Great to see you. Thanks, everyone, for joining us today, and thanks for the team from Itsy or Intra-Cellular for joining us as well. Maybe just we could start with a brief overview. If you could, brief overview on where the company stands today and what you see as key value drivers over the next 12- 24 months. Right. Thanks. It's great to be here. Although it's nice and warm in here, that's really terrific, as opposed to out there, where it's pretty cold. Let me just give you an overview on the company. We started the company in 2002. What's great today, first of all, is our first product, CAPLYTA, which first got approval in 2019 for the treatment of schizophrenia in adults. Fast-forward to December 2021, received a label expansion for the treatment of bipolar depression. Really, in the past year, since that launch for bipolar depression, we've seen scripts triple with revenues last year of $249 million, a little over. You know, we've also given guidance for 2023. It was the first time we've given revenue guidance, we gave guidance of $430 million-$455 million for the year. I think we're very happy with that, we're looking forward to delivering on that. To that end, we have, in the first quarter, we had a very good quarter. I think that life is good, as to how we're doing at the company, I think life is great. We've also recently had a readout in mixed features in both bipolar depression as well as in MDD. Again, I'm sure we'll get into this, the robust results of that study. What is so exciting there is that we've shown that what we have thought all along is that CAPLYTA may be a very great treatment for across many mood disorders. What we saw in our studies in schizophrenia, in patients with comorbid depression, in our bipolar studies, and in the mixed feature studies, that across different patient populations, we were able to treat a major depressive episode, which is a mood disorder. We're very, very pleased about that. In addition, we have our other platforms that I think we'll get into in the Q&A. I don't know how much more you want in the overview. Yeah, that's great. We can start there. I mean, you mentioned this, the drug's been approved in schizophrenia and bipolar disorder. How do you think about the differentiation between this asset and some of the others that are on the market in those indications and in some of the other indications you're pursuing? First, I think in bipolar depression, there aren't many approvals. In schizophrenia, there are many products approved, and many are generic. There are 19 at least approved in schizophrenia. In bipolar depression, there's only four products approved, and in fact, within that, there's only one other product that's approved for both Bipolar I and Bipolar II. Bipolar II patient population is about half the patient population. We think that there aren't very many competitors in that space. In addition to that, our safety and tolerability profile has, in our clinical trials and both now that we've launched and we're seeing the same thing in real world that we saw in the clinical trials, a very favorable safety and tolerability profile. Other products have had either metabolic or motor side effects they had to deal with. We don't have either of those. We think that our safety and tolerability profile is very favorable. Yeah, great. You recently hired 50 additional people for the sales force. I guess, what did you see in the marketplace that drove you to make the decision to expand there? How long till we see that sales force be fully optimized in terms of their productivity? Maybe Mark should take that. Yeah, sure, Ingrid. Yeah, what we were seeing was, you know, continuously strong demand and prescriber adoption of CAPLYTA in the marketplace. Quite simply, we saw an opportunity to fuel that growth even further. As you mentioned, we brought on 50 new, highly experienced neuroscience specialists. They came on board, I'd say, midway through the first quarter. They were in onboarding and training for the balance of the quarter, so they've really only been out there for about a quarter. They're highly experienced, so they're coming up to speed very quickly. They're probably not at full productivity yet, so we would expect... We're pleased with the results that we've seen so far, and we would expect that to continue to build throughout the year and especially in the second half of the year. What this is allowing us to do with those 50 additional representatives is to increase the frequency of our contacts with our highest volume prescribers, as well as extend our reach into the target audience that we have for both bipolar and for schizophrenia. Great. As you think about them ramping to full productivity, do you see this as something that could drive an inflection further in adoption, or do you think this is more of a gradual build? I think more of a gradual build. I don't know if you'll see a sharp inflection, but I think it'll definitely contribute to more robust growth as we go on, especially in the second half of the year. As you think about the current size of the sales force versus the label. Yep. Opportunities that exist today, are you right-sized at this point, or should we expect any additional growth? No, we think we are. A little bit of background, we target about 43,000 physicians, predominantly psychiatrists and the nurse practitioners that support them. There is a segment of primary care who are high-volume prescribers of antipsychotics for bipolar depression. They don't treat a lot of schizophrenia, but they do treat bipolar depression. Those 43,000 physicians are responsible for about 85%-90% of all the branded prescriptions written for either bipolar or schizophrenia. We cover the vast majority. We think we have appropriate coverage on them with the salesforce size that we have, and we think it gives us a good share of voice in the sales force. We're happy with where we are at this point. Okay, great. You've spoken to gross to net being kind of mid-thirties over the course of the year. As we look beyond that, do you expect it to kind of stabilize there over the long term, or should we expect any movement as we move into additional years? I can take that too, Sharon, if you want. Sure. It's been our practice to just provide guidance on gross to net for the coming year. Yeah. We've done that for the past couple of years, and we've been pretty good at predicting what the gross to net was going to be. For this year, we said it would be in the mid-30s. First quarter came in a little bit lower. We had some more favorable formulary placement, especially on the tiers, so that reduced some of our co-pay assistance. We're in the low 30s, but we expect that to continue to move towards the mid-30s for the year. This is a category that... to answer your question, without answering your question specifically... Yeah on guidance for future years, it's a category that you don't see wild swings in gross to net, so it is fairly stable. Each year, we'll reevaluate that, and as I said, it's been our practice to provide guidance for the coming year. Right. And speaking of guidance, you obviously provided it this year. Like you said, $430 million-$455 million. As you think about, like, the drivers that go into that and any puts and takes that could put you either at the top end of that range or lower, like, how do you think about the risks and the upside to that guidance? Our guidance really is the end result of doing our trending around the historical prescription performance. Since our launch in bipolar, about 18 months ago now, it's been a pretty steady, consistent climb upwards. We trended that out. There's always gonna be some variance around that, so that accounts for some of the range that you see. Then we take a look at any market events that we might anticipate in the coming year that might change, either positively or negatively, that trend. There weren't too many of them this year when we set our guidance. We feel good about the guidance. We'll review it each quarter and determine whether it stands for the rest of the year or not. That's how we got to it. Yeah That's where we are now. With respect to market events. Yeah. generic lurasidone Yep came to market, but it sounds like- Yeah that didn't, wasn't a huge factor in your expectations and hasn't played out yet today. Is that a fair assumption? It's played out exactly as we thought it would play out, which we didn't expect it to have any significant impact, for a couple of reasons. When you look historically at this category, when a brand goes generic, the remaining branded products, their growth trajectory really isn't impacted very much by that. Generic lurasidone's been out there for over a quarter now, and it really hasn't impacted our growth. In fact, we continue to hit new all-time highs in prescriptions each Friday when we check them. It's played out exactly as we thought it would. As do we all. Yeah, we do. Um- We sweat them out every Friday morning. Right. Exactly. Maybe shifting gears here to the clinical side. You've recently highlighted it, the mixed features data came a couple weeks ago, or a couple months ago. Maybe you can just refresh us on what you saw there and what was so distinguishing about it. Let me first tell you what the study was. We were looking at patients with mixed features. That means that within a depressive cycle, they have these bouts of hypomania or mania. Okay? That's what makes it mixed features. We looked in both a bipolar patient population, a bipolar depressed patient population, as well as in an MDD patient population. The primary endpoint was looking at the combined patient population, and then the key secondary endpoint was looking at the CGI. We were very successful at both the primary and the key secondary. We had a, you know, an effect size of 0.64-0.67, depending on which population we looked at. I should say, we looked at each patient population independently, as well as the combined patient population, and we were very successful there as well. We were very pleased with this, and of course, because it was very robustly positive in the combined patient population and in each patient population individually, but more so, as I was saying earlier, because it demonstrated that across different patient populations, we were able to treat patients with these mood disorders. We look forward to our MDD data, which again is a slightly different patient population. The mixed feature patient population was monotherapy, whereas the MDD patient population we're testing right now in the registration studies is an adjunctive study, so it's an add-on to, you know, to the SSRI or SNRI that they're on. Again, all these patient populations have in common, is a major depressive episode. That regardless of your status, if you have a major depressive episode and a mood disorder, we can help those patient populations, is what we've shown to date. Right. One of the things that was notable about that study was that it was pretty consistent across all groups, and the placebo response was pretty well managed. How do you think about that execution and how it might map to the MDD readouts later this year or potentially next year? Sorry, I know you haven't provided that guidance. Right. We, I would love to say we've solved the placebo response, but you solve it for that particular study you're doing. That is the bane of the existence of every company in CNS- Mm-hmm Is can you control your placebo response? We have been very successful. We try very hard. We've implemented a, you know, a lot of different things within our clinical studies, that we do, you know, to try to make sure that you're getting in the appropriate patient population, that you're monitoring them throughout, that you have chosen your clinical sites. You know, we all would like to say we do a great job at it, but these patient populations have gotten very smart. In other words, those who want to be, quote, "a professional patient," et cetera. It is. I think I would be remiss if I said we've solved it, because you try and solve it. You do the best you can. That's my summary. Before we move on to MDD completely, mixed features, is there anything you can share in terms of the path forward and when we could get updates on that? Yeah. What we said before, and it's still the case, is we will meet with the FDA. We have not yet met with them, and that's because it takes time to put the entire package together and go to them. We will be doing that, and we would hope to have some information for you later this year. If you can share, as you go into that meeting with the FDA, are there any key asks you have for them that you would really look to have? Yeah. I think, as you know, there are no products approved for this indication. I think that it's a discussion to have with the FDA on the exact path forward on how we will be progressing with the mixed feature data. Okay, understood. In terms of the major depressive studies that are coming, obviously, statistical significance is one thing, but as you look at how this agent could be differentiated versus the others, what would you like to see out of those results? Out of the MDD study. Yeah you're saying? Again, I think, again, many patients, 21 million patients, these are patients who are on SSRIs or SNRIs now, but they're not optimally treated. We think, again, there are a couple of antipsychotics that are approved for adjunctive treatment within MDD. We, again, think that our safety and tolerability profile really supports differentiation in this class. I think that we also think that we have. I guess maybe I should just leave it at that for right now. Okay. How do you think about where CAPLYTA would fit relative to this patient population? Obviously adjunctive, where in the treatment paradigm would there be the most natural case for this agent? I think the most natural place for the agent would be to, as an add-on to those patients who are on an approved SSRI or SNRI. Mm-hmm Who is not seeing an optimal response. Okay. That's more than 50% of the patient population who are not being optimally treated, so I think it's a large patient population. Understood. How do you think about the expansion of the sales force pending positive results here? You want me to take that, Sharon? Sure. Yeah. We would anticipate likely expanding the sales force to some degree, but we will already have some built-in leverage of the existing sales force. What do I mean by that? We have about 43,000 physicians on our target list that are responsible for bipolar depression and schizophrenia. Virtually, all 43,000 of those also treat large numbers of MDD patients. Mm-hmm. Those physicians, by that point in time, will have four or five years of experience with CAPLYTA, of awareness of CAPLYTA, so we'll be able to leverage that infrastructure that we have. As I mentioned before, there is a component of our target list that is primary care, a segment of primary care physicians who are comfortable treating bipolar depression, and they write antipsychotics to do that. Not every primary care physician out there is comfortable doing that. When you look at MDD, there is a broader group of primary care physicians who are comfortable treating MDD but weren't comfortable treating schizophrenia or bipolar, and it would be for those targets that we would look to expand our sales force to make sure that we get appropriate coverage for them as well. As we get closer to that time, we'll come to you with more specifics about that, but we would expect some expansion of the sales force, even though we'll be able to leverage a good deal of the sales force and the infrastructure that we currently have. Could you give us a sense in terms of order of magnitude from 43,000 target physicians to what, how much larger? Yeah, the most I'd be comfortable saying, it's not going to be a doubling of the size of the audience. Okay. It'll be more than a few. Okay. Understood. In terms of the addressable market here, I guess the size of MDD versus bipolar and schizophrenia, once you adjust for what population is appropriate, like, how do you think about the increase in the addressable market? I would say similar to bipolar patient population. Okay. At least. Yeah. in terms of the competitive landscape within MDD versus some of these other indications, what do you anticipate with respect to the, like, trajectory of the launch or the pace of adoption that we could see? Yes, I think if you look, we always look historically at what have other products done when they got a new indication. With bipolar, for example, we looked at what did Latuda do? They had schizophrenia, they got bipolar depression. You saw a bit of a hockey stick trajectory. VRAYLAR, they had schizophrenia, they had bipolar mania, subsequently got bipolar depression. You saw a very similar hockey stick. We had schizophrenia, we got bipolar depression, almost the exact same hockey stick. For MDD, you look at a product, now this goes back a ways, but you look at Abilify that came out with schizophrenia, that didn't really become a big blockbuster product until it got the MDD indication, it really took off. REXULTI is a little different because they had both schizophrenia and MDD from the start. All that to say, we would expect another inflection with a successful MDD indication. In, you know, another 6- 12 months, we'll know what VRAYLAR's inflection looked like because they were just recently approved with it, and they're doing a very good job with it. They've had a nice bump in their new-to-brand Rx's. I think what that's indicative of, these are large patient populations. MDD is a large patient population, there remains a very significant unmet medical need, which we believe will still be there if and when we get the indication for MDD. Great. One of the things you've started to implement with the bipolar launch was a direct-to-consumer campaign. Yep. How do you think about where that fits in the marketing portfolio, both from this year as well as once you have an MDD approval? Yeah, we've always felt that in this category, that our consumer promotion is an integral part of our marketing mix, as is the professional side with physicians, and we continue to believe that. With all of our investments, we have a great deal of discipline around those. We monitor ROIs, we make adjustments when necessary, but we've been very pleased with what we've seen on the consumer side and specifically with the DTC efforts, we would expect to continue to do that. Can you share anything quantitatively around how you track your DTC and what you've seen to date on that? I can't share anything quantitatively. I would say qualitatively, I mean, the ROI calculations are the ultimate guide for us, but that takes time and that takes data to do all those calculations. We do look from the very early days of a new campaign, at, for example, making sure we're hitting the target audience that we intend to hit with our media placement, and there's ways to do that, and we've been doing that very well. We take a look at our traffic to our website when we're on air with a DTC campaign, and very consistently, when we're on air, you see a real spike in the visits to caplyta.com. It's not only the number of visits there, but they also take what we call high-value actions, meaning they download a co-pay card, or they download a patient brochure. We know the individuals going to the website are likely individuals with that condition. We also survey physicians, and what we've been seeing regularly since our DTC campaigns is that an increasing number of physicians are reporting an increasing number of patients specifically asking about CAPLYTA. That's another good metric for us to follow that the DTC is having the desired effect. Understood. Maybe shifting gears a bit to the earlier clinical side with lumateperone and some of the related, the long-acting, et cetera. First, what criteria do you use to evaluate indication expansion for those assets? First, we look at mechanism of action. Mm-hmm. Which is very important, and you might say, well, so the label for all of these drugs, the first line says the mechanism of action is not clearly understood or it's not unknown, or it's unknown. It's a little bit of a Catch-22. We do know, for instance, with CAPLYTA, we do know the mechanism of action is consistent with what in animal models is beneficial... Mm-hmm. To treat a certain condition. We look at the mechanism of action, and then if you're looking at early clinical, you do. It's really how you set up your animal models to test for, you know, a certain disorder. We, we use that to help guide us. Now, in the case of lumateperone, in fact, we've elucidated the intracellular signaling pathways, and there are many indications for which CAPLYTA could be beneficial. That has been the guidance for us, as it is for, you know, some of our other compounds in development. Great. In terms of some of the next step, sort of indications, like agitation and Alzheimer's disease comes to mind, can you share with us or remind us what you're pursuing right now and where we could see updates over the next year or two? Sure. That's regarding our next compound, called ITI-1284. Right. which is the deuterated lumateperone. What we've shown, we have done Phase I single ascending dose study in normal, healthy volunteers. In that patient population, ITI-1284 has been safe, generally safe and well tolerated. We do know that what we've seen first with lumateperone, and now with ITI-1284, we believe the parent is responsible for many of the beneficial effects we're seeing in certain indications. What the deuterated form of lumateperone does is, in fact, express more parent. Qualitatively, the metabolites are the same, and the parent is the same, except quantitatively, there are very big differences with much more of the parent. We do know with lumateperone, we did see, we do see patients in our early studies, our Phase I studies, patients said, always kept saying they felt calmer. We do see this calmness, and we do see in the clinical trials a lessening or a beneficial effect on agitation. We think that with the deuterated form of lumateperone, we will see even more beneficial effects in agitation. We do think that there may be some things about the PK profile that are beneficial in an elderly population. That's how we selected to go into an elderly population with ITI-1284. We're pursuing it for agitation, as you said, in Alzheimer's disease and also for psychosis in Alzheimer's disease, and then for GAD, for generalized anxiety disorder, where again, we think from both the biology, the PK that we're seeing in the deuterated form, and then, of course, in the Phase I clinical studies, that from the PK data, that we should be beneficial to these patient populations. Could you outline for us briefly the development path forward here? For maybe start with the Alzheimer's and then talk about the generalized anxiety disorder. Yeah. For the Alzheimer's, so we will be starting Phase II studies this year for both the agitation in Alzheimer's disease as well as the psychosis in Alzheimer's disease. I think, you know, there now is one product that just recently got approved in agitation, and so I think that's a very good start. I think that there's a lot of room for other products to come on the market in this patient population. On the GAD side, o n psychosis in Alzheimer's disease, again, I think so the agitation in Alzheimer's disease, there wasn't a well-trodden pathway. Psychosis in Alzheimer's disease, it's not well trod, trodden, a well-trodden pathway. However, at least there's some ideas of how the scales to use, et cetera, for that patient population. GAD is a population that typically has been measured with the HAM-A. Mm-hmm. I think there is a well-established scale for measuring this patient population. Again, a large patient population, with over 7 million Americans a year, and more than double that lifetime prevalence. I think that there's there again, is a real need for newer treatments and better treatments for GAD. Understood. Could you give us any sense of when we could get data in those indications or start to see? I think you have to wait for us to first start the clinical studies. All right. We're just going to be starting those studies this year, so stay tuned. Okay, understood. In terms of just within Alzheimer's agitation, there is kind of, as you mentioned, a recently approved drug. There's a number of other companies that are starting to pursue it. How do you see the evolving competitive landscape, and why you think lumateperone in the deuterated form could be differentiated? Again, I think so far there's one. Yeah. I think it's gonna be a while before you get a second. I think that each one of these programs that are ongoing have different strengths, and they can probably be used within different patient populations. I think these patient populations are very large, I think that it will be exciting for us to all be helping patients with these disorders. Okay, maybe briefly on the long-acting. Yeah Version as well, and the decision to pursue that in schizophrenia, and how you expect that to kind of benefit the patient population? Yeah The market opportunity? Right. Let me start with when we first started our development program, for a long-acting injectable, we didn't have all the data that we have now on lumateperone, and we didn't know, just how favorable the safety and tolerability profile would be in that patients, how long they would stay on the drug, et cetera. We're very pleased that the profile is as it is and that patients are taking an oral drug with regularity. I think that long-acting injectables, we don't believe are going to take over the marketplace. In fact, they're under 10% of the market and well under 10% of the market in the United States. I think that. It is important for certain patient populations, either those patients who can't be compliant with taking meds, or those patients who simply don't want to take an oral drug every day. For that reason, we continue to develop an LAI. It's our goal to have more than a one-month formulation. I think we believe ideally it would be a two-month formulation. We have been developing several formulations that could be used for more than one month. Mm-hmm. I think that we've done a clinical study with one formulation, and it was generally safe, well-tolerated, good distribution of drug, but we knew that that formulation would only be good for a one-month formulation. We are still moving forward, and we're also testing other formulations. Understood. Given the opportunity set in front of you across these different indications we've just touched on, as you get through this next set of data and see results, are you prepared to go further in terms of Phase III studies across all of them, or will you make decisions from there in terms of which are most attractive? Everything we've talked about, if we are successful, and if the data supports moving forward, Mm-hmm. We would move forward. I think you always evaluate your data when you come to the end of any study. You know, make sure, first of all, that your drug efficacy and safety profile support moving forward. Then, of course, that the landscape continues to support your moving forward as well. Yeah, of course. How are you thinking about ex-US expansion, and is that something you would consider pursuing, maybe post MDD results? We always consider ex-US expansion. We think that patients around the world could benefit from CAPLYTA. Again, we think that it has to be a partnership that makes a lot of sense, that protects our franchise within the United States, and that is something that can benefit both patients and Intra-Cellular Therapies. Understood. As you think about capital allocation across the CAPLYTA and lumateperone franchise versus some of the other pipeline assets, how do you think about making decisions across that portfolio? We've only given you guidance through this year, and what we've said for this year is heavily weighted towards the lumateperone franchise. Going forward, again, we'll see in the following years how the data proves out from the clinical trials that we have ongoing. Maybe with the last minute or so that we have here, there is obviously other stuff in the pipeline. Anything you'd highlight that you think will kind of come to the fore over the next year or two? Certainly. Our PDE1 inhibitor platform. PDE1 is an enzyme, what our inhibitors do is, so in a normal state, PDE1 is quiescent. When you have too much of it, is when you have pathologies and that occur, our inhibitors bring that down, back to a normal state. We have an ongoing Phase II study in Parkinson's disease, looking at motor disturbances and cognition, and we're excited about that, and we look to that data. I think we're projecting towards the end of next year, I think we move forward there. We also... That's with lenrispodun, our lead molecule in that portfolio. We also have another compound that has recently entered the clinic in normal, healthy volunteers, this is for a cancer indication. This is very exciting to us because normally you can't use cancer compounds in normal, healthy individuals, and this compound is safe enough that it is being tested right now in normal, healthy volunteers. We've also shown that what these PDE1 inhibitors do is prevent neuroinflammation and are beneficial. I guess we're out of time. You're good. Keep Keep going. As a tumoricidal activity, and other cases as immunomodulators, and so we're very excited about both indications there. Great. Thank you both so much for joining us. Thank you. Thanks for everyone for joining us here. Thank you.