar to study 501, we included a measure for patients' voice. We used a Quick Inventory of Depressive Symptomatology Self-Report, QIDS-SR16. This scale is a 16-item, patient-rated scale measuring symptoms of depression. It assesses key symptoms of depression. Lumateperone 42 milligrams robustly improved depressive symptoms by 7.9 points and had a P value of less than 0.0001. Moving to the safety results on slide 9. Lumateperone exhibited a favorable safety and tolerability profile and was generally consistent with our prior studies. The most common adverse events, defined as greater than or equal to 5% lumateperone and greater than twice placebo, were dizziness, somnolence, dry mouth, nausea, diarrhea, and fatigue. Adverse events were mostly mild to moderate and resolved within the duration of the study. There was one serious adverse event in the lumateperone group during the double-blind treatment period that was not drug-related. It was for a polyp removal, polypectomy, during a preplanned colonoscopy. In conclusion, the data is very strong in both efficacy as well as safety and tolerability across two positive phase III studies in adjunctive treatment of MDD. On the MADRS total score, there was a 14.7 reduction from baseline in both trials, yielding a robust effect size. In both trials, lumateperone also was statistically significant on the key secondary endpoint, CGIS, as well as on the patient-rated outcome, the QIDS-SR16. Lumateperone was generally safe and well tolerated. The safety profile of lumateperone is generally similar across our prior clinical trials, including schizophrenia, bipolar depression, and MDD. As you can see, in the pooled data of 501 and 502, the most common adverse events were dizziness, dry mouth, somnolence, nausea, and fatigue. With two positive trials, we expect to file our sNDA in the second half of this year. Thank you. Let me turn the call over to Sharon. Thanks, Suresh. I think seeing the data, you can see why we're so pleased to present this data to you today, before we open the line for questions. I would like to express my gratitude to the patients and investigators participating in our studies and to the ITCI team for their dedicated efforts on this program and our other programs as well. This concludes our prepared remarks. Operator, can you please open the line for questions? Yes. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please limit yourself to one question and a follow-up. One moment for our first question. Our first question will be coming from Brian Abrahams of RBC Capital Markets. Your line is open. Hey, good morning. Congratulations on the data and on the really consistent study conduct. I'm curious if you could maybe speak to just what are the remaining gating factors to sNDA filing here, any additional data analysis or gathering or regulatory discussions you need to have? And then just as a follow-up, curious also, the role that the mixed features results will play now in terms of potential for additional label differentiation. Thanks. ... So, why don't I start? And then if there's anything to add, Suresh, if you could fill in, please. So there are no gating factors. We just have to put all the data together. As you know, we've already started, on all of the shells and on the 501 data, and now we have the 502 data to add to it, and then the safety data, which we also have. So it, it is- it's a process to put all of the data together, and, we're doing that, and we'll be submitting in the second half of this year. On the mixed feature data, I think what we told you was, let us get the data, from, 502, and then remember, we just got this data, so we're putting it all together. We're seeing where mixed features might fit here and what that means, and we'll come back to you on that pretty shortly. Fair enough. Thanks, and congrats again. Thank you. One moment for our next question. Our next question will be coming from Andrew Tsai of Jefferies. The line is open. Hey, good morning. Big congratulations to me from me as well. You know, arguably, with these two data sets, safety profile looks better than any antipsychotic out there in MDD. So do you think you can do more sales than, let's just say, Vraylar, which is expected to do $1 billion at peak? Just maybe talk about how you're thinking about the sales prospects for Caplyta. And then, in the best case scenario, when is the earliest do you think you can launch an MDD? Thanks. So I'll move backwards on that. First, on the earliest we can launch, we are working away furiously to submit as soon as possible, and it will be in the second half of this year. So I would then look to a 10-month process, so it would be in the second half of next year that we would have an approval. I think as we move forward, we might be able to give you a little further granularity on that, but right now, we'll stick to second half of the year. As to the sales of Caplyta, yes, we have said from day one, we think that Caplyta has an exemplary efficacy profile and also a terrific safety and tolerability profile, and it's a very favorable profile at that. I think we haven't yet given you peak sales, but we have said when you've compared it to Vraylar, we have said that we have felt that as while we're a much smaller company, 'cause we get asked that question about the size of our company versus a company that markets Vraylar. We have said from day one that as long as we can maintain our share of voice, we think the product speaks for itself and can do extremely well in the marketplace. We continue to think that. As you know, we're extremely well capitalized, and so we will maintain an equal share of voice in the marketplace. So we're really looking forward to a robust uptake of Caplyta in MDD and continuation of the trajectory that we've been on for bipolar disorder and for schizophrenia. Very good. Thank you. Congrats. Yeah. Thank you. One moment for our next question. Our next question is coming from Jessica Fye of J.P. Morgan. Your line is open. Hey, guys. Good morning. Congrats on the data. Two questions from me. First, can you just remind us what your plans are to scale up the commercial organization to maximize this adjunctive MDD opportunity? And second, curious what you're planning to do, if anything, with the third trial now. Any potential for changes there? Thank you. Thanks, Jess. So we will scale up the sales force as we get closer to a launch in MDD. We will update you on that later this year. So stay tuned for that. We're very excited to be doing that, and we'll tell you more as we go forward. You had a second question and, oh- The trial. On the trial. Yeah. So, you know, we just got this data, so let us give us a week or two, okay? And we'll tell you what we're gonna do with Study 505. But stay tuned, 'cause obviously, that's in our minds as well, and we will have some updates on it. Great. Thank you. One moment for our next question. Our next question will come from Sumant Kulkarni of Canaccord Genuity. Your line is open. Good morning. It's very nice to see these consistent and solid results in a very difficult indication. Thanks for taking my question. In your view, is there any merit in developing a long-acting injectable formulation for major depressive disorder, or is that type of dosing regimen more apt for schizophrenia or bipolar disorder, which are the targets of most currently approved LAIs in the space? Again, boy, you guys are tough. We literally just got this data, okay? And we wanted to get it out to you. These are all great questions to which we will be looking at, but we've had very little sleep. And I think that what we'd like to do is be able to, you know, really have the train running in the right direction on our filing and while we also contemplate our expansion opportunities. We do see expansion opportunities for both lumateperone as well as 1284. So, stay tuned. Thank you. One moment for our next question. Our next question will be coming from Joseph Thome of TD Cowen. Your line is open. Hi there. Good morning, and thank you for taking my question, and congrats on the great data here. Maybe can you go into a little bit about what needs to be done with payers, if anything, given that MDD would obviously add a large patient population to the label? I guess, how are you best positioning to guarantee favorable access and coverage for the new population? Thanks. Thanks for the question. We already have access to Caplyta, and the payers don't manage you by indication. They manage you by the class. So I think that we are good on. Once we have an approval, we will have, for the most part, complete payer coverage that we have right now. Okay, perfect. Thank you. Thank you. One moment for our next question. Our next question will come from Michael DiFiore of Evercore ISI. Your line is open. Hey, guys. Congrats on the very consistent data, and thanks so much for taking my question. 2 for me. Number 1, now that you had some time to process all the data from Study 501, could you give any color with regards to metabolic safety profile and adverse events? And my second question is separate from depression. I noticed that yesterday there are 2 new trials for bipolar mania posted on ct.gov. My question is: Is this a big indication relative to bipolar depression? My hunch is no, but just want to confirm what if any amount of incremental sales could be had from this mania indication. Thank you. Thanks for the questions. They're good questions. I think, I'm gonna just give you the summary answer on the metabolic and ask, Suresh to elaborate a little bit. And that is, first of all, we don't have that data for 502 yet. We have top-line data, and that comes in the second tranche. In the 501, we do have that data. And maybe, Suresh, do you want to just give an overall summary on the metabolic data? Yes. Yes. On the metabolic data, looking at both the adverse events as well as mean changes from baseline, for the metabolic parameters, they were similar to placebo, consistent with what we have seen in our other trials with schizophrenia and bipolar depression. Great. And your second question was about the bipolar mania studies and why we're doing them, and maybe I'll ask Suresh as the Chief Medical Officer to opine on that as well. Yes. So for mania, bipolar mania, we did start two studies. We have an agreement with the FDA in connection with our pediatric exclusivity program, that PK studies in adolescents and children will suffice to submit an approval for adolescents and adults when added to the bipolar mania studies in adults. And population-wise, in terms of the population, there are 55 million children and adolescents in the U.S. About 6% of those children have either bipolar disorder, autism, or schizophrenia, of which about 3 million patients will be having these indications. And also, in terms of safe and effective treatments are clearly needed for these patient populations, including the pediatric population, especially when side effects like EPS, weight gain, and metabolic issues are minimal. Any drugs that have that minimal potential is an advantage also in the pediatric population. Okay, thank you. One moment for our next question. Our next question will be coming from Aaron Spivak. Your line is open. Aaron's line has disconnected. One moment for our next question. Our next question will be coming from Jason Gerberry of Bank of America. Your line is open. Hey, guys, congrats on the data, and thanks for taking my question. Mine's on the early onset of benefit seen now with both Study 501 and 502. And curious if this is something that you plan to pursue in terms of product labeling, and if you think it could be a meaningful differentiator versus other atypicals, like, say, Vraylar, that doesn't have label language. I think Axsome's Auvelity has some language about early onset of action, and that seems to resonate with prescribers. So just curious, you know, how you think about that. Thanks for the question. I think it's a little early for us to be talking about anything other than these results and the fact that we're putting our package together right now. I think, again, stay tuned with how we're going forward. I do think that it's important that patients are given an effective dose on day one, and that they can start and stay on the effective dose, so there isn't all of this titrating up and down, which can be very problematic for patients. And as we saw during COVID, in fact, it was very much appreciated that this wasn't at all necessary, and it, in fact, got doctors comfortable with they can start and stay on a single dose very effectively and safely. So we're very pleased with that. One moment for our next question. Our next question will come from Corinne Jenkins of Goldman Sachs. Your line is open. Good morning. This is Omari on for Corinne. A couple questions: How does the market opportunity with adjunctive MDD compare to bipolar depression? And second, are you fully funded to execute this launch? I missed the first part. How does what? Could you just repeat the question? Sure. How does the market opportunity slash addressable population with adjunctive MDD compare to bipolar depression? Yeah. So, I think, as you know, there are about 2.4 million patients with schizophrenia, our first indication. There are about 11 million patients with bipolar disorder, which is our second indication. And then, while the total patient population of MDD is not accessible, there are 21+ million patients. So you can look at it, though, with the accessible patient population. In other words, those who aren't being successfully treated now or for a variety of reasons, to be at least the magnitude of the bipolar patient population and probably larger. So it is a larger patient population than you see in bipolar. So progressively, we've been adding total addressable patient populations as we go forward. As to, are we funded? Yes. We had, prior to a fundraising that we did a couple of months ago, we had over $475 million in the bank, and we added to that, so that we now presently have about $1 billion on our balance sheet, and we have no debt. So we're very, we're very well funded. We're very able to execute, and so we are working away at doing that. Thank you. One moment for our next question. Our next question will be coming from Charles Duncan of Cantor. Your line's open. Hey, good morning, Sharon and Suresh. Congratulations on a well-conducted phase III program in adjunctive MDD and very clear results. I wanted to ask you a couple of questions. Perhaps you're not yet in a position to answer them, but do you detect any phenotypic, such as age or, or anything else, or background therapy differences in the response rate that you see with lumateperone? And my second question is regarding IP, and if you believe that there are observations from this program that further embolden your- Thanks. So I'll start with the second one, and I'll ask Suresh to address the first one. Yes, with an approval of MDD, there would be additional patents that we would anticipate adding to our Orange Book listings. And the first question, which I think you're right, we're probably not in a place to say anything today, but just to confirm that, Suresh, would you like to speak to, is there anything in particular about either patient demographics or age or et cetera, that you'd like to call out? Yeah, there is no differences. Again, in terms of the discussion points, from, I think the question was asked regarding different antidepressants. We have looked at both SSRIs and SNRIs. There was no difference in the responses. They were very similar, so we don't see any, differences between different demographics. Awesome. Thanks, Sharon and Suresh. Congrats. One moment for our next question. Thank you. Our next question will be coming from Graig Suvannavejh, of Mizuho Securities. Your line is open. Thank you. Good morning, and congrats again from me on the outstanding phase III data. Just maybe piggybacking on Charles' question on IP, could you just remind us what the company's current base case is on IP, in particular, anticipated U.S. loss of exclusivity? And then my second question, and this might be a bit early for you to comment, but on the assumption that at some point we'll get a launch for Caplyta and MDD, what would you anticipate the impact on the trajectory of prescriptions to look like? Are we thinking it could be similar to what we saw for when you got the bipolar depression label, or do you think it'll be something different from that? Thanks. ... Well, first, I'd like to remind everybody that today's call, the purpose of today's call is to discuss the results of Study 502, not to go off in 25 different directions. With that, I would just tell you that we have Orange Book listing. Now we've had three new patents added in the last several months, and that gets us to the end of 2040. And then you had one other question that I don't remember what it was. So- It was on the trajectory of prescriptions. Oh, trajectory. Yeah. We expect the trajectory of prescriptions to keep on the trajectory we have been, which is, I guess, we like to say, to the northeast. And that, yes, you can get a halo when you introduce a new indication, so it can help all of your other indications. In addition, as you know, we now primarily call on psychiatrists, and we do call on primary care physicians who are high prescribers of antipsychotics, but we will be expanding that as we go forward, and we'll tell you about that at a later time. So we would expect the halo effect to happen as we launch in MDD or shortly thereafter. Okay. Thank you, Sharon. You're off again. One moment for our next question. Our next question will be coming from Ashwani Verma of UBS. Your line is open. Hi, thanks, congrats on the data. Just one question for me. In terms of, can you share any early thoughts on potential line of therapy positioning for depression? I mean, typically, like, brands get positioned in third and fourth line, but with these type of remarkable results, like, do you think it can possibly get more broadly used in the first or second line of treatment? Thanks. Suresh, do you wanna take that? In terms of new prescriptions, yes. You know, any good data, you know, with the study, is good in terms of the effect sizes we have shown. And when patients, you know, initially fail SSRIs or SNRIs, the option is to add antipsychotics. And with the robust data we have shown with lumateperone, it's likely that the, again, with the robust sizes we have shown and with also with the safety profile that is, you know, similar to placebo, what we have seen with our overall profile. With safety, it's likely that the prescribers will be adding it as an option. And if you're talking about using it from a last line or third line to earlier, that likely is a very good possibility. Hey, operator, are there any other questions? One moment. Our next question will be coming from Jeffrey Hung of Morgan Stanley. Your line is open. Hi, good morning. This is Catherine on for Jeff Hung. Thank you so much for taking our question, and congrats on the data. To serve as a follow-up there, can you provide any updated thoughts on whether you plan to pursue a path to approval as monotherapy in MDD for Caplyta, just given the strength and consistency of the data that we've seen now in both study 501 and 502? Yeah. So I'll repeat what I said before, and that is that the purpose of today's call is to tell you, the data from Study 502. Please just let us put this data together and submit this, and we'll update you on further plans as we go forward. Okay? Great. Thank you. Thank you. One moment for our next question. Our next question is coming from Ami Fadia of Needham. Your line is open. Hi, good morning. Congrats to Sharon and team for the very consistent results from both the studies. My question is just with regards to, you know, based on the data that has been generated for Caplyta. Firstly, how do you see that impacting the overall utilization of antipsychotics in the market? And more importantly, you know, Suresh just said that there is very much a possibility of using it in the earlier lines of treatment. How do you see, you know, within the antipsychotics, how do you see physicians selecting between a generic product and a product like Caplyta? And from a payer perspective, do you believe that you need to sort of negotiate to make it possible for physicians to choose Caplyta first as an antipsychotic? Thank you. So I'll start, and then I'll ask Suresh to add on. I think that the robustness of the efficacy and the continued safety and tolerability profile that's favorable really does position Caplyta at an advantage as a drug of choice that may be a drug of choice in the treatment of these mood disorders. And I think that just remember, there are only four or five antipsychotics approved in this indication in the first place. And again, I think that we have not seen the robustness in both the efficacy and safety and tolerability profile that exists with lumateperone. So we look forward to those advantages being you know appreciated in the marketplace for the use of Caplyta. Suresh, did you want to add anything? Just to reiterate that again, with the robustness of the data and the safety profile, also with the only few products available, in this space, and that naturally lends itself to, you know, picking a drug that is robust as well as safe and well-tolerated. Thank you. Thank you. Our next question will come from David Amsellem from Piper Sandler. Your line is open. Hey, thanks. So can you remind us how Caplyta profiles versus Vraylar on akathisia? I know that's the limitation of Vraylar. And are there any additional learnings in these studies regarding Caplyta's profile here? That's number one. And then secondly, in terms of certain subgroups of depressed patients, are you getting better signals in, say, patients with anxious depression or lethargic depression, or are you really getting strong efficacy across the board? Help us understand how you're thinking about that. Thank you. Sure. I think we're getting strong efficacy across the board, as we've shown you in the anxious depression, in an earlier study, and we've shown you in, in other studies, different parameters. I'm gonna turn it over to Suresh, on the akathisia question. Just remind everyone that we don't make comparative claims, but we can speak to the fact that, we have not seen, and you do not see it in our label on akathisia, for lumateperone, which is a big advantage on that. We don't have the movement disturbances that you see, with other antipsychotics. Suresh, would you like to add to that? Yeah, I would reiterate that again, we don't make comparative claims. And also, if you look at our data, we, in terms of akathisia, especially if you're talking about this study, 502 as well as 501, the profile was similar to what we have seen in schizophrenia and bipolar. Akathisia is similar to placebo in depression trials also. So we don't have that as a as an adverse event in our label, and that will be the case also with the depression program. Thank you. Thank you. Our next question will come from Marc Goodman from Leerink Partners. Your line is open. Hi, thanks for taking the question. This is Rudy on the line for Marc. Congrats on the data. So, just a quick follow-up to Ami's question. So now with bipolar depression, the MDD and mixed feature, how should we think about the total addressable population for Caplyta versus other antipsychotics like Vraylar? And how important is the mixed feature indication in driving additional RX? Thank you. Thanks. Again, we're here to talk about Study 502 today, but since you asked, I think that the treatment of MDD is a broad label, and we are currently looking at exactly how we think the program should be progressing. And we will get back to you shortly when we have all of this down. We think that the major addition in patient population is with the addition of MDD. And as we said before, there are at least 21 million patients with MDD, and so, and 11 million patients with bipolar. While every patient with MDD wouldn't really be available for treatment, a good proportion of them will be. So it substantially adds to the patient population. So, Suresh, did you wanna add anything, or are we good? Are we good? Yeah. Okay. Great. Thanks. Thank you. That does conclude our question and answer session for today's conference, and I'd like to turn the call back over to Sharon Mates for any closing remarks. Well, thank you, operator, and thank you everyone for participating on our call today. As you can see, we're really pleased with the results of study 502 and with the consistency that we've seen in both study 501 and study 502. And in fact, the robustness of the effect size and the safety profile that we saw in first in 501 and then in 502, and that we've seen in the mixed features, and that we've seen in all of our other studies, really does lead us to conclude that lumateperone may be the drug of choice for the treatment of mood disorders. And we're very excited about that. We're excited to have told you about this study today. And, and we're moving forward. And thank you very much, everybody, for attending. And again, we thank all of the patients and their caregivers, as well as the ITCI team, for all of their work on these studies. So with that, operator, you can disconnect. And thanks again. Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a great day.