Full transcript
**Operator:**
Ladies and gentlemen, thank you for standing by. My name is Krista, and I will be your conference operator today. At this time, I would like to welcome everyone to ACADIA Pharmaceuticals First Quarter 2026 Earnings Conference Call. [Operator Instructions] I would now like to turn the conference over to Albert Kildani, Senior Vice President, Investor Relations and Corporate Development. Please go ahead.
### Q&A Section
**Albert Kildani:**
Good afternoon, and thank you for joining us on today's call to discuss ACADIA's first quarter 2026 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 are Elizabeth Thompson, Ph.D, 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 remarks before we open up the call for your questions. We are using supplemental slides, which are available on our website in the Events and Presentations section. On today's call, both GAAP and non-GAAP financial measures will be discussed, including non-GAAP NUPLAZID net sales and non-GAAP total revenues. The non-GAAP financial measures that are also referred to as adjusted financial measures pertain only to NUPLAZID sales in 2025 and their impact on total revenues. All references to non-GAAP are reconciled with the most directly comparable GAAP financial measures in our earnings press release and slide presentation, which has been posted on the Investors page of the company's website. 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 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.
**Catherine Owen Adams:**
Thank you, Al. Good afternoon, everyone, and thank you for joining us today to discuss our first quarter 2026 results. ACADIA delivered a solid start to the year with total revenue of $268 million in the first quarter, representing 11% year-over-year growth on an adjusted basis. DAYBUE had an especially strong quarter with sales of $101 million, up an impressive 20%, our highest year-over-year growth since the third quarter of 2024, marking an excellent start to the year. We are excited about the successful launch of DAYBUE STIX with strong feedback from both caregivers and health care providers. As announced last month, DAYBUE STIX is now broadly available across the United States, and we're seeing strong early uptake from both new and previously discontinued patients that gives us confidence in our growth outlook. NUPLAZID sales were $167 million in the first quarter, up 6% year-over-year on an adjusted basis. The first quarter performance reflects that some patients were slower to refill than in prior years. We are pleased to report that these refill dynamics have since normalized. Importantly, we saw double-digit referral growth in the first quarter and robust demand growth at 8%, even prior to the expected impact of the recent sales force expansion. I'm pleased to share that we are reaffirming our 2026 net sales guidance for both DAYBUE and NUPLAZID. Looking at our pipeline, we have several significant catalysts on the horizon. Most notably, we are approaching the highly anticipated Phase II readout for remlifanserin in Alzheimer's disease psychosis, which we continue to expect to share results from in the August to October time frame. This represents a key inflection point for our company and could unlock substantial value given the significant unmet medical need in this indication. Additionally, the timing of our Phase III study in Japan for trofinetide has accelerated, and we now expect results in the September to November time frame of this year. I want to remind everyone of the tremendous opportunity we have across our pipeline. We have 4 molecules targeting large markets with a combined full peak sales potential of $11 billion, with approximately $4 billion of that specifically attributable to remlifanserin across the ADP and Lewy body dementia psychosis indications. This underscores the transformative potential of our research and development efforts. With that, I'll now turn the call over to Tom to provide a more detailed insight into our commercial performance.
**Thomas Garner:**
Thank you, Catherine. Let me dive into the details of our first quarter performance. Starting with DAYBUE. I'm pleased to report another excellent quarter with revenue of $101 million, representing 20% year-over-year growth. This was another record quarter for unique patients receiving shipments, highlighting the continued momentum and durability of the DAYBUE franchise. Growth was fueled by robust referral volumes driven by new patient starts, alongside meaningful reengagement of previously discontinued patients following the recent approval and launch of the new powder for oral solution formulation of trofinetide, DAYBUE STIX. During the first quarter, we launched DAYBUE STIX with a focus on centers of excellence to ensure optimal launch execution while gathering valuable real-world feedback. We've been extremely pleased with both the initial uptake and positive experiences we've received from both caregivers and health care providers. Through Q1, we received DAYBUE STIX prescriptions for more than 250 individual patients, demonstrating strong early demand for the new formulation. Notably, nearly 30% of these patients were either treatment naive or restarting therapy, aligning with our expectations and further supporting DAYBUE's growth outlook. In addition, we're also seeing strong interest from existing patients in switching to the STIX formulation. Collectively, this early experience demonstrates how DAYBUE STIX can help retain current patients, bring discontinued patients back into therapy and grow the treated patient population, aligning closely with our long-term growth strategy for DAYBUE. From a patient and caregiver perspective, DAYBUE STIX offers meaningful advantages, including flexible dosing volume, potentially shorter dosing time, a preservative-free formulation, no requirement for refrigeration and enhanced portability. These attributes are resonating strongly with early feedback reinforcing the value of the new formulation, as you can see on this slide. Caregiver response has been particularly positive with more than 80% of those who have tried STIX reporting high satisfaction, complemented by strong endorsement from health care providers across Rett centers of excellence where the product was available through the first quarter. Following the focus launch, we announced in early April that DAYBUE STIX is now fully available in the U.S. We look forward to seeing the continued impact of this broader rollout for patients and caregivers. Outside of the U.S., our global named patient supply programs continue to contribute meaningfully to our growth through the first quarter. The number of patients receiving product through our NPS programs continues to increase over time, providing important access to patients. The recent Delphi expert consensus reinforces DAYBUE's position as the standard of care for Rett syndrome, reflecting broad adoption across centers of excellence and accelerating uptake among clinicians treating Rett patients. This important publication demonstrates that Rett syndrome experts agree that DAYBUE plays a crucial role in patient care, including the importance of initiating treatment early and dosing individualized to the patient's needs. The Delphi publication adds to the growing body of real-world experience supporting DAYBUE, complementing our robust clinical trial programs that support the meaningful impact that trofinetide can make for patients living with Rett syndrome. Taken together, the successful launch of DAYBUE STIX, combined with sustained referral strength and durable patient persistence positions DAYBUE for continued growth through 2026 and beyond. Now turning to NUPLAZID, which delivered sales of $167 million in the first quarter, representing 6% growth year-over-year on an adjusted basis. I'd like to walk through the dynamics behind the quarter and explain why our confidence in full year performance remains strong. Starting at the top of the funnel, physician referral growth was strong at approximately 11% year-over-year, even ahead of the anticipated impact of our sales force expansion, which was completed in the quarter. This level of referral growth reflects continued physician confidence in NUPLAZID, driving strong underlying demand. However, as Catherine noted, first quarter performance was impacted by a temporary increase in patients taking longer than expected to refill their prescriptions. This dynamic emerged in January and extended into early February as refill timing lagged historical first quarter patterns. Importantly, these delays proved temporary. Patients who are late to fill returned in the latter part of the quarter, and we have now returned to normal patterns. Despite the short-term timing impact, NUPLAZID delivered 8% year-over-year demand growth in the quarter, reinforcing our confidence in the full year outlook. As a reminder, our commercial strategy is focused on driving earlier awareness and use of NUPLAZID in the Parkinson's disease psychosis journey through smart, disciplined execution. We're sharpening prescriber reach, improving call quality and maintaining tight segmentation while strengthening field and digital engagement in order to engage physicians earlier and convert strong referral momentum into improved pull-through. Building on this foundation, we expect to realize the full impact of the recent 30% expansion of our customer-facing teams by late 2026 and into next year as we extend these capabilities across a broader target universe. In addition, we anticipate further benefits from our direct-to-consumer efforts. We've recently renewed our partnership with Ryan Reynolds for the unbranded More to Parkinson's campaign, reflecting its strong resonance with patients and caregivers, enabling us to introduce new content and creative to further raise awareness of Parkinson's disease psychosis. Since launching the campaign, awareness of hallucinations and delusions amongst the Parkinson's disease community has increased from 8% to over 30%, underscoring the campaign's significant impact. We're complementing this with refreshed branding creative on nuplazid.com to engage patients earlier in their journey and clearly reinforce NUPLAZID as the only FDA-approved treatment for Parkinson's disease psychosis. I'd also like to highlight a significant milestone for NUPLAZID. This year marks the 10-year anniversary of its FDA approval. Over the past decade, nearly 100,000 patients, along with their families and caregivers have benefited from this therapy. This milestone underscores both the durability of the NUPLAZID franchise and its meaningful impact on the Parkinson's disease community. In summary, NUPLAZID remains firmly on track for another strong year with continued referral momentum, the scaling impact of our expanded sales force and ongoing market development supporting our path towards approximately $1 billion in annual sales by 2028. And with that, I'll now turn the call over to Liz to provide an update on our pipeline developments.
**Elizabeth Thompson:**
Thank you, Tom. Before turning to pipeline updates, I want to briefly address the retirement announcement we shared last week. For personal reasons, I've decided to retire by year-end. But while we seek the right next head of R&D, I remain fully engaged in driving our pipeline forward. We will ensure continuity through this transition, including supporting the upcoming Phase II readouts and early Phase III planning for remlifanserin. With that context, I'll now walk through the key R&D progress for the quarter. I'm pleased to share updates on our pipeline, which continues to offer meaningful opportunity with real momentum building across multiple programs. Across our 8 disclosed programs, we continue to anticipate initiating 5 additional Phase II or Phase III studies by the end of 2027, demonstrating the breadth and depth of our development portfolio. Most recently, we successfully initiated our first-in-human study of ACP-271 in healthy volunteers, and I'm pleased to report that the study is going well to date. We continue to advance enrollment across several key studies. Our Phase II study of ACP-211 in major depressive disorder is progressing as is our Phase II study of remlifanserin in Lewy body dementia psychosis. And of course, both of these programs represent significant opportunities to address substantial unmet medical needs. Looking ahead, we currently anticipate reporting 4 Phase II or Phase III study readouts by the end of 2027. And of course, the closest to these is the top line results from our Phase II study of remlifanserin in Alzheimer's disease psychosis. The Alzheimer's study is still enrolling, and the enrollment dynamics continue to support our expectation for top line results in the August through October 2026 time frame. As a reminder, throughout the study, we focused on ensuring our patient population has biomarker-confirmed Alzheimer's disease, which we think could be an important component of both technical and regulatory success. We're excited for this readout and what it could mean for the future of the company if successful. But most importantly, as a step towards relief for the patients and families affected by this challenging condition. Turning to regulatory and international developments. The trofinetide reexamination process in Europe remains ongoing, and we continue to expect that process to conclude by late June. We remain focused on working closely with European regulators to address their questions and support the positive benefit-risk profile of trofinetide for patients with Rett syndrome. In Japan, enrollment in our Phase III trial with trofinetide has been progressing exceptionally well, and I'm pleased to share that we now anticipate completing enrollment this quarter. This accelerated time line positions us for top line results in the September through November time frame this year, which represents an earlier completion than we previously anticipated. Now as a reminder, this is a small study that was designed with regulators to provide descriptive information on Japanese patients receiving trofinetide. We expect this study to provide the remaining new data needed for our Japanese filing package, which will rely largely on the LAVENDER trial to establish trofinetide's efficacy and safety with an expected regulatory submission in 2027. These pipeline developments underscore our commitment to advancing innovative treatments across neurological and rare diseases, and we look forward to sharing more updates as these programs continue to progress. And with that, I'll turn the call over to Mark.
**Mark Schneyer:**
Thank you, Liz. I'll now walk you through our first quarter 2026 financial results. Starting with our revenue performance. Total revenue for the quarter was $268 million, up 11% compared to adjusted total revenue in the first quarter of 2025. NUPLAZID generated $167 million of net product sales in the first quarter, representing 6% growth year-over-year on an adjusted basis. As Tom discussed, we are very encouraged by the strong demand growth and referral growth in the quarter, which we saw even before the anticipated impact from the field force expansion that was completed in the quarter. The gross to net adjustment for NUPLAZID in the quarter was 22.1%. As stated in our press release, NUPLAZID year-over-year growth metrics are derived by comparing our Q1 2026 GAAP NUPLAZID net sales to our Q1 2025 non-GAAP NUPLAZID adjusted net sales. DAYBUE delivered strong performance with $101 million in net sales, up 20% year-over-year. Our DAYBUE results reflect the robust momentum Tom described in both the U.S. market and through our international programs. The gross to net adjustment for DAYBUE in the quarter was 25.8%. Turning to our operating expenses. Research and development expenses were $76.9 million compared to $78.3 million in the first quarter of 2025. Our SG&A expenses were $171 million compared to $126.4 million in the first quarter of 2025, reflecting our continued investments in our commercial franchises with increased marketing investments for NUPLAZID and the expanded field footprint for both NUPLAZID and DAYBUE, which both took place after the first quarter of 2025, which is an important consideration in any year-over-year comparison. Our cash position remains exceptionally strong with $851 million at the end of the first quarter as compared to $820 million at the end of the fourth quarter. This increase reflects our positive operating cash flow generation and positions us well to execute on our strategic priorities. Moving to guidance. I'm pleased to reaffirm our full year 2026 guidance for net sales and expenses. In terms of quarterly progression, we expect total revenue to be back-end loaded as the year progresses with a greater sales contribution from both brands in the second half of the year, driven by the expected productivity ramp from our expanded NUPLAZID field force, coupled with broader availability and adoption of DAYBUE STIX. With that financial overview, I'll turn the call back to Catherine for her closing remarks.
**Catherine Owen Adams:**
Thank you, Mark. As we wrap up today's call, I want to highlight the key milestones and catalysts that make 2026 such an exciting and potentially transformative year for ACADIA. First and foremost, we're approaching our highly anticipated top line results for remlifanserin in Alzheimer's disease psychosis, which we expect to report in the August to October time frame. This represents the most significant near-term catalyst for our company with the potential to unlock tremendous value and address a massive unmet medical need affecting millions of patients and their families. The ADP market represents a substantial opportunity with no currently approved therapies and successful results could position remlifanserin as a cornerstone therapy in this underserved patient population. We also anticipate top line results from our Japan Phase III trial with trofinetide later this year, which could establish an important new market for DAYBUE. This accelerated time line reflects strong international engagement and our commitment to bringing innovative treatments to patients worldwide. Importantly, as we head into these upcoming data readouts, while Liz has announced her intention to retire at the end of the year, we are grateful that she will continue to lead R&D to provide continuity and leadership while we look to find a strong replacement. Beyond these clinical and regulatory milestones, we have a strong commercial foundation. And we're pleased to reaffirm our 2026 financial guidance for total revenues of $1.22 billion to $1.28 billion. Furthermore, our cash balance of $851 million provides us with significant strategic flexibility, enabling us to pursue business development opportunities, including potential acquisitions, licenses and partnerships that could complement our existing portfolio and further accelerate our growth trajectory. We remain actively engaged in evaluating opportunities that align with our strategic focus on neurological and rare diseases with significant unmet need. Throughout all of these initiatives, we remain steadfast in our mission to turn scientific promise into meaningful innovation for underserved communities. Every program in our pipeline, every commercial initiative we undertake and every strategic decision we make is guided by our commitment to bring life-changing treatments to patients and families who need them most. The combination of our strong commercial performance, robust pipeline and solid financial foundation positions ACADIA exceptionally well for both near-term catalysts and long-term sustainable growth. We're excited about the opportunities ahead and look forward to sharing our progress with you throughout the year. And with that, we're happy to take your questions. Operator?
**Operator:**
[Operator Instructions] Your first question comes from Tessa Romero with JPMorgan.
**Tessa Romero:**
So I wanted to ask a pipeline one here. So where are you more precisely in terms of enrollment of the Phase II RADIANT study of remlifanserin in Alzheimer's disease psychosis? And how confident are you in your time line from August to October of this year? When might you see the last patient in? And then second question is just how is enrollment going in your Phase II ILLUMERA study in Lewy body dementia psychosis? And what is the right way to think about the potential time line to data there as well?
**Catherine Owen Adams:**
Thanks. I'm going to ask Liz to take us through the time lines for remlifanserin.
**Elizabeth Thompson:**
Sure. So Tessa, thanks for the question. So first off, for the ADP program, we continue to feel very good about that August to October time frame. And the study is still enrolling, but we are getting to the last phases of enrollment. So we feel confident about that time line. That said, I'm not yet able to narrow that any further than what we have right now. As we look at Lewy body, I'm pleased with the enrollment progress that we have there. I don't think we've yet shared publicly what our expectations around the end are. We want to get a ways into enrollment. So I do look forward to sharing more about that in the future. But so far, pleased and on track with what I was hoping for.
**Operator:**
Your next question comes from the line of Ash Verma with UBS.
**Ashwani Verma:**
So maybe just on this upcoming Phase II study, I know you mentioned the biomarker-based selection for confirmation of the Alzheimer's patients as opposed to just looking at the clinical presentation. Can you help us explain a little bit why is that critical for clinical trial execution? And just in the real-world setting, I know patients are typically not diagnosed based on the clinical presentation and imaging -- sorry, they are diagnosed based on clinical presentation and imaging and not necessarily biomarker confirmation. So how does that inform the applicability of the results to real world? And then secondly, just on ACP-204. So I mean, NUPLAZID has a black box warning for this increased mortality in elderly patients. Given that this is kind of a connection of that, would the molecule still put the black box warning if it comes to the market?
**Catherine Owen Adams:**
All right. Thanks, Ash. Some comprehensive questions to get to. So let's start at the top and go down.
**Elizabeth Thompson:**
There was a lot in there. I was madly writing down. So hopefully, I captured everything. So in terms of the biomarker basis, I think this has been a really interesting thing to watch in the Alzheimer's field with a number of years back, there was the idea of biomarkers being part of a clinical trial basis way of thinking about diagnosis. And at this point, it actually is considered part of the diagnostic pathway for Alzheimer's. I fully anticipate by the time we would make it to FDA with our potential package for remlifanserin that there would be an expectation that Alzheimer's disease is a biologically confirmed disease. And so we've been -- we put this in place to try to future-proof the program that we have. And I think that probably touches a little bit on your point about real world. I think that the real world is starting to move that way as well. So we think that this has an important component of regulatory success. I should note, it may also have a potential opportunity for improving technical success. There is a possibility that this helps you be more confident that the patient population you have is truly Alzheimer's and that there's less heterogeneity in that patient population from a response perspective. So we think it's important on both aspects. Finally, to your point about the black box warning it's a really great question. There was an FDA workshop probably about 1.5 years ago at this point. And one of the discussion points was about the black box warning and for future agents, what kind of data might be necessary to help FDA make data-based decisions on individual agents. So we attended that eagerly, learned from it and have taken into account feedback that we got both through there and through other discussions about the kind of information we need to collect to be able to let FDA make a specific decision on remlifanserin and whether it does or does not warrant such a box warning. So right now, I don't know. But we know the data we need to collect, and we do think that there is good reason to think that this could be a path forward without a black box, but it's going to depend on the data at the end of the day.
**Operator:**
Your next question comes from the line of Ritu Baral with TD Cowen.
**Ritu Baral:**
I've got some more remlifanserin questions as well, extending from clinical into commercial. One, as we think about that Phase II data that's coming, what should our expectations around either effect size or delta on the SAPS-H+D? Is there an accepted minimal clinically important difference here? And what frames success on a statistical level? And then as we look at our market model, just given the recent competitive approval Alzheimer's agitation drug, how should we be thinking about differential diagnosis between the two indications, accurate diagnosis and sort of decision -- treatment decisions between the two?
**Catherine Owen Adams:**
With all the interest in remlifanserin. So I'll ask Liz to kick that off and then maybe Liz and Tom can both talk to the market a little bit as well.
**Elizabeth Thompson:**
Yes, absolutely. So in general terms of what we should all be looking for and what defines Phase II success for us as we are walking into this readout, there are a few things that I'm looking for. I mean the main thing really with any Phase II is what you're looking for is Phase III enabling data. You're looking for information that helps you know what to do in a Phase III, any modifications you may need to make, et cetera. Beyond that, I'll be looking for continued information that suggests that remlifanserin is delivering results that are consistent with our TPP. We're not going to know all of those definitively coming out of Phase II, and there will be some things that we already feel pretty good about, but I'll be looking -- we want to make sure that we've got something that can be dosed once a day that can be done easily with respect to conmeds, with respect to food, anything that makes it easy for patients to take their drug. We are, of course, looking for efficacy. We'll be pleased with an effect size that's in line with what we're powered for, which is a 0.4 or moderate effect size. We'd be pleased with safety that looks similar to the pimavanserin profile. And this part, of course, we definitely won't be able to definitively answer out of Phase II, but continued data that suggests that there's no deleterious impact on movement, on cognition, which from the overall pimavanserin data set, we do feel good about. And hopefully, we'll get some directional sense there. To the question about MCID on SAPS-H+D, that's not a well-established one at this point. Part of what we would be doing for a dossier that would go into FDA eventually is establishing that MCID based in part on the Phase II data that we have. We are, however, also looking at, in addition to just the delta, some responder levels those who have improved by at least 30%, those who have improved by at least 50%, which we think help contextualize the meaningfulness of those results. And then I think there was also a question about the recent Otsuka approval in agitation. I'll just briefly say we're always happy to see more options for patients. Alzheimer's disease is a complex disease with many manifestations that are really profoundly impactful for patients and their families. What I think is important to keep in mind is that we always did envision as we looked at our business opportunity for remlifanserin that there is a potential competition, particularly including agents that would be approved for agitation and that there are distinctions between agitation and psychosis. Agitation is complex. There are a lot of things that can play into it. It can stem from pain. It can stem from cognitive challenges, and it can stem from psychosis. For remlifanserin, we are optimistic. There is some pimavanserin data suggesting that in those patients who have significant agitation and significant psychosis, if their psychosis improved, it did seem to suggest that their agitation improved as well. So there may be an aspect of agitation, but I wouldn't expect that we would have impact on pain-induced agitation, et cetera. And sort of on the flip side, if you look at molecules that are effective in agitation, there's not necessarily a good reason to believe that they can be impactful on any of the things that are actually driving that agitation like psychosis. I mean, actually, if you look at de -- goodness, if you look at various components, they actually can be associated with an increase in psychosis. So taken together, I think we think that there's ample room for multiple players in this space and that effective players in agitation are going to be meaningfully impactful for the opportunity we see with remlifanserin.
**Operator:**
Your next question comes from the line of Yigal Nochomovitz with Citigroup.
**Unknown Analyst:**
This is Caroline DePaul on for Yigal. So switching gears to DAYBUE STIX, you disclosed that 30% of patients are either treatment-naive or returning after previously discontinuing the liquid formulation. Just wondering how this compares to your expectations for the launch? And do you still expect to capture 400 or over 400 incremental patients with STIX? And if so, what is the anticipated cadence for capturing those patients?
**Thomas Garner:**
Perfect. Thanks for the question, Caroline. So let me provide some additional color on your question just regarding kind of our expectations and performance through the first quarter. So just as a reminder, our launch strategy was very focused on COEs through the first quarter. So we've not yet gone broadly into the community. However, we have been very, very pleased with the initial uptake that we've seen. So the 250 patients that -- or the 250 prescriptions that we had, we actually shipped 220 of those in the quarter, which, again, I think just talks to the fact that we're able to get this drug into patients' hands quickly. In terms of how it's doing versus expectations, we would actually say that the ramp in terms of speed that we're seeing here is actually going quicker than we anticipated. I mean I think the 450 that you referenced is what we had spoken about at JPM, we still think that, that holds true. And we had modeled that over a 3-year period, which would basically get us to STIX being the dominant SKU by the end of that time. I think we may end up in a situation where it goes slightly quicker than that. But again, I think the 30% that we're seeing is broadly in line with our expectations. And we're encouraged by the fact that it's not only returning patients but naive patients as well, supplemented by the fact that we're also seeing significant interest from patients already receiving the liquid formulation. So I think taken together, it gives us real optimism for the future of DAUBUE more broadly and the role that STIX can really play in fueling that growth.
**Operator:**
Your next question comes from the line of Brian Abrahams with RBC Capital Markets.
**Brian Abrahams:**
Maybe going back to remli. As we think about remli and what could generate success in the upcoming study, I guess, can you -- what exactly are the key differences on potency, saturation and receptor binding properties that you might expect from 60 milligrams of remli as compared to the marketed and current and previously tested dose of pimavanserin? Or should we think about this more as being just having a more homogenous population in a study design that leverages prior learnings and uses a more sensitive endpoint?
**Elizabeth Thompson:**
It's a great question, and I think we can think of it as potentially a little bit of both. What we do know from our prior pimavanserin work is that if you look over the exposure response range, there does seem to be a suggestion that at exposures that are higher than what you can get to with the currently marketed dose of pimavanserin, you are able to get greater efficacy. So there is at least a good reason to think that we're able to push to higher exposures as we are with the 60-milligram dose, we may be able to get further up on that exposure response curve. That said, even if that doesn't play out exactly the way that we're expecting it to, I do think that having a study design that is really specifically focused in on the Alzheimer's population. I think that's first and foremost, our learning from regulatory in times past is that they're going to need data that are specific to that population, which as I mentioned before on this call, we're going the extra step in biomarker confirming. That's going to be important. And we think that it's going to be -- we've done other modifications of things like trying to make sure that we have a slightly more severe baseline population in terms of their psychosis based on pim data that suggested you get better responses there as well as the fact that we're looking at endpoints that we think SAPS-H+D as well as other things that we have in our study like the NPIC that we think may be better suited to being able to distinguish differences than the NPI-NH that we used way back in the day in our Phase II trial. So I think it's a little bit of all of the above.
**Operator:**
Your next question comes from the line of Tazeen Ahmad with Bank of America.
**Tazeen Ahmad:**
How are you thinking about the read-through from the Phase II study for Alzheimer's onto the Lewy body study itself? Going back to a few years ago when a similar study was done, pima did seem to show a pretty strong signal there. So regardless of how it turns out for Phase II for Alzheimer's, how should we be thinking about the derisking for Lewy body for next year?
**Elizabeth Thompson:**
Love that question, and I love what's baked into it. I agree that while it's in small numbers of patients, I've always found the data in pimavanserin in Lewy body to be fairly striking. In the HARMONY study, just for people who are a little less familiar than you are, the withdrawal study, there were about 20 patients per arm with Lewy body. And of those who had their treatment withdrawn about 55% of them relapsed and those who continued on only about 5% did. So striking while in a small number of patients. So that actually, to your point, regardless of how the ADP study turns out, and we do have high hopes for that based on all the things that I just talked through in the last few answers. But regardless, I think we remain very optimistic about the Lewy body study. I think the one thing that could be a read-through would be something significant from a safety perspective. I'm not currently anticipating that. But obviously, we only know that when we get the data at the end of it. Thus far, though, we're optimistic about Alzheimer's. But regardless of that, I think we're very optimistic about Lewy body.
**Catherine Owen Adams:**
Can you talk a little bit about how we think the formulation of remli might suit the Lewy body patient as well in terms of the fragility in the dose set?
**Elizabeth Thompson:**
So we do think that, obviously, the Lewy body patient population, both of these patient populations, obviously, are complex and with significant needs. Lewy body, generally speaking, is, I think, accepted to be a little bit more frail, and we think it is even more important to have something that is very safe and something that is very easy to take, which again has been something we've really prioritized with remlifanserin.
**Catherine Owen Adams:**
We look forward to seeing you next week.
**Operator:**
Your next question comes from the line of Marc Goodman with Leerink.
**Marc Goodman:**
Yes. My question is on NUPLAZID. And if we had a delay in patients that you know are kind of getting on therapy, but they were delayed from January and part of February, why would we not have a great second quarter that kind of makes up for that low first quarter because your guidance is kind of all this back-end loaded discussion. So I think you understand the question.
**Catherine Owen Adams:**
Yes. So let me kind of address that initially. I think we are expecting a strong second quarter, Marc. The dynamics that Tom referred to are definitely showing that from the current sales force. When we talk about the back end of the year, it's really the impact of the additional expansion. But let me just hand it over to Tom to sort of talk you through those specifically.
**Thomas Garner:**
Absolutely. So thanks for the question, Marc. So as a reminder, we executed the 30% expansion of our sales team in Q1. That team has been in the field for now around kind of 6 weeks by the time we got to the end of the quarter. So we're really not seeing the full quarter impact of the productivity ramp that we anticipate seeing. You are correct. We saw a very nice increase in referral volumes, 11% year-over-year. We saw good demand growth. But we did have this issue just in terms of late returning patients through the quarter, which was kind of further impacted by the normal Q1 dynamics you would expect to see for Medicare population. So moving forward, we anticipate that the productivity ramp will continue to impact us moving into the second quarter and beyond. We're continuing to push on the DTC efforts that I mentioned, both in terms of our unbranded, more Parkinson's and branded efforts. And in addition to that, all of the additional work that we're putting into place just around the expanded target universe that we're now going after. As a reminder, we've now increased to a target universe of just over 10,000 HCPs. We believe that tackling that is going to lead to significant uptick for the brand more broadly because we still have plenty of share growth that we can continue to drive over the coming quarters. In terms of the question just guidance, I don't know if Mark wants to add.
**Mark Schneyer:**
The one thing I'd add -- thanks for that comment. Just from a financial perspective, it's more late to refill of existing patients, not new patients. So those patients that were late to refill essentially missed the script in the year. So it's kind of a lost revenue. The good thing, though, is it's not a lost patient. Those patients have come back based upon our historical numbers and have refilled in the quarter. So it positions us strong going forward, but not necessarily just a rebound of recouping what was missed in January and early February.
**Operator:**
Your next question comes from the line of Jack Allen with Baird.
**Jack Allen:**
Just two quick ones from us. On remli, in the ADP study, this is a placebo-controlled study, and the FDA has started to put out a lot of guidance around potentially allowing for filings on single trials. I just wanted to hear any thoughts you had on the potential to file on positive results in a placebo-controlled setting for remli. And then briefly on DAYBUE, it seems like you're making a lot of progress with the STIX formulation, and you have thrown out the $700 million kind of aspirational sales number for 2027 longer-term guidance there. I'm curious to what extent you factor in gene therapy in Rett into that longer-term guidance as well?
**Catherine Owen Adams:**
Do you want to take this?
**Elizabeth Thompson:**
Sure. So great question about the single trial. And obviously, we've had lots of discussions about this. What I'd say is, thus far, I think we're all still waiting for a guidance document around this to have a better understanding of the thought process. It's not clear some of the things which I anticipate will likely still apply things like the size of the safety database. And those are the types of considerations that make it such that my current expectation is that our base case assumption, which is that we need our Phase II and we need Phase III is going to be what we're going to need at the end of the day. I do want to note that, obviously, if we were to see really striking results in this trial, we certainly would go have a conversation with FDA to explore what possibilities exist. But right now, again, our base case assumption is that we are going to need more than the single study just purely based on the size of exposure that we would have.
**Catherine Owen Adams:**
Just a top line basis, I think we continue to be very confident in our $700 million guidance for 2028. We have, of course, thought about competitive dynamics through that period, including gene therapy. Tom, do you want to add anything else that the team has been thinking through?
**Thomas Garner:**
Yes, absolutely. So again, very pleased with the initial progress that we've seen with STIX. Obviously, this is complementing what we've already been driving over the last year with liquid as well as we continue to expand into the community. I think it's worth reminding everyone that our penetration for DAYBUE across both COEs and community physicians is still in like the 40% mark. So we still got significant headroom for growth for this brand, and we believe with STIX, we can capture both naive and restart patients who may have stopped. And as a reminder, we have around 1,000 patients who have tried DAYBUE, but are no longer continuing treatment. We believe that we're going to be able to reengage those, and we've already seen that through the first quarter. As it relates to gene therapy, as we mentioned on the call, we've also been very pleased to see the Delphi consensus published, which clearly positions DAYBUE as standard of care for patients living with Rett syndrome. Our view is that I think it will be good news to have more treatments available for the Rett disease for the Rett syndrome population. I think we have to wait and see what the data actually tells us as the gene therapies come to the fore, and we're going to be interested to see how that plays out. But irrespective, we believe that DAYBUE will have a role to play across all of these patients moving forward, whether gene therapies exist or not. So again, as Catherine said, we feel really good about the $700 million that we stated by 2028.
**Operator:**
Your next question comes from the line of Ami Fadia with Needham.
**Ami Fadia:**
My question is on remlifanserin. With regards to the powering of the study, I think you mentioned that you're looking for a 0.4 point change. What is the minimum effect size that you need to see for the study to be statistically significant? And then as we also are expecting data from Cobenfy study, where they'll be looking at the endpoint of NPIC, when you give us the top line data readout, would you be providing NPIC data? And at what time point is that being measured? Just trying to get a sense of how will we compare data across trials just to sort of understand the competitive profile for this product when the data reads out?
**Elizabeth Thompson:**
Well, I always feel like I need to start with saying, you need to be careful in cross-study comparison. in this case. I think an important thing that I should note is that NPIC was an addition to our study after it had gotten started. It was actually one of the earlier things that I did in my tenure here. And accordingly, we don't -- we will not have NPIC data on all patients who are participating in the Alzheimer's study. So we think that this is going to be important in the Phase II Alzheimer's study, sorry, I should be clear there. We think this is going to be important information, but I don't know that I would anticipate it would be, for example, part of a top line result. It is an exploratory endpoint with a subset of patients. In terms of powering expectations, so we are powered at 80% for an effect size of 0.4. So you can imagine there's a little bit of flex around that with scenarios that could still be statistically significant, but that's generally what we're looking for.
**Operator:**
Your next question comes from the line of Sean Laaman with Morgan Stanley.
**Katherine Delahunt:**
This is Katherine on for Sean. We had another one on DAYBUE STIX. As adoption scales, can you just provide some color if you expect any meaningful change in persistency versus the liquid formulation? Or is the primary benefit improved front-end initiation and reduce early friction? And then just as a quick follow-up. I think you mentioned about 1,000 patients have previously tried DAYBUE. Can you share more about your strategy to reengage these patients?
**Thomas Garner:**
Absolutely. So let me take that for you, Katherine. So starting with persistency. What I would say is we are monitoring this very, very closely because as you would imagine, if we can improve persistency further over and above what we're seeing with liquid, obviously, that would be very advantageous for us. Just as a reminder in terms of the latest data that we have, just regarding persistency with the liquid formulation, at 12 months, we are now north of 55% remaining on treatment through 12 months, and we're retaining about 50% of patients through 18 months. So persistency for liquid actually continues to improve over time. And the latest data that we have is that 74% of our active patients have actually been on treatment for 12 months or longer. So we continue to be pleased with just the growing group of like persistence -- persistent patients who are continuing to see benefit with DAYBUE. STIX, to your question, we believe it can help in terms of initial friction. Obviously, there is some significant advantages that we believe exist that go beyond the liquid formulation. But as it stands at the moment, it's probably too early to be definitive as to how STIX will perform in the real world in comparison to liquid, but we will be sharing more detail in due course.
**Catherine Owen Adams:**
Do you want to talk to the 1,000 patients then how many of those we think might be up for grabs?
**Thomas Garner:**
Yes, absolutely. So as you think about the 450 patients that we spoke about earlier on in the year and you kind of break that down, we think that roughly 3/4 of those would be naive to treatment and the remaining quarter would be restarts. If you look at what we're seeing so far, through Q1, it's roughly a 50-50 split of that 30%. So we're seeing both naive. We're also seeing returning patients. But as I mentioned on the call, we're also seeing significant interest from existing patients receiving the liquid formulation in switching to STIX. So taken together, that's where we are. And just to close this one, the momentum that we saw in Q1 actually has continued into Q2 as we've gone broader into the community. So again, excited to share more details in due course, but we're very pleased with the initial uptake of STIX.
**Catherine Owen Adams:**
I think Q2 will be a much more descriptive story about STIX and the types of patients we're seeing, but we look forward to sharing more then, Katherine.
**Operator:**
Your next question comes from the line of Evan Seigerman with BMO.
**Malcolm Hoffman:**
Malcolm Hoffman on for Evan. Asking about STIX again. I just wanted to see if there was any specific stocking for the STIX formulation this quarter. And then also, I want to get a sense of how you can ensure patients proceed with refills for the STIX formulation to kind of continue the strong momentum we've seen in this quarter. Appreciate it.
**Thomas Garner:**
Perfect. Yes, happy to take that,. So first question in terms of stocking, what I would say is very similarly to what we see with liquid. We supply everything through a single specialty pharmacy, and it really is on a patient-by-patient basis. So there is very limited stocking that we are anticipating or have seen. And then in terms of refills, as I mentioned, of the 250 prescriptions that we actually had in the quarter, over 220 were actually filled. So we're not seeing any issues as it relates to payers or formulary issues on the whole. We're actually seeing it seems to be very smooth and in line with our expectations, which again is a nice proof point that the strategy that we've employed here in terms of a limited launch has worked well for us.
**Operator:**
Your next question comes from the line of Rudy Li with Wolfe Research.
**Guofang Li:**
Just a quick follow-up for LBDP trial. So how will these two endpoints being measured in the ADP trial help inform the benefits in LBDP, which is measuring a different endpoint of SAPS-LBDP? And to what extent their components overlap?
**Catherine Owen Adams:**
I think it was a little bit difficult to hear some of that Rudy, but I think it was to do with the different measurements of endpoints in ADP and LBD and tau versus maybe the alpha-synuclein view of biomarkers. Okay.
**Elizabeth Thompson:**
Thank you. I missed a bit of it appreciate it. So first off, I guess, a couple of important things with respect to the biomarker considerations. There are a number of more established biomarkers at this point that are considered to support the Alzheimer's diagnosis. And so we are actually requiring a biomarker confirmation for -- of the diagnosis for entry into Alzheimer's. The Lewy body field is in a much more exploratory phase. And so we are including an assessment of alpha-synuclein, but it's not a requirement to get into the trial. It's a thing that we think is going to help inform us in terms of potential future trial design and also hopefully contributing to the science. In terms of the endpoint, there is a fair amount of overlap between the SAPS-H+D and the SAPS lewy body. They are both derived from the overall SAPS scale and are a similar but not exactly the same subset of attributes. The SAPS Lewy body, in particular, was based on those aspects that we saw in the PDP and the pimavanserin PDP trial that seem to be most impacted. So that was the driver behind that, but a lot of overlap between those two endpoints.
**Operator:**
Your next question comes from the line of David Hoang with Deutsche Bank.
**Samuel Beck:**
This is Sam on for David. Back to DAYBUE, is there anything else that you're able to share on the prescribing penetration dynamics in the quarter as it relates to the community setting versus centers of excellence? And as a follow-up, noting that the STIX formulation was initially launched in centers of excellence. How should we be thinking about the impact of that formulation in terms of how you think it would resonate prescribing in the community through the rest of the year in the future?
**Thomas Garner:**
Absolutely. So happy to take that question, Sam. So as you would imagine, given our strategy for DAYBUE STIX is really focused on COEs at launch, we did actually see an increase in terms of the number of prescriptions or the overall volume of prescriptions that was coming from COEs in the quarter. So I think we were at roughly 79% was coming from the community in the quarter. -- from the COE versus a lower number from the community. And I think that, again, that's just reflective of the fact that there's been this significant excitement amongst the community around STIX. As you think about kind of the penetration that we have, which again, we've spoken about in the past, we still have significant opportunity. So our penetration within COEs, even with STIX is around 60%, our penetration in the community currently sits at around 28% before the launch of STIX. Of note, both of those have grown significantly over the last year. Most importantly, though, our penetration within the community, which, as a reminder, is about 65% of the overall available volume has grown by about 7% on an actual basis over the last year. So again, I think a nice proof point that the strategy that we've employed to kind of focus on COEs, but expand our reach into the community and STIX is very much going to be a part of our strategic road map there is working for us, and that's what's giving us real confidence in the outlook for DAYBUE for this year and moving forward.
**Operator:**
Your next question comes from the line of Yatin Suneja with Guggenheim.
**Yatin Suneja:**
Just a quick one on the reexamination process happening in Europe. Could you just talk about where you are? What do you expect to learn from the process there on trofinetide?
**Elizabeth Thompson:**
So the reexamination process, there are a few points along the way. There is the original intent to request reexamination. We did that very shortly upon receiving the original negative opinion. There's submission for -- there's assignment of new rapporteurs, which has occurred. There is -- my voice is going today. There is submission of the ground for reexamination, which we have completed. We anticipate an upcoming SAG meeting, and then there may or may not be an oral examination meeting. So we are just past the submission of our ground for reexamination.
**Operator:**
Your next question comes from the line of Paul Matteis with Stifel.
**Julian Hung:**
This is Julian on for Paul. Really quickly on BD, just curious if anything has changed and how you may be prioritizing external innovation versus internal, especially with the announcement disclosed last week elsewhere. Also just curious on -- do you plan on disclosing total number of shipments at all moving forward? I know it's something that you disclosed in 4Q. And I know you said there was a record number this year, but I just want a clarification on that.
**Catherine Owen Adams:**
I'll get the team a rest from answer and give Liz the rest and tackle both of those. So in terms of BD, as we've stated, we remain very active and focused on our BD strategy. As you pointed out, we do have a very rich internal pipeline and our late stage is certainly looking great in the next 2 years. But obviously, we're managing this for the longer term, and we're really focused on kind of two areas really right now. One is later-stage assets that we could bolt on to our current commercial franchise, which Tom is leading with such great success. And so we're looking there. But we're also looking at continuing to refresh our early-stage pipeline, which Liz and her team are managing. So those kind of our two main areas of focus right now. We have a lot of ability to flex with our balance sheet, and we know that it's a very competitive process. We are actively involved in processes, and we continue to look for the right fit for ACADIA. We're not under any particular pressure right now, but we are looking for strong fits for our business moving forward to drive that long-term value and growth for our shareholders, but also more importantly, the patients that we aim to serve. In terms of the shipping, we did commit to kind of moving now towards financial dollar top line. We feel after 3 years of launch that sort of specific patient level metrics on shipping to DAYBUE is probably not the right way to assess the brand. We will continue to give clarity like Tom has to say on the STIX dynamics, you can see that playing forward. But in terms of patients shipped, we're not going to be sharing that anymore, but it just does continue to grow, and we're very confident again in our full year forecast for both brands, and thank you for the question.
**Operator:**
Ladies and gentlemen, that does conclude our question-and-answer session. And I would now like to turn the conference back over to Catherine Owen Adams for closing comments.
**Catherine Owen Adams:**
I just like to thank everybody for the great questions today and the team here for answering them and specifically Liz for all the great answers on remlifanserin. We're very excited about the next few quarters for ACADIA, both with our commercial brands, but also obviously, the top line results of remlifanserin. And we look forward to continuing to discussing with you and to our conferences in the next coming weeks. Thanks again for your interest in ACADIA today.
**Operator:**
Ladies and gentlemen, this does conclude today's conference call. Thank you for your participation, and you may now disconnect.
