Great. Thanks very much for listening in. It's my pleasure to be introducing the ACADIA Pharmaceuticals Management Team. With me is Catherine Owen Adams, CEO, Elizabeth Thompson, Head of R&D, and Mark Schneyer, CFO. I'm sure most folks listening in here know the company well, but maybe I'll ask Catherine to just give a quick couple-minute snapshot of where ACADIA is at with the commercial business and the pipeline, and then we'll do Q&A. Thank you very much, and take it away. Thanks so much for having us. Yeah, ACADIA, we have a focus on neuroscience and neuro rare. We have two commercialized products right now guiding to over $1 billion this year. We have Nuplazid for the treatment of hallucinations and delusions in Parkinson's disease and Daybue for the treatment of Rett syndrome. We have a strong balance sheet and are looking to be active in our BD space as well this year. Beyond that, we have a really great pipeline with two products in late phase two, phase three in Prader-Willi syndrome and ACP-204, which is in clinical trial for Alzheimer's disease psychosis and also the psychosis of Lewy body dementia. We recently acquired a new product for essential tremor, but all of that will be revealed in more detail on R&D Day on the 25th of June. That's my elevator speech, Paul. All right. I like it. Thank you. Let's talk about Daybue for a bit, right? The launch has been up, up, up, and then kind of flattish to down for a period. It feels like we're at kind of an inflection point, right, where we're either at a steady state or we're going to see a new sort of inflection based on an evolving commercial strategy. You know, what gave you the confidence to give guidance for Daybue that implies, you know, a real rebound in organic growth by our math? Yeah, let's sort of break that down into your component parts. Yes, we came out the gate very strong. Lots of demand for Daybue amongst the Centers of Excellence treating Rett patients. Once we'd hit a lot of the Centers of Excellence, we moved out into the community. That's when our kind of patient demand, I would say, plateaued. The last two or three quarters has been very steady. Not unlike many other rare disease launches, the key to a rare disease launch is getting to those patients that are treated outside the Centers of Excellence. We know for Rett syndrome, that's about 65% of patients who will be treated by physicians outside of a Center of Excellence. When I came in and looked at our field force and our go-to-market model, we were underpowered to reach those physicians and have the right conversations with them. Immediately what we've done is to increase the size of our customer-facing model. That includes not only our sales reps, but also additional customer-facing teams which support the whole of the Daybue, the whole of the Daybue value chain. That is going into place now and will allow us to reach that extra 65% of patients at the right reach and frequency, I believe, to drive additional growth. We've guided to that with seeing that growth coming in towards the back end of this year. I feel very confident that we will be able to achieve that, having led quite a few commercial launches now and understanding how it works. We were just underpowered. I feel very good that we can reach the rest of our market and really see that increase towards the back end of this year. Okay, great. I'm sorry, the automatic light just turned off in my office, so I'll have to throw something across. All the time. Happens all the time. That's great. Okay, that's a great overview. I guess, you know, there's a couple of variables here, right? One is the NRx variable. One is the persistence variable. On the latter, persistence, like, do you feel like we've seen or we've hit like the curve or to some degree on an average basis with the existing patient base where we're like seeing a plateau in the discontinuation rate? Like, how are you thinking about that? Let's think about the journey of the patient on Daybue. What we're seeing is over time that at around 12 months, we still have over 50% of patients still taking Daybue and seeing a clinical effect. For me, that's a pretty high persistency rate for any product, particularly in the rare disease space. Over 50% at 12 months. Over time, we've been launched nearly two years now. Our patient base has become more stable and the amount of patients on product at a steady state is increasing, right? If you look at a point in time now, over 62% of our patients have been on Daybue for more than a year. Again, we've got a persistency rate that's stable. We've got a steady state of patients that are increasing their time on Daybue. For us, that sort of base is a lot more consistent than it was even two quarters ago. Now we're building on that. Now the strategy is to get more referrals in the top of the funnel. That is why we're increasing the field force to drive those increased referrals. Yeah. Yep. Okay. And why, you know, your commentary that you're really thinking about this being back half loaded, why is that? Like, why wouldn't you? I mean, you have a lot of experience in the commercial side. Like, why wouldn't it be, you know, a more immediate impact? Because it takes time for reps to reach their doctors and have the right number of conversations to drive that first script. You know, this is a conversation that needs to happen three, four times before a doctor feels confident in the main to start Daybue. There's obviously some that need less and some that need more. Just having led a lot of launches and field forces and looked at the numbers, it takes about two or three months for the field force to start having an impact on prescribing. You know, we've factored that in. We're being pragmatic and we're being, I think, achievable in the way we've guided. I want us to achieve all of our guidance this year. Fair enough. Anything about these non-COEs where the marketing message has to be like fundamentally different? You know, I mean, the academics, right, they're much more aware of the clinical data. What do you like, what are the questions you get from these community doctors? Are they different? Actually, they're not different. It's just that they see fewer Rett patients. They need to ask more questions and they need to have more understanding of the clinical data. I think, you know, the medical affairs and the MSL side of things becomes more important. They need to have somebody to call on and to understand and to ask questions of. For us, it's bringing that data to life. If you only see two or three Rett patients a year, you really need to understand what our data means. What does the CGI mean in real life? What do the changes in scores mean in real life? Again, we're evolving our messaging to your point to make that more tangible and just more obvious to physicians that treat less Rett patients. That way, they're armed with all the questions that the families will ask them. Fair enough. Do you want to talk, Catherine, about your efforts ex U.S. and? Sure. We have approval in Canada, as you know, and we have filed for approval in the European Union. In Canada, we're in talks with the health authorities right now for reimbursement. We expect to get some outcomes of that in the next few months. In Europe, we're preparing to launch and we are getting our teams ready. We have MSLs out there in the countries. Our big countries are, as you would expect, based on population, Germany and France and Spain and Italy and nothing strange there. We are building a team out in Europe. We're going to be launching this ourselves. I'm very comfortable launching products outside the U.S., and we are building that team up, but we're being judicious and we're looking at it on a country-by-country basis. Rett is treated pretty similarly in most European countries. There's a lot of localization and Centers of Excellence in most countries. It is not that different to the U.S. It is just making sure we're in the right countries at the right time. Makes sense. You know, when I look at the rare disease space and, you know, look at very different drugs every day, very different diseases, sometimes it feels like it's almost arbitrary, like what drugs are able to kind of hold US pricing in Europe and what aren't, right? I mean, I can think of examples like amazing medications, like things for cystic fibrosis where they're nowhere close or medications where the effect size is really, really small, like an ERT, but the pricing is very, very tight. How much visibility do you have into this at this point as to whether or not you can get US pricing ex US? I don't think there's any markets really where there's US pricing ex US at the end of the day, because as you know, you start in some countries and you come down. You have to look at the European Union over time, knowing that prices will always sort of erode. I think, you know, we feel very strongly about the value story that we have for Daybue. We feel very strongly that we have a lot of global demand for. We're getting requests every day from physicians in these countries, which is why we're also opening up our named patient program as soon as we can. There's a lot of demand for Daybue. I feel back to the price that we're going to get, we're going to get a good price, but every market will take on its individualities and we'll make decisions based on that. Great. Let's talk about Nuplazid for a few minutes and then we can talk about the pipeline. For Nuplazid, I mean, I followed this drug for a long time. I sat through the adcom nervously. I have a lot of the history there. I think it's really impressive what you guys have done to reinvigorate growth like this late in the life cycle of the drug after it went through a number of years where growth kind of languished a bit. What has been so effective about your new strategy and how sustainable is it? You know, I think the team already knew that this was a promotionally sensitive market. What I mean by that is patients and caregivers need to be continually educated that hallucinations and delusions are associated with Parkinson's disease. It's relatively low awareness when a loved one gets Parkinson's that they might suffer from these symptoms. Keeping that awareness up is really important. The team stopped doing a lot of DTC during COVID and started in the middle of last year when we realized that the levels of awareness were actually pretty low. That has really been impactful and is really starting to pay dividends now in terms of more patients coming into offices and asking for Nuplazid. We've also had a lot more real-world evidence generated for the efficacy of Nuplazid versus off-label antipsychotics, which continues to look really strong. We had some label clarity about whether you could use Nuplazid with patients with dementia, which was always a little bit of a gray zone for a few physicians. With the label clarity, the real-world evidence, and the DTC campaign, I feel very confident that we can really continue to drive growth into Nuplazid. We have a 25% market share, and I think there's a ways to go, yeah. Makes sense. Do you want to comment briefly on the two upcoming IP cases that we're going to get results from? I know there's not, I know there's not a lot you can say, but I think, you know, the question I get most commonly is sort of framed as a version of this. It's framed as a version of, you know, your predecessor, Catherine, was guiding to generics coming to market in 2030 for a while, right? And now there's this potential optionality where it could be later than that. Is there a reason to think that, like, not that something changed, but that, you know, this was IP optionality that was discounted by Steve, but actually might be something where there's a real upside driver? Like, how are you guys thinking about that? I'll let Mark answer that for you. Yeah, I can jump in here. I think for us, the way we look at it is it's really bookends, right? I think we're, you know, on the October 2030, the kind of the short end of the bookend, we remain highly confident that we will prevail in the composition of matter, you know, appeal, which is still yet to be scheduled. I, you know, to use your words on kind of optionality, you know, time and, you know, litigation is advanced, right? The formulation patents, which, you know, lots of people just discount by nature, you know, we think as we went through the trial and the steps leading up to it, we have the better argument on both invalidity and non-infringement. Obviously, we'll have to see how that plays out, but we think we have the better position and we'll get a ruling on that in the first half of this year. It's our expectation. Okay. Ruling on both that and. It should come out, right? I think we're a little surprised on that the appeal hasn't happened yet. You know, kind of stop guessing on the timing there. We should, again, there's no like PDUFA clock for, you know, trial rulings, but our expectation and advice from counsel is we'll hear sometime in the first half of this year on formulation as that trial took place last December. Yeah. Okay. Mark, while I have you answering questions, I did get a question from an investor who's listening in who was curious to hear about, you know, and it's actually not clear to me which franchise he's talking about. I think it's Daybue, but we can just maybe comment on both for Daybue and Nuplazid. What were the gross-to-net dynamics for Q1'24? Should we be considering those as coming into play again for Q1'25? Yeah. So on Nuplazid, I think what we've specifically said, it will change for Nuplazid, right? Nuplazid is a high Medicare patient population, about 75% is Medicare. We're, you know, the gross to net dynamic changes with the Medicare Part D redesign. What we saw in the past was a very high gross to net in the first quarter as we had to pay our manufacturing obligation for both new patients in the quarter and essentially every patient that was, you know, renewing therapy from the previous year. In the new design, it'll be more even over the course of the year. We don't expect kind of quarter to quarter fluctuations. We do for Nuplazid expect a benefit in gross to net as we qualify as a small company manufacturer under the Inflation Reduction Act. Our gross-to-net will go down this year and that's factored into our guidance. I think that's it. If there's a Daybue question, you know, I think Daybue, again, we guided up a little bit due to a number of changes from, you know, the Medicare impact on that as well as just pricing dynamics that's taken place year over year. Again, for that, you know, we expect that to be, you know, mostly consistent quarter to quarter. You always have fluctuations as any patient mix for payer in any quarter can change. That has fluctuations for our medicines just like any other medicine. Yeah. Okay. Great. All right. Maybe I can ask a few questions about the pipeline if that works. Go ahead. Yeah. So I'd love to ask about 204 and the ADP program. And this is my weighted question. So I would love to hear the countercase and I'm open-minded to countercase. But my perception was always that the ADP parallel group data for pimavanserin was kind of messy, right? Like it hit SAPS at week six, but not four, nine, and twelve. And, you know, there was a whole discussion we don't have to get into about the FDA adcom about how that data was somewhat noisy. So I guess in the context of that, maybe a couple of things. One, you know, why should we be confident that this 5-HT2A selective mechanism truly works in ADP? And two, are there things on the design side that you can do with 204 to better maximize probability of success? Okay. Thanks for that. I'm going to start back just a tiny bit, even though I know you all, you know all of this, but, you know, quick grounding, ACP-204 is our new 5-HT2A inverse agonist. We designed it to improve on Nuplazid in three ways. You know, we're looking to reduce or eliminate QT prolongation, achieve higher exposures, and shorten time to steady state. So far, preclinical and clinical data that we have are supportive that we are accomplishing all of these. We're getting some of those data out into the public medical literature and we'll be sharing more of it at R&D day. That's a little bit of basic grounding more for the audience than for you, really. There was a prior parallel group study in ADP. As you note, you know, it did meet its primary endpoint. Week six was the primary endpoint for that trial and there was efficacy demonstrated there, but there was less consistency across other time points. Some of them numerically look like they separate, but did not meet statistical significance. You know, some of them did not even quite do that. I think that, you know, as we look at a number of learnings from the Pim program broadly, which we considered when we are looking at 204, that is information from the parallel group trial as well as other trials. You know, really, I think at heart, we think that what we need here is more robust efficacy to get greater consistency across the data set. We do think that the data set that we have are supportive of signals of efficacy in Alzheimer's, but we need to have stronger efficacy in order to more robustly demonstrate that and demonstrate that across numerous endpoints. As I think about that, there are a couple of things in the molecule that contribute to that. You know, prior work on Pim does show some suggestion of an exposure response relationship from an efficacy perspective. Like I said, we demonstrated 204 for the possibility to get to greater exposure. That could contribute to that. The other thing that we did was designed to get to a shorter time to steady state that, you know, it's not definite that that's going to translate into earlier onset of efficacy, but it could. As you note, you know, some of those earlier time points, there was some indication of efficacy, but not statistical significant separation. We think that those are a couple of important things about the molecule itself that gives us the potential for more robust efficacy. There are some aspects to trial design as well, you know, certainly looking at a more severe patient population and focusing in specifically on the Alzheimer's disease subset in an adequately powered way. Is there something about this mechanism that makes it more potent for Parkinson's? I think even in the randomized withdrawal study, the hazard ratio in PDP was 0.09, which is unbelievable, right? In Alzheimer's, it was good. I'm not dismissing it, but it was closer to maybe 0.6 or 0.65. Like why do you think there's been that discrepancy? Yeah, I will say that, you know, the data in Parkinson's and in Parkinson's has been striking, obviously most striking there. I don't think that we have a clear explanation as to why that would be the case. It doesn't seem, for example, that it's a difference in exposure levels in the different patient in the different disease populations. We explored that. Again, I think even within Alzheimer's, it's a question of how much more can you do with this mechanism? The exposure response we have is suggestive. You know, we're testing this in our current trial. We're looking at higher exposures to allow us to actually identify whether higher exposures do get you better efficacy. The exposure response analyses we have to date suggest that that's a possibility. We're looking to maximize that with 204. Okay. Okay. Do you want to talk briefly about Lewy body dementia and the thought process there? Absolutely. Jumping a little bit off of what you just said, part of what we like about this is the fact that this is an area with small subsets, but some strong data from a Pim perspective. Again, I'll take a step back and say Lewy body dementia is, you know, it's associated with abnormal deposits of alpha-synuclein. These Lewy bodies can impact thinking, movement, behavior, mood. Psychosis is a huge, huge issue in this patient population. The hallucinations and delusions here are really significant. I'll say that there are antipsychotics that are commonly used in other psychoses that can actually be harmful for patients with Lewy bodies. The unmet need is significant. As we look at data from Pim, I'll be very clear that this is a small subset of patients. It's about 20 patients per arm from the Harmony study, and that was our withdrawal study. What you see there is in patients who had Lewy body dementia psychosis in that patient population, those who remained on Pim, only about 5% of them relapsed, whereas those who were on placebo, about 55% of them relapsed. We do think there's some good reason to believe from our historical Pim data, and we think that 204 again has the possibility of being able to bring potentially more here as well as in Alzheimer's. Yeah. What are, can you leverage the same endpoints in DLB, like the SAPS, or do you need something different? I anticipate, you know, we're going to be in phase two with DLB. What we're going to be doing here is looking at a variety of different endpoints to see which one is most useful. We will be looking at SAPS as well as others. Yeah. Okay. Okay. Great. Do you want to briefly talk about 101, the Prader-Willi program, and just give us a quick intro before I have a couple of follow-ups? I will do it as quickly as I possibly can. ACP-101, intranasal carbetocin, as you know, this was in a prior phase three trial that did not meet its primary endpoint, which was with the high dose, but a lower dose did show, did suggest that there was efficacy. There was a complete response letter for this, but we are running a new randomized placebo-controlled phase three trial looking at the dose that did seem to be effective in the prior trial. That is a quick intro. I like it. You know, why did Acadia look at that data and think that the inverse dose response was not noise, but indicative of a real drug effect at the lower dose? You know, I like to look at a few things in this instance. Do we believe the mechanism makes some sense? Do we see some internal consistency to the data set? Do we have any kind of alternative hypothesis for what could have happened here? You know, we do think that mechanistically there's some reasonable reason to believe here about the relevance of oxytocin and Prader-Willi. We looked at the prior phase three and did see some consistency across time points, but also across endpoints that was reassuring. You know, while it's not proven, there is at least a plausible hypothesis for the underperformance of the higher dose, which is about off-target impacts through the vasopressin receptor. It is a reasonable reason to believe at the end of the day, we're going to need a, we expect that we'll need a positive trial in order to support registration. We design our currently running trial with those learnings from the prior phase three in mind, and we'll see what comes out of it. Yeah. Fair enough. Catherine, maybe one last question for you. You mentioned business development in your opening remarks. Anything you can say there about Acadia's strategy and what we should expect in 2025? I'll start with the strategy and let Mark maybe add something. In terms of our strategy, what we've decided to do is open the aperture a little bit beyond just neuropsych and neuro rare to adjacencies of rare disease. We believe we have the capabilities to be successful beyond neuro rare. We are looking at rare cardio, rare endocrine, rare metabolic, et cetera. We have a pristine balance sheet, which Mark is eager to put in the right place. I'll let him maybe share a little bit more about our strategy there. Yeah, I think from a financial account, we've got over $750 million in cash, no debt. You know, that positions are strong to execute to expand the portfolio. You know, as long as we find the right assets and they meet our financial metrics and everything, things are actionable, you know, we'll execute. Anything you can say about like capacity for size? Yeah, I think we don't. Yeah, go ahead. Go ahead. No, please go. Yeah, I mean, for us, I mean, our bias is to invest, right? I think for us, you know, we'd lean in and, you know, I think what we've said since I started as CFO and, you know, we've turned cash flow positive, our bite size gets bigger every day as we kind of add cash to the balance sheet and you kind of don't put an upper limit on it. Obviously, there's a certain level of just actionability and transactions that we've said kind of you kind of wouldn't do things, you know, or not likely to do things more than half your market cap. If we find things that we, you know, we are excited about, we'll deploy the cash. We're not afraid to raise capital if there's things above our cash bite. You know, that would have to be exceptional or not likely to happen, but things that we still look at. If something's excited, we'll lean in, as I said. Fair enough. All right. Thank you very much. Thanks for engaging with me and thanks for joining the event. We appreciate it. Thanks to everybody for listening in. Thank you both. All right.