We're gonna get going here with our next company presenter at the BofA Annual Healthcare Conference. I'm pleased to be introducing Intra-Cellular Therapies and Juan Sanchez from Investor Relations, and Mark Newman, Chief Commercial Officer. My name is Jason Gerberry, one of the mid-cap biotech analysts here at BofA. I'll turn it to Juan, just to maybe set the agenda in terms of kind of coming out of the quarter, coming out of positive phase III data for Caplyta in adjunctive MDD, and more data to come. So just maybe if you wanna maybe some introductory remarks, and then I'll jump into my questions. Thank you, Jason. We're gonna make some forward-looking statements based on current information, assumptions, and expectations. I refer you to our corporate website and our SEC filings for updates and additional information. As you know, the company was founded in 2022. Caplyta is our lead program, product. It was approved for schizophrenia first. It was also approved for bipolar depression in late 2021. Last year, we reported year-over-year growth of 85% versus 2022, so our bipolar launch is doing really well. Our guidance for 2024 is between $645 million-$675 million. We just reported the quarter recently, which we can discuss later. As you know, our vision is to expand the label of Caplyta into adjunctive major depressive disorder, and also to establish the drug as a go-to drug, as a very important drug across multiple mood disorders, and I think we are progressing very well. We recently had very positive results from Study 501, evaluating Caplyta as an adjunctive therapy on top of antidepressants for patients with MDD. The results were very, very robust, so that give us more confidence that our plans for Caplyta are going well. Besides Caplyta, in the current indications that I just said, we are very committed to our psychiatry franchise. We have a long-acting injectable program with Caplyta, with lumateperone. We have a pediatric program going on to continue to address this unmet medical needs in children. Our psychiatry franchise expands beyond Caplyta into other assets, including ITI-1284, our ITI-1549 franchise in non-hallucinogenic psychedelics. Complemented that psychiatry franchise, we have a phosphodiesterase 1 inhibitor program and also ITI-333, which we can discuss in our. Okay. Well, maybe just some high-level talking points first. You know, I think on your most recent quarter call, maybe there was a little bit more discussion around BD than past quarters. And so maybe if you can just frame, you know, how much of the BD focus is maybe adding a complementary asset to Caplyta to leverage your commercial infrastructure versus more filling maybe gaps within the portfolio based on certain stages of development. I think that would be helpful just to kinda help investors understand how you guys are thinking about BD. I mean, our approach to BD hasn't changed, right? Our priority as a company right now is to continue to invest in Caplyta, in our current approved indications. We are doing very well there. Now, following the data that we have in adjunctive MDD, we need to focus on making sure that if we get an approval for MDD, we execute very well and maximize the opportunity there. We have a very rich pipeline, as I explained earlier, so we are investing in our pipeline. And then when it comes to BD,, we are always looking for attractive assets and attractive ideas to complement what we have internally. But primarily, all of the resources and most of the resources are being focused on our internal activities, and if the right opportunity from external innovations occurs, we will be happy to, to-... to do something. But at the moment, our focus is on Caplyta and our pipeline. Got it. So it sounds like- ... always being opportunistic. Nothing necessarily like a tone shift in terms of, No, no - appetite to do something and no specific boxing yourself into certain stages or types of- No - assets. Does that maybe first- , that's right. I mean, it's the same approach we're having for some time, right? We have an internal engine that is working, that we need to make sure that it continues working, the pipeline continues to advance. And as a psychiatry company and as an established company, we're always looking for opportunities outside the company, and if the right opportunity comes along, we will be happy to do something. Yep. So maybe Mark- Coming out of the quarter, anything you'd highlight about, you know, sort of the Caplyta growth trajectory, and, you know, this is still a market that I think is pretty underpenetrated, bipolar depression specifically. So, where do you feel like you're at in terms of the launch cycle in BPD indication specifically? So we're very pleased with the underlying fundamentals in the business. We continue to be pleased with the robust growth that we're seeing in prescriptions. Our schizophrenia business is growing steadily. Clearly, the real robust trajectory that you've seen is being driven by bipolar depression. Caplyta is being used very much in line with our label, so it's being used across both Bipolar I and Bipolar II. It's being used monotherapy and adjunctive therapy. It's being used as a switch from both generic products as well as branded products. And all of our metrics are continuing to be very strong. So in the last couple of weeks, we've hit new all-time highs across all of the prescription metrics. Earlier this week, we got our weekly new-to-brand prescriptions, and we hit new all-time highs both in volume and market share, so we continue to penetrate the market as well. Each quarter, we are adding 3-4 thousand new first-time prescribers of Caplyta since the launch. So, we continue to increase our reach into the target audience, and we're now up to nearly 40,000 physicians who have tried Caplyta, and at the same time, continuing to grow the breadth as well. Okay. So the trajectory is very good. The feedback that we get on our messaging is resonating, and the experience that both physicians and patients are having with the product is very good and very strong. So, so at a high level, not looking for like, you know, specific market shares and things like that, but if I think about BPD, right? You had initially one generic in Seroquel XR, now Latuda's generic. I think it's a space that generally has one generic step at it, so it's a little bit more favorable relative to some other areas like maybe schizophrenia, where you have maybe multiple steps. And so how the market has evolved when Latuda became generic, you know, I've heard anecdotally, Latuda then becomes like the first go-to generic step, and there's a lot of churn in the market. And then, so should investors think about you playing in that kinda, you know, second, you know, third option, kind of post-Latuda, kind of just fighting with Vraylar or, or maybe working with AbbVie to grow the market? How would you kind of frame that at a high level? , I think it's a little more nuanced than that. I think that with payers, they don't manage these products at the indication level. So if you have a step edit, it applies to all of the indications. If you're unrestricted, it applies to all of the indications. And there's a mix out there for Caplyta, and we're very pleased with both the breadth of coverage that we have. Over 99% of lives are covered in both Medicaid and Medicare, and in commercial, about 90% of the lives are covered. The utilization criteria that they use, it is unrestricted on some plans. There's an electronic step edit on others, and in others, there's a prior authorization. But even the prior authorization is not onerous. Basically, payers that employ that just want to ensure that it's being used on label. So if it's prescribed for schizophrenia or bipolar depression, it goes right through. So I think we see all usage in all different lines of therapy. It is being used first line in those situations where physicians and the patient's insurance allows for unrestricted use. But as I said before, it's also being used as a first switch from generics. It's being used as switc ... from branded products. So, we're not being niched in any particular area. We're seeing broad use across, ... a variety of different areas, and to us, that's a very healthy sign of a robust launch. And so is the playbook for growth really here, just market expansion, right? Of the brands that are in the space and just continued broadening out of the diagnosis and treatment rates for BPD. Is that a fair way, versus the zero-sum game share battles, you know, with existing agents? , I would say it's both. We are seeing market growth, and particularly with the indication for Caplyta in Bipolar II, we're seeing really good market growth there. But we're also, as I said at the outset, continuing to increase our market share and penetrating the market further. So we're seeing growth coming from both additional market growth, that we're fueling, AbbVie's fueling, but also more and more physicians are seeing Caplyta as a first choice option in bipolar depression. I guess how, when you bring more prescribers on or maybe bring more - make more high prescribers, right? Or influence, you know, physicians or educate them, right, to- ... to use it, is an aspect of this, you know, about getting that prescriber base broadened from here? Sure. We continue to work both at broadening the prescriber base. As I said, each quarter since we launched bipolar depression, we've been adding 3,000-4,000 new first-time prescribers, and that hasn't slowed down at all. So we anticipate we'll continue to add- a good number of new prescribers, but at the same time, we'll be adding depth in each one of those physicians. So, each physician falls somewhere on an adoption curve. There are some physicians who, the day a new product is approved, they wanna be trying it. That's the minority of physicians. Not a lot of them do that. There's others who literally will wait a couple of years until they prescribe a new product, because they wanna see it on the market, they wanna see their colleagues use it. That's also the minority. Everyone else falls somewhere in between, and we're just working our way up that adoption curve ... right now. Once they try it, they'll try it in a couple of patients, they'll take a pause, they'll see how their patients react to it, they'll see how the product feels in their hands, and then if they get positive feedback like they're seeing on Caplyta, that's when they begin to broaden use in their practice. They reset their own practice and where they see each of the agents falling in. Can you speak to the incremental prescriber? Is it more primary care, more psychiatrist? And then, as you bring in MDD to the label and time- ... and expand your commercial effort and your field force, what opportunities that affords you to have maybe a synergy and benefit to your BPD business as well as your MDD business? So our current call list includes about 43,000 physicians, predominantly psychiatrists and the nurse practitioners that support them. We do have a segment of primary care that we call on. Primary care plays, I would characterize it, as an important role in bipolar depression, and there are some primary care physicians who are high-volume prescribers of antipsychotics in bipolar depression, so they're on our call list. And so we are seeing new prescribers come in, both from the psychiatry community, who are the later adopters, but we're also seeing new prescribers come in in primary care. Now, as we think about a potential launch in MDD, the opportunity there is to leverage the 43,000 prescribers now who already will have had a number of years of experience with Caplyta, and we would expect a rapid uptake from those physicians in a new indication in MDD. But also to begin to penetrate the primary care market much deeper than we do for bipolar depression, because in MDD, primary care plays a much more important role in terms of prescribing adjunctive antipsychotics for augmentation therapy in MDD. So we would, we would expect to see an expansion there as well. Okay. Maybe as we think about MDD, you know, assuming approval, how do you see the commercial field force evolving? How are you sort of sized relative to AbbVie, and how does that change now that you've got, you know, follow-on proceeds and look to kind of play to win there? , so as I mentioned, the 43,000 will be able to leverage the experience they've had with Caplyta. 'Cause virtually all 43,000 of them that are high-volume prescribers for schizophrenia or for bipolar depression, they're high-volume prescribers for MDD, too. So we'll be able to leverage a lot of the existing infrastructure that we have thus far. However, the expansion will come in primary care. And so we haven't quantified that yet publicly. As we get closer to the time of a potential approval and launch, we'll come back to you with more specifics around that. But we do envision a significant expansion into primary care with our sales force, to be able to make sure that we provide the right kind of coverage to optimize the launch and the growth of Caplyta in primary care, as well as in the psychiatry community. Okay. And now that you have phase 3 data in hand from your first studies, Study 501, how do you see the value proposition of Caplyta in MDD, the unmet need that you kind of feel like you address, and you know, assuming how important is it for Studies 502 and 503 to sort of recapitulate what you saw on... What people were probably surprised with the treatment effect size? How important is it to replicate that? So I think that, going back to the first part of your question, I think that, in MDD, the launch that AbbVie has done with Vraylar, which has been very successful in MDD, really validates what we believed all along, which is there remains a very significant unmet medical need in MDD for augmentation therapy with an adjunctive antipsychotic. So that for us, that validates that the unmet need is there. What we saw in Study 501 were very, very strong results across the board, both in efficacy as well as replicating the favorable safety and tolerability profile- -that we saw in schizophrenia and bipolar depression, and we have a convenient dosing regimen that's a 42 milligram dose. The physician can start the patient at the effective dose and maintain them on that dose. That is a very powerful value proposition to physicians today in bipolar depression, and certainly will be in MDD as well. And I think not only for the psychiatry community, but for the primary care community, they're looking for a product in MDD that they know is gonna work, that has good safety and tolerability, and that is simple to use. And we think the messaging for Caplyta, assuming the data holds up and, and we get an approval in MDD, will resonate very well, both with primary care and with psychiatry. Remember, Caplyta has shown antidepressant efficacy across multiple patient populations suffering from depression, right? Including the patients in our schizophrenia program with comorbid depression, our bipolar depression program, our mixed feature study for patients with MDD and patients with bipolar depression, and now as an adjunctive therapy in patients with MDD, right? So that's part of the- The breadth of the package you feel like- Exactly. will be, have a knock-on effect. , for physicians, they care about what evidence you have about different patient... across different patient populations, right? How do you feel like having that data in mixed features, which, you know, is unique relative to other atypicals in the space, might be an important aspect of driving use in MDD specifically? So I mean, I can from a- I can speak from a commercial perspective. I think anytime within an indication that you have additional data in a specific patient population that physicians see every day in their practice, and you can actually point to data with your product in that patient population, in this case today, in Bipolar depression with Mixed features, and in the future, potentially in MDD with Mixed features, that really resonates with physicians because these indications are broad. So for example, Bipolar depression, we have a broad indication across Bipolar I and Bipolar II, which encompasses patients with Mixed features. But if you can sit down and share the Mixed features data with them, that's data that gives them a lot of confidence- ... to prescribe specifically in that patient type for your product, and I think the same would be true in MDD if eventually we get that. Remember, mixed feature patients, when it comes to MDD, they are less likely to respond to antidepressants. Their trajectory of the disease is a little bit more complicated over time. Some of them might be misdiagnosed with MDD, and- Over time, they're diagnosed with something else, including bipolar. So it's important to have that data out there for people to... for physicians to assess. Since that data was made available, has that had any impact on your growth in BPD? Is it too hard to track? You know, how would you frame- ... the impact you've seen so far? Or is it, you know, you need it in some capacity in your labeling to really see the benefit of that? ... specifically in MDD or- Specifically in BPD, because I want t Keep this as an on-label discussion. , so- I expected you were going to- Tell me that's how you promote and give me the riot act on that. You're right. That is what I would tell you because that's what we do. But I would say it particularly when you get down to... Because now you're talking about a patient with bipolar depression with mixed features. We believe it's im-- having an impact. The data gets a little light as you get that far down. There's coding issues- sometimes they get miscoded. So it's a little... I would say it's our data is a bit limited in that way, but certainly, the feedback that we get from physicians about the data is very strong. Okay. Within MDD, adjunctive MDD, and how these, you know, atypical antipsychotics get used, it's probably... It's really hard for us to know how penetrated, right, as a class- Atypicals are. Maybe you have a view on how penetrated the class is, and is it more about expanding that pie or redistributing within the pie? So I think we're still in the early innings of adjunctive antipsychotic use in MDD- -which means there is a tremendous amount of growth opportunity still there. Just- 15 years post the first approval. , and there's still a lot of penetration. There is. So, and quite honestly, it's because the patient population is so large. You have 21 million patients out there with MDD. That's not the total addressable market for antipsychotics, because some of those patients are, their unmet need is satisfied by SSRIs and SNRIs. But when you have patients that have had some partial response on their SSRI or SNRI, and they need more, that's when they go to the augmentation therapy with the antipsychotic. Right now, each year, there's about 68 million antipsychotic prescriptions written. MDD represents the largest proportion of those of any of the indications, so about 30% of those 68 million are for MDD. Bipolar is not far behind. It's 25, 26, 27%. Schizophrenia is much further back. MDD, that segment, is also the fastest-growing segment of antipsychotic use. The branded antipsychotics with the Vraylar launch- have a three-year compound growth rate of about 26%, and the penetration is still in the low teens. So there's a lot of opportunity, we believe, for market growth as well as share capture- ... with the right profile. Not to ask you a question that's far out and speculative, but I'll try my best to. You know, so we follow a lot of companies that are working on novel approaches to depression. You know, Aimovig, for example, new mechanism, Xenon, which has the KV channel opener. They're moving into pivotal Stage III. What I wonder ultimately is like you have these adjunctive options, maybe, and then between that, you have SSRIs, SNRIs, which are going to be your first go-tos. Then everything in between. As new mechanistic alternatives come to market, I mean, everyone will just say, "The pie is so big, we can all win," right? But somebody has to lose, and maybe does utilization of atypicals get impacted at all as new innovation comes, and there's something else to go to after SSRIs and SNRIs, before you go to, say, an adjunctive strategy? , I'd say... So I, I'd agree with the statement that it's a, it's a large patient population. There's a lot of opportunity there for, for all, all mechanisms. Secondly, it's, it's a little difficult to speculate about future entrants until you really see what the profile looks like ... and what it's going to emerge to be. As you mentioned, the use of adjunctive antipsychotics in MDD has been around for a while. It's well-established, it's well-accepted, and yet there's still a lot of opportunity for growth. So certainly in the near- to medium-term future, we see nothing but opportunity for Caplyta with the potential indication there. And also, it's a combination of efficacy, safety, and tolerability, and we feel very good about Caplyta's profile in those three aspects of the drug. And also that coupled with patients being very heterogeneous. Yep. There is space for new mechanism of actions and everything, but at the end of the day, you want to try to use drugs that work, that are safe and are well-tolerated, and I think Caplyta's profile is right there. So when you got the BPD approval and you launched that- ... there was obviously a very noticeable inflection in your TRX. Yep. Right? You presumably are still going to be growing BPD nicely. So as we think about the impact of MDD, I guess, what are the observations from the recent Vraylar launch and how you'd kind of communicate to investors thinking through the potential launch impact in however way you want to describe that? , I think we've always looked at Vraylar as a good comp for us. And by that I mean, you know, they have the schizophrenia indication, they got the bipolar depression indication a little bit later- ... and now they've got the MDD indication. So we're following a similar path. As you mentioned, when we launched in bipolar depression, we saw a similar sort of hockey stick trajectory change in the prescription pathway for Caplyta, as they saw with Vraylar. And if you look back over the past, a little over a year now, for Vraylar, they've seen another inflection with the MDD launch. I think they're... If I remember the data right, I think their new to brands doubled during the launch period in MDD. We would anticipate a similar type of uptake for Caplyta with the profile we see emerging from the ... the clinical trials. So, you know, obviously a lot of focus on Caplyta, and when we think about your pipeline, I know that there's a lot of different things going on. What do you view as maybe the most promising thing, you know, where you'd be wanting to focus investors in on, you know, beyond Caplyta? I mean, all of them are promising. There are different stages, and they face different risks. But, at the moment, I mean, the... You focus on 1284. We are, this quarter, starting three programs. The first one is in generalized anxiety disorder as an adjunctive therapy to approved drugs for anxiety, including antidepressants. It will be followed by a phase 2 clinical trial in agitation associated with Alzheimer's disease, and also another clinical trial in psychosis associated with Alzheimer's disease. These three trials are phase 2 trials, but they are powered and sized to be potentially pivotal trial and important trials. You should assume that 1284 will gain some importance as we- ... when we begin these clinical trials. Then, you think about what I mentioned in the beginning, the continuation of the psychiatry franchise, right? We have the pediatric program, which will for Caplyta, which can open a lot of opportunities. We had 1284, which is a continuation or an enhancement of our position in psychiatry. And then you have, the 1549 asset in preclinical development that we believe we can be in human next year. I think it's very exciting to have the potential of having a psychedelic that doesn't cause hallucinations. So that's, we're very excited internally about it, but, the other ones are very important too. We just have to continue developing those assets and see what the data looks like to make decisions, right? Yep. So with the deuterated lumateperone and the Alzheimer's indications, what sort of underpins the confidence to go to a trial that has the potential to be registrational, in terms of understanding, you've got the right dose, you're exploring maybe the right dose range. So maybe if you can just- Share with us a little bit more there. So you'll know more about the aspects of the clinical trial design soon when they get published in ClinicalTrials.gov. But 1284 is deuterated lumateperone. So we know a lot about lumateperone and these mechanism of actions, and we do know that 1284 expresses more of the parent molecule versus Luma. So you have the same metabolites and parents, but the ratio changes, so we express more of the parents, and they have potential important benefits that we're testing. So we understand enough about Luma and deuterated and the deuterated form to make decisions to embark in relatively large clinical trials. And also mechanistically, right, you think about GAD, our results in the aspects of MADRS and other scales in our clinical programs that relate to anxiety. When you think about our... Remember that in our mixed features study, we presented some results in anxious distress in the patient population that had anxious distress at baseline. So the combination of the pharmacology and data in some anxiety aspects in our clinical trials feed the confidence in GAD, right? What we know about Luma, the deuterated form, and the pharmacology in general, fits into our agitation and psychosis program, right? And then you have another brexpiprazole, which was approved for Alzheimer’s agitation. That also helps to, as a proxy, a proof of concept to- , drugs that have worked in psychosis Have worked in these settings. I guess the question that I have is, like, Otsuka had deuterated, ... their, their drug and looked at AVP and didn't see the same results that they saw. And so I guess there's, there's a question out there, did the deuterating somehow impact the, the molecule? And I guess I, I wonder what gives you confidence that, you know, deuterating, lumateperone, you know, adds benefit beyond, you know, giving you IP, that you'll have for, for an approach, that, that maybe is a better way to go from that standpoint? I mean, I think you have to assess every molecule independently and individually. Every program is different with its own molecules, pharmacology, and everything. We did a lot of work trying to find the best way we can possibly find to deuterate lumateperone. I think we were very successful, and we do understand the pharmacology of the drug. And from our perspective, not all deuterations are the same, and so I encourage you to analyze our program for its own merits as opposed to other programs out there, you know? Okay. And then just your non-hallucinogenic, psychedelic, ... program, any gating items to the IND? We need to continue doing the work, the in vitro, in vivo, the animal talks, all these scaling up, all these things that require for us to be able to be in humans, and we expect to be in humans sometime in 2025. All right. Well, great. We're out of time, but, gentlemen, thank you so much for joining us. Perfect. Thanks, Jason. Thank you.