Good day, ladies and gentlemen, and welcome to the ACADIA Pharmaceuticals Conference Call. My name is Gerald, and I'll be your host for today. I would now like to turn the conference over to Al Kildani, Senior Vice President of Investor Relations and Corporate Communications at ACADIA. Please proceed.

Thank you. Good afternoon, and thank you for joining us on today's call to discuss ACADIA's second quarter 2025 financial results. Joining me on the call today from ACADIA are Catherine Owen Adams, our Chief Executive Officer, who will provide some opening remarks; followed by Tom Garner, our Chief Commercial Officer, who will discuss our commercial brands, DAYBUE and NUPLAZID. Also joining us today is Elizabeth Thompson, PhD, Executive Vice President, Head of Research and Development, who will provide an update on our pipeline programs; and Mark Schneyer, our Chief Financial Officer, who will review the financial highlights. Catherine will then provide some closing thoughts before we open up the call for your questions. We are using supplemental slides, which are available on our website's Events & Presentations section. Before proceeding, I would like to remind you that during our call today, we will be making several forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements, including goals, expectations, plans, prospects, growth potential, timing of events, future results and 2025 financial guidance are based on current information, assumptions and expectations that are inherently subject to change and involve several risks and uncertainties that may cause results to differ materially. These factors and other risks associated with our business can be found in our filings made with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of today's date, and we assume no obligation to update or revise these forward-looking statements as circumstances change, except as required by law. I'll now turn the call over to Catherine for opening remarks.

Thank you, Al, and good afternoon, everyone. Our second quarter performance reinforces the momentum we're building across all facets of our business from commercial strength to our clinical pipeline and global expansion. We delivered total revenue of $264.6 million this quarter, driven by strong growth across our portfolio. This includes $96.1 million from DAYBUE with patient uptake continuing to grow for the second successive quarter and $168.5 million from NUPLAZID, bolstered by new patient starts and commercial execution. DAYBUE has now passed stabilization, moved into growth and is entering a new phase, expansion and acceleration. Our investments in patient support, community engagement and field expansion are starting to make a positive impact, as Tom will highlight in more detail. On NUPLAZID, we're encouraged by continued growth across all leading indicators, bolstered by recent litigation wins enforcing our intellectual property. These victories validate our long-term strategy and reinforce our ability to deliver NUPLAZID to patients through 2038. Our full year revenue guidance reflects this confidence. We are raising the low end of our NUPLAZID guidance based upon a foundation of disciplined execution and momentum delivered by our DTC campaign. We also hosted our first R&D Day, a milestone event that showcased our exciting and expanding pipeline, with 9 disclosed programs in development and 5 Phase II or Phase III data readouts expected through 2027. The excitement within ACADIA is palpable. Liz will walk you through that shortly. First, let's start with commercial. Over to Tom.

Thanks, Catherine. Let's begin with DAYBUE. Q2 sales were $96.1 million, up 14% from a year ago. We observed steady progress across key performance metrics in the quarter. In Q2, 987 unique patients in the U.S. received paid shipments, increasing from 954 in Q1 and 920 in Q4 2024. The upward trend reflects encouraging signs of growth in both new patient starts and persistency. Long-term persistency remains a key strength for DAYBUE. Our 12-month persistency rate continues to exceed 50%, and we're now pleased to report that our 18-month persistency rate is above 45%. This trend reflects the growing and stable base of patients who remain on therapy over time. When we look at length of treatment among patients currently on therapy, 70% have been on treatment for at least 12 months, highlighting the sustained benefits that DAYBUE continues to deliver and the durability of our growing patient base. Notably, we're seeing more new prescriptions from the community setting, signaling progress in broadening reach beyond academic centers, which was a key element of our field force expansion, which is now complete. We finished hiring and training earlier this quarter, and we're already seeing encouraging signs that the new customer model is gaining traction. One of the most promising indicators in the second quarter is a meaningful uptick in our proportion of new referrals coming outside of Centers of Excellence, where a majority of Rett patients receive their primary treatment. Encouragingly, this increase was underpinned by a further increase in the number of new community-based writers for DAYBUE with 900 total HCPs now having written. Additionally, we launched a direct-to-consumer campaign for DAYBUE in July, and we are already seeing positive signs of early engagement from the Rett community. During Q2, we welcomed Allyson McMillan-Youngblood as Senior Vice President of our…

Thank you, Tom. Let me begin by revisiting the highlights from our inaugural R&D Day held in New York on June 25, where we showcased the strength and breadth of our pipeline. We were pleased with how the event came together, and I want to thank many of you on this call who were able to join us. While we had already disclosed all the programs on this chart, R&D Day gave us a great opportunity to provide more details, particularly for 2 newer molecules. The first is ACP-211, an orally administered, selectively deuterated form of R-norketamine, which we're developing for the potential treatment of major depressive disorder. Data to date support the potential for efficacy without significant sedation or dissociation, a profile we will continue to explore in Phase II and beyond. The second is ACP-271, a GPR88 agonist with potential applications in tardive dyskinesia and Huntington's disease. This is some of the most novel biology in our pipeline, and we believe it to be the first GPR88 agonist that will enter clinical trials. If you weren't able to participate in our R&D Day, I highly encourage you to visit our website, where you can access the webcast and the full set of presentation slides. The event was a clear demonstration of the momentum building across our pipeline. We're advancing with purpose and clarity, and the progress is tangible. Across our 9 disclosed programs, we anticipate initiating 7 Phase II or Phase III studies over the course of 2025 and 2026. Moreover, between 2025 and 2027, we expect 5 Phase II or Phase III readouts. These milestones underscore both the breadth of our pipeline and the strength of our R&D strategy. Specifically, we have several important trial initiations and data readouts on the horizon. In Q3 2025, we plan…

Thanks, Liz. Let's now review our second quarter 2025 financial results. The second quarter was strong across the board with $264.6 million in total revenues, up 9% year-over-year. Second quarter DAYBUE net product sales of $96.1 million represented 14% year- over-year growth, including 12% volume growth, primarily reflecting the increase in unique patients receiving shipments in the quarter. The DAYBUE gross to net adjustment for the quarter was 23.3%. Turning next to NUPLAZID. Second quarter net product sales were $168.5 million, up 7% year-over-year with 5% of that growth attributable to volume. The NUPLAZID gross to net adjustment for the quarter was 24.6%. R&D expenses were $78 million in the second quarter, up slightly from $76.2 million in the second quarter of 2024. SG&A expenses for the second quarter were $133.5 million, up from $117.1 million in the second quarter of 2024. The increase was primarily driven by increased expenditures for both DAYBUE and NUPLAZID in the U.S., including the planned expansion of the DAYBUE commercial team. We ended the quarter with a cash balance of $762 million, up from $681.6 million at the end of Q1 and $756 million at the end of 2024. Let's turn to our 2025 guidance. We are raising the low end of our NUPLAZID guidance range, reflecting the strength of the business and its performance to date. We now expect NUPLAZID net product sales for the year to be between $665 million and $690 million. This compares with our prior guidance range of $650 million to $690 million. Accordingly, we are also adjusting our U.S.-only total revenue guidance to reflect this change. As you can see on the slide, we are reiterating all other prior guidance ranges from our Q1 call. We're confident in our ability to execute against these targets and to continue creating value for patients and shareholders. I'd now like to hand it back to Catherine for closing remarks.

Thanks, Mark. As you've heard, quarter 2 was a quarter of progress and momentum. Our teams are executing with urgency and precision, and we remain focused on accelerating DAYBUE's commercial trajectory, sustaining long-term growth and differentiation for NUPLAZID, advancing a deep pipeline through rigorous clinical development and continuing to build the pipeline through business development and expanding globally to reach more patients in need. The next major milestone is ACP-101's data readout in early Q4, and we're hopeful for what that could mean for families living with Prader-Willi syndrome. Thanks for joining today's call, and thank you for your continued support of ACADIA. And I'll now open it up for questions. Operator?

[Operator Instructions] Our first question comes from Tess Romero from JPMorgan.

So I actually wanted to ask about ACP-101 today. Liz, maybe could you orient us to the approach you plan to take with your top line? How much detail will you provide? And will this be more qualitative or quantitative in nature? And are there any secondary or other end points that you will think will matter beyond HQCT? And then as a follow-up, where are you really most focused from a clinical trial conduct perspective to manage any key risks?

Thanks, Tess. Great question. So in terms of our approach to top line and for that matter, in terms of our approach to how we're thinking about this trial, first and foremost, is the primary end point and success there. We will be looking at our secondary end points, which are a combination of clinician assessments as well as a responder bar for the HQCT as well. In terms of what we're going to release, certainly, I would anticipate that there would be a focus on the primary end point and sort of key overview of safety and tolerability. And that's what you should anticipate out of our top line announcement. In terms of the areas that we are focusing on in terms of clinical trial conduct, we have been -- throughout, we have been robustly keeping on top of how the assessments appear to be performed and whether variability was within our expected ranges. So those are the areas that we've been focusing on in terms of conduct and making sure that we have as consistent a behavior as possible across the sites.

Our next question comes from Ritu Baral from TD Cowen.

I wanted to talk a little bit or ask a little bit about the new momentum in DAYBUE. Could you tell us what percentage of patients or new patients specifically came from the community setting? And you mentioned the new number of 900 HCP writers. What percentage or at least movement of those writers were in the community setting on a quantitative basis? And then I have a Prader- Willi follow-up as well.

Thanks, Ritu. We'll take the DAYBUE question first. I'll ask Tom to give you some more details on that.

Perfect. So in terms of your first question regarding the penetration that we've seen as a result of the increase in the sales force, which, as a reminder, that went live kind of through May, so we're kind of fairly early on in terms of seeing the impact, but we're pleased with what we're seeing already. In the quarter, we actually saw that the number of referrals that were coming directly from our non-COE accounts actually grew to about 3/4 of our overall number. So that was up from about 2/3 the quarter before, which I think is a nice increase in terms of being able to penetrate that large group of patients that we know exist that fall outside of our COE. So just as a reminder, roughly 65% of our patients fall outside the direct care of 1 of the COE centers -- 1 of the COE-designated centers. With regards to your second question as to the additional writers that we saw through Q2, the vast majority of those new writers fell outside of the COEs, which given the fact that we saw this nice uptick in terms of penetration through the quarter, I think, again, it's a nice leading indicator that the new model that we have in place is beginning to pay dividends for us.

Thanks, Tom. Do you want to ask your 101 question, Ritu?

Yes. And just mopping up after Tessa's questions, can you talk to how the conduct, specifically dropouts of the Phase III Prader-Willi have gone? Are they within expectations? And are all the DSMB looks for the trial completed and if the SAP has been finalized with FDA?

So I'm not going to comment on data from a currently ongoing trial aside from to say that, generally speaking, we are continuing to see this trial unfolding in an acceptable way. But obviously, it's blinded, and I'm not going to comment any further on that at this point. We do have an SAP in place. I do consider that we have the right to continue to modify until before we unblind the trial, but we do have our planned analyses established at this point.

Our next question comes from Sean Laaman from Morgan Stanley.

This is Mike Riad on for Sean. Congratulations on the quarter. So thinking about DAYBUE, the 987 new patient adds suggest a good steady growth rate quarter-over-quarter. How should we be thinking about this trajectory? Like given the relative lower prevalence, is it reasonable to expect that this would ever accelerate and doesn't need to? Or how should we be just thinking about that trajectory?

So it's Tom here. I'll take that one. Thank you for the question. So we're pleased with the steady growth that we've seen over the last 3 quarters. I think as we mentioned in the call, if you look at Q4, we had around 920 patients. That increased to close to 954 in Q1, and we're pleased with the continued growth that we saw through Q2 with 987 active patients on therapy. Obviously, the plan that we have moving forward is that, that will continue to accelerate as we see the impact of our new customer model. And our goal is to make sure that we have more new patient starts continuing week-over-week and month-over-month and quarter-over-quarter. And I think now we have this very stable and growing group of persistent patients, many of whom have now been on treatment for 12 months or longer, I think, gives us a real sense that we can really continue to grow this brand and take it to new heights.

Our next question comes from Jason Butler from Citizens JMP.

Just one on NUPLAZID. Given that you're seeing a return on investment on, for example, DTC activities and now that you have the greater visibility with intellectual property, are there more investments or longer-term investments that you're considering for the franchise?

Jason, thanks for the question. I think as we think about our strategy with NUPLAZID, I encourage us to sort of bifurcate the commercial strategy that we're putting in place now with the longer-term ability to now maximize the brand. So direct-to-consumer decisions that we're making are sort of relative to the 2038 shorter term. We're seeing impact of the DTC. We would have continued to invest regardless of the outcome of the IP trial because it has a strong momentum for the next sort of 2 to 3 years potentially depending on how long we continue to invest. Beyond that now, what we have been able to do is think about the longer-term strategy for NUPLAZID. I'm looking forward to sharing a little bit more about that as we head towards the back end of the year in terms of how we now think about the investment longer term. But for right now, the DTC campaign is certainly paying dividends, as you point out, and we're excited about the continued momentum. And indeed, in terms of the More to Parkinson's campaign and raising awareness of hallucinations and delusions, we're delighted that Ryan Reynolds has agreed to continue supporting that campaign because we believe that's been one of the main drivers of increased awareness. And once the caregiver is aware, they're encouraged to go in and talk to their doctors. So it's been a very strong impact to caregivers, and we're excited to continue that.

Our next question comes from Brian Abrahams from RBC Capital Markets.

Congrats on the quarter. Just 2 for me, I guess, just both on DAYBUE. As you've expanded the sales force, can you talk a little bit more, I guess, qualitatively around your learnings from the Rett patients outside of the Centers of Excellence just in terms of physician receptivity, number of prescriptions per physician, any early persistent signals and how well educated the docs are around the titration? And then can you also maybe talk about any hints of changes you may be seeing in overall DAYBUE persistence, both quarter-over-quarter and bigger picture trends and just how much the education around AE management and the efficacy message and importance of staying on therapy is resonating?

Thanks, Brian. I'll let Tom come up with his thoughts on that.

Yes. Thanks for the question. So yes, we've already had a number of learnings as we've expanded beyond kind of the COEs. One of the key things is there is clearly receptivity to DAYBUE outside of the COEs. We know that there are physicians who are treating Rett patients who won't necessarily have been called on yet, and we're appreciating that they require kind of ongoing education to make sure that they fully understand the profile of the product, they fully understand how to utilize the product. And we're utilizing the full mechanics of the system that we've built to make sure that we can educate all of those prescribers as quickly as possible. So I think one thing that you probably need to be thinking about as you look at modeling is that the buying process, the number of calls may be slightly longer for this group of prescribers versus those that we see for COEs. And that's purely because they just don't see Rett patients as frequently. As you talk about persistency, I mean, we're really pleased with the persistency that we're seeing. So as I mentioned on the call, 12- month persistency remains well above 50%. And as we also mentioned for the first time, our 18-month persistency, although not yet fully mature, is above 45%. So I think that, that gives us a real good sense that we have a -- we've kind of reached a nice kind of plateau as we go into the longer-term outlook for the product. And that gives us, with this growing group of patients who are now receiving therapy, a sense that we can continue to grow DAYBUE to new heights, as I've mentioned, as we get new patients started.

Our next question comes from Ami Fadia from Needham & Company.

I have 2 quick ones. Firstly, just with regards to NUPLAZID, it continues to remain really strong with the number of shipped bottles that you mentioned. Can you give us some sense of what's driving the strength and maybe give us some color around where the growth is coming from across channels? And then with regards to DAYBUE, as you see increased adoption outside the COE setting, can you give us a sense of what you saw in your open-label study in terms of persistency out at 12 or 18 months in -- with regards to patients that are being treated outside the COE setting, if you have that?

Ami, thanks. I'm going to let Tom answer both of those and Liz maybe in terms of the longer term in the trial. But Tom?

So in terms of NUPLAZID, yes, I mean, we're seeing a nice uptick in terms of referrals, NBRxs and ongoing TRx volume. I think if you look at the second quarter and kind of the impact that we saw, we were pleased with the fact that our NBRx volume was kind of reflected across all channels. So we saw it both within the community setting, but we also saw nice increases across the LTC setting as well. As a reminder, the vast majority of our patients do sit within the community setting, where -- the fact that we have a group of patients that sit within long-term care, where we also promote -- showed kind of just continued strength across the breadth of patients that we serve for NUPLAZID. So very pleased with that kind of ongoing uptick and the strength that we have now going into the second half of the year. In terms of the question around DAYBUE and the real-world data, I think the real-world data that we have, and we had a recent publication, I think, at IRSF that showed that 18 months, we had about a 40% persistency rate. So I think the real-world data that we're now seeing through the latest data with a 45% persistency rate through 18 months I think, really kind of begins to match up with that very, very nicely and I think, again, gives us a real sense that this drug is performing as we've seen in clinical studies and moving forward. We don't expect to see any sign of kind of significant deviation versus this very kind of stable kind of plateau that we're now seeing.

And I'll just add on -- thanks, Tom. I'll just add on that in our actual clinical trial experience, we really only have about 9 months of data that you can kind of count on from a persistency perspective because in the later part of the open-label extension, we had patients going off to marketed drug and so coming off of the program. If you look to that 9-month experience at that point, you've got something like 45% persistency. So I think what we continue to see and what we've seen sort of all along is that actually the real- world persistency is a little bit better than we're seeing in the clinical trials.

Our next question comes from Marc Goodman from Leerink.

Can you talk about discontinuations for DAYBUE and what you saw in the quarter? And was there any inventory changes that were of any significance for either product?

Thanks, Marc. I'll let Tom talk to that.

Yes. Discontinuations, Marc, we were very pleased that we had another quarter where discontinuations remained well below 10%. Again, I think as you think about discontinuations as part of the overall story that we're now telling in terms of DAYBUE, very stable but growing group of active patients, discontinuations remaining relatively low. And I think that this all speaks to the fact that we really now have a very good understanding as to the profile of the product, how we can engage with the patient community and ensuring that as we move forward, again, with a real focus on the efficacy profile of the product, which continues to be strengthened, thanks to the work of Liz and team that we feel very good about the direction of travel for DAYBUE as a whole. I'll ask Mark to ask the -- answer the second question.

Thanks for the question. Yes, there's nothing to report on in-channel inventory. NUPLAZID is consistent quarter-over-quarter. And then just as a reminder, that concept really doesn't exist for DAYBUE as our single specialty pharmacy really only takes control of the inventory for like a nanosecond before it goes directly to patients. So the DAYBUE model has always been really a sell-through model.

Fair enough. Mark, can you also comment on just the tax rate and how to think about it this year and going forward?

Yes. So our tax -- so I guess if you look at our P&L, our book tax rate year-over-year is a little higher because for GAAP accounting, we're not able to account for all the credits and NOLs that we're actually using. For modeling purposes, our cash tax rate remains currently in kind of the mid-teens rate. Long term, we guide more towards mid-20s, and that's before considering anything for OB3, which will start to be implemented, from our standpoint, in the next quarter. And with that, we have about $400 million of kind of U.S.-based activity R&D expense that had been capitalized and that, in the near term, we'll be able to have some accelerating expensing for U.S. tax purposes. So in the next year or 2, our tax rate will actually go down.

OB3 is our internal vernacular for One Big Beautiful Bill just in case.

Our next question comes from Ash Verma from UBS.

So for NUPLAZID, I know like you've outlined that this is a largely Medicare patient population. Roughly by when do you think that it will be eligible for IRA price negotiation and implementation? And then secondly on the ACP-101, I wanted to ask like is it the same formulation from Ferring that required refrigeration? And do you think that could potentially become a hindrance at all in terms of thrice daily administration for this patient population? And then is there a plan for a room temperature stable variant here?

Thanks, Ash. I'm going to let Mark answer the IRA question and then Liz on 101. And some of that was a little bit unclear. You broke up for a little bit, so you might have to just say your 101 question again for Liz, so she can make sure she answers it correctly. But let's start with the IRA.

Yes. In terms of potential timing for negotiation under the IRA, 2029 will be the first year that NUPLAZID is eligible for negotiation unless there's changes in the legislation like getting rid of the pill penalty. That's probably the year we anticipate we'd potentially be subject to negotiation. Just to remind you, as a small company, we have a limit on the discount we have to offer. It's in the range of 25% to 34% as outlined in the legislation. And then after that would be subject to negotiation like any other drug. From our standpoint, just due to the launch timing of NUPLAZID, if the pill penalty is removed, that could add another year before negotiation would likely be expected.

Right. And the small company is for 2 year, right, 2 years...

Two years, yes.

And with respect to ACP-101 and the question there, and then obviously tell me if there's anything that I didn't catch about your question that I neglect here. But we are using the same formulation as Levo used. And an important thing to remember is that part of what we're doing here is a resubmission to the complete response letter. And so the intent is to provide the new information that FDA requires, which is an additional study to demonstrate efficacy while changing a few things as possible about the overall initial presentation. We have seen that to be acceptable and usable in our clinical trials, have not found it to be a concern. In terms of your question about next generation, we're always considering whether there are things that we can do to our products to make them more patient friendly. And so I anticipate that we'll be thinking about that for 101 as well as we do for other things.

Our next question comes from David Hoang from Deutsche Bank.

Congrats on the quarter. I just wanted to ask on ACP-101. Can you comment or say anything on the, I guess, open label extension for the Phase III study, like what you're seeing in terms of rollover rate? And would you ever consider adding a randomized withdrawal portion to the plan that I think was used by a competitor with improved product in the market to get that product approved?

Great questions. So first off, on the OLE, I'm not going to comment too specifically at this point, but I will say that we have seen generally good interest in our open label extension and are continuing to collect information on patients who are enrolling into that. To the question about the randomized withdrawal, it's an interesting question. At this point, we really are focused on the results of our current parallel arm study that we're looking at those data coming in, in early Q4. And we think a real advantage of that is that that's going to be able to give a clear -- if it's positive and it turns out the way we hope, it's going to give a clear demonstration for regulators, for physicians and for patients and families of what you could expect upon initiation of therapy. A randomized withdrawal study could be something that we might consider in the future, but at this point, we think the most important data set really is this parallel group study that we're currently running and eagerly anticipating the data.

Our next question comes from Uy Ear from Mizuho.

This is Leo on for Uy, and congrats on the quarter. For each of your brands, NUPLAZID and DAYBUE, what is the right way for us to be thinking about 2026 from a growth perspective? What are the key factors and drivers we should be thinking about? And maybe on the heels of the recent R&D Day, excitement is clearly growing in the pipeline. Which pipeline programs is the team most excited about?

Thanks, Leo. I'm going to ask Tom to comment on how to think about growth in '26 for both brands and then Liz to tell us which is her favorite child in her pipeline.

Yes. Thanks for the question. So let me start with DAYBUE. So as we've mentioned during the call, we've seen very nice continued growth for the last 3 quarters in terms of active patients. We do anticipate through the second half of the year that the rate that we are growing that number will accelerate as we see the impact of our new field force model really begin to pull through. As a reminder, our penetration rate in general across the entire Rett community remains kind of in the low 30%. So we've still got a significant opportunity here for this brand to continue to grow, and that's our goal through 2026 and beyond, is to really make sure that we engage with the Rett patient community in the right way. We really meet patients where they are, which is what we are doing with our new customer model. And we can really make sure that we take DAYBUE to the height that we know it can be. So that's our goal for '26. So it's really a story of continued and we plan for accelerating growth through the year. As it relates to NUPLAZID, it's a similar story in a way. I think we've seen this year and this quarter, in particular, some very nice numbers in terms of leading metrics. The team in the field continue to execute very well. Our campaigns are working for us very well and are giving us a nice tailwind as we think about the second half of this year. And we believe that, that sets us very nicely up for 2026. So I think the outlook for both brands from a commercial point of view is one of strength, and we really look forward to really capitalizing on that as we head into 2026.

I love that Catherine teed this up as my favorite child because what I was going to say is I would never say who my favorite child is. I think that across our pipeline, we have a nice mix of assets that are relatively derisked from a mechanistic perspective, things like ACP-204, where we are following in learnings that we have from NUPLAZID as well as some areas of really novel biology like ACP-271. I think that we are excited about the fact that we've got a number of different ways we could potentially serve patients living with rare and neurological diseases. So there's a lot in our pipeline that we're very enthused about, and I'm not going to pick a favorite child today.

Maybe I'll just come on top of that with, I think, what was exciting for us at R&D Day was to be able to share our expectations on the market opportunity that these brands, these new brands potentially, if approved, offer to ACADIA in terms of potential expansion. And we shared at R&D Day that we believe all 5 of the new products could hit blockbuster potential. And we believe 3 of them have the ability to achieve over $2 billion should they be successfully approved. So we're moving into bigger markets with still high unmet medical need, and we're excited to continue to focus our development on really differentiated assets and ensuring that we're developing a pipeline of valuable innovation that patients from those underserved communities will really feel adds to their opportunity to see more memorable moments with their families. So we're excited for that.

Our next question comes from Tazeen Ahmad from Bank of America.

I wanted to ask about whether the 204 study in Lewy body dementia has started. I think your guidance had been that it's supposed to start soon or this quarter. And then I also wanted to get your thoughts about the ADP data that's expected in the middle of next year. If that's positive, what's your view about the likelihood of the Lewy body study working, knowing that you had -- the company had looked at Lewy body as part of a previous study with pima a few years ago?

Okay. The first easy one, which is we do continue to anticipate that the Lewy body study will get started this quarter, so hasn't gotten the first patient randomized yet, but we are confident we'll get it in the quarter. In terms of ADP and potential for read-through, I guess what I'll say is that I think that the data, while limited in terms of its numbers that we have from NUPLAZID, is pretty supportive of Lewy body. Again, there's a relatively small number of patients in that study, but roughly 20 patients in the active arm and 20 patients in the placebo arm, and there was a marked difference in relapse rate of patients on placebo versus patients who continued on drug. So I think we have some good reason to believe just based on the existing NUPLAZID data set. A positive ADP data set is certainly going to make me feel better, in particular, because that gives you clear evidence that this particular molecule is active, though we, of course, expect it to be based on all the nonclinical and Phase I work that we've done to date. So certainly, we are anticipating that ADP readout with a great deal of anticipation and feel good about Lewy body and its potential for success.

Our next question comes from Sumant Kulkarni from Canaccord. Sumant Satchidanand Kulkarni Canaccord Genuity Corp., Research Division Nice to see the progress this quarter. Could you give us some specifics on how ACP-2591 fits into your plans for Rett syndrome relative to your current efforts with DAYBUE?

Thanks for the question. We haven't had a 2591 question for a while, so I'll let Liz answer that.

Yes. As we think about ACP-2591, I mean, I think what originally attracted us to the program was the fact that there are some similarities mechanistically speaking to DAYBUE and so that derisks it with a potential for a differential penetration from a brain perspective. So there's a possibility that you've got a difference on the benefit/risk profile there. Obviously, that's going to have to play its way out in Rett patients in order to know how that would -- how we would use that in the context of DAYBUE. What we're doing right now on this one is some additional work to verify how -- the information we need to specifically take forward in Rett, and I look forward to providing some additional updates on that at an appropriate time.

Our next question comes from Salveen Richter from Goldman Sachs.

For PWS here beyond HQCT and CGI-S and CGI-C, do you plan to evaluate functional end points such as hyperglycemia control and weight loss in the Phase III trial? And what would be a clinically meaningful bar for success in this study?

In terms of clinically meaningful bar of success, I'll be very pleased if what I see out of this study is similar to the magnitude that was demonstrated with the 3.2 milligram dose in the prior study. That would be -- I think we feel confident that that's going to be a meaningful change, and we feel confident not just from ourselves but from talking to physicians as well as patient advocacy organizations. We think that, that would be a meaningful note. I mean I will say that the -- I think your other question was about things like waist circumference. We aren't specifically looking at that. We do think that this is a complex interplay of the disease itself as well as the mechanisms that families have put in place to manage their children and their access to food. So that hasn't been a focus here. We are looking at adverse events and typically at blood profiles, and at least based on the data that we saw in the prior study, we have no reason to anticipate that routine monitoring is going to be necessary. That's going to be subject to the data we see in the study, of course.

Our next question comes from Yatin Suneja from Guggenheim.

Question is on 204, ACP-204. Could you just comment on the pharmacology that you think is better addressed with this molecule, which was not addressed with NUPLAZID, specifically as it relates to this ADP population? Just trying to get a sense in terms of how the setup is or how different the setup is into this ADP readout versus the DRP study that's ran with NUPLAZID.

So I think -- so thank you for the question. As I think about the differences with 204, they kind of go into a couple of different categories. There's the molecule differences and then there's program design differences. And I do think both of those play into what we could be looking out of the ADP study. So on a molecule perspective, just hitting on this really briefly, NUPLAZID does have that QT prolongation. It's not significant -- it's not clinically impactful. But in an elderly and frail patient population, you do need to think about it, but also it limited our ability to dose range. And we do see some differences in the exposure response that suggest that higher levels of exposure could get us to higher efficacy. We think that this is a reason to think that we've got increasing reason to believe with 204 in our ADP program. And then on the design of the program itself, I think one of the biggest things that we learned from our prior experience was the importance of having our program specifically focused on the disease that we are studying. I don't want to go through the whole history of DRP, but obviously, that was one of the challenges that we had there. So the program that we've designed with ADP is very specifically identifying that patient population. It's specifically looking at a patient population that's a little more severe in their psychosis, which we also found to be more responsive, and we're biomarker confirming that patient population. So if we take all of these things together, we think that we have set up -- we think we have a good setup for ACP-204 to show what it can do and some good reasons to think that it might be more likely to be successful.

Our next question comes from Evan Seigerman from BMO Capital.

Malcolm Hoffman on for Evan. Back to DAYBUE. I noticed an improvement in the percent of active patients who have been on therapy for 12 months or longer from 65% to 70% this quarter. Can you just expand on this a little bit further? Is this more a factor again of just providers handling treatment, becoming more comfortable with the GI profile and how to manage it over time? Just would appreciate any color there.

Yes. I'll take that question. So thank you. I think it's a few different factors. I mean, as I mentioned a few minutes ago, we are learning more about the product as we go. We are clearly educating the -- both the patient community and the caregivers and the HCPs regarding how they should go about utilizing the product. If you look at the overall kind of usage that we see, I mean, our percentage to dose remains in the 70% range, which I think also just talks to the fact that our user base is just getting more comfortable in terms of titration as well. And I think, over time, as they see the benefits of the product and as we lean in more in terms of the efficacy profile, I think that there is more that we can kind of pull through there as we think about kind of DAYBUE for the long term. So I think it's a story of continued knowledge. I think we continue to educate in the right way. We make sure that all of the learnings that we have from our COEs are now being amplified into the community as well. And I think that this is all being reinforced with our kind of updated customer model and strategy as we think about DAYBUE moving forward.

And I think just finally, the persistency that we continue to see sort of amplifies that. So the 65% to 70% is really a recognition of everything that Tom has just talked to, just a much more stable base than we were a quarter ago and then we were a year ago. So again, lots of steadiness and now we're driving the momentum into DAYBUE. Thank you for the question.

Our final question comes from Paul Matteis from Stifel.

This is Julian on for Paul. Congrats on the progress. I just want to circle back to something that was mentioned earlier in the Q&A about the SAP for ACP-101 and how you guys "retain the right to modify" SAP while you remain blinded. Just curious what types of modifications could potentially qualify or could be sort of in the realm of possibilities. Just curious if you could expand on that. And I have one quick follow-up as well on DAYBUE.

Yes. No planned modifications. I purely meant that as just from a practical point of view, until you have unblinded your database, you can consider your SAP subject to the possibility to change. But no, there are no planned modifications.

Got it. That's helpful. And then on DAYBUE, it just sounds like things are going well. You're starting to see increased scripts in the community in addition to higher persistence or I guess, greater line of sight to the persistence of your patient population. I guess just thinking about the second half of the year, you've sort of messaged how you expect to see greater growth. Why the decision to not narrow guidance this quarter? It just seems like you'd kind of easily hit if you continue to add the patients that you have this year. Just curious if that's being conservative out of sake for being conservative or if there's anything else to that.

Yes. I wouldn't read anything in the guidance. I think what I would say maybe on the reason why we adjusted NUPLAZID is we started the year with a wider range than we normally do kind of coming into the year not knowing all the puts and takes for the Medicare Part D redesign. So when we looked at the NUPLAZID range, we just thought it was just too wide kind of halfway through the year. As we look at all the other ranges, we left them, including DAYBUE, and we'll revisit those in the third quarter as we would typically -- it would be a typical point to start narrowing.

Thanks, everybody, for the questions, and thank you, operator. We really appreciate everybody joining us today, and we look forward to updating you on our progress next quarter.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.