Good morning, everyone, again. Welcome to the next session of the Needham 24th Year Healthcare Conference. I'm Ami Fadia, Senior Biotech Analyst here at Needham, and it's my pleasure to be hosting Acadia for this next session. Good morning, team. Thank you for being here for this fireside chat. Maybe if I could just turn it over to Catherine to just kick us off with some opening remarks and just priorities for the company for this year. Yeah, no, absolutely. Thanks, Ami, for having us. I'm joined by Mark Schneyer, our CFO, and Liz Thompson, our Head of R&D, and we're looking forward to taking the questions. Just to sort of set the scene for Acadia in 2025, we're really excited that for the first time we're guiding to over $1 billion for our two commercial products in total. That's Nuplazid for the treatment of hallucinations and delusions of Parkinson's disease and Daybue for the treatment of Rett syndrome. For the first time, they'll come in over $1 billion, which is an exciting landmark for us at Acadia. As well as that, we've got two late stage programs coming through. We have ACP-101 for Prader-Willi syndrome, which is a late phase III, and looking forward to completing that enrollment towards the end of this year. ACP-204, which is our phase II, phase III clinical trial for the treatment of Alzheimer's disease psychosis and also initiating a Lewy body dementia psychosis study later this year. Very excited about both of those readouts, which will come in 2026. Finally, we have a newer product into our pipeline, ACP-711 for essential tremor, which is fairly early stage, phase I now, but starting phase II next year. We are really excited to hold our first ever R&D day in June of this year, June 21 in New York, and Liz and her team will be sharing much more about our pipeline. Those are the headlines for Acadia, Ami. Excellent. Great. Thank you for giving us that overview. Perhaps maybe just before we jump into some of the details, detailed questions on Acadia, I wanted to just maybe ask you around two topics. Firstly, maybe just the recent changes that we've been seeing with the FDA. Can you comment on, kind of how you, as you know, one of the industry representatives, are kind of thinking about this changing environment at the FDA? Any comments you could provide would be helpful. Yes, I mean, I think we're amongst the many biotech companies that are watching very carefully. The situation, as we all know, is fairly fluid right now, with the changes at HHS, you know, in leadership and now at the FDA. You know, we're all watching. We're fortunate that we have a very strong industry group, with BIO led by John Crowley and his team, and they keep us abreast. More importantly, they represent us on the Hill and ensure that our voice is heard in terms of any concerns about changes that we're hearing. You know, in terms of effects on anything that's happening within Acadia, for right now, we haven't seen anything in terms of any effect on any of our trials. We watch with bated breath like everybody else and are hoping that we can get through the next few months of maybe relative uncertainty and come out the other side with more of an idea. Beyond that, Ami, not really a lot to say right now. Fair. That's fair. Just separately with regards to the tariffs, which are also front and center for everyone. Yeah. Would you like to provide any color on, you know, where the company's in-market drugs are manufactured and, you know, what investors should keep in mind as they think about the implications, for Acadia? I'm going to let Mark take that because he leads our, he leads our supply chain group. Mark, why don't you share your thoughts? Yeah, I'm happy to jump in. I think the first thing I would say, obviously there's another topic that we're paying close attention to and evaluate what the potential implications may be for the company. I think the first thing I would say for both Nuplazid and Daybue, we have at least a couple of years of inventory in the U.S. today. That gives us some flexibility to see how this plays out without expecting any immediate financial consequences on the company if there are any. I think if we look at that to your question of, you know, historically tariffs have flowed with API for pharmaceutical companies. Today, Nuplazid API or pimavanserin API is manufactured in Switzerland, and trofinetide API is manufactured in Italy. We do have alternative sources. Those things can be changed over time. They can't be changed immediately. That is where it sits today. And then the one other thing I'd point out for investors, if location of IP comes into play here, our prevention IP is located in Switzerland and all other IP for the company, pipeline, and trofinetide resides in the U.S.. Okay. That's super helpful. Thank you. Okay. And just as a quick reminder to our listeners, if there are any questions you want to send along, feel free to use the dashboard. Maybe let's switch gears and talk about Daybue. Sure. Talk about sort of the current penetration of Daybue in key segments, you know, Centers of Excellence and high volume institutions and community practices, and also remind us how the treated patients are split across these settings. Yeah. Let's start with that actually. About 30-35% of our Rett patients are treated inside our Centers of Excellence. That means, obviously, correspondingly 65% outside. Those outside centers are really sort of large, larger hospitals, but also can be down to sort of small community neurologists. There is a very variable treatment setting outside of the Centers of Excellence. In terms of the penetration, Ami, we have in our Centers of Excellence, so there are 21 of those, about 50% penetration of Daybue. Obviously, there is still quite a lot of room to grow there. Outside the Centers of Excellence, where the 65% of patients are treated right now, we have a relatively lower penetration, around 25%. That is why we are restructuring our field force and also feel very good about the opportunity to grow the brand. I'm happy to share a little bit more detail around that. Okay. Yeah. I mean, I guess, so maybe we could sort of just focus on the non-Centers of E xcellence for now. Yeah. and maybe talk about where you have that 25% market share coming from, perhaps qualitatively, and how are you thinking about approaching kind of building upon that? Yeah, no, absolutely. Comes from all over, all different types of settings. We're sort of two years, nearly exactly into launch now. Those physicians who have seen and treat Rett families outside of the Centers of Excellence are quite often calling their Centers of Excellence for advice. There is a lot of phoning in and just double checking on how to treat. What we've realized is that these doctors outside of the COEs need more rep time. They need more MSLs and they need more education. As a result, right now we're increasing our field force by about 30% so that we can actually get to those physicians and really support them through the prescribing of Daybue. We are now putting that into place in the market. We will be able to see those physicians much more frequently and really ensure that they're educated and comfortable about initiating Daybue and helping the families through the first few months. That's a really important point. Obviously, with only 25% penetration, it really gives us confidence that once we get those people in place and they're active and supporting our physicians, we've got quite a lot of headroom to grow Daybue beyond where we are now just in the U.S. Could you sort of clarify? You know, how of the total reps, how many are going to be focused on COEs versus non-COEs? What does this expansion really mean in terms of, you know, the frequency with which they can, sort of call on the non-COEs? Yeah. Yeah. The way we structure our territories is that the reps are geographically based, so they may or may not have a center of excellence in their territory, but if they do, they will also cover other physicians. They are geographically oriented. What we are now able to do is have smaller territories and therefore a higher reach and frequency over the year. What we do know is that doctors need about six to eight calls from either an MSL or a representative, so combined a total of six to eight calls. Now we have the capacity to achieve that. Our focus right now is to really still educate within the centers of excellence. We're not losing our focus there, but also now expand beyond and really ensure that those patients that are treated elsewhere have the right education and support. That's the strategy. We're getting those teams in place right now, which is why when we guided on our first call earlier this year, we're talking about seeing the impact of that towards the second half of this year, after the team are embedded and after they've started making their calls. We expect that growth to start really climbing towards the back end of the year. Can you qualitatively give us some color on what exactly do the physicians need the most amount of sort of time, and kind of discussion? Is it sort of managing the GI symptoms? Do the, does the office need support with kind of the reimbursement process? Maybe just color there. Yeah, no, absolutely. If you can think about the physician that we're talking about, they're generally a neurologist or a pediatric neurologist, and they're not expert in Rett. They may have one or two patients. Actually, initially there's some real support around the data, the clinical evidence, the confidence in prescribing, the clinical trials and how they've worked, and also updating on the real world evidence that we now have after two years of market to help them understand the patient types and really give them confidence to initiate that script. To your point, once they've initiated, we have family service managers who are out in the field to help support the family. That is really from managing the GI side effect side, but also our MSLs are educating our physicians on how to use Daybue with all the evidence we now have, and understand what they can and cannot do around titration. Importantly, managing, additional focus on ensuring that the patient's nutrition is good so that they are taking their fiber. They are also thinking through managing their anti-constipation meds and titrating those down. There are a lot of things that the physicians need to think about. In the back office, we have reimbursement teams now who are able to support the back end and getting the patient on to Daybue. It is a real team effort that we now have really going very well in our field force. Every doctor's different, but that is pretty much how it works. Okay. How is the persistency level different, in the COE versus non-COE so far? Actually, you know, what we're seeing is relatively similar across all settings. We're seeing, as you know, that our persistency rates at 12 months are just above 50%. We're seeing that it's important to manage the patients in the first three months, but we're not seeing a difference in persistency across the COEs versus the other physician settings. That's actually great because it means that our physicians are well educated and supported, and we're not seeing one better than the other. Okay. You had indicated at the most recent earnings call that there was sort of a step up in the average dose that was being utilized in the real world setting. I think previously it was more closer to 70%. Mm-hmm. It now seems to be inching up towards 75%. What's really driving that? Are there specific types of patients or treatment centers, or is it just, you know, maybe, maybe sort of talk about where, what might be driving that and whether it may be even driven by center of excellence or non-center of excellence? Yeah. So let's get clarity on that. I think when we, when we guided and talked about Q4 in particular, we did talk about a dynamic that we saw, which was pulling forward some prescriptions from patients into Q4 from Q1. That is sort of a normal dynamic that we see when patients want to have enough bottles on hand for getting through the holidays, making sure there's no New Year situations with pharmacy. We had this pull through. That sort of automatically shows an increase as an increase in utilization. That is really the explanation for the 70-75%. We continue to monitor the 70-75%. It does fluctuate a little bit, but really we're not expecting that to sort of continue to change through the year. Now that we have a fairly stable and very stable patient base, we're really seeing that settling in. We continue to educate doctors about titration and getting patients up to the right dose, but it seems to be hovering around that 70% mark. That 75% was more of a Q4 dynamic. Okay. That's helpful. Maybe just, you know, stepping back, you mentioned earlier that you expect a lot of the impact of this sales force or field force expansion to come through in the second half of the year. You know, just sort of to set investor expectations, maybe, you know, what are some of the metrics that they should follow, you know, or what metrics will you share with us through the course of the year? Absolutely. No, we'll continue to share and update as we see the field force coming online. Just to get specific, coming online now, and as we guided, we expect them to be fully embedded after two to three months. They need to get out there, make their relationships, make their call plans, et cetera. From July onwards, we're expecting the impact of that field force. If you think about what we're expecting, we're expecting more scripts in the top of what we would refer to as the funnel. We will continue to update you on the metrics associated with that. Actually, the key metric, if you like, is what we report every quarter, which is the active patients on Daybue. Obviously, if more patients are starting, there should be more active patients. I believe that is the key metric that the analysts should be looking and watching for. As I say again, we expect that to start ticking up towards Q3 and Q4. No, I just would like to add to that, Ami. I'd add one thing is I think what we've said and what Catherine just reiterated is the kind of operational metrics we expect improvement in the second half. If people are focused on their models of what the kind of the sequence of revenue or net sales is gonna be quarter over quarter, since we do expect, you know, seasonality in the first quarter, for and have a decline, a sequential decline in net sales, we set, we expect kind of the growth trajectory of net sales to be more even over the course of the year as kind of Q2 will be a normal quarter versus Q1, and then Q3 and Q4 will have the expected operational benefits, that Catherine mentioned. Okay. I wanna come back to, sort of how we should think about growth in COEs in a second, but since you touched upon first quarter dynamics a little bit, maybe if you could sort of close that topic, can you, can we sort of lay out what are the factors that we should think about as we model first quarter? You talked about some of the pull through of, volume. Yeah. So Catherine mentioned, right, the kind of the pull forward of bottles as patients kind of would get in in front of their, you know, holiday period and, you know, insurance reauthorization process. So that on our fourth quarter call, we quantified about at $3.5 million of net sales. So if you just unwind that kind of like for like, that's a $7 million reduction quarter over quarter. And then in addition to that, we just expect typical seasonality across our metrics, which tend to be lower in the first quarter. So that can impact volume further in the fourth quarter. We do expect a sequential decline in net price, which is primarily related to the changes in Medicare Part D as part of the Inflation Reduction Act, because trofinetide was launched after the, you know, the date cutoff for us to qualify as a small company manufacturer for Daybue. We do for Nuplazid, but we do not for Daybue. There will be some increased rebates associated with that, which will impact net price in 2025, but certainly a sequential decline from Q4 to Q1. All that taken together will impact our net sales in Q1, which we discussed on our last call. Okay. Maybe just going back to the penetration and COE setting, Catherine, you mentioned it's about 50% currently. How should we think about the growth potential there or deepening of that market share over time? Yeah, I mean, we feel very confident that we can grow that. Obviously there's a delta there that is fairly significant, not as significant as outside of the Centers of Excellence, but definitely there. Just to think about the 21, they're not all the same. We've got some that are, you know, relatively highly penetrated up in the eighties, and we've got some that are lower. The median is 50, but we're definitely not the same across all of them. We continue to focus on them. Importantly, their experiences are very influential outside of their immediate COE. There tends to be a regional influence of those physicians. As I said before, other neurologists will call in and get advice. As well as generating prescriptions, they actually have a positive effect on the confidence of other neurologists in the area. Very, very important part of our focus and continued part of our focus as we move forward. Okay. Let's switch gears and think about Europe. And you know, you have an application under review there with the EMA. Can you share some details on where you are with the review and what the next steps might be? And, you know, are there some countries where you can make the drug available even prior to approval? Yeah. Let's talk to that. We filed in Europe in the first week of February. In terms of the way we have clock stops and responses to questions, et cetera, we expect our approval to be around about Q1 of next year if everything goes towards a normal clock and a normal kind of number of days in between the clock stops, which it usually does. We feel fairly confident about that. As you rightly say, there is the ability in Europe to do a managed access program or a named patient program depending on the different country. They have a different vernacular. They all have different regulatory approaches to this, but we are partnering with a third party to help us support anybody in Europe that has a country system that allows them to legally ask for Daybue before it's approved. We are launching that in the next few months in some of the main countries. Just as an example, Germany has a program, Italy has a program, France has a program. We will be supplying that demand as we get it, but that's generated by key opinion leaders or physicians in the countries, and it's specific to a named patient. Okay. What's the opportunity for the product in Europe relative to the U.S.? And how should we think about kind of where patients get treated, you know, and how that could look like relative to the U.S.? Yeah. The opportunity is fairly substantial. It's a larger prevalent population at 9,000-12,000 patients with Rett syndrome across Europe. It's proportional to the size of the countries because, as you know, it's genetic and it's one in 10,000 to 15,000 live births. There's not one country that has any more or less than the other. It's purely population based. Obviously, therefore, Germany would have the largest population of patients. As you know, each country tends to have a very different approach to treating their population. The same is true for Rett syndrome. Just as an example, Germany's actually a very diffuse system. They treat them at social centers across Germany. There's no really centers of excellence in Germany, just about, you know, 100 or so treating facilities. Contrast that to France, where we probably have about five or six Centers of Excellence across the whole country, a very, very focused treating pattern. We are approaching each country slightly similarly, slightly differently in terms of how we are setting up and how we are actually getting to these physicians. We have our MSL team out there now, gathering information and also working with patient advocacy groups to understand the specific needs of patients in Europe. You know, as we think about pricing and, you know, we are aware of the differences in the pricing dynamics in Europe relative to the U.S., the general sort of back of the hand way of thinking about it is somewhere in the 30-40% of the U.S. price. Is that a fair way to think about that? I think we'll be, we'll be as specific as we can as we get the first reactions to our dossiers. And you know, obviously there are analogs and you can, you can find an analog that's 20%, you can find one that's 80% and everything in between. So we're focused actually on generating the right evidence for each healthcare system and each dossier is being developed specific to those needs. We have a very strong team in Europe. We have a team now, full-time in Switzerland that's managing all of that. And so we'll, as soon as we get the sort of the reactions from each of the countries, we will guide and give an idea. But we are fairly hopeful that we'll get a strong price for Daybue in Europe. Okay. Why don't we switch gears to ACP-204? Can you maybe just give us a sense of where you are at with the studies, and maybe we kick off from there? Oh, I'm gonna let Liz take over, Liz. All right. I thank you so much. I will go ahead and start with a very brief introduction to ACP-204 and then talk a little bit more about the studies and where we're going. First off, 204 is our new 5-HT2A inverse agonist. We built this based on learning from Nuplazid. Briefly, the things we were looking to improve there were to reduce or eliminate QT prolongation, to enable dose ranging in particular, to let us go up to higher doses because we believe that higher exposures may lead to greater efficacy. Finally, to get a faster time to steady state, which, while not for sure, gives at least the potential for faster time to onset of effect. Thus far, the data that we have does support that we've been able to hit all three of these things. We've been publishing non-clinical and, and we'll be publishing phase I data to give you, to give the outside community some sense of the reality of this. But so far, we think that 204 is meeting the profile we're looking for. Now, what we're doing with 204, our first program is in Alzheimer's disease psychosis. And this is in a phase II trial, a master protocol that includes a phase II followed by two phase III trials. It's probably worth pausing briefly on the advantages of that. It gives us the opportunity for seamless enrollment. So once a trial site is done enrolling in phase II, they can move directly to enrolling in phase III, which gives us some potential time advantages. However, it's also important to note that we did set this up so the studies are statistically separate. That means we have the opportunity to analyze the phase II portion and make modifications as needed to the phase III. It does give us the opportunity to learn, which we think is an advantage of this program. Generally speaking, the phase II is three arms. The lower dose is the same exposure as the currently marketed dose of Nuplazid, and the higher dose is roughly twice that exposure. Like I said, we think one of the advantages here is the ability to go to higher exposures and potentially get greater efficacy. This is really gonna let us try that out. Overall, it's about 300 patients in this study. We're gonna have a six-week, primary endpoint. As I think Katherine mentioned at the beginning, we anticipate completing enrollment in this trial by the first quarter of next year and therefore having, in the phase II portion, I should be clear, and therefore having data in roughly mid-year next year to share. Okay. All right. Now can we just go back to the data that was generated for Nuplazid previously, in the Alzheimer's disease patient population? Of course, there, you had a broader study and then you'd looked at the Alzheimer's disease patient population as well. As we just think about the phase II study that's being run, what are the similarities or differences with versus the Nuplazid study that had been run previously? There were actually a couple of prior pimavanserin studies, one that was specific to Alzheimer's and one, as you say, that is in broader dementia-related psychoses. You know, what I'll say generally is that there are, particularly compared with the DRP or the dementia-related psychosis trial, there are a number of differences. Population-wise, we are focusing in here on Alzheimer's and actually going the extra mile and not just requiring a clinical diagnosis, but also confirming that with biomarker confirmation. So a much more refined and directed patient population. It is a parallel group design versus the withdrawal study that was used in DRP, and there's some specifics around the use of endpoint. We did use SAPS-H+D in both cases, but they're being used a little bit differently. You know, that said, we have been able to take information from a large number of studies with Nuplazid and the Harmony DRP study, as well as our prior use in Alzheimer's and some of the learnings from PDP as well that help us inform what we're doing with ACP-204 in this program. Mm-hmm. Now, you mentioned SAPS-H+D, you know, that specifically targets hallucinations and delusions, whereas the NPI-NH provides sort of a broader assessment of various sort of neuropsychiatric symptoms, including psychosis, depression, anxiety, et cetera. Can you tell us about kind of how pimavanserin may have done in the SAPS-H+D endpoint? Yeah. I think the background of this question is that in that phase II ADP trial, the endpoint, what we looked at, NPI-NH. I do think it's important to note that even in that study, there was a focus on the psychosis component as the primary endpoint, not some of those other facets like depression, anxiety, and agitation. Even looking at the NPI-NH, we were focusing in on the psychosis component in Alzheimer's. It should be noted that that phase II did meet its primary endpoint in the Alzheimer's disease population, focusing in on psychosis and hallucinations and delusions. That, you know, that's generally consistent with what I think we know that Pim is good at. You know, our labeled indication is based on psychosis and hallucinations and delusions, but in particular about the endpoint SAPS-H+D and our prior use of it. We have actually used this in a couple of different settings. The first of these is it was in our pivotal PDP study, and it was also used in Harmony in that dementia-related psychosis study that I just referred to. We do have a variety of experience to draw upon. In both settings, I think it's worth noting that there was separation from placebo using this instrument. We do have good experience with this instrument itself, as well as, of course, some learnings about Nuplazid's general focus on psychosis, hallucinations, and delusions. Could you remind us, it sounds like it was a second, one of the secondary endpoints that was measured in the DRP Harmony study. Is that right? It was included in DRP. Yeah. Was there a P value for that? There was a P value. I will say, obviously, a withdrawal study is set up rather differently from a parallel group perspective study. It is difficult to draw specific comparisons there, but definitely with SAPS-H+D, we have seen separation from placebo, in a couple of different settings, which is reassuring. Okay. Maybe just, dwelling a little bit more deeply, you, you mentioned that, you know, with all the experience that you've had with pimavanserin, in, in studying this, in ADP population as well, you've kind of taken some of the learnings and, you know, the obvious sort of differences, around, you know, QT prolongation and kind of the PK curve, through sort of, you know, faster titration, et cetera. All, all of those are, you know, fundamental differences of ACP-204 with pima. But in terms of maybe clinical trial design or any other learnings that we may not have spoken about, anything else that's worth highlighting here? Yeah. I mean, I think we have touched on many of them. There are inherent differences of 204 versus pimavanserin in terms of what we think it can do from an exposure perspective. Again, we think that exposure response potentially gives us the opportunity for better efficacy. That is a very important component of what we're doing differently in this study. I did touch on the fact that, you know, I think we have learned a lot about conducting ADP trials. In particular, one of those things that we've learned is the importance of dedicated trials that's focusing specifically on that population. I do think that focusing in on not just a clinical diagnosis, but biomarker confirmation to be very clear that what we're looking at is an adequately powered specific to Alzheimer's disease population is going to be helpful. There are other things that we've done in terms of, you know, slight modifications to have a more severe patient population because we did see some, you know, some evidence that there was a higher signal and that's, that's not an unusual outcome. Generally I think it really is about a molecule that we think helps us achieve some important things from a TPP perspective, as well as focusing in specifically on that Alzheimer's disease population. Mm-hmm. Okay. Just from a regulatory standpoint, of course, you know, you're gonna launch two phase IIIs off of the phase II. You, does the phase II potentially serve as a phase III should down the line one of the phase IIIs not work? You know, that's always gonna be very subject to the data we actually see out of the program. But what I will say is certainly there are precedents, generally, but specifically in the neuropsychiatric space of drugs getting approved with one or sometimes even more than one failed study. So I think that, you know, subject to compelling data at in some portion of the program, there at least would be an opportunity to engage with regulators even in the context of having at least one of those trials not work out the way we might want it to. Sure. Of course. Okay. Maybe just, switching gears to the Lewy body dementia trial that you guys announced. You know, how would that phase II study design be relative? You know, would it look exactly like the one that you're running in ADP? And, why not wait to at least learn about the doses from the ADP study before you start that one? I'll briefly say that we are very enthused about the Lewy body program. While the amount of data we have direct from Pim is limited, certainly what we did see is in patients with Lewy body, there was a pretty compelling separation in the Harmony trial and that withdrawal trial. Of those patients who stayed on drug, only about 5% of them relapsed, whereas those who were withdrawn from drug, more than 50% of them relapsed. There was a pretty striking distinction between those two patient populations. Mind you, limited number of patients is about 20 patients per arm, but we thought that this was really quite interesting and we are excited to be able to take 204 here. In terms of your point about differentiation, this is maybe, we'll call it, a slightly more traditional development approach. We're gonna start with a phase II trial and then we will have a completely separate phase III program. It won't be that seamless enrollment that we're doing with ADP. We're taking a little bit more of a staged approach here. We do think though that starting this program now gives us some opportunity to jumpstart learnings that are specific to this disease and this population that's gonna help us better design a phase III program. You know, while there are some things we could learn about dosing, we do feel confident in the two doses of 204 and that they're gonna be acceptable from a tolerability perspective. Obviously, we're gonna have to run the studies and see. We think that running this study now gives us the opportunity to learn some things that are specific to Lewy body that we would want to know before we go into a later stage program. Overall, we're committed to maximizing 204's potential and we think Lewy body's an important part of that. We wanted to keep those programs going as consistent in time as possible. You're studying the same two doses and the same endpoints in Lewy body? I guess what I'll say is I'm really looking forward to discussing the design in more detail at R&D Day in June. All right, then I will keep my ears open. We are gonna be looking at multiple doses. I will at least say that. Nice. That makes, now, now it kind of makes sense. Okay. All right. That's helpful. All right. Why don't we talk about the ACP-101 asset, in hyperphagia and PWS? Can you maybe talk about that trial and, you know, where you are with regards to enrollment and, maybe just, you know, I think PWS seems like a difficult disease to treat with multiple different, you know, symptoms. So maybe just talk about kind of your confidence level that, you know, hyperphagia can be addressed with ACP-101. Where we are now is we have a phase III study that is running currently. We're pleased with how enrollment is going along. We have said that we expect to have this enrolled by the end of the year and expect therefore to have data out of it in the first half of next year. PWS has been a challenging space historically, but I will note there is now the first approved agent there, which I think gives us some confidence that with a robust positive result in this phase III study as designed, we think we would have a very compelling data package to discuss with regulators. We do have data from ACP-101 in a prior phase III trial that is supportive of efficacy, but I should be very clear that in that study, the primary endpoint, which was based on the higher dose, did not meet statistical significance. We did see some good consistency of information at the lower dose. The lower dose is what we're focusing in on in our phase III trial. Maybe just as a follow-up to that, should we not have seen a dose-dependent improvement in response or, you know, is there a rationale for why we are not seeing that in this case? Yeah. You know, when I'm looking at trials that didn't, you know, didn't hit their primary endpoint, I look for a few things. The first thing I look for is mechanistic rationale. There is a number of different points that suggest the relevance of oxytocin in Prader-Willi. I look for some consistency of data within the place where you saw positivity. With a 3.2 milligram dose, we do see positive impact on more than one endpoint and more than one time point. That is generally reassuring. To your point, the last thing I look for is, is there a plausible, plausible alternative explanation? You know, the data we have aren't enough to be able to specifically prove that this is the case, but there is reason to believe that there is the potential for off-target impact through the vasopressin receptor and that that off-target impact could interfere with our ability to see a positive outcome on the primary endpoint. That is our hypothesis. I think it is a reasonable one. We are gonna run the study and see. Okay. Great. I think we have maybe just maybe time for one quick question on Nuplazid, if I may. Sure. Maybe if you could sort of just touch upon, some of the recent, you know, volume growth trends that we've seen with Nuplazid and how you're thinking about continuing to drive growth, with that. Yeah, no, absolutely. Let's just sort of consolidate what we saw in 2024, which was really a couple of things. The first was clarification of the label that Nuplazid can be used in patients with or without dementia. That clarity has provided a lot more physicians' confidence to start and continue to prescribe Nuplazid. On top of that, we had a lot of new real-world evidence data in very large Medicare patient populations to show that Nuplazid had a significant effect versus not off-label antipsychotics in both mortality and morbidity endpoints, which again gives physicians a lot of confidence in prescribing. We realized that we needed to start educating a new generation of caregivers because we had not done a lot of DTC education since really COVID. We started an education campaign making people aware of the symptoms of that, that can be associated with Parkinson's disease. What we've seen is a lot more inquiries on our websites, et cetera, wanting to look to learn more. As a result of that, we've actually now seen an increase in patients going into their physicians and asking to learn about Nuplazid. All of those sort of three areas, label clarification, real-world evidence to support the use of Nuplazid, and a campaign that's educating doctors and their caregiver families around the symptoms, those three things gave us a change of momentum in Q4, which we believe will continue as we move into 2025. We look forward to sharing the impact of all of that as we move through this year, but we do feel very confident that we can continue to grow Nuplazid. Okay. All right. That was really helpful. Thank you so much for the time. We are out of time, unfortunately, but thank you so much to our listeners as well. Thanks a lot, guys. Thank you.