I guess it's officially afternoon here, so good afternoon, everyone. We have Intra-Cellular Therapies. I'm Sumanth Kulkarni, a senior biotechnology analyst for Canaccord Genuity, and it's really my pleasure to have this company here. We've been following them for a long time, ever since they never had a product approved, and then we had one, and then you have so much success with that product, and it's really doing more things as well. So you have a bunch of things going on. You have a pipeline that most people don't talk about, which we will talk about today. So with that, I'll turn it over to Chairman, CEO, and Founder Sharon Mates, and we also have our Chief Commercial Officer, Mark, and I guess in the audience, we have Juan Sanchez, who knows everything about the company as well. So please, Sharon. Great. Just set the stage a little bit to where the company's at right now, and then I'll hop into Q&A. Great. Thanks, Sumanth. It's a great pleasure to be here, and we're happy to tell you about Intra-Cellular Therapies. You're right, it's been a long time that we have been developing our pipeline. We started the company in 2002, with technology out of the Greengard laboratory, when Paul Greengard had received his Nobel Prize for intracellular signaling pathways. Fast forward, the technology allowed us to look at intracellular signaling pathways in the brain, so we could compare products that were approved, as well as look at products that we wanted to develop. So, one of them was lumateperone, what became lumateperone, and which we have received our first approval in 2019, and we launched right as the pandemic was beginning, and the world was shutting down in March of 2020 for our first indication, the treatment of schizophrenia in adults. We believe it or not, even in the pandemic, were very successful with our launch, and 2 years later, in December of 2019, we received approval for bipolar depression for patients with both Bipolar I and Bipolar II, and we launched our product for bipolar depression. So now, here we are, just having completed studies for our next label expansion in major depressive disorder, in using lumateperone as an adjunctive treatment for MDD. And, our 2 pivotal studies were remarkably robust in both in terms of efficacy and safety, and which is allowing us to go forward with our sNDA filing, which we are expecting in the second half of this year. So I'm sure we'll we'll tell you a lot about that as we go forward. I know Sumanth also has some questions on our pipeline. We have a very rich pipeline, and our pipeline includes, in addition to lumateperone, where we have both a very strong pediatric program ongoing, we also have a long-acting injectable program ongoing. For other molecules in our pipeline, we have phosphodiesterase 1 inhibitors for the treatment of Parkinson's disease and in cancer. We also have other molecules. One that's very early, but we're very, very excited about, is the 1549 series, which we call our neuroplastogens now, which are non-hallucinogenic psychedelics, and I'm sure we'll talk about that too. That's just a brief overview, and we'll go from there. Thanks, Sharon. I'll start with a few commercial questions, and then we'll move to the pipeline. Sure. Mark, you've been kind of in the commercial hot seat for some time now, and the product's been doing really well. Given the number of quarters we have behind you now, what's your latest thought process on persistency, compliance rates, and things like that, and also what line of treatment CAPLYTA is being used as? Yeah, so we continue to see real strength in the compliance and persistency profile of CAPLYTA in line with our expectations. And we owe that, we think, to the very favorable safety and tolerability profile that CAPLYTA possesses. There are a lot of reasons why patients don't comply and persist with their medication, but one of the biggest ones is the tolerability of the agent, and that's really where CAPLYTA shines. We think that's a reflection of the very benign safety and tolerability profile that we see with the product. In terms of lines of therapy, that's another very encouraging area for us. CAPLYTA is being used across multiple lines of therapy, really given the dynamic in both bipolar depression and schizophrenia, where these patients churn through various antipsychotics because all of the existing antipsychotics have some safety and tolerability liability, whether that's on the metabolic side, with weight gain and increases in cholesterol and glucose, or it's on the movement disorder side. CAPLYTA is comparable to placebo on both of those sides, and so physicians want to use that in an earlier line of therapy. So when you look at bipolar depression, specifically, more than 50% of our use is either first or second-line therapy. So we're very encouraged by where CAPLYTA is finding its place in the treatment algorithm, and it is certainly not being niched for later lines of therapy. Got it. So the product's been doing really well. How would you characterize what the need for improvement might be, short of your sales force expansion effort, which is ongoing? ... Yeah, so I would say, I don't know that there's a lot of areas for needs to improve. What we continue to do, though, is focus on increasing both our breadth of our prescriber base as well as the depth of prescribing. So, at the end of the Q2, our prescriber base stood at about 43,000 unique healthcare providers. Each quarter, we're adding 3,000-4,000 new first-time prescribers of CAPLYTA. In the most recent quarter, in the Q2, we reported we had over 3,600 new first-time prescribers. So that prescriber base continues to grow. It's up over 43,000, and we expect that to continue to grow into the future as well. In addition to that, the average number of prescriptions that each of the physicians is prescribing continues to grow quarter-over-quarter as well. As, physicians get more and more experienced with CAPLYTA, they experience the favorable safety and tolerability, and the strong efficacy, and the convenience of the once-daily dosing, single dose, they find more and more patients that are appropriate for CAPLYTA. So those are the two metrics that we really focus on, and ever since the launch of bipolar depression, both of those, quarter-over-quarter, have continued to grow very nicely. So clearly, there's some excitement in the neuropsychiatry space with some of these large acquisitions that we've seen recently. So how would you characterize the level of competition that's out there for salespeople as you plan to embark on this expansion? Yeah, there's always competition for salespeople out there. We think we have an extraordinary sales force. From the very beginning, when we established our initial sales force in schizophrenia, we really looked for a profile of experienced representatives. I've worked in a lot of different therapeutic areas over my career. I've never seen a therapeutic area like psychiatry, where the representatives really align themselves to the product that they represent. And with a product like CAPLYTA and the type of profile that it has, that's what really drew them to our company, and that's what keeps them at our company. As you said, we've had a great deal of success. The sales force has done a terrific job, and we continue to draw talent to our company because of that. Got it. Then going to the data you had in major depressive disorder, that was really impressive, super consistent across two trials, which is really tough to pull off with that indication. So there's been a lot of positive buzz around the trial data. Psychiatrists are potentially reading all this. What do you think their propensity is to use this product for MDD even currently? Because it's out there, the data. Yeah, typically, what you see, Suman, when you have data like this in the marketplace, there's a pattern to how and when physicians, on their own, might choose to spontaneously use a product off-label. When the initial results get reported out, for example, in a press release, you're certainly very much aware of it, the average prescribing physician is not. The KOLs are, and they probably begin to use some of that off-label. When that data gets into the scientific literature, whether it's presented at a medical congress or it's published in a journal, you see a bit of an uptick in some of that usage because now physicians have access to the full database, and they can make good decisions about whether they want to use it with their patients or not. Where you see the real increase is upon approval, when our organization, on the commercial side, gets involved and continues to promote the product, then you see a real uptick in prescribing. Got it. You also see, as physicians become more aware, and we are going to be going to a lot of scientific and medical meetings starting this fall, and publications will start as well. So we're looking forward to that. It's a very busy fall season. This is more of an executive decision type question. You have two phase III trials that were positive in MDD. You had one mixed features trial that was also positive. So at what point would we know when you would want to do the next trial that you have planned? A 505, I think that is. At what point do you expect to communicate whether you will actually go ahead with that trial or not? Yeah. So 505 is a trial that we initiated. We always have a backup trial because in CNS, 50% of these trials at times are not positive, so you wanna have a backup trial. So we are currently contemplating the fate of 505 because we do not need that trial to read out for our filing package. So we hope to be able to come to the conclusions and put that on clinicaltrials.gov in the short term. So just stay tuned. Got it. So on mixed features, you know, now this is the easy part, right? We can ask the questions. You do the real work. So, the thing is, I've characterized the MDD program run at Intra-Cellular as, quote unquote, “smart.” Yours was the only company that ever targeted mixed features in depression. Why was that, and what does that mean for actually targeting that patient population? Right. So we're not the only company, if I could just amend what you said a little bit. We're not the only company to look at mixed features. We're the only people, frankly, who were bold enough to do prospective trials - Thank you ... rather than just looking retrospectively. And that's because these trials are so difficult to do. Not because there isn't a need, there is a huge unmet medical need here. And also the DSM, which is the manual that physicians look at for diagnosing patients, et cetera, has evolved over time, and really, it was only in the DSM-5 that this became very clear what you should be looking for in MDD. So that's how the DSM-5 came out, and that's how we were able to take advantage of that opportunity and look at this patient population, and we are very excited about it, and we are contemplating what our next path will be with that program. ... This, going back to the commercial side of things, once you get the MDD indication on the label, how would you expect your target gross- to- nets to change now that you're adding a really large indication on, over on top of what you have already? So an interesting thing, Sumanth, about the antipsychotic category with the payers, they don't, like a lot of other categories, they don't manage the utilization criteria by indication necessarily. They look at it as the brand level. So we would expect to be sort of grandfathered in to the existing coverage that CAPLYTA has today in schizophrenia and bipolar depression, in major depressive disorder as well, and we don't expect to have a major change in our strategy from an access perspective. So we wouldn't expect there to be a significant impact on gross to net. Mm-hmm. Let's say you go to a point next year when you have the approval, you have your sales force fully locked and loaded in place. What are some of the internal things you track to qualify when leverage could start kicking in on SG&A in terms of a timeline? So, as you mentioned, we do plan to... We talked about on the Q2 earnings call a week or so ago about the initial phase of the expansion that we've done with our sales force. 150 sales representatives we'll have on board by the end of this quarter. For the time being, they'll focus on our existing indication of bipolar depression. That will give them about a year's time prior to an expected approval on MDD to for us to go deeper into primary care, for those primary care physicians to become more aware of the CAPLYTA brand, for them to have the opportunity to try the product, get experience in their patients with the product. So that if and when an approval comes with MDD, which we certainly expect, then they'll have had a years of experience with CAPLYTA, before that. We think there'll be tremendous leverage in that. We did announce that we'll also have a second phase of a sales force expansion next year. As we get a little bit closer to approval by the FDA, we'll come back to you with more of the details, as we've done in the past, around the magnitude of that expansion and the timing of that expansion. So I promised to talk about the pipeline, so we'll go there now that we're a little bit past the halfway mark. We'll stick with lumateperone for now. You have a long-acting injectable formulation in the works. Given how safe the product is, why would you need a long-acting formulation? That's the first part. And second, is there any merit in developing a long-acting injectable formulation for MDD as well? Yeah. So to the first part, when we started the development of the program, we didn't have all the safety and tolerability and patient exposure that we have now. So we're very pleased with the safety and tolerability of the product. So now, the reason for development of the product is for that patient population who either does not want to take a pill every day, or who is totally non-compliant and won't take a pill every day. So then there's a long-acting injectable. So we are excited about that. We are excited about looking at other indications as well. We haven't exactly narrowed it down to exactly what we would be doing if we would be doing it, but we do think about that. And we are very excited that we did test one formulation for a one-month duration, and we did not think that was optimal. So we have developed several other formulations that will be starting their testing very, very shortly, and for both one-month and two-month durations. Right. Then, your pediatric studies are really interesting because autism spectrum disorders, clearly, there's a lot of unmet need in that indication. When could we expect to see that data set? Well, first we have to list it on clinicaltrials.gov, and so stay tuned for that, and we will be listing it shortly. We do have a very robust pediatric program, both in bipolar disorder as well as in, autism spectrum disorder. As you said, there are about 6 million patients in the pediatric patient population, so it's a large, unmet need, and we're very much looking forward to development in that program. Got it. I think I should start checking clinicaltrials.gov right now. So on 1284, that's a really interesting molecule because it's a deuterated version of lumateperone. It's a new chemical entity. So I think we've seen only one other instance of a new chemical being approved using the 505 pathway. What's your thought process on using that pathway, granted that this is new chemical, it's completely different indications? Yeah. So I think that we need to first do the study we're doing now. Right now, we are looking at a total NCE pathway here. And so I think that the importance of 1284 is that we do think that there are some advantages in the PK that we've done so far in phase I studies over lumateperone, and certainly in certain patient populations, like the elderly. So hence, and we've started a study in psychosis in Alzheimer's patients. We will soon be starting a study in agitation in Alzheimer's patients. And we have an ongoing program that are very large studies in generalized anxiety disorder. We have two studies, one study ongoing as a monotherapy in GAD, and one study that we'll be starting shortly as a monotherapy in GAD. ... You alluded to this briefly, but how do you think deuteration of lumateperone could help patients with GAD or with Alzheimer's disease, psychosis, or agitation? Again, it all goes to the PK profile. And so, you know, we have data from the phase 1 studies. I think that once we do the next studies, which are ongoing, which are called phase 2, but they are powered as phase 3 studies, and so if positive, could be used for our package for approval. So we'll have to stay tuned for further data on that. Got it. Thanks for taking me back to my chemical engineering days with- Yeah. Pharmacokinetics and stuff. How would you place the data that you expect to receive with 1284 versus the low-dose lumateperone data that you had earlier for Alzheimer's disease agitation? Yeah, I think the low-dose data that we had, first of all, we didn't have... I think we didn't have enough patients, and secondly, I think it was exactly that. It was too low a dose. So, it had great safety again, but I think it was too low a dose. And plus, again, I think that there are some qualities about the 1284 molecule that can help allow us to see signals and very robust signals early on. Mm-hmm. How do you think 1284 might be differentiated versus brexpiprazole, for example? They're very different molecules. First, lumateperone, it acts very differently at the D2 receptor than brexpiprazole does. Also, we have a SERT activity, serotonin reuptake inhibition activity, that brex doesn't. We also, the brilliant one of the really brilliant things about lumateperone is it, you very rapidly saturate 5-HT2A receptor, and then you can dial in how much you want of the other receptor profiles simply by raising or lowering the dose. And brexpiprazole can't do that. Got it. So I've got to slip a psychedelic therapeutics question in here because you're also developing 1284 for GAD, or generalized anxiety disorder. How would a product like yours, which is more conventional, participate in the marketplace versus something else that might come in where the durability of that might be greater than what we've normally seen with the chronically dosed product? Huh. Well, I would, I would put it a little bit into perspective. Our drugs are being developed to treat chronic diseases which afflicts millions and millions of patients. I do think there is a place for the psychedelics. I think it remains to be seen, though, how, how they're implemented, where they're implemented, et cetera. I think, as I said, I think there's a place for all of these drugs in the marketplace, but I think that we're, we're, we're not going after typically the same patient populations. Yep, and certainly a long way to go on the psychedelic therapeutics, given all the regulatory stuff that's still to come there. On your recent Conference Call, there was a lot of discussion around the endpoint you've chosen for the 1284 trial, it was the BEHAVE-AD scale. And you mentioned that you've had some discussions with the FDA on that. What was the tone of the interactions? What were some of the competing endpoints that you would have contemplated using, and why did you end up choosing what you did? We wound up choosing the BEHAVE-AD because it's a scale that you can look at both the severity and the frequency of events. Both we and the FDA felt that to be very important. Some of the other scales that have been used over time can't do that in quite the same way. I think we did look at other scales, and we thought this one would be the best one. Got it. Going to a Neuroplastogen program, what excites you most given what you know about your candidate so far? So that's the 1549, and it is a neuroplastogen, also a non-hallucinogenic psychedelic, in contrast to, molecules you were just mentioning. I think our excitement is the ability to have a rapid-acting molecule that can be an antidepressant or treat other CNS disorders without having the hallucinations and delusions. In addition to not having the hallucinations and delusions, another differentiating feature is this is not a takeoff on a psychedelic molecule. This is a totally de novo synthesis molecule. It is a new molecule developed by our chemists based on our deep understanding of serotonin biology and how you fit into the pocket of the serotonin receptors and the downstream effects, which is what we were started on. And what happens with the psychedelics is you go down both a beta-arrestin and a G-coupled protein pathway. We have shown that with 1549, we go down the beta-arrestin pathway and not the G-coupled protein pathway, and we think that's important. And in our animal studies, we have not seen the, what is the biomarker for hallucinations and delusions, and which is called head twitch. And also, we have, in the animal models, seen good safety and tolerability. Got it. On lenrispodun, could that be the next data set that we could see from Intra-Cellular in 2025, the Parkinson's disease phase 2? It will be one of the data sets that you see in 2025. Will be in next year for Parkinson's disease. That's correct. And then just a last one, a buzzer-beater type question. How would you characterize the general business development landscape and, especially from the point of view of either hunting or being the hunted? Yes and yes. Mm-hmm. I think we do always look at a BD potential to bring things into the company. And there's always ongoing discussions on doing things with different people in different places.