We're gonna kick it off just to stay on time. Good Morning again, everyone. Welcome back to the 2024 RBC Global Healthcare Conference. My name's Greg Renza, one of the Biotechnology Equity Research Analysts here at RBC. We're very pleased to have Acadia Pharmaceuticals with us today. Joining us from the company is the CFO, Mark Schneyer, as well as the SVP of Global Strategic Planning and Execution, Kimberly Manhard. It's great to see you. Great to see you. Thanks for having us again. Look forward to the discussion. Always a great deal going on with Acadia and the portfolio. Mark, We could just have you sort of tee up the latest brief overview of Acadia, the Neuropsych and rare disease platform and the latest updates on DAYBUE and NUPLAZID. Maybe I'll give you the quick elevator pitch and then we can go into the Q&A. A s you mentioned, Acadia is a biotech company focused on neuroscience and rare disease. We're a commercial stage company, have a pipeline behind it and a strong balance sheet to support all of our initiatives to tick on those, we have 2 commercial assets. Both are the first and only approved FDA medicines for their indication. NUPLAZID for Parkinson's disease psychosis and Daybue, as you mentioned, for Rett syndrome. NUPLAZID is, I would say, in its mid-life cycle. It's 8 years on the market. T his is a medicine at least from a financial perspective, that we're managing to maximize cash flow. Both increase the top line, but be prudent on expenses to look at current and near-term profitability as opposed to long-term profitability. That franchise on an annualized basis generates over $300 million in cash flow on a fully cost allocated basis. Daybue is a new launch asset. So we're about a year into it, very pleased with the success we've had over the last close to 12 months, or now 12 months in the market, but close to 12 months from a financial perspective. We've generated over just over $250 million in sales at that time and are very pleased with our progress to date and the opportunity we have in front of us. While we've had about 25% of diagnosed and treated Rett patients in the U.S. try Daybue over the initial one-year period. We're very pleased with that. But that means that we have 75% in front of us and potentially more as the diagnosed and treated population may converge with a higher number of expected prevalent population in the U.S. The pipeline, just to quick point, we've got a late and early stage pipeline. T he two things that are latest stage are our Phase 3 program for Prader-Willi syndrome, which we started in late fall of last year, as well as our next generation 5-HT2A asset, ACP-204. The initial indication which we're exploring is Alzheimer's disease psychosis that also started in late last year and as I briefly mentioned, from a financial perspective we have just over $470 million of cash on our balance sheet, no debt and we're a cash flow generation positive company. It's great. Certainly NUPLAZID setting up the company for success on cash flow positivity, finding a historic launch with Daybue just last year, as you mentioned and all eyes continue to be on Daybue and Mark, you and the team have really emphasized providing that transparency on the metrics to help investors and even the community, right. Gauge the launch trajectory. Recent report for the Q1 and we know that real-world persistence for Daybue is something that we are all tracking and you're obliging by providing that data that you have maybe let's start with some of those factors that are driving the persistency for Daybue over the clinical experience for the study periods. Maybe just refreshing. Give us the latest on those metrics and what you and the organization and even the clinical settings are doing up-to-date. We're very pleased with our performance to date. A s we shared with the market pre-launch rate, Daybue is a medicine that was approved based upon subjective endpoints. Similar to NUPLAZID, when you have that, it doesn't work for every patient. You expect some level of discontinuation. In addition to that the known side effect for Daybue is diarrhea. GI tolerability. We want to make sure operationally that patients that can get up get good efficacy out of Daybue and can use best practices in GI tolerability can stay on long term. T hat's just a preface to get to your question, which have served important for Wall Street and doing financial modeling. F or us, maybe there's 2 metrics that I'll point to because one it's the persistency we've seen to date. But also, what's the long-term persistency What's the enduring patient population. On that second point, when we look at patients that took trofinetide at any point during our clinical trial. W hether you were in our LAVENDER phase 3 trial, or you were a placebo rollover patient in our LILAC open-label extension, about 40% of those patients are on therapy today and all those patients have been on therapy 2.5, 3 years or more that's a baseline perspective of an enduring patient population. But that's also with patients that have gone through clinical trials and all the hassle of that and time. O ur expectation and I mentioned just earlier there was a known but unexpected, say, level of diarrhea in the phase 3 program, which wasn't addressed at the onset of those trial patients that received trofinetide and had an AE related to diarrhea that it wasn't managed or dealt with in any specific way in the commercial setting. We can, right. We know a lot more about the drug from what we studied and what our label says in discussions with the FDA of how best to treat the GI tolerability. The expectation has always been we should be able to outperform the clinical trial experience in the commercial setting and we've consistently done that over time. What we've been able to show from our data and share with the street that at each point in time, as we track these monthly cohorts of how long you've been on therapy and we'd have enough data that it's robust enough to share it that we've seen a 10 percentage point incremental, meaning that the patients that are in the commercial setting are outperforming our best comparator from the clinical trial experience. That best comparator, just to remind everyone, is we're looking at people, patients that were placebo in phase 3, but rolled over to active in the open-label extension. Now, while those patients didn't know what they were on in the double-blind, they at least know when they started the OLE that they had the active. In the commercial setting you're getting the FDA-approved drug. We think, well, there's no perfect comparison. We think that's the best comparison and the latest data point that we released of cumulative nine months, or patients that could have reached nine months of therapy, about 58% of them are still on it in the commercial setting, while 47% of the placebo rollover patients in LILAC-1 were on then as you try to converge those two metrics, because we don't have patients in the commercial setting on therapy for 2.5-3 years that we think if we can keep and our expectation. We think a good assumption for financial modeling is we can keep 50% of patients who start and hopefully hope to exceed that on therapy. It's a good benchmark to look for. What's the enduring patient population for Daybue in the commercial setting. That's great and certainly smarter, more established strategies to manage the tolerability that you can and anticipate. But there's also presumably a network effect, as you sort of regain the reputational comfort not regain, but establish the reputational comfort and as you think about the Centers of Excellence that you have penetrated and emerging, but beyond this to higher volume institutions, to community institutions. How do you look at a gauge of this persistency of these new starts, but then also the eventual maintenance. F or us, From a Wall Street context these are great questions, because it helps meet people take a financial perspective. I n the real world patients, caregivers and HCPs, they care about efficacy. Does the drug work. Does the drug work for my patient, for my loved one. Right and it does, right. It doesn't work for everybody. F or those that have worked, we still see great stories of tangible efficacy that matters to patients and their loved ones and so those are the things. When we talk about operational, those are the stories that we want to make sure we communicate to have people. All right. What am I gonna get. What's the benefit. Am I gonna get and oh, by the way. If I'm able to use the best practices for GI management, that's manageable, right. So I can manage that. But I can get to efficacy and have benefit for my loved one. T hat's our operational focus. From a for where the patients are on the channels. So about 25% of patients are primarily and these patients have multiple HCPs. So I would say about 25% are primarily cared for in the centers of excellence. Probably another 60% are cared for primarily in what we call high volume institutions. The large ones of which function just like COEs. They just don't have that designation from the patient advocacy groups and then 15% or so are primarily treated by community physicians. A ll of these have as I said, multiple doctors as you'd expect, which was our intention expectation of early in launch the we had high engagement, because a lot of the physicians and COEs were investigators in our trial and had experience with Daybue. So we had probably half of our prescriptions in the earlier stages of launch came from the COEs, which have 25% of patients. Now, as we're later in launch, but still in, I would say, early phase of the drug, that's just broadening out more and we see prescriptions that are more like a third, a third, a third between COEs, high volume institutions and the and the community. I n each setting there's there's more to grow a nd then you were asking about. There's not really. Again, we don't. It's hard to slice and dice all of this, right. W hat we see on persistency is it's not that one of those commercial settings is better than the other. But there is variability. F or us it's the HHCPs that are most engaged with actively treating their patients and making sure they're following the various. They're following the best practices and they're multiple. There's no one answer and you're tinkering. People can titrate up the dose. They can start at the highest dose and titrate down if it's needed for the patient. T he great, the best success is where there's active engagement between the HCP and the family to get the patient to the most effective dose for that patient managed through tolerability and then hopefully ensure long-term success. O ur goal as a commercial organization and also part of our medical efforts, education efforts, is to get the best practices more widely used than the variability that we see today. If you've mentioned variability and you also certainly helped folks understand some of the seasonality in the 1st quarter. Maybe some of the implications on clinical visits. You certainly spoke that before they were happening. So we have sort of a shaking off that 1st quarter. But we have that consistency and the guidance is unchanged. So well, let's just talk through that trajectory, because we should be seeing growth from the 1st quarter onward and we got through that lumpiness. W hat we saw is primarily 2 things in the 1st quarter, right. A level of numerical discontinuations that were high for the quarter, but not high for expectations, right and it goes back to the persistency questions earlier, right. It was. It's a normal rate of discontinuations, but actually high number relative to, or not, or relative to previous quarters and that's really just the history of who started when, right. right and so and so that in and of itself, as we said, is we think we're past that hit the peak level of numerical discontinuations and we see now on a weekly basis our discontinuations are significantly lower than they were through most of the 1st quarter and the other element is seasonality. S ome of these, there's it's a little bit of an overlapping Venn diagram, because you could have discontinuations due to seasonality as people go through the holiday period and their insurance reauthorization process. But I would say that's the minor. I would say that the super majority of patients that discontinue was just normal persistency rate and then you add some seasonality on top of that and then you have other typical seasonal factors and what we did see in January, that a much lower rate of new patient starts due to lower Rett clinic days lower Rett patient visits to Rett physicians that rebounded in February and stayed relatively consistent in March. That low point of seasonality we're past. W here we are in new patient starts through the end of the 1st quarter is still a little bit lower than where we were in the 4th quarter and then the other elements of seasonality is slower conversion time, lower refill rate. That all is just your typical year-end 1st quarter process. It's just and we if you look at if you look at the quarter I would say about the sequential decline in revenue on order of the magnitude 50, 50, maybe a little bit more than 50% of the decline related to the numerical discontinuation. The other half, or slightly less than 50%, is due to seasonality. That's helpful and how it nets out. What was the latest metric that you and the team are sharing on the number of patients on Daybue. I believe you shared it on the Q1 call. I just want to make sure. W e had on the 1st quarter call or on the second, on our 1st quarter call in the Q2. We had 862 patients active on therapy, similar number to what we had at the time of our 4th quarter call back in February. But patient levels did continue to decline from that we were flat from February to early May. We went lower and then came back. G ood a nd the other metric that we found helpful is just how to think about the gross -to -net and just remind us of those levels that you've shared and how that should maybe just shape over time. That as we've talked about through launch, it bounces around in the early days. It certainly last year, on a quarter-by-quarter basis, it did bounce around, which is why we said, give us some time. Our expectation is it should be about 20% on an annual basis and unlike NUPLAZID, we don't, just due to the payer mix. We don't expect it to vary much quarter to quarter, but we're still running a little lower than that and that's what we saw in the Q1. All right. That's great and then certainly with patients in the trials. You've had clinical supply. So just one question that certainly comes in is just how to think about that inventory, that zero-cost inventory that you're burning off. How long is that. Does that last and how should we think about that with respect to the P&L. Yes, we do have 0 cost inventory. We expect to still, I guess it probably take us until sometime next year to utilize all of that. W hat we've said from a if you think about our cost of goods sold, inclusive of the deal payments and financial obligations to Neuren the all in steady state COGS should be in the range of 20% or a little less than that and the 0 cost inventory you're talking handful or more. It's in the mid to high single digits. That is the pure inventory cost, which is then not in our COGS to date, because we're still working through the 0 cost inventory. That's great and when is the right time to maybe think about patients returning to Daybue after they've had that experience of the discontinuation. So we're almost developing a patient pool. Right and maybe they haven't optimized their start doses. Is that a population that we will return to. That is one of our areas of focus. It's not been big to date, right. We've had people return that declare they were discontinued, not just in this they had a very long gap and they wound up refilling. That's just those patients were really just continuing patients, just utilizing a low amount of drug between fills. But for those who stopped, we've had some that have come back. They've had good experiences coming back. A lot of those patients discontinued due to GI tolerability. Many of them weren't titrating. So they've come back with more of a plan on how. So that is definitely a source of potential patient population. To date, it's not been big. We are with our Family Access Management. We're in touch with all of our families and we continue to be in touch with a lot of the families who've discontinued because they want to stay in touch with us and many of them have said at the right time for them, they'll consider restarting therapy. But, like I said, that's to date, it's been a relatively small number. That's great. I want to save some time for NUPLAZID in the pipeline. But why don't we knock NUPLAZID off and just your up-to-date comments on thinking about NUPLAZID growth and PDP in 2024 and beyond. For us, as I said, we've frame-shifted our financial focus, right and so the financial focus is to maximize cash flow and you do that 2 ways, right. Driving top line and being diligent on expenses. T hat's what we're going to continue to do and what we've seen in the top line is a modest level of volume growth and that should be that's our expectation for the future. W e're constantly evaluating what's the right mix of commercial support and so that could dial up or down. We over the last couple of years, we've taken it down meaningfully, right. More than about $100 million on an annual basis of spend. From where we are today, we think we're at a nice level that supports the brand. Remember, this is a dynamic patient population, because people who are diagnosed with Parkinson's disease psychosis really are. They're diagnosed with that towards the end of their life, unfortunately. So our patients, they're not. It is not like a young person who gets on an antidepressant that's going to stay on beyond your patent life. So we're adding and losing patients all the time due to that. So there is a base level of commercialization that's necessary to maintain the level of volume in the brand and then to grow on top of it and as I said, we'll tinker that up and down, depending upon how we see the what is the best investments in front of us. Great, great. Last moment on the pipeline, maybe with the Prader-Willi 101. Let's just frame up how the study is progressing, what we should be looking for with the latest updates. Sure. Yes. So ACP-101, which we're developing for the treatment of hyperphagia and Prader-Willi syndrome. We started the phase 3 study at the end of last year and it's really a little bit faster than expectations. We have a lot of interest and support from the Prader-Willi community. But we're still saying. It's going to be about two years before we're able to report out that study is what we're anticipating. Great and then at ACP-204, maybe viewed as a life cycle for PIM. E xploring in ADP. I know folks are starting to ask about how the updates there. But a seamless trial. Just give us the latest and what we should be looking towards. For the ADP. Alzheimer's disease psychosis study. The seamless phase 2/3 started the end of last year as well. The phase 2 portion of it will read out in about 2 years. So similar timeframe there. But the study will continue. They'll keep enrolling and moving straight into the phase 3 studies without waiting for those results. T hose results could influence little tweaks to the phase 3 program and all 3 studies are replicate. They're identical. They're all adequate and well controlled trials. 2 doses and a placebo control. We're very happy, too, that based on the design of ACP-204, we're able to go to a much higher dose with that drug, since it lacks any QT signal. We're able to go to 60 mg, almost twice the pim dose and we're also really happy. It has a short half-life. So we expect a faster onset of activity. Great. As always, there's so much to talk about. We're out of time. Guys, thank you so much. Good to see you. Thanks for having us. Appreciate it. Thank you. Thanks, everyone, for joining.