Good morning, everyone. I'm Sumant Kulkarni, a senior biotechnology analyst here at Canaccord Genuity, and it's my pleasure to have Acadia Pharmaceuticals here today with us. They made the trip all the way from San Diego, so it's nice weather there. I like to joke, the only fault with California is San Andreas. So it's nice that you've come here. So for Acadia, we have CEO Steve is here, and Mark, the CFO, and Al, who knows everything about the companies and the audience as well. So thanks for making the time. I'll jump right into Q&A. We'll keep this interactive, so if you have any questions, please feel free to raise your hand, and I'll get a mic across to you. We'll start with the topic of the day, and that's Daybue. So why do you think the new patient starts were slower than you expected in the last quarter? Yeah. Yeah, thank you. I mentioned it, Sumant, before we started that I've unfortunately got an ear infection, so I can barely hear right now, so I'll do my best. So I think, as we mentioned on our last earnings call, we, in the last quarter, as we grow our share in the high-volume institutions, in addition to the business that we're continuing to get out of COEs and in community practices, that growth in these other areas that are outside of the COE has gone a little bit slower than we anticipated. We're getting good growth there. We feel like we're getting very good traction, but it's just growing at a little bit slower rate. So we continue to get a lot of business out of COEs. That's a very good source of business and revenue stream for us. As we've cited previously, the majority of Rett patients are treated outside of COEs, and so as we're moving forward, we're continuing to get good traction there, but it has come at a little bit slower rate than we initially expected. So you've said, I think, that 30% of the 5,000 or so diagnosed patients with Rett's have started Daybue. Now, can you talk about the rest of the 70%, where they are concentrated, how you plan to reach them, any targets you can share on reaching that base that's not yet using the product? Yeah. Yeah. So, as Sumant mentioned, today, about 16 months into this launch, we've penetrated about 30% of the five thousand diagnosed Rett populations, five thousand diagnosed Rett patients, who've now initiated Daybue. When we launched, the majority of that, significant majority, came right off the bat out of COEs. That's not surprising. They were the investigator sites in our Phase III program. There's a high concentration of Rett patients there. But as we've progressed through the launch, we've continued to get very good penetration and very good business from COEs. We feel like we're now at about 50% penetration in COEs. But these high-volume institutions and in these community practices where, as I mentioned, a significant majority of Rett patients are treated, we're pulling more and more business from there. So that mix of where we're pulling our business from has shifted as we expected it would. So we're continuing to get a good deal of business from COEs, but the high-volume institutions, which many times are, in some cases, look and feel a lot like a COE. In other cases, they don't have the infrastructure of a COE. As we pull more and more from those channels, the high-volume institutions and community practicing physicians, we expect to get very high penetration overall in the overall Rett community. So that's where we stand today, and again, as I mentioned, we feel very, very good about the traction we're getting. It just takes a little bit longer to get them up to speed, because many of these institutions that we're getting further penetration in now were not involved in the clinical studies, and because they don't have the high density of patients that a COE has, they don't have as much familiarity. And Rett is not as big a part of their practices. But we're making, I think, very, very good progress and feel very good about the ultimate penetration there. I might just for context say, when we look at where we stand today in this launch, and we look at our pre-launch expectations, on every significant, every meaningful parameter, we're significantly ahead of where we projected we'd be. As we all know, we had a big bolus or a big surge of patients that came through, principally from COEs, when we launched, and we're at a more constant demand flow now. But we're—we still remain significantly ahead of where we expected to be at this point, and we've got, as Sumant mentioned, 70% of the diagnosed patients have not yet initiated therapy with Daybue, and we're adding new patients every day, and the prescriber base that we have is now well over 700 prescribing physicians, so a very good breadth there and continue to get more and more depth. Just going to your sales outlook range of $340 million-$370 million for Daybue this year, do you have an implied number of patients that you could exit the year by if at the top and bottom end of that range? Yeah, I'm gonna ask Mark. Yeah, I can talk about that. So let me talk about it qualitatively, right? I think there, you know, as we've talked about the kind of the three key assumptions that we have that underline, you know, the range, you know, and we have a variety of cases that support the range, not just one point case for, for, say, high, middle, and low, are, you know, new patient adds, persistency, so how many patients stay on the drug that are already on it, the inverse of discontinuations, and then the product utilization. ... So we have a range of assumptions across all of those. You know, specific to your question on, on net patient adds, you know, we're at about 900, you know, you know, right at when we announced our second quarter earnings. And so as I look over kind of the var- the variety of the cases, it's adding from here across all of them, right? And I think what we've said, the, you know, the slightly below or kind of the lower half of the, the the midpoint of our range is kind of where we're tracking on key metrics today. We see more upside than downside for the remainder of the year, which is why we're skewed a little bit, in the direction of, of more above where kind of the metrics that we're going today. But as far as kind of net patient adds, all of our cases kind of have adds and, you know, growth quarter-over-quarter. We expect revenue growth quarter-over-quarter, and we do expect a moderation in discontinuations, even from this level. We were expecting the first quarter, just as the patient mix was established at that time, we had a large number of numerical discontinuations, which reduced over 40% sequential quarter, quarter one to quarter two. So we don't expect that big of a drop, kind of the swell of discontinuations is behind us, but we do also expect a little bit of a moderation of discontinuations across our range. Got it. So on the discontinuations, how, how would you characterize those in terms of patients who discontinued because of side effects or something else? Like, what categories are the key ones, and what, what fraction do they make up of the discontinuations? Yeah. So, let me take a little bit of a running start at that. So with drugs that are approved on subjective endpoints, we see this a lot in neuropsychiatry. You tend to have a higher discontinuation rate in the early months, and then it flattens out. So that's what we've expected to see in Daybue. That's what we, in fact, saw in our clinical studies, and that's what we've seen in the real world as well. But as we've cited previously, we have data going out to nine months of therapy from our clinical studies, where we see a certain discontinuation curve or a certain persistency curve that follows that shape. It's more rapid in the beginning, and then it flattens out. So as we've progressed through this launch, we keep comparing the data we have in the real world to what we had from our clinical studies. The data that we're comparing there to is data for patients who were on placebo during the Phase III study and rolled over to drug in the open-label extension study. That's the most relevant, the closest example we have to the real world, 'cause they know they're on drug, they're not on placebo. And so we've continued to track about 10 percentage points above what we observed in our clinical studies. That bodes really well for the long run. In addition, if we look at all the patients who started on Daybue during our Phase III program, and including those who rolled over, as I described earlier, in open-label extensions, 40% of those patients who initiated therapy on Daybue are still on therapy today. So at this point, they've been on therapy well over three years. So we kinda have data from nine months to compare it to, and then we leapfrog out to about 3+ years. Actually, they were 2+ years at the time that we launched the drug, and since that time, we've had one discontinuation from that group, that 40% that stayed on therapy, and because these patients have a lot of medical challenges, very medically compromised, I think one patient passed away, unfortunately. And so we know that there's a very sizable enduring population that we should expect to have with Daybue. If we take that 40% and we add where we're tracking now, 10 percentage points above that, we would project that to have about 50%, patients that become these enduring long-term patients on therapy. I think we can actually improve on that because at this point of the launch, there's still a fairly wide degree of application of the GI management strategies that are outlined under our label and that we promote, too. We know this from our real-world evidence study, where we're collecting data from patients who are on therapy in the real world, in the commercial setting. I think that while we see good adoption, it's certainly far from perfect adoption of these, and we and the medical community has not yet arrived at best practices. That will happen over time, of course, we're doing everything we can to try to facilitate that, but I think there's an opportunity to actually improve even further from where we stand today. Back to the question. The nature of discontinuations, the most common reason for discontinuing is tolerability. We expected this to be the case. We know that in our clinical trials, 80% of patients had diarrhea, 97% of the time, it was mild to moderate. It's a little bit of a trade-off because Rett patients normally don't have diarrhea. They have, or they can have diarrhea, but they normally have a very high incidence of constipation. The numbers coincidentally are the same. About 80% of Rett patients have constipation. It's a little bit of a trade-off there, but we... They have a lot of GI issues, so we knew that navigating that, helping them manage through that, would result in a certain number of discontinuations, and that's what we've seen. You know, beyond that, it falls into a variety of things. You know, again, when you have a drug that it's approved on subjective endpoints, you will have some patients that don't respond to therapy. So we knew that would be the case. We do see some of that. But everything else makes up the kind of complexion of discontinuations. I guess I would just sum up by saying the reasons for discontinuing are exactly what we expected. Continue to run ahead of plan when we look at these long-term persistency curves. Got it. Have you seen any patients that have discontinued come back to the drug? Yeah, we certainly have. I think, we have—when we have patients who discontinue, we try to stay very much, make ourselves very much available and stay very close to those families. And we have had a number of instances where families have said, "We need to discontinue for a while." Again, these, these patients typically have very, very complex medical conditions, and they may have medical reasons that they need to discontinue therapy to focus on some other comorbidity, or other reasons. Or there may be, just family, considerations where they need to pause or discontinue therapy, and we stay, try to stay very close. And we have had certainly a number of them who have, who have, reengaged. When patients do discontinue, we track those patients very well as well, and we typically hear from them, unfortunately, lost the benefits of the drug as well. And so many times that does motivate them when they can, if they can, to reinitiate therapy at a later date. Is there a specific time point at which these discontinuations are clustered around? Is that time point something that you can utilize to lend more patient support services around that time point, if there is one? Yeah. Well, it's very important to us to support the community in everything we can do as it relates to initiating therapy, help provide them support to the extent possible as they continue therapy and when they discontinue therapy. So we certainly do. To your question, Sumant, about, you know, is there a particular time frame? I would say every case is different. So when they discontinue, you know, it's a variety of reasons, and it happens in it's a pretty wide range of time frames. And for those who do restart, there, I would say there's not a... They don't gravitate to a certain time frame. Got it. So we'll move on to questions now on Nuplazid. I don't think you get as much credit as you probably should for commercializing a drug in the Parkinson's disease market- Thank you. That is now annualizing at $560 million-$590 million. Because there hasn't been really any excitement, you know, in the Parkinson's market, from a fundamental, the disease itself basis for some time now. So I think $560 million-$590 million is really impressive for a product that manages around the symptoms associated with Parkinson's. You had the product do really well in the second quarter. You took up your financial outlook for the year, sales-wise, for that product. Do you think that that is a temporary thing, or do you think that the whole nuance around the labeling around dementia is something that could last and could drive more growth than people think right now? Yeah. Yeah, thanks for the question. There's a fair amount to unpack there. I'll try to do it economically. We're in year eight of launch with Nuplazid, and we've seen a very attractive growth range until we hit the pandemic. This population was hit very hard in the pandemic. A lot of... We, we honestly, we just lost a lot of patients. We all know about what happened in nursing homes, et cetera. And since then, we pulled back on some of our spend in this franchise. We felt like just the environment was not supportive of some of the things that produced very good benefits for the community and positive ROI for us. So we said, you know, we're gonna focus on cash flow for this franchise, but if the environment changes, there may be an opportunity to make some new investments, and we'll continue to monitor that very carefully. Our number one priority in this franchise is to optimize cash flow, but we can do that one or two ways, I should say: continue to very carefully manage the expense base, which we're doing, but also grow the top line, and we've had some really nice growth in the top line. The growth that we're seeing right now has come principally from three real-world evidence studies that we've talked about over the course of the last year or so, that were published, that demonstrated in two studies with almost identical results, that there's a statistically significant benefit on mortality for PDP patients who take Nuplazid versus those that take other atypical antipsychotics. The first of those real-world evidence studies was, it's not done by us, but it was done, written by two members of the academic community at Stanford, two members of FDA Drug Safety Group, and two members of CMS. So that was very helpful information in the medical community. The third real-world evidence study was a study looking at healthcare utilization costs of Nuplazid versus other atypical antipsychotics, and there, too, a statistically significant difference or benefit in the use of Nuplazid versus the other, these other drugs. So, you know, many times it takes a while to kind of really get the yield of new information in the medical community, but I think, I think as we look back at the first half of this year, we've got some, you know, really getting good benefit from that now. The second thing that has changed in that franchise is. There was some portions of the medical community found parts of our label confusing regarding the question: Can this drug be used in a Parkinson's patient that has psychosis, that also has dementia? There was a little bit of a double negative in the language that, you know, if you read it and thought about it, you understood it, but it was a little bit confusing. We worked hard with the FDA to try to get that clarified, and we were ultimately successful in doing that. So we got that clarification late last year, and that's also helped. And it's very clear now that if you have a patient that has Parkinson's disease psychosis, and they also have dementia, you can treat them with Nuplazid. That is on label, that is part of the addressable population. And so that, we were seeing some benefit from that as well. And then the third thing I'll point to is what's to come. I think from here, we'll continue to build on that momentum. And one of the things that has changed in the Parkinson's community from the time of the pandemic to today is, one, it's now stabilized. So we see a much more stable market there. And during the time frame that we have pulled back on a lot of our disease education for very appropriate reasons, just the environment was not ripe for that to really benefit the community and to benefit us. That's changed, too. That has created a situation where the awareness of hallucinations and delusions has dropped precipitously. The awareness of Nuplazid has gone down. The request for Nuplazid has gone down. What hasn't changed is physicians' willingness to write Nuplazid when the brand is requested. And so that's put us in this, what I would characterize as a very ripe opportunity to change that. So we've recently initiated, we described on our earnings call, a campaign to fill that gap, to launch new disease education, to familiarize the community with hallucinations and delusions. And the reason it's so important in this community is Parkinson's patients develop psychosis late in the disease, typically. Average lifespan is 4.4 years after being diagnosed with psychosis. And so that means it's a community that's, that has a lot of turnover. It's a very dynamic community. So if you think for a second, last disease education we ran was in 2021. Now we're in the middle of 2024. It's almost a new community now, and that's why it's important when the opportunity is ripe, to provide that disease education, because we're going out to a pretty naive audience now. And I think there's a real opportunity for us to fill that gap. We're making new investments there that I feel very, very... I'm very excited about. Some of you may have seen this morning, a component of that is a campaign that we've launched today, partnered with Ryan Reynolds, who's a well-known actor, as I'm sure many of you, you know, recognize the name. But more importantly, he's a very staunch advocate for mental health and a very strong supporter of the Parkinson's community. The reason he's a strong supporter is his father died of Parkinson's. His father had Parkinson's psychosis. It was very, very challenging and disruptive to his family, I think he would say. And I think you'll hear in some of the press that you'll see him tell that story. And he has a very compelling story about the impact it had on his family, the impact it had on his father, and is really reaching out to the Parkinson's community to say, "If you have, if you're dealing with hallucinations and delusions, talk to your doctor." So that's an important part of the overall messaging that we're sponsoring and focused on getting out. And I think there's, as I mentioned before, just this really ripe opportunity that I think we'll be able to leverage further growth in that franchise. What percentage of the Parkinson's disease patients that you could target also had dementia and were not being able to use that product because of this confusion? Yeah, so I want to be really clear here. Between a third and a half of Parkinson's psychosis also have some form of dementia. Not all physicians had the, some confusion around the label, but a significant portion of them did. So I do think we'll continue to get benefit from that clarification of the label. I think we're seeing strong benefit from it now. As we talk to doctors, many doctors are saying, "Thank you. Thank you for getting that clarification. I feel confident now." So I, I think it will continue to have a meaningful impact as we go forward. A question for Mark here, cash flow question. Yeah. I think when the product Nuplazid was annualizing at around $500 million, you'd said that there was about $200 million cash flow associated with that product. Is the math simple now that it's almost a $600 million product in terms of cash flow, or is there something else? I mean, there's a lot of operating. I think for that, you know, kind of going way back when, that we were still in the, the, you know, optimizing expenses, so as we were kind of working through the pandemic. So last year, at $550 million of, you know, historical sales for 2023, you know, we generated about $300 million of cash flow on a fully burdened basis. There's high operating leverage, you know, in this franchise, so I'm not saying dollar for dollar increase in revenues goes to the bottom line. We're also, Steve just talked about a new campaign that we initiated, so there's some investment there, and the vast majority of the benefit we'll get from that investment, you know, will be realized in 2025 and 2026, rather than 2024. The increase in guidance up to a midpoint of $600 million, you know, is. We're generating based upon the success that Steve talked about, kind of that is behind us, and will continue. So there's high operating leverage. Expenses can move around a little bit, depending upon what level of investment that we're thinking, but it continues to grow even with this existing, you know, this new range of investment. It's growing beyond $300 million, and you know, we'll continue to you know, give color on that as we move forward. Got it. We have a few seconds left, and I definitely want to ask you a pipeline question. So, you have ACP-101 in Prader-Willi syndrome, and you have ACP-204 in Alzheimer's disease psychosis. Which dataset could we see first, or which one are you most excited about if you had to pick and? I love all my children, so I'm excited about both of them. I think if I had to say which one is most likely to read out first, it's probably Prader-Willi. It's a rare disease, high enthusiasm in that community, where the enrollment's going ahead of plan, enrollment's going tracking to plan into Q4, but probably Prader-Willi. In the last second, I just want to mention one other thing, because I'd be remiss if I didn't. Many of you might have seen an intellectual property case involving Allergan that they won recently. It just came out yesterday. It has potential implications for us, too, because we are working on an appeal, or defending our the trial court decision we won with Nuplazid. We've always felt very confident in our IP. The Allergan case has very similar facts to one of our arguments. We have two arguments that we both won decisively at the trial court level that are being now appealed. We only needed to win on one at trial court. We only need to win on one, the Allergan decision, because the facts in that one argument are so similar, are certainly very, very supportive. We expected them to win. They did win, and it has, you know, positive implications for us as well. Okay. Thanks. We'll, we'll track all those things very closely on the legal front. Yeah. I'll actually squeeze one more in. Yeah. What sort of landscape do you see as a buyer of rare disease assets? What sort of landscape do you see as a buyer? Yeah, thanks. You know, I think, you know, the biggest competitor we have in business development, and it certainly applies to rare disease assets, is you. It's the investment community. You know, it's your funding of assets, and obviously, that's modified somewhat in the last couple of years, and so it's creates a, you know, better environment for us. At the same time, we've become a strongly cash flow positive company. We have a very healthy balance sheet. We have two commercial assets. You know, we're, you know, at a billion-dollar run rate, revenues, we're gonna continue generating cash. So we're in a very strong position, and so I would say the environment is pretty ideal for us. You know, we're an established rare disease company, now, so we're, we're, we're continuing... It continues to be an important part of our business. Thanks a lot, and thank you everyone for coming, and thank you for tuning into the webcast as well. Thank you, all. All right, thank you. Thanks to you. Thanks a lot. Thank you, Steve.