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Date

Wednesday, May 6, 2026 at 4:30 p.m. ET

Call participants

  • Chief Executive Officer — Catherine Owen Adams
  • Chief Commercial Officer — Thomas Garner
  • Executive Vice President, Head of Research and Development — Elizabeth Thompson, PhD
  • Chief Financial Officer — Mark C. Schneyer
  • Vice President, Investor Relations — Albert Kildani

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Takeaways

  • Total revenue -- $268 million, reflecting 11% year-over-year growth on an adjusted basis.
  • DAYBUE net sales -- $101 million, representing 20% growth year over year and highest annual growth rate since 2024.
  • DAYBUE STIX launch -- More than 250 prescriptions written, with nearly 30% of patients being treatment-naive or returning from discontinuation.
  • NUPLAZID net sales -- $167 million, achieving 6% year-over-year growth on an adjusted basis.
  • NUPLAZID demand metrics -- 11% rise in physician referrals and 8% demand growth year over year, as reported ahead of the finalized sales force expansion.
  • Gross-to-net adjustments -- 22.1% for NUPLAZID and 25.8% for DAYBUE for the quarter, as detailed by the CFO.
  • SG&A expenses -- $171 million, an increase from $126.4 million in the prior year, attributed to expanded commercial investment and sales team growth.
  • Research and development expenses -- $76.9 million, down marginally from $78.3 million in the previous year.
  • Cash position -- $851 million at quarter-end, increasing from $820 million in the prior quarter, reflecting positive operating cash flow.
  • 2026 financial guidance reaffirmed -- Projected total revenues of $1.22 billion to $1.28 billion maintained.
  • Upcoming remifanserin readout -- Phase II top-line data in Alzheimer's disease psychosis expected in the August to October timeframe, per management.
  • Japan trofinetide trial timeline -- Phase III top-line results newly anticipated in the September to November window of 2026, accelerated from earlier expectations.
  • Peak sales potential -- Management estimates full peak sales potential across four pipeline molecules at $11 billion, with remifanserin alone targeted at approximately $4 billion for two indications.
  • Field force expansion -- 30% increase in customer-facing teams for NUPLAZID completed in the quarter, with expected productivity ramping through late 2026.
  • International DAYBUE programs -- Named patient supply programs continue to add incremental growth outside the U.S.
  • R&D pipeline breadth -- Five additional Phase II or III studies are planned to launch by 2027 across eight disclosed programs.
  • Trofinetide Europe regulatory update -- Re-examination process ongoing, expected resolution by late June.
  • DAYBUE persistency -- Over 55% of liquid formulation patients remain on therapy at 12 months, and 74% of active patients have greater than one year exposure according to commercial update.
  • DAYBUE penetration -- Penetration across centers of excellence and community physicians currently at approximately 40%, offering room for further expansion.
  • Milestone for NUPLAZID -- 10-year FDA approval anniversary reached, with nearly 100,000 patients treated to date.

Summary

Acadia Pharmaceuticals (ACAD 3.89%) provided data indicating strong annual growth in both its commercial brands and highlighted major clinical catalysts that could reshape its addressable market in the coming quarters. The company maintained financial guidance for 2026 while outlining accelerated regulatory timelines for key products in both the U.S. and Japan. Management discussed a pipeline with substantial estimated sales potential, a robust cash position, and ongoing business development initiatives supported by cash flow.

  • Catherine Owen Adams said, "we are approaching our highly anticipated top-line results for remifanserin in Alzheimer's disease psychosis, which we expect to report in the August to October timeframe," positioning this as a critical catalyst.
  • Elizabeth Thompson, PhD, announced her planned retirement by year-end but will remain fully engaged to ensure continuity through significant R&D milestones.
  • Management expects full-year sales for DAYBUE to benefit from new formulation adoption and for NUPLAZID to realize additional productivity gains from recent sales force expansion in the back half of 2026.
  • The company reiterated that new launches, international program growth, and planned study readouts form the basis of its near- and medium-term revenue expectations.

Industry glossary

  • DAYBUE STIX: Powder-for-oral-solution formulation of DAYBUE (trofinetide) designed for improved dosing and patient convenience in Rett syndrome.
  • Named Patient Supply (NPS) Program: A mechanism allowing physicians to access investigational or unapproved therapies for individual patients in markets outside the U.S. prior to local approval.
  • SAPS-H+D: Scale for the Assessment of Positive Symptoms–Hallucinations and Delusions subscales; an instrument for measuring psychosis severity in clinical trials.
  • NPI-C: Neuropsychiatric Inventory–Clinician rating; a tool for assessing neuropsychiatric symptom domains in disorders such as Alzheimer's disease.
  • Centers of Excellence (COEs): Specialist clinical sites recognized for expertise in complex disease management, commonly used as focal points for new product launches.

Full Conference Call Transcript

Albert Kildani: Good afternoon, and thank you for joining us on today's call to discuss ACADIA Pharmaceuticals Inc.'s First Quarter 2026 Financial Results. Joining me on the call today from ACADIA Pharmaceuticals Inc. are Catherine Owen Adams, our Chief Executive Officer, who will provide opening remarks; followed by Thomas Garner, our Chief Commercial Officer, who will discuss our commercial brands, DAYBUE and NUPLAZID. Also joining us are Elizabeth Thompson, PhD, Executive Vice President, Head of Research and Development, who will provide an update on our pipeline programs; and Mark C. Schneyer, our Chief Financial Officer, who will review the financial highlights. Catherine will then provide closing remarks before we open the call for your questions.

We are using supplemental slides 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, 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 have 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 will now turn the call over to Catherine for opening remarks.

Catherine Owen Adams: Thank you, Albert. Good afternoon, everyone, and thank you for joining us today to discuss our first quarter 2026 results. ACADIA Pharmaceuticals Inc. 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% year-over-year, our highest year-over-year growth since 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 are 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 am 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 remifanserin in Alzheimer's disease psychosis, which we continue to expect in the August to October timeframe. 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. We now expect results in the September to November timeframe of this year.

I want to remind everyone of the tremendous opportunity we have across our pipeline. We have four molecules targeting large markets with a combined full peak sales potential of $11 billion, with approximately $4 billion of that specifically attributable to remifanserin across the Alzheimer's disease psychosis and Lewy body dementia psychosis indications. This underscores the transformative potential of our research and development efforts. With that, I will now turn the call over to Thomas to provide 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 am 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, 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 have been extremely pleased with both the initial uptake and positive experiences we have 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 are 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. 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 our centers of excellence where the product was available through the first quarter. Following the focused 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 to patients and caregivers.

Outside of the U.S., our global named patient supply programs continued 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. We delivered sales of $167 million in the first quarter, representing 6% growth year-over-year on an adjusted basis. 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 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 were 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.

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 are 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 have 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 disease community increased from 8% to over 30%, underscoring the campaign's significant impact. We are complementing this with refreshed branding and creative on nplazid.com to engage patients earlier in their journey and clearly reinforce NUPLAZID as the only FDA-approved treatment for Parkinson's disease psychosis. I would 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 thousand 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 toward approximately $1 billion in annual sales by 2028. With that, I will now turn the call over to Elizabeth to provide an update on our pipeline developments.

Elizabeth Thompson: Thank you, Thomas. Before turning to pipeline updates, I want to briefly address the retirement announcement we shared last week. For personal reasons, I have decided to retire by year-end. 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 remifanserin. With that context, I will now walk through the key R&D progress for the quarter. I am pleased to share updates on our pipeline, which continues to offer meaningful opportunity with real momentum building across multiple programs.

Across our eight disclosed programs, we continue to anticipate initiating five additional Phase II or Phase III studies by 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 am 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 remifanserin 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 four Phase II or Phase III study readouts by 2027. The closest of these is the top-line results from our Phase II study of remifanserin 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 timeframe. As a reminder, throughout this study we have 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 are excited for this readout and what it could mean for the future of the company if successful, but most importantly, as a step toward relief for the patients and families affected by this challenging condition. Turning to regulatory and international developments, the trofinetide re-examination 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 with trofinetide has been progressing exceptionally well, and I am pleased to share that we now anticipate completing enrollment this quarter.

This accelerated timeline positions us for top-line results in the September through November timeframe this year, which represents an earlier completion than we previously anticipated. 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. Thank you.

Mark C. Schneyer: I will 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 2025. NUPLAZID generated $167 million of net product sales in the first quarter, representing 6% growth year-over-year on an adjusted basis. As Thomas 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 Thomas 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 2025.

Our SG&A expenses were $171 million compared to $126.4 million in 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 2025 and are 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 am 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 will 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 transformative year for ACADIA Pharmaceuticals Inc. First and foremost, we are approaching our highly anticipated top-line results for remifanserin in Alzheimer's disease psychosis, which we expect to report in the August to October timeframe. 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 Alzheimer's disease psychosis market represents a substantial opportunity with no currently approved therapies, and successful results could position remifanserin 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 timeline reflects strong international engagement and our commitment to bringing innovative treatments to patients worldwide. Importantly, as we head into these upcoming data readouts, while Elizabeth 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 are 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 disease with significant unmet need. The combination of our strong commercial performance, robust pipeline, and solid financial foundation positions ACADIA Pharmaceuticals Inc. exceptionally well for both near-term catalysts and long-term sustainable growth. We are excited about the opportunities ahead and look forward to sharing our progress with you throughout the year. We will now open the call for questions.

Operator: Your first question comes from Tessa Thomas Romero with JPMorgan. Please go ahead.

Tessa Thomas Romero: Hey, thanks so much for taking our questions this afternoon. A pipeline one here. Where are you more precisely in terms of enrollment of the Phase II RADIANCE study of remifanserin in Alzheimer's disease psychosis, and how confident are you in your August to October 2026 timeline? When might you see the last patient in? And then, how is enrollment going in your Phase II study in Lewy body dementia psychosis, and what is the right way to think about the potential timeline to data there as well?

Catherine Owen Adams: Thank you. I am going to ask Elizabeth to take us through the timelines for remifanserin.

Elizabeth Thompson: Hi, Tessa, thanks for the question. For the Alzheimer's disease psychosis program, we continue to feel very good about the August to October 2026 timeframe. The study is still enrolling, but we are getting to the last phases of enrollment, so we feel confident about that timeline. That said, I am not yet able to narrow it further. As we look at Lewy body dementia psychosis, I am pleased with the enrollment progress. I do not think we have yet shared publicly our expectations around timing of data; we want to get further into enrollment before guiding. I look forward to sharing more in the future, but so far we are pleased and on track.

Operator: Your next question comes from the line of Ashwani Verma with UBS. Please go ahead.

Catherine Owen Adams: Thanks for the questions. Elizabeth will take the biomarker and black box topics.

Elizabeth Thompson: There was a lot in there, so hopefully I captured everything. On the biomarker basis, this has been an important evolution in the Alzheimer's field. Biomarkers are now considered part of the diagnostic pathway for Alzheimer's disease. I fully anticipate that by the time we would make it to the FDA with a potential package for remifanserin, there would be an expectation that Alzheimer's disease is biologically confirmed. We put this in place to future-proof the program. Regarding real world, practice is moving that way as well. Biomarker confirmation may also improve technical success by reducing heterogeneity and ensuring we are studying true Alzheimer's disease patients.

On the black box warning question, the FDA held a workshop about a year and a half ago discussing the mortality boxed warning for elderly patients with dementia-related psychosis and what data might allow agent-specific decisions. We attended, learned from it, and have incorporated feedback into our data collection to enable the FDA to make a decision specific to remifanserin. We do not know the outcome yet, but we know what data are needed and believe there is a path forward without a boxed warning, depending on the totality of the data.

Operator: Your next question comes from the line of Ritu Subhalaksmi Baral with TD Cowen. Please go ahead.

Ritu Subhalaksmi Baral: Thanks for taking the question. More remifanserin questions, extending from clinical into commercial. As we think about the upcoming Phase II data, what should our expectations be around effect size or delta on the SAPS-H+D? Is there an accepted minimal clinically important difference? What frames success statistically? And from a market perspective, given the recent approval of an Alzheimer's agitation drug, how should we think about differential diagnosis between agitation and psychosis, accurate diagnosis, and treatment decisions between the two?

Catherine Owen Adams: Given all the interest in remifanserin, Elizabeth will kick off, and then Thomas can add market context.

Elizabeth Thompson: On what to look for and what defines Phase II success: Phase II should be Phase III-enabling. We are looking for information that informs Phase III design and any needed modifications. We will look for data consistent with our target product profile: once-daily dosing, ease with concomitant meds and food, patient-friendly administration, efficacy with an effect size in line with what we are powered for (0.4, a moderate effect size), and a safety profile similar to pimavanserin. We will also monitor for any signals on movement or cognition; based on the pimavanserin dataset, we feel good there but will look for directional signals. There is not a well-established MCID on SAPS-H+D at this point.

For a future FDA dossier, we would establish MCID in part based on the Phase II data. We are also looking at responder analyses (≥30% and ≥50% improvement) to contextualize meaningfulness. Regarding the recent agitation approval, agitation and psychosis are distinct. Agitation is multifactorial (pain, cognitive challenges, psychosis). Pimavanserin data suggest that in patients with both significant agitation and psychosis, improvement in psychosis may be associated with improvement in agitation. We would not expect to impact agitation due to non-psychosis drivers like pain. Conversely, agents effective for agitation may not impact underlying drivers such as psychosis, and some components can be associated with increased psychosis.

We believe there is room for multiple players, and agitation treatments should not be meaningfully impactful to the psychosis opportunity we see for remifanserin.

Operator: Your next question comes from the line of Yigal Nochomovitz with Citigroup. Please go ahead.

Analyst: Hi, this is Caroline DePaul on for the team. Switching gears to DAYBUE STIX, you disclosed that 30% of patients are either treatment-naive or returning after previously discontinuing the liquid formulation. How does this compare to your expectations for the launch? Do you still expect to capture over 400 incremental patients with STIX, and what is the anticipated cadence?

Thomas Garner: Thanks for the question. Our launch strategy focused on centers of excellence in the first quarter, so we have not yet gone broadly into the community. We have been very pleased with initial uptake. Of roughly 250 STIX prescriptions, about 220 were shipped in the quarter, showing we can get drug to patients quickly. The ramp is tracking faster than anticipated. The 450 incremental patients we referenced earlier this year still holds, modeled over a three-year period to make STIX the dominant SKU by the end of that time. It may go slightly quicker.

The ~30% mix of naive and restart patients is broadly in line with expectations, and we are also seeing significant interest from existing liquid patients switching to STIX. This gives us real optimism for DAYBUE growth and the role of STIX in fueling that growth.

Operator: Your next question comes from the line of Brian Corey Abrahams with RBC Capital Markets. Please go ahead.

Brian Corey Abrahams: On remifanserin, what are the key differences on potency, saturation, and receptor binding you might expect from 60 mg remifanserin compared to the marketed and previously tested dose of pimavanserin? Or should we think of success as being driven more by a more homogeneous population and a design leveraging prior learnings with more sensitive endpoints?

Elizabeth Thompson: It is a bit of both. From prior pimavanserin work, exposure-response analyses suggest that exposures higher than achievable with the currently marketed pimavanserin dose may yield greater efficacy. With the 60 mg dose of remifanserin, we can potentially achieve higher exposures and move further up the exposure-response curve. Independently, the study design is tailored to Alzheimer's disease: biomarker-confirmed AD, slightly more severe baseline psychosis (based on PIM data indicating better responses at higher baseline severity), and endpoints we believe are better suited, like SAPS-H+D and the NPI-C, versus the NPI-NH used in older studies. All of the above should help.

Operator: Your next question comes from the line of Tazeen Ahmad with Bank of America. Please go ahead.

Tazeen Ahmad: How are you thinking about read-through from the Alzheimer's Phase II to the Lewy body study? Pimavanserin showed a strong signal in Lewy body previously. Regardless of how ADP turns out, how should we think about de-risking for Lewy body next year?

Elizabeth Thompson: Great question. While the numbers were small, I have always found the Lewy body data with pimavanserin striking. In HARMONY’s withdrawal design, about 20 patients per arm with Lewy body dementia were included; roughly 55% of those withdrawn relapsed versus about 5% who continued therapy. Regardless of the ADP outcome—though we have high hopes for it—we remain very optimistic about the Lewy body study. The only possible read-through that could negatively impact both would be an unexpected safety signal; we are not anticipating that, but we will know when we see the ADP data. We also believe our remifanserin formulation and dosing approach should suit this frailer population, emphasizing safety and ease of administration.

Operator: Your next question comes from the line of Marc Harold Goodman with Leerink. Please go ahead.

Marc Harold Goodman: On NUPLAZID, if patients were delayed in refilling in January and February, why would we not have a great second quarter that makes up for the low first quarter? Your guidance talks about back-end loading.

Catherine Owen Adams: We are expecting a strong second quarter. The back-half weighting we referenced is primarily tied to the incremental impact of our additional sales force expansion. Thomas will add detail.

Thomas Garner: We executed a 30% expansion of our sales team in Q1. By quarter-end, the new team had been in the field for about six weeks, so we did not see a full-quarter productivity impact. Referral volumes were up 11% year-over-year and demand growth was solid, but late refills, coupled with typical Q1 Medicare dynamics, affected the quarter. We expect the productivity ramp to continue through Q2 and beyond. We are also pushing on DTC efforts (both unbranded and branded) and have expanded our target universe to just over 10 thousand HCPs, which should support further share growth over coming quarters.

Mark C. Schneyer: From a financial perspective, the delay was largely late refills from existing patients, not new starts. Those late refills effectively missed a script in the quarter—so lost revenue in Q1—but not a lost patient. Those patients returned and refilled later in the quarter, positioning us well going forward, but not necessarily resulting in a full rebound that recoups all January/early February revenue.

Operator: Your next question comes from the line of Jack Allen with Baird. Please go ahead.

Jack Allen: Two quick ones on remifanserin and DAYBUE. First, the ADP study is placebo-controlled, and FDA has discussed potential single-trial filings in certain settings. Thoughts on filing on a single positive placebo-controlled trial? Second, on DAYBUE, you have referenced $700 million as an aspirational sales number for 2027/2028. How do you factor potential gene therapy for Rett into that longer-term guidance?

Elizabeth Thompson: On single-trial approvals, we are all awaiting formal guidance to better understand FDA’s thinking. Key considerations like the size of the safety database likely still apply. Our base case remains that we will need the current Phase II and at least one Phase III. If we were to see truly striking results, we would certainly discuss options with FDA, but our planning assumes more than a single study given exposure requirements.

Catherine Owen Adams: At a top-line level, we remain confident in our $700 million DAYBUE sales target by 2028. We have of course considered competitive dynamics, including gene therapy.

Thomas Garner: We are very pleased with early STIX progress, which complements our liquid formulation and community expansion. Our penetration across COEs and community physicians is still around 40%, leaving significant headroom. We also have roughly 1 thousand patients who have tried DAYBUE but are no longer on treatment; we believe STIX can help reengage many of them, and we have already begun to see this in Q1. Regarding gene therapy, the Delphi consensus positioned DAYBUE as standard of care for Rett syndrome. We welcome more treatment options for the Rett population and will evaluate gene therapy data as they emerge. Irrespective, we believe DAYBUE will have a role across these patients. We feel really good about the $700 million by 2028.

Operator: Your next question comes from the line of Ami Fadia with Needham. Please go ahead.

Ami Fadia: On remifanserin, you mentioned powering for a 0.4 effect size. What is the minimum effect size needed for statistical significance? Also, as we expect data from other trials that use the NPI-C, will you provide NPI-C data at top line, and at what time point, to enable cross-trial comparisons?

Elizabeth Thompson: A brief caution that cross-study comparisons require care. NPI-C was added to our Phase II ADP study after it had started—one of the earlier changes I made—so we will not have NPI-C on all patients. It is an exploratory endpoint on a subset; I would not expect it to be part of the formal top line. In terms of powering, we are 80% powered for an effect size of 0.4. There is some flexibility around that with scenarios that could still be statistically significant, but that is generally what we are targeting.

Operator: Your next question comes from the line of Sean Laaman with Morgan Stanley. Please go ahead.

Analyst: Hi, this is Catherine on for Sean. As DAYBUE STIX adoption scales, do you expect any meaningful change in persistency versus the liquid formulation, or is the primary benefit reengaging discontinued patients?

Thomas Garner: We are monitoring persistency closely. Improving persistency over liquid would be a significant advantage. For context, with liquid DAYBUE, more than 55% of patients remain on treatment through 12 months, and about 50% through 18 months. Persistency continues to improve over time, and 74% of our active patients have been on treatment for 12 months or longer. For STIX, we believe it can help reduce initial friction and improve convenience. It is early to be definitive on real-world persistency versus liquid, and we will share more in due course. As for recapturing discontinued patients, of the ~450 incremental STIX patients we discussed earlier in the year, we estimate roughly three-quarters would be naive and one-quarter restarts.

In Q1 STIX experience, among the ~30% naive/returning share, it is roughly a 50/50 split, and we are also seeing significant interest from existing patients switching from liquid. On logistics and refills, we supply via a single specialty pharmacy on a patient-by-patient basis, so there is very limited stocking. Of the ~250 prescriptions written, over ~220 were filled in the quarter. We are not seeing payer or formulary issues; the limited COE-focused launch approach has worked well and should support ongoing refill momentum.

Operator: Your next question comes from the line of Analyst with Wolfe Research. Please go ahead.

Analyst: Thanks for taking my question. On diagnostics and endpoints for the Lewy body dementia psychosis study: you have biomarker confirmation for Alzheimer's disease entry. The Lewy body field is more exploratory; are you including alpha-synuclein measures? And can you comment on endpoint overlap between SAPS-H+D and SAPS-Lewy body?

Elizabeth Thompson: For Lewy body dementia psychosis, we are indeed exploring alpha-synuclein assessments to inform future design and contribute to the science, but it is not required for trial entry. Regarding endpoints, there is meaningful overlap between SAPS-H+D and the SAPS-Lewy body scales; both derive from the broader SAPS and focus on relevant subsets of symptoms, though they are not identical. Our endpoint strategy is intended to be sensitive to changes most characteristic of Lewy body psychosis while maintaining consistency with our broader program.