Right. Thank you, everybody, for being with us this afternoon at the Citizens Life Sciences Conference. Really excited to be joined next by Acadia Pharma, and, you know, we're gonna turn it over to CFO Mark Schneyer just to give a quick 30-second intro and start there. Yeah. Great. Thanks for having us again. We appreciate it. Always enjoy joining you here on the stage. At Acadia, we're a neurological and rare disease company. We have a commercial portfolio as well as a robust pipeline. Our two commercial stage assets are NUPLAZID, treats a disease called Parkinson's disease psychosis, and DAYBUE that treats a rare disease called Rett syndrome. Together, those products for the first time in the company's history have over $1 billion in net sales combined. We're guiding to about $1.25 billion in the midpoint of our range this year. As far as pipeline, our latest, or most advanced asset is remlifanserin, which we're investigating in two indications, Alzheimer's disease psychosis and Lewy body dementia psychosis. From an investor standpoint, the ADP phase II trial is gonna read out this year in the August to October timeframe. We're very excited about that. In addition, from a financial perspective, we're a cash flow positive company with over $800 million in cash on our balance sheet and no debt, so very strong financial position. Would love to jump right into what we think is one of the most exciting catalysts this year, and that's the AD psychosis readout. Maybe just start off with mechanism. It's a mechanism we know well. Like it's been validated by NUPLAZID. Just talk about the drug and mechanism for a second. I'll hand it over to my friend to my right. Yeah. Sure. Srdjan, Head of Clinical Development at Acadia. Great question. The current program is with remlifanserin, which is our new 5-HT2A inverse agonist. We have validated this mechanism with pimavanserin. Pimavanserin, as you recall, provided us a proof of concept information. We ran two clinical trials. One was a parallel group study in Alzheimer's disease psychosis, which demonstrated efficacy. We ran a dementia-related psychosis study, which included a number of dementia subtypes, including Alzheimer's. It was a randomized withdrawal study where also within that subgroup there was a suggestion of efficacy. Taken together, it gives us confidence. We have learned along the way with pimavanserin several lessons. Four in particular I will emphasize. One is we learned that if you get patients with severe psychosis in the clinical trials, then we see a stronger effect size, and we have published that information. The second is that if we select a more sensitive outcome measure, we have tried two for Alzheimer's disease, NPI-NH, and SAPS-H+D. I can spell them out if you want. We found that SAPS-H+D is way more sensitive to change and differentiate sensitivity versus placebo. If we pick up the right instrument, we can optimize for success. The third we learned was that in patients who achieved a higher blood level, you know, in the population level, there's variability, and some people achieve higher blood levels, there was better efficacy. We wanted a drug that where we could push the dose. That was a key lesson. The fourth lesson is that for Alzheimer's disease it is good to have a dedicated program, replicate studies, et cetera, full exposures. We are applying all these lessons in the remlifanserin program, and gives us confidence and improves probability of technical success. Great. The question we get asked most about this trial is about the placebo rate and how we should think about what the right benchmark is for placebo. Any thoughts you can give us there, Srdjan? A very important question because we measure efficacy versus placebo. Now, why is this important is because if the placebo response, the slope is very steep, it attenuates our signal. The second is if the absolute drop at the primary time point is tremendous, it does not leave any room for showing a signal of efficacy with the drug. Now, we can address it in many different ways. One way is if you have a patient population that have severe symptoms to begin with. So if you start high up, even if the placebo drops, there's still room for showing improvement. And we are deploying that. The second piece is that if you have patients with durable symptoms of psychosis. You know, there are various kinds of patients. Some people experience a lot more variability, others have persistent psychosis. If you get those patients, then the placebo response is likely going to be lower. The third reason for noise in the placebo and placebo response is that the diagnosis of the patient population is not precise enough, homogeneous enough. What we are doing is, other than clinical criteria for AD, Alzheimer's disease, and other than clinical criteria for psychosis, we are also employing blood-based biomarkers. Everyone has to qualify on blood-based biomarkers and they get in. As I said, severe patient population, confirmed diagnosis. Plus, we are training our raters in a rather stringent manner. Everyone gets qualified. We monitor the raters independently with a third party who listens to the ratings, and if there is rater drift, they are retrained. We are feeling confident on how the study is going and things are being monitored diligently at the patient level, at the site level, at the region level, et cetera. Great. How do you think about defining success from this trial beyond statistical significance from the primary endpoint? Yes. I think we see success in the context of the overall target product profile. What we are testing is once-daily dosing, with or without food. If it delivers convenience with dosing, plus favorable safety and tolerability similar to pimavanserin, which is no adverse effects on motor symptoms, no adverse cognitive effects, with statistical significance in this population, the threshold is relevant, because nothing is approved. Mm-hmm. Nothing is approved, and even more important, that the off-label treatments that we prescribe, I'm a physician, so I have prescribed these, they don't work. They come with significant adverse effect burden. There is a tremendous need for a therapy that works and that has safety and tolerability and convenience similar to pimavanserin, and we think remlifanserin can offer that. Fantastic. Maybe if we flip back to the commercial portfolio for a minute. Sure ...... Mark. NUPLAZID had a really good year last year. Yep Guidance seems strong for this year. Can you just talk about what the key drivers of growth have been in the last couple quarters? Yeah. I think last, you know, as you remember over the last maybe year and a half, right, we kind of reinitiated our direct-to-consumer investments, starting with an unbranded disease awareness campaign, partnering with Ryan Reynolds, as well as running a DTC you know, specific NUPLAZID-branded campaign. You know, that after kind of pulling back in the kind of COVID years, investments from, you know, as they were not meeting our return thresholds during that timeframe, you know, the kind of awareness in the kind of caregiver community for NUPLAZID was very low, and that brought that back, increased kind of the dialogue around Parkinson's disease psychosis, increased patients' and caregivers' you know actions to go talk about this disease with their physicians, and then led to an increase in prescriptions. We've seen over that timeframe, you know, while nothing happens overnight, you know, a meaningful increase in new prescriptions, new patient starts, and overall volume growth. For a drug that's been on the market for, you know, close to 10 years, we had 9% volume growth last year. We expect we're gonna continue to invest and expect, you know, growth again this year as well. Can you maybe talk about the field force expansion was, you know, fully deployed at the beginning of the year, so it's too early to say what's the impact. Correct. Like, what's the early signals out of that? I mean, have you achieved what you wanted to achieve with the sales force and targeting, and Yeah. Well, I think the answer is too early. Yeah. I kind of answered your own question. You know, we see a meaningful, you know, opportunity in front of us. It's kind of building upon success of what we've done over the last year plus. We've just kind of finished in the first quarter, kind of the hiring and training and kind of deployment of our commercial-facing personnel for NUPLAZID and, you know, it's kind of all signals are in the right direction. Mm. You know, at this point, I mean, it takes six to nine months to, you know, to see a real impact, so anything at this point is just we're doing exactly what we expected to do. We're very excited about it. It's just premature to share any results from it. Can you talk a little bit about the patients that are coming onto NUPLAZID in terms of, you know, how progressed are they in their disease? I know it's been a focus to get earlier and earlier stage patients. Are they coming, you know, from community centers? To what extent are you know, do you have traction growing in the long-term care centers as well? Yeah. I mean, our patients, you know, it's roughly three-quarters are in the community, living at home, you know, serviced by their community physician. The other 25% are in long-term care facilities. You know, we've seen growth among both segments, because our primary kind of investment vehicle over the last year and a half has been direct-to-consumer. That's just more effective in the community, so because of that, we've seen maybe a higher proportion of our growth coming from the community setting, but we've also seen it in long-term care. You know, as far as kind of disease state, you know, NUPLAZID is the only approved medicine to treat Parkinson's disease psychosis patients. It works in patients that are, you know, more advanced in their disease and are earlier in their disease. I think what we're trying to do through kind of the opportunity that we've seen in front of us, and as I say, building upon success, is to expand our footprint to really be able to cover kind of a broader universe of physicians and patients, and be able to talk to them and educate them on the benefits of using NUPLAZID in this patient population rather than, you know, the off-label antipsychotics, which my friend to my right explained don't work. You told us about, you know, really compelling demand growth, even, you know. Yep Like you said, roughly 10 years into the launch. What does guidance assume for 2026? Well, I think our guide, you know, for both brands, and we can get to DAYBUE as you get there, it's really a volume-based forecast. You know, there's some price benefit, but, you know, it's about a 2%- Yeah kind of price benefit. It's really all volume growth, and it's really, you know, of all the things that we're trying to do, it's just a spectrum of being better or less than better on those that get us into the range. Okay. Great. Maybe switch over to DAYBUE. Again, I think a lot has been changed and stabilized and now returned to growth. Just walk us through where you know, you think we are with DAYBUE today and how well it's set up for 2026. Yeah. We're very excited about DAYBUE. I think, you know, kind of your intro words are a way to talk about it. I mean, we're now approaching kind of the three-year anniversary. Mm-hmm Of being on the market. I mean, we came out very strong out of the gate, a really super strong launch, great interest. We got to a period of really plateauing, which is, you often see in rare disease as the early adopters are there right away, and it takes more effort, more education to kinda get to that next phase of growth. What we did was, you know, stabilize the business for a period of time, and now we're investing for growth. You know, last year, we increased our field force for DAYBUE in the second quarter of last year by about 30% to really be able to have the right kind of, you know, reach and frequency into the community physician population that are treating Rett patients so they can be educated and have the right number of conversations to be confident to prescribe, you know, DAYBUE to their patients. We've seen success from that. In addition to that, we've this year, you know, late December, we announced and got approval for a new formulation of DAYBUE STIX, which offers benefits for those that for those patients who never tried DAYBUE or stopped DAYBUE due to formulation issues, there are benefits for DAYBUE STIX that are available for these patients now. This year, as we look to, you know, for growth in DAYBUE, it's kind of the benefit of rolling out DAYBUE STIX, further penetration into the community in the United States, as well as providing DAYBUE through our named patient supply programs for patients that qualify outside of the United States. Well, let's stick with DAYBUE STIX for a second. Well, just walk us through the product profile and where do you think it allows you to address patients in a way that you haven't before or different patients than you have before? Yeah. I think there are a number of benefits to the formulation. You know, kind of the key ones are, you know, these patients have highly compromised kind of GI systems and, you know, the ability to intake food and medicine can be challenging for a number of these patients. DAYBUE, the original formulation, is a liquid that the volume of that liquid is large for some of our patients. Mm-hmm. With DAYBUE STIX, it's kind of like Liquid I.V. where you know, are able to pour the active ingredient into the beverage of your choice, anything that's non-dairy. Patients or their caregivers can pick the amount of volume of that liquid they put in. You know, you can use about half of the volume of the liquid. I'm looking at a can of Coke Zero. It's probably not a good choice. But like, you know, you can use, you know, your Gatorade or Yeah Orange juice or apple juice is probably about half the volume that is in the existing formulation of DAYBUE Liquid. The taste profile is not as strong. It's a natural strawberry flavor. You don't need to refrigerate it. There are some excipients in the DAYBUE Liquid formulation, like Red Dye 40 that certain patients don't like or don't wanna have an impact from because they're on keto diet. There are a number of aspects to this formulation that are beneficial to this patient population, and we think beyond the growth that we would expect with the liquid formulation, we think we'd have access to an incremental 400 patients that either never tried DAYBUE Liquid or had stopped DAYBUE Liquid due to the formulation itself. Right. So maybe, like, take a step back. Can you just walk us through the numbers of the Rett market and where the number of patients DAYBUE has already been in? There are 6,000 diagnosed and treated Rett patients in the United States due to kind of you know, medical records and claims databases. If you just look at prevalent population, the estimate is 6,000-9,000. The difference in those numbers has actually been, as you see in most rare disease, have been shrinking over time. When we first launched, we had identified through the you know, medical records about 4,500 patients. That's increased over time. In the fourth quarter, we treated you know, rough numbers, about 1,000 patients on DAYBUE. About 2,000 have tried it. Mm-hmm ... to date. There's a meaningful number of patients have yet to try or could come back. Yeah As they may see benefits from DAYBUE STIX. How do you think about persistency and the durability of patients remaining on DAYBUE? Yeah, that's a good question. You know, we've shared these metrics over time. They've kind of really kind of solidified, I would say, right? From a persistency standpoint, you know, about 55% of our patients who start DAYBUE have remained on therapy, you know, by month 12. That's a really strong number for a chronic therapy. At 18 months, it's over 45%. We kind of see a plateauing kind of after that. We see strong persistency and kind of our patient base today are largely patients that have been on therapy for a long time. Greater than 70% of our patients have been on therapy 12 months or longer. It's a stable patient base who are receiving benefit from the therapy. Obviously, as CFO, there's financial value. Right. to the company, and it positions us to grow from here. Okay. Just thinking about outside the U.S., you got disappointing news from EMA on DAYBUE, trofinetide. You've now responded and asked for re-examination. What were the key things that CHMP raised, and how are you addressing them? Yeah. The CHMP's position is that the primary endpoints that we deployed are not adequate. We, of course, disagree. In our clinical trial, we had two primary endpoints. One is the Rett syndrome behavioral questionnaire. It has 45 items. Mm-hmm on which DAYBUE, trofinetide, beat placebo. Then we also had the Clinical Global Impressions of the clinician's perspective, and we had these as co-primary, and it's a higher hurdle than a typical clinical trial. A typical clinical trial would have only one primary endpoint. We certainly believe that, with these two endpoints, we have sufficiently demonstrated efficacy. We, in the re-examination, are allowed to bring in, new analyses, but not fresh data. Yeah. We can bring in patient perspectives and caregiver perspectives, and so we will make a strong case. The odds are against us because it is said that 20%-30% of these re-examinations succeed. I think we owe it to the patients over there and to the business to give it a fair shot. Got it. Can we talk about the pipeline for a few minutes? I'd like to talk about 211 to start with. Mechanism's pretty straightforward here, but just walk us through the background and the differentiation of the asset. Yes. No, we are very excited about ACP-211. Mechanism is also differentiated. I want to underscore that. It is a major metabolite of ketamine, and it is deuterated. Where it is different from ketamine or some of the other isomers that have been tried is that they are dissociative anesthetics. Mm-hmm. At a certain dose, it results in anesthesia, and so people pass out, and at lower doses often comes with dissociation, which is an out-of-body experience kind of feeling or psychotomimetic effects, which is psychosis, it mimics psychosis, so like hallucinations and delusions. The ACP-211 does not have the anesthetic properties, so we can really push the dose. In our phase I data, it has so far demonstrated that it does not have psychotomimetic effects and dissociative effects are contained. We are hoping that to demonstrate efficacy similar to Spravato or IV ketamine and with much better patient experience and need for much lower level of supervision at the time of administration. Got it. Just walk us through where you are with that program and when we'll get the next update. We are in early stages. If you like, I can give you some idea of the clinical trial. We are still getting a feel for how the recruitment would go. When we have a better sense, then we will disclose when it reads out. In patients with major depressive disorder, they could have inadequate response to antidepressants, and they, a subgroup will have treatment-resistant depression. Once the diagnosis is confirmed, they get randomized to a high dose, a low dose, or placebo. The patients are treated for four weeks, and we are going for four weeks as opposed to six or eight weeks, which is the traditional antidepressant design, because we anticipate faster onset of efficacy. The duration is similar to the Spravato clinical trial. The endpoint is the well-accepted. Mm-hmm MADRS endpoint that Spravato and others have deployed. Okay. Maybe moving on to the essential tremor program. Yeah. GABA alpha-3. Yes. Really exciting mechanism there. Just, Indeed Just again, give us a quick overview of the program. Yeah. First of all, the mechanism is very exciting. Some people equate it with the other GABAs that have been studied. In our hands, we have tested it non-clinically as well as clinically, in volunteers on EEG and others. It is very distinct from other approved GABA agents or GABAs that have been tried for essential tremor. We are anticipating beginning our phase II program. It is still in phase I, so in a phase II program, towards the end of the year or early next year. Okay. That trial, will that be a true proof of concept study? It would be a proof of concept study, but as you might understand that if the results are overwhelmingly successful, we'll put it to best use. Yep. Yep. Okay. There's a lot more of the pipeline we could go through, but maybe just touch on the next Rett program, the Fragile X as well. That's. Yes. ACP-2591. Yeah. It does get into the brain much at a much higher level than trofinetide, and so there would be differentiation and we'll have to test it out, but we are getting ready to test it in Rett syndrome first. We will share the progress as we get close to it. Yeah. Let me loop it back to Mark with one last, you know, finance question. You mentioned before you're generating cash. We just talked about you have a broad pipeline. Yep ...as well as the commercial investment. How will you manage that investment and maintaining the positive cash flow? Yeah. I think the company now is robustly cash flow positive, so we have enough cash to really fund all the initiatives that we have, both on the commercial stage and the pipeline, so we're not constrained from a cash standpoint. Then beyond that, we'll continue to look to broaden the portfolio through business development, which, you know, many of the things that you mentioned and are excited about, that's how we got them in the first place. Great. Well, Mark, Srdjan, thank you for being here. Appreciate it. All right. Thanks a lot. Thank you.