Thanks for continuing to participate in the BofA Healthcare Conference. Our next presenting company is ACADIA Pharmaceuticals. We have several members from the management team up here with me. I will introduce each of them. There's Catherine Owen Adams, who is, of course, Chief Executive Officer, Mark Schneyer, who is Chief Financial Officer, and Elizabeth Thompson, who is Head of R&D. Team ACADIA, thank you so much for coming to Las Vegas to see us today. Thanks for having us. We've been starting all conversations with macro questions. I'm sure these are all things that are not going to be new to you. We'll start in the most recent of updates, which was yesterday's executive order as it relates to Most Favored Nation. Can you talk about, just in general, what you think the interpretation of that announcement is and what the implications are specifically for ACADIA? Yeah, so as we know, Most Favored Nation is not a new idea from this administration. It came around during the first administration. It is certainly not a surprise that it is back on the agenda. I think for ACADIA, for right now, we do not sell products outside the U.S. For right now, no immediate impact of MFN. As we look at DAYBUE, our aspiration is to commercialize DAYBUE outside of the U.S. We have ongoing regulatory approval process in Europe, looking to get DAYBUE approved in Q1 of next year. As you know, it takes then a number of months and years to get each product reimbursed in each individual of the 27 member states. The first country we can launch is Germany. We have free pricing for the first six months, all to say that we've got about 18 months to see how this plays out and make differential decisions according to where it lands. For right now, keeping a strong eye on it, joining the forces at BIO to ensure that our voices are heard on the Hill and actively participating in the discussion. For right now, no immediate impact on ACADIA. As we move into Europe, we will make those strategic decisions depending on what eventually happens. Okay. Next question is on tariffs in general. Yeah, and I'm going to ask Mark. Yeah, I would say from where we stand today, we don't believe we have a meaningful exposure to tariffs. I'll explain why in a couple of points. On NUPLAZID for pimavanserin, we have inventory in the U.S. that could last us from a volume standpoint to the mid to late 2030s, really because of investments the company made on the R&D portfolio or in the indication expansion strategy previously. So we have that, and that's here already. DAYBUE, we have a couple of years of inventory in the U.S. And so there's no immediate exposure there. We don't own manufacturing facilities, so there's no kind of physical investment we would need to make to make any changes. With manufacturing, like any company, we want to make sure we're working with high-quality suppliers, have redundancies, have low cost, and over time, anything in manufacturing can change. If something needs to be changed because of some future issue with tariffs or cost imposed upon us, that's something we can evaluate over time, but no meaningful exposure today and certainly on pimavanserin for a very long time. Okay. And where does your IP reside? The IP for pimavanserin is in Switzerland, and the IP for everything else in the portfolio, except for maybe one small early-stage asset, is all in the U.S. Okay. And how would that IP in Switzerland impact the company? I think for, again, going back to the tariff question, the inventory is already, the product's already here. Okay. So even though the IP resides there. Even though the IP resides there, the product is already here. If there is anything that comes up there, again, there is no physical plant or infrastructure along with the IP. If anything in the future came up related to the IP, that is also something we can consider unwinding. Okay. Got it. Last question is on FDA interactions. Maybe Elizabeth, you can talk about that. Sure. I think what you'll get here is a sort of theme of no clear immediate negative impacts to ACADIA. Obviously, we are watching the news like everybody else is. There are a number of dynamics at play in terms of FDA. Certainly, we do know that there are companies that have reported delays in their interaction. To date, in the routine interactions we've had with FDA, we're getting the kind of feedback and communication that we expect in the timeline that we expect. So far, so good from that perspective. Okay. And the people that you've been interacting with, have they stayed the same? Have there been any changes? Thus far, they've stayed the same. It has been pretty consistent. Okay. All right. Enough about the macro. Let's get into specifics about the company. I think a topic that's been front and center for the better part of the last year and a half to two years has been the DAYBUE launch. Catherine, as you continue to adjust to being CEO, how long has it been now? Seven months. Seven months. No one's counting, right? No. What have you learned about the DAYBUE launch that's enabled you to kind of figure out what's needed as next steps in order to kind of have the growth curve go back to being close to the steepness that they saw initially? Right. As you know, just to rewind, came out the gate very strong, a bonus of patients with pent-up demand. After two quarters of fairly strong numbers, we saw some flattening. The last three quarters of last year were flat. As I came in at the end of September, beginning of October, the commitment was to look at this with fresh eyes, commercial eyes, and to think about things we could enhance or evolve as the team had seen this stagnation. I think the immediate decision I took was to bring in a new Chief Commercial Officer. Tom started with us in December and has made immediate impact on both brands, and we can talk about that in a second. In terms of DAYBUE, we really re-looked at the fundamentals. That is where I start with commercial execution. Do we have the right people? Are they calling on the right customers at the right frequency? It's fairly fundamental in sales. I felt that the team was underpowered. In Rare, it's important to get to the centers of excellence. There are 21 of those for Rare in the U.S. We were proud to get to those centers. The most important part of Rare is that you can get to the tail. You can get to the patients that are being treated in the communities who, over time, become the strength of your numbers. 65% of Rare patients are treated outside the centers of excellence in local pediatric neurology centers, PCPs, et cetera. We were not powered to get to the right number of physicians in the community. We took the decision to upsize the field by 30% immediately. Those people were put in place last month. We will start to see the impact of them probably from the second half onwards, hopefully. In addition to that, we really doubled down on the efficacy message. I felt that the efficacy message had got a little bit outvoiced with the focus on side effect management. Bringing to life the efficacy in terms of peer-to-peer interactions, in terms of families going on video, talking about the impact that Rare has had on their loved one, and bringing that data to life in a way that people and families could relate to, we really doubled down on that. In addition to that, we've had a focus on managing the titration and the side effects to the point where each doctor now feels comfortable with their own approach to it. We are also ensuring that the patients are interacting with ACADIA with the same person. Last year, they had two or three people that they were interacting with. We've now gone that to one-to-one relationship. They have one person they can go to with every single issue that they might have. That might sound like a small change, but again, in Rare, it's very important to have that one-to-one interaction. Those are the things that we put in place almost immediately in addition to thinking about predictive analytics in the field. The other thing that we've put in place is a more analytically driven field so that now they have data to say where the Rare patients are, where they're likely to turn up, which doctors are seeing them, so that they can get there and have those precious conversations at the right time. Those are a number of things that we've done differently. As you saw from first quarter, we've seen the first large jump in net new patients for the last three quarters. We're pleased with the progress, but we hope to continue to drive that. Where would you say these patients are being found? You have put in a lot of effort to really expand awareness about the efficacy of the drug, for example. Is it with doctors who had never prescribed DAYBUE before, or are you seeing reinvigoration of doctors who would have prescribed it for a couple of patients and are trying it again on others? I would say the encouraging news is we've seen a lot of new writers in the last quarter. Many of whom have come from the community. We're seeing that sort of strategy start to play out. It is a little bit of a blend, but definitely new writers coming in to experience DAYBUE. Just remind everybody, what type of physician is treating a Rare patient? A pediatric neurologist in the main. How many of them are there? There are, within our focused universe, there are about 5,000 physicians in the U.S. who are treating Rare patients on a regular basis. Of those, on average, how many, I guess, touch points does a sales rep need in order to motivate a doctor to write a script? Back to the basic numbers, right? What we've learned over time is that each doctor, it obviously depends, but they need about four to five interactions to feel confident to prescribe DAYBUE for the first time. Again, back to the underpowering of the field, we weren't able to have those conversations in a reasonable timeframe. Again, by increasing the amount of people in the field, you can have those conversations more quickly and therefore stimulate that growth in new patient demand. Just to say that year to or launch to date, 35% of Rare patients have ever tried DAYBUE. There's 65% still to go. That's the belief in terms of that ability to drive that growth further now that we can get to these doctors more regularly. Going back to patients who have tried it and you tell me the reason that they have dropped out of taking or discontinued taking therapy, what percent or can you track of those patients have come back on? We track all of them. Relatively few have come back on. I think we're seeing every month we see patient restarts. They may have stopped because of side effects. They may have stopped because of other things that are happening in the family dynamic or in the child's life. There's variable reasons. The majority of the reasons to stop are side effects. For right now, a lot of those families don't feel like they can come back on. The ones that are restarting are hearing about the titration schedules and are coming back and starting the dose slightly differently. We're now seeing those patients come back. It's still a relatively small number, but they're there. Okay. So how should we be thinking about the cadence between what you saw in the first quarter and how to think about each successful quarter this year, for example? Mark can talk to sort of the financial cadence. If we just look at new patient starts, we're expecting new patient growth in subsequent quarters throughout the year. As I've already said, the inflection point that I believe will happen, we'll start to see in the third quarter as that sales force increase starts to have impact. Now, why do you have to wait those three or four months? Because they need to have those three or four calls. That's the reason for waiting for the impact. Would you expect 2Q to be a stronger quarter than 1Q? I expect 2Q to be a strong quarter, but I think the inflection point will come in the back half of the year. I think from a financial perspective, I think Catherine's right. Operationally, the investment we're making and the timeframe we expect that investment to come is more of an inflection in the second half. Just remember, our first quarter is a low seasonal quarter, both in terms of price and volume. We'll expect that seasonality to unwind in the second quarter. If you're looking at a net sales standpoint over the course of the year, it should be more consistent Q1, Q2, Q3, Q4. Okay. With these interactions that your sales force is having with the physicians, what are the questions that they feel need to be addressed a few times before the doctor is comfortable? Now that we've got the balance back to efficacy, it's understanding which of the domains the child might see improvements in. They like to see the long-term LOTUS data where we look at the eight domains that the original trial endpoints cover, and we talk about the possibilities within each of those domains. They like to talk to other clinicians about how they have started their patients on DAYBUE. It is a variety of needs. They like to speak to the MSLs about maybe some of the publications that have just recently come out. It is overall. I think the real focus is, why should my patient go through two or three months of titration and understanding the side effect profile? What's in it for them to believe that it's worth the journey? Sort of back to the old L'Oréal commercial, what's in it for me? Am I worth it? It is really having that conversation with the families and bringing that to life. Okay. Do you think that your sales force is now right-sized to do that? I do. They're right-sized and they're highly motivated. We've brought some new people in with real skill sets and passion around this space. I'm excited to see what they can achieve. Let's switch over to Europe. Part of your area of expertise in your previous jobs has been to manage launches ex U.S. How would a launch like DAYBUE need to be managed differently than what's been done in the U.S., if at all? The first thing about Europe is ensuring that the physician staff feel comfortable with prescribing. Otherwise, you have to go up a similar learning curve as we would do here. That's the reason why we've put in place in countries where we're able to a name patient program. That allows physicians who are motivated and have patients who are asking for DAYBUE to source it from us and to start using DAYBUE prior to approval. Now, that will be a modest number of patients, but it still allows the European community to talk to each other about managing a patient within a European healthcare system, which is different to a U.S. healthcare system. In a single-payer space where you've got sort of patients that are much less likely to be moving between doctors, you've got a much more sort of consistent theme. You've got health records that are longitudinal and can be tracked over time. These physicians want to see progress. They want to understand how the patients are improving over time. Having that experience is important. I think overall, the importance is that we learn from the lessons in the U.S. and we apply them in the EU. We will do that. It is all about setting expectations, managing the patients appropriately, but also talking about the possibilities of DAYBUE. Okay. Let's move on to NUPLAZID. This is a mature launch. What do you think is an area that has not been touched yet? What's giving you confidence that it's worth investing more resources into it at this particular stage? I think what the team had started before I arrived was a refocus on an awareness campaign. What the team had seen prior is that if you educate patients around Parkinson's disease, one of the areas that they are very unaware of is the possibility of a psychosis in terms of hallucinations and delusions in a patient with Parkinson's. Very well aware of motor symptoms, very unaware of anything else. The ability to educate and make patients aware is highly impactful, and it's a promotionally sensitive market. The fact that we've had Ryan Reynolds on board in terms of an unbranded campaign has been amazing in terms of the impact it's had on awareness. We've seen very significant increases in the awareness that patients and their families now have about the possibility of hallucinations and delusions. What we've seen that translate into is a very strong increase in patients going into their doctors and having conversations about treatment for hallucinations and delusions. We've now had the best quarter in five years for new patient starts on DAYBUE. Sorry, on NUPLAZID. Joining the docs, the awareness campaign has had an impact. The patients have gone into their physicians, and they've now been prescribed NUPLAZID. We believe now that the team can really focus on the efficacy messages and the story around NUPLAZID and really underlining the great data that we now have, including an impact on all-cause mortality versus what's normally used in these patients, which is off-label, unapproved antipsychotics. Having a clinical argument which is able to talk to that and now encouraging physicians to have conversations about earlier diagnosis of symptoms. There is lots going on to try and really stimulate the growth that I believe is truly possible for NUPLAZID. Yeah. Where would you say the next range of profile of patients is? What we're working with the medical team on is generating information, publications, data around the use of NUPLAZID earlier in the treatment diagnosis journey and ensuring that doctors are aware that you can use NUPLAZID earlier in the treatment diagnosis journey. There is a strong focus on that right now. The earlier diagnosis of patients is a very strong focus, as well as the other data that we have on efficacy. Okay. Now, is the diagnosis of this something that requires family members to also be involved as opposed to, obviously, the patient may not be aware even that this is happening to them in certain cases? I mean, I think a lot of our patients do have insight into the fact that they are thinking things that may or may not be true. There is definitely, depending on the age of diagnosis, insight. More often than not, though, it's the family that notices. It is really the family that is required to be educated around this. Even if patients know that they're having these thoughts, they're very reluctant often to share them because it's scary. They don't know why it's happening. Again, a lot of patients are unaware of that as well. I don't know if you want to add anything to that, Liz. No. I mean, I think that that's, we know that something like 50% of Parkinson's disease patients will develop psychosis. And we also know that something like 10% of them will self-report. There is an aspect to that that is about sort of the stigma and the shame and the confusion. There is an aspect in some cases, I'm sure, of inability for patients to recognize that about themselves. So I think that both increasing the awareness within patients, decreasing the stigma through talking about how this is a normal part of the course of the disease, and educating patients' families as well so they can keep an eye out for things with their loved ones, all of these, I think, are pretty important. If you had to kind of talk about the cadence of impact of the efforts you're making here with NUPLAZID, it's a much more mature launch relative to the efforts you're making with DAYBUE. How should we be thinking about those? I think this is a much more steady increase over time. I mean, I don't know if you want to talk about the financials as well, Mark. But NUPLAZID this year, as you know, we've guided to $660 million-$690 million. We still reiterated that guidance in our Q1 call. We're seeing that growth come now. It's a much more steady increase as that awareness increases. Yeah. I think maybe you look at the patient population. The size is very different, right? And so DAYBUE, two years into launch, was still penetrating the existing patient population. They have a long ways to go. NUPLAZID is a much bigger market. And it's a market where patients are getting diagnosed late in their disease progression for the most part, right? So it's a patient population that's kind of ever-turning. And that's why awareness is important because the patients and caregivers today are different than patients and caregivers five years ago. And we also lived through a global pandemic. So a lot's changed, which is why the investment today makes sense and it's starting to pay off. Okay. Let's move on to pipeline because you do have some updates coming up. Elizabeth, your turn to talk now. For ACP-101 for Prader-Willi, can you talk to us about that phase III trial design and what would be good data? Absolutely. First off, I do want to recognize that we were very pleased that we were able to accelerate timing on this. We're now expecting full enrollment in the trial in this quarter, which leads us towards top-line data roughly early fourth quarter this year. Really pleased with that combination of good hard work by the R&D team, as well as, I think, a real groundswell of support from the community. We work closely with patient advocacy organizations. We were really pleased with the uptake we saw with that. As far as the clinical trial design is concerned, we've got a phase III trial that's currently ongoing. It is roughly 170 patients that we're looking to have enrolled in total. Two arms, parallel groups. At baseline, patients are randomized to start either getting 101 at 3.2 mg or placebo. Our primary endpoints at week 12, we're looking at the Hyperphagia Questionnaire for Clinical Trials. This is a pretty standard endpoint that is used in trials in this space. In terms of what good data look like there, there are a couple of things that I'm looking for that I'd be pleased to see. The first of these is a magnitude of effect that's similar to what we saw in the 3.2 mg arm in the prior phase III trial. The second thing is to see a safety tolerability profile that's fairly consistent with what we saw there, where I at least don't see any clear reasons where we would need to exclude parts of the patient population, have significant burden of monitoring, anything like that. Obviously, we'll see what comes out of this trial, but those are the things that I'm looking for here. What are the most common side effects? The most common side effects that we saw, again, I do not know in the phase III that we are currently running. In terms of what was seen historically, most common was flushing. Even that was only seen by something like 20% of patients. Generally, it was fairly transient. This is thus far, I think, a safety profile that, again, does not seem as though it is going to lend itself to needing to exclude significant groups of patients or anything like that. Okay. This is an area of intermittent need, but it looks like it's becoming crowded at kind of the same time. That is good for the patients. Soleno is launching its product. Can you talk about the differences mechanistically for your product? It seems like it's a big enough market where there's room for multiple players. If you were to try to, let's say, speak to a physician about differentiation, what would you, without knowing the phase III data, be talking about? Yeah. So I'd make a couple of comments. I do want to start with the, I mean, we, and I think the Prader-Willi community, and we are thrilled that there is actually something available for them now. This has been a patient population that has been waiting for a very long time. That said, entirely consistent with what you say, this is a larger, certainly compared with Rett population, something like 8,000-10,000 patients in the U.S. And I think these are patients with truly complex medical situations. I think we firmly believe this is the kind of space where one agent is not going to be the solution for everyone. We think there's ample room for multiple drugs to come forward and make meaningful differences for patients. In terms of differentiation, it is awfully hard for me to be too specific in the absence of the phase III data. I will say we are really, I think that the study design that we have, if we have a positive outcome of that trial, we're going to have a pretty clear clinical story for physicians and for patients. Here's what you can expect when you start on our drug. The ViCAT approval was based on a randomized withdrawal trial. Typically, that's a little bit more informative for things like maintenance or rebound. It makes it a little harder to set expectations. Catherine may want to comment on that from a commercial point of view. I think that's going to be an important part of the story. Certainly, there are going to be aspects about different administration profiles that are going to be relevant to different patients. There are going to be patients that will prefer one versus the other. Again, I'm sure there will be things on the safety and tolerability in terms of what's appropriate for a given patient. Anything you want to expand on with the commercial case, Catherine? I think while two products sounds crowded, for me, it's not very crowded. I think to Liz's point, it's going to be potentially very exciting to offer a different alternative mechanism with different data, different profile. As she said, talking to the community, they welcome that opportunity. I think for us commercially, there's plenty of space for us both to play. We look forward to a successful trial in order to achieve that. Yeah. I guess the best compliment is if someone else wants to pursue the indication. So, Rhythm is actually trying to. Exactly. There are different aspects people are looking at, right? I think it points out how complex these patients are. Each of these drugs seems to be taking a slightly different spin. That's great because each patient has very different needs. Okay. As you think about how to integrate, let's say that all good things happen with this program, you apply and you get approval. How would that fit in with the launches that you would already have been managing at that point, the two other launches? Yeah. I think this fits very nicely into our rare disease team. The core points are very similar in terms of the physicians that treat. There's definitely an overlap. There's obviously, in all spaces, different physicians in different hospitals that have very specific focuses. But roughly, neurologists treat both patients. Our expertise in rare and neurology, patient support, commercialization, I think that will all come to bear hopefully when we can launch 101. Okay. And then last question is on ACP-204. Back to Elizabeth. Can you just talk to us about where you are on that? Sure. Really quickly, ACP-204 is our new 5-HT2A inverse agonist. We designed this based on learning from pimavanserin. We were looking for a few things. First is that NUPLAZID is associated with QT prolongation. While it's not massive, it is something that you need to think about in an elderly, frail patient population. It is important in and of itself. We were looking to reduce or eliminate that. It is also important because it limited our ability to dose range with NUPLAZID. There is indication sort of in a number of disease states, there is some suggestion of an exposure-response relationship suggesting we have not gotten as much efficacy out of this mechanism as we could. We think the ability to dose range here is going to be important. Finally, we were looking for a faster time to steady state so a potential better onset of action. We're currently in a study in Alzheimer's disease psychosis. We're in the phase II portion of a phase II, phase III overall program. We're looking to have that completely enrolled in the first quarter of next year and get data roughly mid-year. We are also starting a Lewy body dementia psychosis program. We're looking to get that started in phase II in the third quarter. A lot of activity going on with 204. How is Alzheimer's psychosis different from Parkinson's psychosis manifestation-wise? There certainly is some overlap in terms of hallucinations and delusions. There can be some differences in terms of the relative proportion of those. Certainly, sort of when you see that in the disease course and the number of patients who suffer from it. We do have some data with pimavanserin in Alzheimer's disease psychosis. Obviously, that would take us more than the 40 seconds I think we have left to go through. What I will say is that there are signals of efficacy there that I think we can build on both from a potentially better molecule perspective as well as some study design learnings that I think give us good opportunity to maximize success for 204 and ADP. Okay. We'll continue this. We'll schedule this here. Sounds good. Sounds good. Thanks. If I could just say we have an R&D day on June 25th. Yes. You can hear more about all of what Liz has just explained. All those things. That way we have a place to go. We'll do that live. Yeah. Okay, guys. Thanks for your time. Thanks so much to the patients.