Thanks, everybody. Welcome to UBS Biopharma Conference in Miami. My name is Ash Verma. I'm a SMID-cap biotech and spec pharma analyst at UBS, and our next company is Intra-Cellular Therapies. And with me today, I have Sharon Mates and Mark Neumann from Intra-Cellular. How are you doing? Very good. Very good. Thanks. Great. Yeah, thanks for joining us. I mean, so yeah, like Intra-Cellular Therapies, or ITCI, is something that I've been following for a while, with the CNS focused biotech. Maybe, Sharon, it might be helpful if you can just give us, like, a quick background for investors that might not be familiar with the story, and then we can dive into the questions. Sure. Thanks. So we started Intra-Cellular Therapies in 2002, and we started it to take technology from the Greengard lab at Rockefeller. And Dr. Greengard had been studying for many years, not just the cell surface, but looking downstream of the cell surface. So looking at the integration of signals from the receptor through its output and how this affects, how drugs affect this intracellular signaling pathway. So we started the company to set up a platform and to develop drugs based on intracellular signaling. And we did that, and we worked for many years, and I'll skip the whole middle part, and I'll get to 2019, with approval of our first product, which everyone knows today as Caplyta, and our first approval was for Caplyta for the treatment of schizophrenia. We launched for schizophrenia in March of 2020, just as the world shut down because of COVID and the pandemic. But we very effectively were able to work through the pandemic. And then two years later, in December of 2021, we received approval for our second indication, and that's for bipolar disorder and bipolar depression, and both for bipolar I and bipolar II, and as a monotherapy and as adjunctive therapy. This is very important for us and for patients because schizophrenia patient population, and schizophrenia is an important disease and needs treatment, but there are 2.4 million adults with schizophrenia, whereby the patient population size for bipolar depression is 4-5 x the size of that, so there are about 11 million patients. So, we launched for bipolar depression in the very, very end of 2021, really 2022. And you can see our trajectory has been a hockey stick, and I'm sure Mark will discuss in great detail the trajectory of our scripts during the bipolar depression launch. So we're very pleased with that. We continue with our launch for bipolar depression. We think that Caplyta is a very important drug for the treatment of mood disorders. We've done several studies showing that we treat several different mood disorders, and of which, a major depressive episode is the hallmark of these mood disorders. We have upcoming studies that we'll read out in Q1 and Q2 of next year as adjunctive treatment in MDD, and I'm sure we'll talk more about that. And then we have a pipeline of products that I'm sure we'll discuss as well. So I'll leave it there, other than, and I'll let you ask the questions. Yep, that's great. I think that's perfect. So I guess I wanted to understand, so I mean, some of the sales performance for Caplyta has been pretty encouraging when you reported third quarter earnings last week. Just wanted to understand, so from other companies, the conversation that I've heard is that there was a fair bit of seasonality in the antipsychotic market this past fall. And I'm curious, is that something that impacted the Caplyta sales for 3Q for you? What I'm trying to get at is like a more normalized quarter sales performance, where it is, and kind of like use that to draw conclusions for subsequent quarters or years to follow. Well, I'm going to give the summary, and then- Sure. I'll ask you to do the particulars. And I have to say, we had a great quarter. So, I'll leave it at that, and I'll ask Mark to give you all the particulars. Yeah, I'll pick it up from there. I would say we had a very good quarter, despite the typical summer seasonality that you see. If you go back in time and you look at the third quarter prescription growth of the overall antipsychotic market, at least for the last three years, there's been zero growth. There's been no growth in the marketplace, and that's an outlier compared to other quarters. And yet we grew our prescriptions 7%. So that means that we penetrated the market further, we gained market share during the quarter, but certainly, our performance was suppressed just like everybody else in the quarter because of the summer seasonality. What happens, you get beyond Labor Day, and you begin to see the market pick back up, and you begin to see prescriptions pick back up. In our case, for example, we've already had two weeks in a quarter that are new all-time highs for total prescriptions. And a week and a half ago, we also had our highest new-to-brand, NBRX, week that we've ever had as well. And that's the best metric to indicate new patients coming to CAPLYTA... So we're, we're confident that we're gonna see a re-acceleration in the market this quarter and a re-acceleration in a further acceleration in our growth for CAPLYTA as well. Whether this quarter was more suppressed than prior years in the same quarter, it's a little difficult to tell, maybe based on how some other companies reported, but there's definitely a summer seasonality that you see in antipsychotics. Got it. And so you took the guidance up a little bit for Caplyta for 2023, and, like, if you, if you analyze, like, where you are run rating at Q4, you get to, like, a $540 million, whereas I think consensus is forecasting $650 million in 2024 sales. So, like, from your perspective, like, where, like, where is that growth coming from? Is it just, like, continuation of the same commercial efforts that you have? Any new sources of growth that you see that you might not have been able to tap into right now, and that might become more, more of, like, the focus for 2024? Do you want me to- Yeah. Yeah. So, so we continue to work our way up the physician adoption curve. Every physician for a new medicine has a certain way in which they begin to use a new product. Some physicians, the first day a new medicine is out, they wanna be the first one to try it. That's, that's the minority of physicians. There's another set of physicians that they won't try a new medicine, any new medicine, for two or three years that's been on the market, because they wanna see what happens in the marketplace. Fortunately, that's the minority of physicians as well. All the others fall somewhere in between in how quickly they adopt a new medicine. So two metrics that we look at very closely are our ability to expand our prescriber base. So how many new first-time prescribers are we adding each quarter, each month, each quarter? And what is their depth of prescribing? And with both of those metrics, we're now in our eighth quarter of the bipolar depression launch, and each and every quarter, we have added thousands of new first-time prescribers, and we've increased the depth, on average, of their prescribing. Those are two very healthy signs of robust growth that's gonna continue into the future. Now, as we think about 2024, some specifics that I think are gonna help to continue to drive that growth, as you know, Ash, at the beginning of this year, in the first quarter, end of the first quarter, we added about 50 new sales representatives. It takes about six months for them to get fully up to speed and be optimized in their territory, and we're just now hitting that time frame. So we think we'll benefit from that this quarter, but certainly even more so in 2024. We also announced on our earnings call that we had got two big Part D plans to change their utilization criteria for CAPLYTA from a prior authorization and two generic steps before you got to CAPLYTA to unrestricted. And one went into effect September first, the other one went into effect October first. It'll take a little while for that also to begin to be reflected in prescriptions. So we think we'll see some benefit in the fourth quarter here, but that will really help to drive volume in 2024. And then all of our other marketing activities, whether it be on the physician side with our promotional medical education programs, or it be the comprehensive DTC program, which has been- Right Very effective for us, we would see continuing that in the next year as well. So I think all of these things will continue to expand our base, and they'll continue to increase the depth of prescribing of our physicians. Yeah. Yeah, thanks for that. I mean, I wanted to just, like, ask a big picture question. I mean, in terms of, like, antipsychotic drugs, I mean, there have been several examples of, like, multi-billion dollar franchises, in this area. And, like, one of the most recent examples of this is like Vraylar, where consensus is forecasting, like, a $7 billion sales. I feel like you are kind of, like, following the same template. So you got, like, schizo, bipolar depression, and now, you know, hopefully, if things go right with the MDD. And so you have a product that can potentially be fit into that category. Although, like, the big difference, the pushback that I get from investors is that, in terms of, like, where the commercial engine is, like, that, like, is it really possible to push that type of, like, level of sales in a small company, versus, like, can this only be done a big, in a big pharma? So that's something I wanted to understand, like, your, your perspective. I know, Mark, like, you, you were leading BMS and leading the CNS franchise. Like, how do you bring that kind of commercial capacity, and drive that kind of sales execution in a, in a small biotech? Yes. So in my experience, it's really three things, and it's not rocket science. It's your product, it's the people that you have, and then it's the capabilities and resources you put behind the brand. We believe we have a best-in-class product, okay? We think we'll continue to have that. We'll be able to differentiate on the product. Number two, even though we're a new, fairly new commercial organization as Intra-Cellular Therapies, myself, my leadership team, all have 20, 30 years of experience launching products such as this. As you mentioned, at one point, I was running the neuroscience business at BMS when Abilify was in the middle of its life cycle. Everyone on my leadership team, my head of marketing, my head of sales, my head of market access, all of them have extensive experience, so we're not a new commercial set of individuals. Thirdly, from a capabilities and resource perspective, we think we have the infrastructure necessary to support a multi-billion-dollar brand in CAPLYTA, and we're investing to grow the brand behind it. We feel that we have been able to achieve a comparable share of voice, both with our sales force efforts and bipolar depression, as well as on the DTC side. And as long as you have a comparable share of voice you have good access, which we do, we think, having a best-in-class product profile and experienced people will carry the day in that. So that's how I think about it. We're very confident that we can do that, as the organization that we are. And I would just add to that, I think it's a reasonable question for an investor or for anyone to ask prior to the launch of a product, is how can this small company make an inroad and behave, you know, similar to a larger company? But guess what? We did it. So that's been done, and I think it's as Mark says, it's really about maintaining our share of voice. And I think we're doing that very well. And so I think we're off to a great start, and you can see from the trajectory of Caplyta, I think we're off to a great start, and we think we absolutely think we can grow the franchise as Vraylar, as bigger companies have done. Yeah. I mean, one of the differences like that investors highlight to me, like, yeah, I mean, having portfolio level product offering helps with the payer discussions quite a bit, whereas like... I'm just curious, like from your perspective, and is there anything specific to the antipsychotic market that you don't necessarily need, like other garden variety of other products to throw into the mix to have a better, you know, contracting aspect with the payers? Yeah, no, that's actually a very good point, Ash, 'cause the antipsychotic category is different from many other categories that I've worked in in my career. The antipsychotic category has a fairly open formulary. In other words, most products, if not all of them, for most formularies, are covered to some degree. Yes, there's different utilization criteria, but this isn't a category like some I've worked in, where they only have one in the class, or they only have two in the class, and you have the two products and companies competing against each other for exclusive access. That doesn't happen, 'cause if you think about it, this is serious mental illness. The last thing a payer wants to do is to deny an appropriate patient the medicine that the physician believes is the right medicine for them. Yes, they, they wanna make sure it's on label. Yes, they wanna make sure it's the right product, but they don't wanna deny the patient. And there's an awful lot of churn in the marketplace with these products because of the limitations of the existing antipsychotics on the safety and tolerability side. So these patients work through a number of different antipsychotics to find the one that works for them and they can tolerate. And this is really where CAPLYTA shines, because it's very effective, and it has a very favorable safety and tolerability profile, whether you're talking about on the metabolic side, with weight gain, with increases in cholesterol or glucose, CAPLYTA is comparable to placebo. On the movement disorder side, the same thing, comparable to placebo. There's no other product in the category that has that profile. We haven't seen access be a barrier to the growth of CAPLYTA and the trajectory. Yes, we continue around the margins to look for ways to improve it further, but we're very happy with the broad coverage that we have. We're happy with the utilization criteria, and where we see opportunities, as we did with these two large Part D plans last quarter, to get even more favorable access at a reasonable rebate, and we think we can drive more volume to offset the increase in the rebate, then that's a decision that we'll take. And we'll continue to look at those opportunities into the future, but I would say don't expect any change in strategy from us as it relates to how we think about market access. Yeah, I mean, one of the things that I'm, you know, noticing in some of the other companies that play in this space is that, you know, commercial payers' expectations have, you know, changed a little bit, like, over time. And, like, and that might be partly driven by, like, how Latuda was pretty aggressive in terms of contracting or some of the other companies have been willing to give price, just in terms of trying to get more of, more of a volume pull-through. The way that you think about it, like, is there any kind of like a transition towards, expectations change from the payers compared to a couple of years ago? And, like, where does this go in the long run? Like, do you think they might get more aggressive in terms of how much pricing they would want from you in return for more volume pull-through? We don't think so. This is a category that's been around for 25 years now. And payers have gotten very comfortable in the way they manage this category. You mentioned Latuda. Latuda was an outlier. Latuda took a very different strategy. And you could say, maybe it worked for them, maybe it didn't. You know, I won't judge that. But they were really an outlier, and it's because of the dynamics I was saying before, that this is a category that the payers don't want to limit the number of products that they have on formulary, because they know these patients churn through them, and so they don't look to play one company against the other for exclusive access. It's broad access, and as long as we feel we can drive the volume that we need to drive Caplyta growth, then we think we have a good access position. If we don't, as in these two that we moved on this last quarter, then we'll act, and we'll take that decision. Great. So just switching topics to MDD, and we have a big, big catalyst coming up here in the first half of 2024. Just like if you can kind of focus on like why do you feel confident in this opportunity? And like more from the efficacy that you can show and also like how quickly can CAPLYTA start to work? I mean, some of the antidepressant like key value propositions sometimes becomes like you know like is it working in like one or two weeks? So how... Like in terms of how you look at the CAPLYTA profile what can we expect to see, and what would be good data, in your view? ... So what will be good data is we separate in the study, okay? And what does that mean? That means typically in these studies, we're using MADRS, and in the MADRS, you wanna have a two to four point change, depending upon the design of your study. And if a study is designed as a monotherapy, you expect it to be towards the higher range. And then as an adjunctive study, which ours are, both studies are designed the same way. They're both adjunctive studies to the SSRI or the SNRI that the patient is presently on. So these are patients who are being helped by their antidepressant, but just not optimally. So they are, because they're already improved somewhat, you expect them to be towards the lower end on that improvement. So that's but the study is powered to detect that difference. And so we and we know from other studies we've done, we've been very effective in treating a major depressive episode. We've got many studies now where we've shown, regardless of their underlying disorder, if it's bipolar depression, if it's MD, major depressive disorder, if it's schizophrenia with comorbid depression, what these patients all had in common was a major depressive episode. And so we've, we've been very, very robustly successful on, on several studies. That gives us great confidence in Caplyta in the treatment of major depressive disorder as an adjunctive treatment as well. Yeah, I mean, I guess I've asked you before, but in terms of like, placebo response, I mean, this can be a lot of times a confounding factor and something to watch out for in the post-pandemic environment, like, is there anything that has changed in terms of clinical trial conduct or how you're including the patients that might result in more of a different placebo effect versus like what we have seen in the past? We hope not. We don't think so. I think pre-pandemic, in the pandemic, post-pandemic, placebo is always the bane of everybody's existence. And so what we try and do is, ensure that we enroll the right patients into a study, that, in other words, that we have appropriate patients for the study. So that means both in the placebo as well as in the, drug treated, because remember, the placebo, everybody coming into the study has the disorder that you're studying. It's just some people are gonna get drug to treat it, and other people are not getting drug. They're getting a placebo to treat it. So, we try our best. You know, everybody likes to say, yes, you know, we solved the problem. We haven't, as an industry, solved the problem. That is the bane of everyone's existence. We are really confident that Caplyta treats these mood disturbances. Can we be 100% certain that every study we're gonna do is gonna be positive? No. And that's, that's where the issue is. It's, can you control your placebo response? And we try the best we can to do that. Great. Okay. So just, just on mixed features, I mean, can you remind us, like, where you are? Like, what can we expect, what, what is kind of like the base case assumption that you have, that FDA might- would they, would they want you to do another study, or could they accept your filing, based on one study that you have, generated positive data? Well, we haven't done a filing. Okay. What we've done, just for those who may not be familiar with this, we've done a study that, again, was very robustly positive, where we allowed both patients with MDD and patients with bipolar depression into the study. What they had in common were these mixed features. In other words, bouts of hypomania during a depressive episode. So again, it's a mood disturbance of a major depressive episode while these patients have their other underlying disorders. So we know right now. So now we have asked the FDA for a meeting. We had told you that we were gonna get the data, and we're gonna go to the FDA and discuss this data. And we now do have all the data. We have got the CSR, the clinical study reports. We have asked the FDA for a meeting, and we will have a meeting with them either the end of this year, beginning of next year. The purpose of this meeting is to go over this data with them, and to talk to them. We know we have a very broad label right now in bipolar depression. We don't yet have a label in MDD. So the point really is to talk to them about the path forward there. I think that when we have our meeting and we get our minutes, we'll come back and tell you what was described at that meeting. Yep. Yep. Okay, so just a couple of, like, pipeline questions. So, on the, on the LAI, can you update us, like, where you are? I, I feel like the investor feedback has been that it, it could be a potentially good program, but I think, you it seems to be taking a little bit longer than people expected. Is that because, like, you're trying to go after a unique value proposition here, or what, what's at play as, as you look at the competitive landscape and how to differentiate that product? Right. So, we do think it can be a very differentiated product, and that's why we have developed. So we had one formulation that we tested for a one-month duration. Now, we have made four different formulations and that we are going to go into the clinic with next year. And it's to look at the differences. So we can look at different routes of administration, sub-Q versus IM. We can look at one month versus two months. And so we would like to develop not only a one-month formulation, but a two-month formulation as well. And so that's the focus of these different formulations, is to test them all together so that we can be looking at one against the other and see which one we think really is the best in class in order to go forward with. Great. All right, with that, we are out of time. Oh! Thank you so much. Yeah. It went pretty fast, but- Went fast, yeah. Thanks, thanks for joining us at the conference. Great. Good luck- Thank you for having us. Yeah. Great.