ACADIA Pharmaceuticals - Earnings Call - Q2 2025

Transcript

Speaker 9

Today, 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 at Acadia. Please proceed.

Speaker 6

Thank you. Good afternoon, and thank you for joining us on today's call to discuss Acadia Pharmaceuticals' second quarter 2025 financial results. Joining me on the call today from Acadia Pharmaceuticals 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 and 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.

Speaker 5

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, fostered 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, fostered 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 nine disclosed programs in development and five Phase 2 or Phase 3 data readouts expected through 2027, the excitement within Acadia Pharmaceuticals is palpable. Liz will walk you through that shortly. First, let's start with commercial. Over to Tom.

Speaker 6

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 (DTC) campaign for Daybue in July, and we are already seeing positive signs of early engagement from the Rett community.

During Q2, we welcomed Alison McMillan Youngblood, a Senior Vice President of our rare disease franchise. Alison brings a breadth of commercial experience across the U.S. biopharma business, including many launches. Her leadership will help to drive this critical business forward. As we look ahead with the expanded team now in place, we're continuing to execute against our strategy to drive long-term, sustainable growth for Daybue. We expect this will translate into an increase in new patient starts towards the back end of the year. At the International Rett Syndrome Foundation meeting in June, our presence as a leader in the Rett therapy field was felt. As Liz will detail, we shared multiple compelling posters that add to the body of evidence for DAYBUE. Let's now turn to our plans for trofinetide outside the U.S.

In the EU, where the prevalent population is estimated to be between 9,000 to 12,000 Rett patients, named patient supply, as requested by local HCPs, is available through Flynn Pharma. We've received requests from multiple countries and are continuing to support patients where regulatory frameworks allow. Named patient supply, based upon HCP request, is also in place in Israel through Rafa, and in select rest of the world countries through Pharmamondo. Overall, we're pleased with the continued momentum of DAYBUE in the U.S. and with the global interest in trofinetide, where we have already started serving patients through these programs. Now, turning to NUPLAZID, our commercial team delivered another strong quarter with revenue of $168.5 million, up 7% from a year ago, driven primarily by volume. We saw strength across all key metrics in Q2.

Referrals were up 17% year over year, driven by continued momentum in our direct-to-consumer (DTC) campaign. As a result, for the first time ever, both referrals and new prescriptions increased sequentially from Q1 to Q2. Another of the quarter's highlights was shipping the highest number of NUPLAZID bottles since launch, a strong indicator of growing demand as we continue educating both healthcare providers and patients with PDP about the product's unique and differentiated profile. The DTC campaigns are doing exactly as we intended, sparking meaningful conversations with healthcare providers and reinforcing our commitment to educating caregivers about the symptoms of hallucinations and delusions related to Parkinson's disease. Visits to nuplazid.com have surged, with a 17-fold increase in consumer traffic year over year, helping to drive more patients to speak with their physicians.

To carry this momentum forward, we're pleased to extend our agreement with Ryan Reynolds and the MOVE to Parkinson's campaign through February of 2026. The campaign continues to drive meaningful awareness of hallucinations and delusions in Parkinson's disease, and we believe a strong push through year-end is essential to build on that success. This quarter's NUPLAZID results reflect the strong executional focus of our field teams, coupled with the ongoing positive impact of our DTC efforts. Taken together, we expect to see sustained growth through the second half of the year and beyond. With that, I'll hand it to Liz to review our pipeline progress.

Speaker 5

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 two 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 2 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 nine disclosed programs, we anticipate initiating seven Phase 2 or Phase 3 studies over the course of 2025 and 2026. Moreover, between 2025 and 2027, we expect five Phase 2 or Phase 3 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 to initiate a Phase 2 study of ACP-204 in Lewy body dementia psychosis. Also in the third quarter, we expect to initiate our Phase 3 study of trofinetide in patients with Rett syndrome in Japan. In early Q4 2025, we expect to report top-line results from the COMPASS PWS Phase 3 study of ACP-101 in Prader-Willi syndrome, following the completion of enrollment in Q2. Also in Q4 2025, we anticipate initiating a Phase 2 study of ACP-211 in major depressive disorder. Wrapping up the year, we plan to begin a first-in-human study of ACP-271 in healthy volunteers before year-end. Finally, we also continue to progress through the review process with BMA for trofinetide, with agency decision expected in the first quarter of 2026. In addition to these upcoming milestones, we continue to make meaningful contributions to the scientific literature for our marketed and pipeline products.

The second quarter was a busy one for Acadia Pharmaceuticals-relevant medical meetings, with major conferences for Rett syndrome, Prader-Willi syndrome, and Alzheimer's. There were multiple Daybue-related presentations at the International Rett Syndrome Foundation meeting, continuing to expand the body of evidence describing Daybue's long-term impact in the Rett community. There were posters focused on caregiver-reported outcomes and real-world data, which, importantly, continue to align with what we have observed in clinical trials. Additionally, there were analyses evaluating treatment utilization in less commonly studied populations, such as males and older patients. Acadia Pharmaceuticals shared an analysis of our clinical trial data, suggesting that most patients who are going to benefit from Daybue show a response within six months, reinforcing our guidance to providers and caregivers. Together, these data points reflect a growing and maturing evidence base that continues to shape how Daybue is understood and used in the real world.

In the pipeline, both ACP-101 and ACP-204 teams had important meetings in the quarter. In Prader-Willi syndrome, the end of June marked the United in Hope meeting, the joining together of three separate PWS organizations in a combined meeting. Those of you who tuned in to R&D Day will recall that our PWS panel, in part, was live from United in Hope. As we await data out of our Phase 3 trial, we nevertheless are contributing to the knowledge and understanding of PWS, with posters about the experience of patients and families exploring comorbidities and the associated burden. In the Alzheimer's space, I'm also pleased to report multiple ACP-204 presentations at the Alzheimer's Association International Conference held last week in Toronto. This meeting represented a significant step in our public disclosure of detailed data from non-clinical and early-stage clinical studies, supporting ACP-204's attainment to date of its desired profile.

Presented data included the specificity for 5-HT2A and the supported PK profile, indicating a faster time to steady state, support for daily dosing, the lack of QT prolongation, and the ability to dose with and without food. We also shared clinical data primarily focused on the 60 milligram dose across several Phase 1 trials with supportive safety and tolerability profiles to date, including in healthy elderly subjects. Collectively, the data provide support for the potential utility of ACP-204 and key aspects of its target profile. Lastly, I'll touch briefly on ACP-101, where we continue to expect top-line results in early Q4. Just as a reminder, this is a 12-week placebo-controlled parallel group study. That design is important because, if successful, it would allow us to clearly describe for physicians and patients what to expect upon initiating therapy in a Prader-Willi syndrome patient population.

Should the data be positive, we anticipate being in a position to file in the first quarter of 2026. We continue to anticipate that this will qualify as a resubmission with the FDA, with the associated shorter potential review clock, with the potential to do for date in the third quarter of 2026. Now, I'll pass over to Mark for a financial overview of the quarter.

Speaker 0

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.

Speaker 5

Thanks, Mark. As you've heard, quarter two was a quarter of progress and momentum. Our teams are executing with urgency and precision. 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, continuing to build the pipeline through business development, and expanding globally to reach more patients in need. The next major milestone is ACP-101 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 Pharmaceuticals. I'll now open it up for questions. Operator?

Speaker 9

Thank you. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you will need to press *11 on your telephone and wait for your name to be announced. To withdraw your question, press *11 again. Please stand by while we compile the Q&A roster. Our first question comes from Tess Romero from J.P. Morgan. The floor is yours.

Good afternoon, team. Thanks so much for taking our questions. 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? Are there any secondary or other endpoints that you think will matter beyond HQCT? As a follow-up, where are you really most focused from a clinical trial conduct perspective to manage any key risks? Thanks.

Speaker 1

Thanks, Tess. Great question. 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 endpoint and success there. We will be looking at our secondary endpoints, 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 endpoint and sort of key overview of safety and tolerability. 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 robustly keeping on top of how the assessments appeared being performed and whether variability was within our expected ranges.

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.

Speaker 5

Thanks, Liz. Thanks for the question, Tess.

Speaker 9

Thank you for your question. Our next question comes from Ritu Boral from TD Cowen. The floor is yours.

Good afternoon. Thanks for taking the question. I wanted to talk a little bit or ask a little bit about the new momentum in Daybue. Could you tell us what % of patients or new patients specifically came from the community setting? You mentioned the new number of 900 HCP writers. What % or at least movement of those writers were in the community setting on a quantitative basis? I have a Prader-Willi follow-up as well.

Speaker 5

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

Speaker 3

Perfect. Good afternoon, Ritu. Hope you're doing well. 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, went live kind of through May, we're 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 grew to about three quarters of our overall number. That was up from about two-thirds 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. Just as a reminder, roughly 65% of our patients fall outside the direct care of one of the COE centers, one 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 is a nice leading indicator that the new model that we have in place is beginning to pay dividends for us.

Speaker 5

Thanks, Tom. Do you want to ask your one-on-one question, Ritu?

Yes. Just mopping up after Tess's questions, can you talk to how the conduct, specifically dropouts of the Phase 3 Prader-Willi, have gone? Are they within expectations? Are all the DSMB looks for the trial completed, and if the SAP has been finalized with FDA?

Speaker 1

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. 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.

Great. Thank you.

Speaker 9

Thank you for your question. Our next question comes from Sean Lamont from Morgan Stanley. The floor is yours.

Hi. This is Mike Riyad on for Sean. Thank you for taking our questions, and congratulations on the quarter. 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? Given the relative lower prevalence, is it reasonable to expect that this would ever accelerate and doesn't need to? How should we be just thinking about that trajectory? Thanks so much.

Speaker 3

Sorry, Tom here. I'll take that one. Thank you for the question. We're pleased with the steady growth that we've seen over the last three quarters. I think, as we mentioned in the call, to 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 will continue to accelerate as we see the impact of our new customer model. Our goal is to make sure that we have more new patient starts continuing week over week, month over month, and quarter over quarter. 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 it gives us a real sense that we can really continue to grow this brand and take it to new heights. Thanks so much.

Speaker 9

Thank you for your question. Our next question comes from Jason Butler from Citizens JMP. The floor is yours.

Hi. Thanks for taking the questions. 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?

Speaker 5

Hi, Jason. Thanks for the question. I think as we think about our strategy for NUPLAZID, I try to 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. 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 intellectual property litigation because it has a strong momentum for the next sort of two to three years, potentially, depending on how long we continue to invest. Beyond that, 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. For right now, the DTC campaign is certainly paying dividends, as you point out. We're excited about the continued momentum. Indeed, in terms of the MOVE 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. Once a caregiver is aware, they're encouraged to go in and talk to their doctor. It's been a very strong impact to caregivers, and we're excited to continue that. Thanks for the question.

Thank you.

Speaker 9

Thank you for the question. Our next question comes from Brian Abrams from RBC Capital Markets. The floor is yours.

Congratulations on the quarter. Thanks for taking my questions. Just two for me, both on Daybue. As you've expanded the sales force, can you talk a little bit more qualitatively around your learnings from the patients outside of the centers of excellence, just in terms of physician receptivity, number of prescriptions per physician, any early persistency signals, and how well educated the docs are around the titration? 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.

Speaker 5

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

Speaker 3

Yeah, thanks for the question. 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. 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.

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 to COEs. That's purely because they just don't see Rett patients as frequently. As you talk about persistency, we're really pleased with the persistency that we're seeing. As I mentioned on the call, 12-month persistency remains well above 50%. As we also mentioned for the first time, our 18-month persistency, although not yet fully mature, is above 45%. I think that gives us a real good sense that we've kind of reached a nice kind of plateau as we go into the longer-term outlook for the product.

That gives us, with this growing group of patients who are now receiving therapy, a sense that we can continue to grow Daybue to newer heights, as I've mentioned, as we get new patients started.

Speaker 5

Thanks, Tom. Thanks for the question, Brian.

Speaker 9

Thanks a lot. Thank you for your question. Our next question comes from Ami Fadia from Needham. The floor is yours.

Good evening. Thanks for taking my question. I have two quick ones. Firstly, just with regards to NUPLAZID, it continues to remain really strong with the number of sip 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? 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 with regards to patients that are being treated outside the COE setting, if you have that? Thank you.

Speaker 5

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

Speaker 3

In terms of NUPLAZID, yeah, I mean, we're seeing a nice uptick in terms of referrals, MBRXs, and the ongoing TRX volume. I think as you look at the second quarter and kind of the impact that we saw, we were pleased with the fact that our MBRX volume was kind of reflected across all channels. 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, but the fact that we have a group of patients that sit within long-term care, where we also promote, showed continued strength across the breadth of patients that we serve for NUPLAZID. Very pleased with that 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 at IRSF that showed that at 18 months, we had about a 40% persistency rate. 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. I think, again, gives us a real sense that this drug is performing as we've seen in clinical studies. Moving forwards, we don't expect to see any kind of significant deviation versus this very stable kind of plateau that we're now seeing.

Speaker 1

I'll just add on, thanks, Tella. I'll just add on that, you know, in our actual clinical trial experience, we really only have about nine 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 market a drug and coming off of the program. If you look to that nine-month experience, at that point, you've got something like 45% persistency. 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.

Speaker 5

Thanks, Tess.

Speaker 9

Thank you for your question. Our next question comes from Mark Schneyer from Canaccord Genuity. The floor is yours.

Can you talk about discontinuations for Daybue and what you saw in the quarter? Was there any inventory changes that were of any significance for either product? Thank you.

Speaker 5

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

Speaker 3

Yeah, discontinuations, Mark, we were very pleased that we had another quarter where discontinuations remained well below 10%. 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. 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 forwards, 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 answer that question.

Speaker 0

Yeah, thanks for the question. There's nothing to report on in-channel inventory. NUPLAZID's consistent quarter over quarter. 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. The DAYBUE model has always been really a sell-through model.

Speaker 9

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

Speaker 0

Yeah. Our tax, 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. We have about $400 million of U.S.-based activity R&D expense that has been capitalized, and that in the near term will be able to have some accelerating expensing for U.S. tax purposes. In the next year or two, our tax rate will actually go down.

Speaker 5

OB3 is our internal vernacular for one big useful bill, just in case. Thanks, Mark. Next question.

Speaker 9

Thank you for your question. Our next question comes from Ash Verma from UBS. The floor is yours.

Hi. Thanks for taking our question. For NUPLAZID, I know you've outlined that this is a largely Medicare patient population. Roughly by when do you think that it'll be eligible for IRA price negotiation and implementation? Secondly, on the ACP-101, I wanted to ask, is this the same formulation from FedIn that required refrigeration? Do you think that could potentially become a hindrance at all in terms of price daily administration for this patient population? Is there a plan for a room temperature stable variant here? Thanks.

Speaker 5

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

Speaker 0

Yeah. In terms of potential timing for negotiation under the IRA, 2029 would 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'd have a limit on the discount we'd have to offer. It's in the range of 25% to 34% as outlined in the legislation. After that, we'd 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.

Speaker 5

Great. Is the small company the two-year?

Speaker 0

Two years, yes.

Speaker 5

Yeah.

Speaker 1

With respect to ACP-101 and the questionnaire, tell me if there's anything that I didn't catch about your question that I neglect here. We are using the same formulation as Lebo used. An important thing to remember is that part of what we're doing here is a resubmission to the complete response letter. The intent is to provide the new information that FDA requires, which is an additional study to demonstrate efficacy, while changing a few things, if possible, about the overall initial presentation. We have seen that to be acceptable and usable in our clinical trials and 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 product to make them more patient-friendly.

I anticipate that we'll be thinking about that for 101 as well as we do for other things.

Speaker 5

Thanks, Ash.

Speaker 0

Thank you, Tess.

Speaker 9

Thank you for your question. Our next question comes from David Huang from Deutsche Bank. The floor is yours.

Speaker 0

Hi there. Congrats on the quarter and thanks for taking my question. I just want to ask, on ACP-101, can you comment or say anything on the open label extension for the Phase 3 study, like what you're seeing in terms of rollover rate? Would you ever consider adding a randomized withdrawal portion to the plan that I think was used by a competitor with approved products in the market to get that product approved? Thank you.

Speaker 1

Great questions. 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. We think a real advantage of that is that it's going to be able to give a clear, if it's positive and 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. Randomized withdrawal study could be something that we might consider in the future.

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.

Speaker 5

Thanks, David.

Speaker 9

Thank you for your question. Our next question comes from Oi Ear from Mizuho. The floor is yours.

Hi. Thanks for taking our question. This is Leo on for Oi, 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? Maybe, you know, on the heels of the recent R&D day, excitement's clearly growing in the pipeline. Which pipeline programs is the team most excited about?

Speaker 0

Thanks.

Speaker 5

Thanks, Leo. I'm going to ask Tom to comment on how to think about growth in 2026 for both brands, and then Liz to tell us which is her favorite trial in her pipeline.

Speaker 3

Yeah, thanks for the question. Let me start with Daybue. As we've mentioned during the call, we've seen very nice continued growth for the last three 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 impacts 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%. We've still got a significant opportunity here for this brand to continue to grow, and that's our goal through 2026 and beyond, 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.

We can really make sure that we take Daybue to the height that we know it can be. That's our goal for 2026. 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. We believe that sets us very nicely up for 2026. 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.

Speaker 1

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 de-risked 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. There is a lot in our pipeline that we're very enthused about, and I'm not going to pick a favorite child today.

Speaker 5

Maybe I'll just come on top of that with, you know, 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 Pharmaceuticals in terms of potential expansion. You know, we shared at R&D Day that we believe all five of the new products could hit blockbuster potential. We believe three of them have the ability to achieve over $2 billion should they be successfully approved. We're moving into bigger markets with still high unmet medical needs, 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. We're excited for that.

Speaker 3

Awesome. Thanks.

Speaker 9

Thank you for your question. Our next question comes from Tazin Hamed from Bank of America. The floor is yours.

Hi. Good afternoon. Thanks for taking my question. I wanted to ask about whether the ACP-204 study in Lewy body dementia psychosis has started. I think your guidance had been that it's supposed to start soon or this quarter. 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 the company had looked at Lewy body as part of a previous study with NUPLAZID a few years ago? Thanks.

Speaker 1

Okay. The first easy one, which is we do continue to anticipate that the Lewy body study will get started this quarter. It hasn't gotten first patient randomized yet, but we are confident we'll get it in the quarter. In terms of ADP and potential for read-through, 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. There's a relatively small number of patients in that study, roughly 20 patients in the active arm and 20 patients in the placebo arm. There was a marked difference in relapse rate of patients on placebo versus patients who continued on drugs. 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 non-clinical and Phase 1 works that we've done to date. We are anticipating that ADP readout with a great deal of anticipation and feel good about Lewy body and its potential for success.

Speaker 5

Thanks, Elizabeth. Thanks, Tazin.

Speaker 9

Thank you for your question. Our next question comes from Sumat Kilkami from Canaccord Genuity. The floor is yours.

Good afternoon. Nice to see the progress this quarter, and thanks for taking our questions. Could you give us some specifics on how ACP-101 fits into your plans for Rett syndrome relative to your current efforts with Daybue?

Speaker 5

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

Speaker 1

As we think about ACP-101, I mean, I think what originally attracted us to the program was the fact that there are some similarities, mechanistically speaking, to Daybue, and that de-risks it with a potential for a differential penetration from a brain perspective. 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 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. I look forward to providing some additional updates on that at an appropriate time.

Thanks.

Speaker 9

Thank you for your question. Our next question comes from Salvini Richter from Goldman Sachs. The floor is yours.

Speaker 1

Good afternoon. Thanks for taking my question. For Prader-Willi syndrome here, beyond HQCT and CGIS and CGIC, do you plan to evaluate functional endpoints such as hyperglycemia control and weight loss in the Phase 3 trial? What would be a clinically meaningful bar for success in this study? Thank you. 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. 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 think your other question was about things like weight 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. That hasn't been a focus here. We are looking at adverse events and typically at blood profiles. 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 this study, of course.

Speaker 5

Thanks, Salvine.

Speaker 9

Thank you for the question. Our next question comes from Yatin Suneja from Guggenheim. The floor is yours.

Hey, guys. Thank you for taking my question. The question is on 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? I'm 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 you ran with NUPLAZID. Thank you.

Speaker 1

Thank you for the question. As I think about the differences with ACP-204, they kind of go into a couple of different categories. There are the molecule differences, and then there are program design differences. I do think both of those play into what we could be looking at at the ADP study. On a molecule perspective, just hitting on this really briefly, you know, NUPLAZID does have that QT prolongation. It's not significant. It's not clinically impactful. In an elderly and frail patient population, you do need to think about it. It limited our ability to dose range. 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 ACP-204 in our ADP program.

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. The program that we've designed with ADP is very specifically identifying that patient population. It's specifically looking into a patient population that's a little more severe in their psychosis, which we also found to be more responsive. We're biomarker confirming that patient population. If we take all of these things together, we think that 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.

Speaker 5

Thanks, Liz. Thank you for the question.

Speaker 9

Thank you for your question. Our next question comes from Evan Sigerman from BMO Capital. The floor is yours.

Hi. I'm Evan Sigerman. Thanks for taking our question. Back to Daybue, I noticed an improvement in the % 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. Thanks.

Speaker 3

Yeah, I'll take that question. 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 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, 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. I think over time, as they see the benefits of the product and as we lean in more on terms of the efficacy profile, there is more that we can kind of pull through there as we think about Daybue for the long term.

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. I think that this is all being reinforced with our kind of updated customer model and strategy as we think about Daybue moving forward.

Speaker 5

I think just finally, the persistency that we continue to see sort of amplifies that. 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 than we were a year ago. Again, lots of steadiness and now we're driving the momentum into Daybue. Thank you for the question.

Speaker 3

Appreciate it. Thanks, guys.

Speaker 9

Thank you for the question. Our final question comes from Paul Matthias from Stifel. The floor is yours.

Hey there. This is Julian on for Paul. Thanks so much for taking our question and congrats on the progress. I just wanted 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 the SAP while you remain blind." Just curious, you know, what types of modifications could potentially qualify or could be sort of, you know, in the realm of possibilities? Just curious if you could expand on that. I have one quick follow-up as well on Daybue.

Speaker 1

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

Got it. That's helpful. Thank you for clarifying. 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. 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. Thank you.

Speaker 0

Yeah, 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. When we looked at the NUPLAZID range, we just thought it was just too wide, kind of halfway through the year. As we looked 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.

Speaker 5

Thanks, Mark. Thanks, everybody, for the questions. Thank you, Operator. We really appreciate everybody joining us today. We look forward to updating you on our progress next quarter.

Speaker 9

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