ACADIA Pharmaceuticals Inc. (ACAD) Q2 2026 Earnings Report, Transcript and Summary

Ladies and gentlemen, thank you for standing by. My name is Abby, and I will be your conference operator today. At this time, I would like to welcome everyone to ACADIA Pharmaceuticals Second Quarter 2026 Earnings Conference Call. [Operator Instructions] And I would now like to turn the conference over to Albert Kildani, Senior Vice President, Investor Relations and Corporate Development. Please go ahead.

Good afternoon, and thank you for joining us on today's call to discuss ACADIA's second 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 is Elizabeth Thompson, PhD, Executive Vice President, Head of Research and Development, who will provide an update on our pipeline programs; and Mark Schneyer, our Chief Financial Officer, who will review the financial highlights. Catherine will then provide some closing 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'd 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.

Thank you, Al. Good afternoon, everyone, and thank you for joining us today. I'm pleased to report that ACADIA delivered an outstanding second quarter, demonstrating strong commercial execution across both DAYBUE and NUPLAZID. We also continue to make important progress across our pipeline, led by remlifanserin in Alzheimer's disease psychosis. Let me start with our financial performance. We achieved total revenues of $308 million in the second quarter, representing 17% year-over-year growth on an adjusted basis. This performance reflects strong execution and continued demand for DAYBUE and NUPLAZID. Turning to DAYBUE. The brand delivered net sales of $125 million in the second quarter, representing 30% year-over-year growth. This strong performance was driven by meaningful uptake of DAYBUE STIX, our recently launched powder for oral solution, which is resonating with patients and caregivers in the U.S. The strong early adoption of DAYBUE STIX reinforces our confidence in this differentiated delivery option and supports the brand's continued growth trajectory. Based on these strong results, we are raising our 2026 guidance range for DAYBUE to $480 million to $510 million. I'm also delighted that we recently received a positive opinion from the CHMP following a re-examination process. This outcome represents a significant win for patients with Rett syndrome across Europe and reaffirms the value of DAYBUE as a foundational therapy. We're grateful to the CHMP for its thorough review and pleased to be moving closer to the opportunity to bring this therapy to patients in Europe. This positive opinion, along with strong DAYBUE STIX performance, reinforces our confidence to achieve our ambition of $700 million in DAYBUE sales in 2028. For NUPLAZID, the brand delivered net sales of $183 million in the second quarter, up 10% year-over-year on an adjusted basis. The underlying business remains strong, supported by continued demand growth, disciplined execution and impact from our expanded field force. We remain confident in our path to deliver approximately $1 billion in NUPLAZID net sales in 2028. Looking ahead, our most important near-term pipeline milestone is the upcoming Phase II readout for remlifanserin in Alzheimer's disease psychosis. We now expect to report top line results from this study in September to October of this year. If successful, remlifanserin has the potential to be transformational for ACADIA with peak sales potential of estimated $4 billion across Alzheimer's disease psychosis and Lewy body dementia psychosis. With that overview, let me now turn the call over to Tom to provide more detail on our commercial performance.

Thank you, Catherine, and good afternoon, everyone. I'm excited to report another strong quarter for DAYBUE, which generated $125 million in net sales in the second quarter, representing 30% year-over-year growth, driven almost entirely by volume. Performance was led by continued strength in the U.S. business with additional contributions from our named patient supply programs. DAYBUE continues to strengthen its position as the foundational standard of care for Rett syndrome, and our second quarter results reflect what we believe to be the growing confidence that physicians, patients and caregivers have in the therapy. Demand trends accelerated during the quarter as we expanded the launch of DAYBUE STIX beyond center of excellence, which is engaging new patients and bringing previously discontinued patients back to therapy. Importantly, the number of patients returning to DAYBUE reached a record level during the second quarter. Of note, approximately 40% of all U.S. DAYBUE patients were receiving STIX by the end of the quarter. This rapid uptake highlights the significant value STIX is providing to patients and caregivers and reinforces its role as an important growth driver for the DAYBUE franchise. Turning to DAYBUE outside the United States. We achieved a major regulatory milestone late in the quarter with the receipt of positive CHMP opinion for the treatment of Rett syndrome, and we have already begun preparations for commercialization in the European Union following expected approval of DAYBUE by the European Commission. We've assembled a highly experienced team and remain on track to launch in Germany in early Q4. In parallel, we expect to submit pricing and market access submissions in our planned launch markets this year, positioning us for broader expansion across Europe as we work to secure reimbursement approvals. In addition, our named patient supply programs are expected to remain a meaningful contributor to growth through 2026, driven by increasing awareness of DAYBUE globally. Taken together, these trends reinforce our confidence in DAYBUE's increased guidance. And with that, let me turn to NUPLAZID. NUPLAZID delivered another strong quarter, generating $183 million in net sales, representing 10% year-over-year growth on an adjusted basis, driven primarily by volume. We were particularly encouraged by the continued momentum in new patient prescriptions, which have increased 20% year-over-year, representing the highest quarterly volume since the first quarter of 2018. Turning to our expanded field force. Execution remains on track, and we are beginning to see the early benefits of that investment emerge, consistent with the 6- to 9-month ramp period we anticipated. Since expanding the team, we have seen a significant increase in call activity and improve the depth and frequency of engagement with our highest priority customer segments. As a result, we have now reached over 12,000 priority health care providers since February, significantly expanding our presence across the clinicians who care for patients living with Parkinson's disease psychosis. Our direct-to-consumer investments continue to be a meaningful driver of awareness, patient identification and activation. During Parkinson's awareness month in April, our NUPLAZID branded campaign, Mind Your Mind and the refreshed More to Parkinson's initiative delivered record audience reach and generated strong engagement across digital and social channels. More importantly, these efforts are translating into action as reflected in substantial sequential increases in both branded and unbranded patient conversion, reinforcing our ability to connect patients and caregivers with information about Parkinson's disease psychosis and the treatment options available to them. As we pair these awareness building efforts with our expanded field force, we are increasing both physician and patient recognition of NUPLAZID and further strengthening the foundation for sustainable growth. The leading indicators we are seeing across the market, including growing disease awareness, increased patient engagement and rising new prescriptions gives us confidence in the near- and long-term trajectory for NUPLAZID. And with that, I'll turn the call over to Liz.

Thank you, Tom, and good afternoon, everyone. Today, I'll provide a few brief updates across our clinical stage programs. Let me start with remlifanserin, which, as Catherine said, represents a potentially transformational opportunity for ACADIA. We recently announced several updates to this program. First and foremost, we have recently completed enrollment in the Phase II portion of our Alzheimer's disease psychosis program. And with this, we've tightened our range for top-line results, which we now expect to report in September to October. At the same time, we announced receipt of Fast Track designation from the FDA. This designation underscores the substantial unmet need in Alzheimer's disease psychosis, and we believe remlifanserin has the potential to become an important treatment option for patients and caregivers. Now that Phase II enrollment is complete, consistent with our operationally seamless Phase II, Phase III program design, we have commenced screening and enrollment in the Phase III studies. Beyond remlifanserin in Alzheimer's disease psychosis, our pipeline is robust and active with multiple studies underway today and several additional trial starts and data readouts expected over the next 18 months. Starting with the programs currently underway. First is our Phase III study of trofinetide ongoing in Japan. We continue to expect a readout between September and November. We're planning a regulatory submission in 2027, and we'll share more details about our potential filing strategy after we've selected our commercialization partner for the Japanese market. Now for other clinical programs. For remlifanserin, we also have a Phase II study underway in Lewy body dementia psychosis. And as mentioned, the 2 Phase III studies in Alzheimer's disease psychosis are now open for enrollment. We're also advancing ACP-211 in a Phase II study in major depressive disorder and ACP-711 and ACP-271 are progressing through their respective Phase I programs. Beyond this, by the end of 2027, we expect to have initiated 3 additional Phase II or Phase III studies. We also expect 4 Phase II or Phase III readouts over that same period. Of those, the readouts we have disclosed include the upcoming Phase II RADIANT results in Alzheimer's disease psychosis and trofinetide in Japan as well as ACP-211 in major depressive disorder. Together, this cadence of trial starts and readouts represents potential meaningful momentum across our pipeline. One final note before I hand over to Mark. We were very pleased to have achieved a positive CHMP opinion in the EU for trofinetide following the reexamination process. This represents a significant win for patients with Rett syndrome across the EU and brings us one step closer to making this foundational therapy available to patients in Europe. We anticipate a final decision from the European Commission later in Q3, and I'd like to thank the dedicated Acadian who worked so hard to achieve this outcome. In summary, our R&D organization is executing at a high level across multiple programs, positioning us to deliver important milestones that have the potential to create value for both patients and shareholders over the long term. And with that, I'll turn the call over to Mark to review our financial results.

Thank you, Liz, and good afternoon, everyone. I'm pleased to report strong financial results for the second quarter of 2026 that reflect the robust commercial execution Tom and Catherine described earlier. Total revenues for the second quarter were $308 million, representing 17% year-over-year growth on an adjusted basis. DAYBUE delivered net sales of $125 million in the second quarter, up 30% year-over-year, of which 27% came from volume. This exceptional volume growth was primarily driven by the strong uptake of the newly launched DAYBUE STIX formulation in the U.S. The gross to net adjustment for DAYBUE was 24.4% in the quarter. NUPLAZID generated net sales of $183 million in the second quarter, up 10% compared to the same period last year on an adjusted basis, driven by 8% volume growth, reflecting strong underlying demand for this important therapy. Our gross to net adjustment for NUPLAZID in the quarter was 23.9%. Turning to operating expenses. Our investments continue to be focused on advancing our pipeline and supporting our commercial growth. Research and development expenses for the quarter were $82 million compared to $78 million a year ago. SG&A expenses were $160 million for the quarter compared to $134 million a year ago. This increase reflects our investments to expand both the NUPLAZID and DAYBUE field forces and increased marketing investments supporting both brands. We ended the quarter with a cash position of $956 million. This healthy cash balance provides us with the financial flexibility to execute on our commercial plans, advance our pipeline and pursue business development opportunities that align with our strategic objectives. Turning to our full year 2026 guidance. We're raising our DAYBUE net sales outlook to $480 million to $510 million, up from $460 million to $490 million. This outlook reflects our strong performance in the first half of the year and includes all forms of trofinetide available globally, including our expectation for initial EU commercial sales in Q4. Our NUPLAZID net sales guidance remains unchanged at $760 million to $790 million. Taken together, we now expect total 2026 revenue of $1.24 billion to $1.3 billion. As we look to the rest of the year, let me provide a bit more color on expectation for each brand. For DAYBUE, we expect similar year-over-year growth rates for Q3 and Q4. And for NUPLAZID, we expect stronger year-over-year growth in Q4 relative to Q3 due to the greater impact of the expanded field force expected later in the year. Also for DAYBUE, we are slightly increasing the guidance range for gross to net to 23% to 25%. Lastly, on guidance, we are lowering our spend guidance for R&D and now expect R&D expenses in the range of $355 million to $380 million compared to the prior guidance range of $385 million to $410 million. The reduction to R&D guidance is primarily attributable to the shifting of a BD milestone to 2027 and selected portfolio prioritization decisions. All other guidance ranges for fiscal year 2026 are unchanged. With that financial overview, I'll turn the call back to Catherine for closing remarks.

Thank you, Mark. As we close, I want to reinforce why ACADIA is positioned for its next phase of growth, anchored by proven commercial execution, a transformational near-term pipeline opportunity and multiple value-driving milestones ahead. Turning first to commercial execution. Performance remains strong across both brands. We delivered an excellent second quarter led by DAYBUE. These results have led us to raise our DAYBUE guidance. Looking ahead, the upcoming European Commission decision represents another meaningful opportunity as we prepare to bring this foundational therapy to patients, beginning with our planned launch in Germany in the fourth quarter. NUPLAZID also continues to perform well, and we are beginning to see the benefits of our expanded field force as the team ramps and reaches more health care practitioners across specialties. Building on our commercial momentum, remlifanserin remains our most important near-term pipeline catalyst with Phase II data in Alzheimer's disease psychosis expected in the September to October time frame. Beyond remlifanserin, we're advancing ACP-211 and our broader pipeline with additional catalysts ahead, including top line Phase III trofinetide data from Japan later this year. Finally, we remain guided by our mission to turn scientific promise into meaningful innovation for underserved communities. Our second quarter performance and the milestones ahead reflect the progress we are making and reinforce our confidence in ACADIA's next phase of growth. Thank you all for your continued support of ACADIA. And with that, we're happy to take your questions. Operator?

[Operator Instructions] And our first question comes from the line of Tess Romero with JPMorgan.

So Liz, actually a question for you. Thinking through the outcome of the Phase II RADIANT trial, how should we think about scenarios around effect size here around your primary endpoint of the SAPS-H+D? And how should we think about the lower bounds of what could still have a path forward into Phase III? Or put another way, how much room do you think you have in your data to be able to execute on a Phase III plan that is derisked enough in ADP?

It's a great question, Tess, and obviously, one we've been giving a great deal of thought to of what would be really Phase III enabling data. And so I'll make a few comments there. First off, as I'm sure everyone on this call knows by now, we are 80% powered for a moderate effect size, 0.4 effect size on our SAPS-H+D. There is probably a little bit of flexibility around that in terms of what would still be a supportable and Phase III progressable asset. There is a lower level beyond which you start worrying about whether you'd be able to replicate the effect. But I think we've got a ways there. In general, we're going to be looking certainly at the impact on SAPS-H+D, but that's not going to be the only thing we're going to look for at an effect size perspective. We're going to look at responder analyses on SAPS-H+D. There are a number of other endpoints that we're considering as well. But broadly speaking, we're looking to see that we've got something that we think continues to align with what we think would be a meaningful drug in this space. And that's something that's going to be easy for patients to take, something they can take once a day with or without food, something that has evidence of efficacy, a supportive safety profile and some of the stuff we won't definitively answer in Phase II, of course. But we are going to want to feel good about the fact that we don't have negative cognitive impact or negative impact on motor, things like that. So there's a number of different considerations we're going to be looking at, but that hopefully gives you a little bit of a flavor for the thinking.

Our next question comes from the line of Ritu Baral with TD Cowen.

Two questions. One is actually a follow-up to Tess's and specifically, Liz, around the CGI-S. We had previously talked about how you intended to anchor the SAPS-H+D to the CGI-S. Can you talk to like what the NCID for CGI-S is and if you're going to release that data and if there's going to be sort of a correlative analysis with the top line data to the -- with your data announcement? And second, could you speak a little more to some of the presentations that I saw -- that our team saw at IRSF around from the Delphi consensus. They talked a fair bit about improved tolerability, I believe it's an independent group, but improved tolerability with STIX and improved DAYBUE tolerability with new titration regimens and how what they presented at IRSF is making an impact on DAYBUE commercially?

So I'll take a shot at the first part, certainly, and then probably we'll do some tag teaming on the second. So with respect to some of the CGI-S and how we may use that, first and foremost, this is our key secondary endpoint. I will say, I guess we should start with level setting with expectations around what's actually going to be put out at the time that we do our initial press release. I think it's probably to think in terms of what's going to be there for sure is going to be our primary efficacy endpoint and a comment on safety. Additional information, we're going to determine whether that is necessary and helpful at that time and some things we will certainly wait for future medical meetings. I would not anticipate that you're going to see any kind of correlation analyses between CGI-S and SAPS-H+D. I think when I referred to the anchoring before, what I was talking about is in the context of an eventual dossier to support the applicability of an endpoint for regulatory purposes, we do anticipate we would need to have a full dossier explaining the behavior of the instrument, the appropriateness of it, et cetera. And so that is one path that we could take to help support that is through an anchoring with the CGI-S. Generally speaking, it is considered that a change on CGI-S or CGI-I that those in and of themselves are clinically meaningful. And so that's helpful as you're trying to define meaningful change on another instrument. I think that covered everything around the CGI-S. With respect to some of the presentations at IRSF, taking the tolerability or the tolerability with titration piece first. What I will say is some of the information that we have from Lotus has suggested over time that there -- in patients who titrate that you certainly don't see onset of diarrhea with the same kind of rate. And so that can give an opportunity for patients and families to kind of get accustomed to the drug in context of many other tools that are in the toolbox, things that physicians are -- that we have encouraged physicians to make more use of is use of fiber, adequate water intake, making sure that they are discontinuing the antidiarrheals, et cetera. So there are a number of different tools that can help from a tolerability perspective. And I guess, Tom, I'll let you comment on how that is impacting physician use.

Sure. So just a couple of things I would say. So first off, in terms of the Delphi consensus research that you mentioned, and yes, we did present a number of papers at IRSF. As a reminder, the Delphi consensus was actually conducted prior to the launch of STIX. So all of the information that you were seeing there relates to the oral solution. As it relates to STIX and the other experience that we're seeing, what we would say is -- at the moment, it seems to be on par with what we've seen historically with oral solution in terms of tolerability. Obviously, we're learning more as we go, this has only been the first full quarter where it's been in the hands of patients and caregivers beyond COEs. But what I would say is we've been very, very encouraged by the early start that we've made with STIX and have been pleased with the momentum that we're seeing across both COEs and non-COEs as we've moved into the community.

And our next question comes from the line of Ash Verma with UBS.

I've got 2 on ADP as well. Maybe just on the Phase II, the effect size that you're shooting for the 0.4 that you mentioned about the powering. Just help us understand like the prior Study 19 pimavanserin data had shown a 0.2 that was using a different NPI scale, but in RADIANT, you are using SAPS-H+D. So, is that effectively comparable and not the effect size is? And then secondly, I saw that you've started the Phase III screening and enrolling the patients already, but we are waiting the data from Phase II. So if you are having to dose patients in the Phase III before we get the Phase II data, which dose would you be inclined to?

I'll just keep going. Okay. So with ADP, so just to ground a little bit in the pimavanserin data. So Study 19 was the Phase II study of pimavanserin in ADP. It was, as you rightly note, using a different endpoint. There are other differences from a population perspective. In our current study, we are, of course, requiring biomarker confirmation. But I will say on balance, we expect that most patients who were in the 019 study probably would have been biomarker positive as they were fairly advanced in their disease course, but we don't actually have biomarkers to be able to confirm that. And then probably another important thing to keep in mind is One of the things that we have seen in the data set is that there does appear to be a more significant impact in patients with greater baseline psychosis. And so, in the RADIANT trial, we are looking to move that patient population on balance to a somewhat more severe psychosis population than was in Study 019. And so with that context, yes, the Phase II of pimavanserin did have an effect size of about 0.32. We did power for remlifanserin for 0.4 for a couple of reasons. One, of course, is the endpoint where we've changed to something that we think is more sensitive to change, but also the fact that we have enriched for that more severe psychosis population, which if you look in Study 19, actually, if you look at the more severe psychosis population, your effect size goes up to more like 0.6. So we think that 0.4 is a defensible and appropriate powering assumption. And we think that if we meet that or in that vicinity, what we have is an agent that potentially could be meaningful for patients. And then I think the second piece was about Phase III. So yes, the design of our study is operationally seamless. And so what that does mean is that once enrollment completed in the Phase II portion, which we did announce recently, sites we're able to start screening and then enrolling for the Phase III portion. Right now, our Phase IIIs are designed very similarly to the Phase II study. The fact that these are statistically separate does mean we have the opportunity to analyze those data, which we are going to do in the September to October time frame and share those data, but also make modifications to the Phase III as needed. Right now, we are enrolling for both dosing arms, so there would be placebo, 30 and 60. There is a possible future where one of those dosing arms doesn't need to be taken care or need to be taken forward. But for now, we are continuing on with that.

And our next question comes from the line of Marc Goodman with Leerink Partners.

Yes. So now that it looks like DAYBUE Europe is going to happen, can you help quantify that opportunity for us? And you mentioned Germany in the fourth quarter. What other countries are you expecting to launch? And just give us a sense of how fast you think that ramp can be.

Sure. I'll take that one, Marc. So thanks for the question. So I mean, first off, it goes without saying that we are very pleased that we've been able to turn around a negative opinion into a positive outcome for patients in Europe. And as I mentioned in the preparatory remarks, the team are geared up and ready to go. So we anticipate EC decision by the end of Q3, as Liz mentioned, and the team is going to be pretty quickly ready to go thereafter. Germany will be the launch market as we get out of the gates and you would then follow the normal cadence that you'd expect to see in terms of other early launch markets in the EU, which tends to be kind of Nordics and then others that we're working through Austria tends to be pretty quickly after Germany at the same time. In terms of the commercial opportunity, I mean, I go back to what we shared previously, which is as you look at the $700 million guidance for 2028, we estimate somewhere less than 15% of that number to come from Europe. So as you think about kind of cadence of the launch, it will be somewhat gradual through the end of Q4 as the patients who are receiving free drug today in Germany transition to paid treatment, and then you'll see it consistently come online through next year. So more information to come, but we are excited by the opportunity. I think as you think about the 3 pillars of growth for DAYBUE into the future, international expansion in Europe is certainly one, and we're really looking forward to pulling that through.

And just to sort of put a name on that, Marc, as you know, it takes years for countries to come online in Europe. So we will continue to follow the path that Tom laid out. But also in the meantime, where we can supply physician demand through our named patient programs, we will be honoring that as well. So both of those things will be happening depending on the country and what's going on and what the legal system allows. So just to continue that.

Our next question comes from the line of Tazeen Ahmad with Bank of America.

To clarify, do you expect the discontinuation rate to change with the STIX formulations? And then secondly, on pricing in Europe for DAYBUE, on average, what percent discount do you think you'll have to take in the major European countries over time?

Thanks, Tazeen. I'll let Tom talk about STIX and the discontinuation rate.

Sure. So I think as we've been monitoring kind of the STIX performance out of the gate, to date, as I mentioned earlier on, from the early data that we're seeing, it seems to be performing fairly similarly to what we have seen with the oral solution historically. Obviously, what's been very different, though, with the STIX launch is that we are now able to reengage patients who had previously discontinued the oral solution now that we have the new therapy. And it's clear that patients and caregivers, caregivers in particular, are willing to come back to DAYBUE given the efficacy that the brand offers. So we're continuing to monitor closely. What I would say overall, as you think about discontinuation rates, although we don't talk about them publicly as much as we did before, is they are largely in line with what we've shared in prior quarters. They remain under double digits, it remains very, very consistent. And as we see more patients move to the STIX therapy, and we're seeing that happen, that adoption happen somewhat quicker than we anticipated, we'll be sharing additional information on that.

In terms of pricing in Europe, I think for now, we're not guiding or giving any indication to prices in Europe. We will keep you updated as we move through those discussions with the individual national reimbursement authorities starting with Germany. And as you know, free pricing in Germany is for the first 6 months. And after that, we'll start our negotiation. So it won't be until the middle of next year that we start talking about that.

And our next question comes from the line of Yigal Nochomovitz with Citigroup.

Actually, just one more on pricing. You just mentioned the free pricing for the first 6 months. After that, what happens? Is there an accrual period where you estimate the expected negotiated price? And then once you get that price, then you move to the set price. And then with regard, again, back to the ADP readout, I'm wondering if you could just speak to the statistical test. I know I think for the prior study for pimavanserin in ADP, it was a T-test and -- but there was also in the PDP trial used MMRM. I'm just wondering if you could speak to those details.

I'll get Tom to talk about the discussion and Liz can move on.

Yes. So thanks for the question, Yigal. So vis-a-vis Germany, we will be -- as soon as we have the approval, obviously, we'll be launching in Germany, as we said. During that free pricing period, essentially per the legislation that exists in Germany, we have the ability to price as we wish. At the same point, we will be working with AMNOG directly because we'll have submitted our pricing reimbursement dossier and that actually begins the process of negotiating what the price then becomes post that 6-month repricing period, at which point that becomes the price that's recognized on a GTM basis. So essentially for that first 6 months, we recognize the revenue at full price, whatever it may be set at. And then post that 6-month moratorium, that's when we start recognizing a different price from the publicly available price. SO, we will see.

We haven't talked a lot about the statistical considerations in terms of the Phase II study. But what I can say is that it is an MMRM analysis, and we are controlling for multiplicity as you would anticipate with a prespecified hierarchy.

And our next question comes from the line of Malcolm Hoffman with BMO Capital Markets.

Congrats on the quarter. I was wondering if you could provide any color on whether you have seen a normalization of typical refill rates for NUPLAZID. I know you had mentioned new patient starts are really strong, but I just wanted to get a sense whether the scripts are back on track. And then for remlifanserin, can you comment on whether you have had to correct for any rate or drift throughout the study? I know maintaining the consistency of the rating throughout the trials is pretty critical here.

I'll let Tom start on NUPLAZID.

Sure. So yes, NUPLAZID referral and restart rates are exactly where we expected them to be. In fact, if we look at Q2 of '26 versus Q2 of '25 in historical years, that's actually been a particularly good rebound versus prior year. So, I think the phenomenon that we saw in Q1 of this year clearly does seem to have been a one-off. Obviously, we'll be monitoring very closely as we end 2026. But everything as it relates to demand and pull-through and patients returning is exactly where we anticipated it to be.

And as far as commenting on rater evaluation, potential for rater drift, et cetera, we have tried to be mindful of that. We have a rigorous process back in the day for our site and our rater selection, including proven experience in these kinds of trials and psychosis assessments, have extensive training calibration exercises and standardized scoring protocols. But probably most relevant to your question, we are on an ongoing basis, looking at blinded data and having sort of booster training of raters based on review of blinded data on an as-needed basis.

Our next question comes from the line of Sean Laaman with Morgan Stanley.

On DAYBUE STIX, so clearly an acceleration there. But can you quantify how much of the recent demand reflects entirely new patients versus improved compliance, persistence or conversion from the oral formulation? And where do you estimate the current treated patient population penetration stands in the U.S.? And how much untreated or underdiagnosed opportunity remains?

Sean, it's Tom. So, thank you for the question. So let me just provide a little more color on kind of the dynamics that we saw in the quarter. So, if you look at kind of our overall mix in the quarter, both across STIX and the oral solution, around 60% of our referrals were coming from naive patients 40% were returning patients. And as we think about, again, future growth potential for the brand, obviously, naive will remain a focus. I think with STIX, we now have this additional opportunity to engage patients who have previously just discontinued. When we look at STIX in isolation, it's interesting there that we saw 55% of our existing patients on were switching from oral solution, 45% were either new or returning. So, kind of that gives you a little more flavor. We've also been particularly encouraged by just the momentum that we've seen through the quarter. So if we take June in isolation and we look across the entire business, 60% of all of our referrals in June alone for the STIX formulation. So I think that, that gives you a very clear direction of travel as we think about just the uptake of STIX the positive reaction that we've seen from both the clinical community and the patient community. We had a very strong IRSF meeting. And I think the momentum that we're building gives us a real sense of confidence that we can finish this year strong and really build further as we think about 2027.

Next question.

And our next question comes from the line of Brian Abrahams with RBC Capital Markets.

This is Nevin on for Brian. So maybe just one on the DAYBUE opportunity in Japan. Can you remind us maybe what the Phase III trial design is there and what efficacy endpoints those regulators might require? And then just what the addressable Rett syndrome population is in Japan?

We'll start with the addressable and then we'll move to Liz just to give her an opportunity to take a breath. So Japan, we're looking to commercialize after we get our registrational study completed, which Liz can give you details on. The epidemiology of Rett around the world is similar. It's 1 in 10,000 to 1 in 15,000 live female births. We believe there's around 1,000 patients in Japan who have Rett syndrome, various different sources give slightly different numbers, but it's around that. And we're looking forward to our Phase III trial, which Liz can give you a little bit of a description.

It is a bit atypical as Phase IIIs go. I think it's important to think of this in the context of through discussions with PMDA. The primary support for an eventual indication should we get there, is going to be our LAVENDER data. The Phase III study that we're running in Japan is primarily to give some experience in Japanese patients. It is a very small trial, I think on the order of 20-ish patients. There is a placebo control, but obviously, it is in a very small number, again. We're looking at week 12 endpoints. We are looking at the same kinds of endpoints that we looked at in the trofinetide global program. Here, though, it is CGI-I as the primary with RSBQ as a key secondary endpoint. But again, the intent here is more to get experience in the Japanese population. There's no expectation that we would be able to hit a p-value, for example, with this kind of trial. So that's -- it will give us some sense of how the drug behaves there, and we think will be hopefully supportive for what is primarily going to be a LAVENDER-based package.

And our next question comes from the line of Sumant Kulkarni with Canaccord Genuity.

I have 2, one on remlifanserin and one on peak sales potential. So it looks like Bristol's enrollment for ADEPT for ADP is going somewhat slower than that company initially expected. So given your experience with the ongoing ADP trial, do you think that space is something specific to their program? Or does it have wider implications for other ADP programs, including yours?

Probably should be careful on how much I'm speculating on somebody else's program. But I guess what I'd comment on there is essentially we took a while in enrollment because we were looking to make sure we were enrolling the right patient population. And so I think that anybody who is considering trials in this space should be thoughtful about how they are enrolling their patient population and ensuring that they have the patients enrolled that they're looking to. And so one of our versions there, of course, is the biomarker confirmation. But overall, we are being careful in that.

Got it. And given where you are today with your solid performance on NUPLAZID and you have now European approval for DAYBUE, do you have anything to add relative to your earlier $1.7 billion in peak global net sales in 2028 for those products?

I think we're talking about our confidence now of hitting those numbers as we move through the end of this year and we look at the continued uptake of STIX and we see how NUPLAZID ends the year, we will revisit that at that time. But for right now, both for the $1 billion on NUPLAZID and the $700 million on DAYBUE, we are confident that we will achieve those numbers during 2028.

And our next question comes from the line of Rudy Li with Wolfe Research.

Congrats on a strong quarter for DAYBUE. Maybe just a quick follow-up to the patient dynamic for the STIX formulation. Can you maybe talk about the trend moving into July and August across different patient segments? And another question is based on your recent market research and physician feedback. How should we think about the market dynamic for Rett syndrome with potential gene therapies in the coming years?

Yes. I'm going to ask Tom to talk about July and August and then talk about our view on gene therapy.

Yes. So a few things that I would say, and thanks for the question is as you look at kind of the momentum that we saw during Q2, and as I mentioned, 60% of our prescriptions at the end of June, we're already for STIX. And we are really now beginning to focus our team's efforts beyond the COEs as we think about pushing STIX more broadly. We feel pretty confident that the momentum that we saw during Q2 is going to continue into Q3. Early signs are indicating that way in addition to all of the additional programs that we have outside of the U.S. for inbound request name patient sales as well. So I think as you take that together, this gives us confidence in the guidance that we shared. Obviously, we have lifted both the bottom and the top as we think about the end of this year, and we feel good about where we're situated as we think about the remaining 5 months of 2026.

And in terms of gene therapy, just as a top line, we don't see any impact to our commercial forecast either in the short or long term with the potential introduction of a gene therapy, while we welcome any new option for patients with Rett syndrome. We believe that DAYBUE will remain the standard of care for patients with Rett syndrome, both in the U.S. and globally. Tom, I don't know if you want to talk any more about that.

Yes. I mean I think, obviously, we're watching with a keen interest these first-generation gene therapies. I think there's optimism amongst certain patient types and certain members of the treating community. But again, we believe in the foundational standard of care that DAYBUE offers. Obviously, it can be used either pre or post gene therapy. And we think that, that inherent flexibility and the fact that you can use DAYBUE is completely reversible. We know the profile of the treatment very closely that DAYBUE will remain an important treatment for Rett syndrome moving forward. And I think the advent of DAYBUE STIX actually just makes us even more confident in that.

Next question.

Our next question comes from the line of David Hoang with Deutsche Bank.

Congrats on the quarter. I want to ask about the development of remlifanserin in ADP versus Lewy body. Is there any reason to think the probability of success would be different between those 2 indications? And then on the commercial side, I know you've talked about the $4 billion peak sales number there for remlifanserin across indications. Directionally, how should we think about how that might break out between ADP and Lewy body?

All right. I'll let Liz start on that one. I'll come up behind.

I was so busy writing things down. I may have missed the second part of the question. So broadly speaking, we are enthused about both the possibility in Alzheimer's as well as in Lewy body. These are both areas with tremendous unmet need and really nothing available for these patients. In broad terms, I don't think we see the probability as wildly different across the 2. We have more data in Alzheimer's with pimavanserin certainly, but the data that we do have in Lewy body, though in a smaller number of patients is pretty striking in its magnitude. So we're looking forward to the first readout coming in September to October. And while we haven't disclosed the Lewy body readout, we are looking forward to that in the future as well.

I think in terms of the commercial opportunity we've described before and so many others, the size of these markets, which are both considerable in the U.S. and beyond. I think in terms of how we see the $4 billion split out I would say it's roughly 60% ADP, 40% Lewy body. Obviously, that highly depends on the data, the competitive frame and who else is also on the market at the same time. So I would say we're sort of roughly around 60-40, but that will evolve as we get there. And let's cross the data threshold first. And with that, we'll take the next question.

And our next question comes from the line of Jack Allen with Baird.

This is Chris on for Jack. Just turning back to DAYBUE. Regarding the STIX uptake, I heard you just mentioned that 45% of STIX users were either new or returning. Can you provide what percentage of that 45% were new -- and then are you seeing higher rates of uptake in a certain patient demographic age, for example? And if so, do you see that changing over time?

Yes. So as you think about kind of the 45% that I mentioned, so if you kind of zoom in on STIX, it's roughly 60% were new, 40% were returning that we saw in the quarter. Again, as we go further into community, we anticipate that those dynamics may shift. I mean it's notable that we actually saw a very significant shift in Q2 to community prescriptions versus what we saw in Q1, which you'd expect because obviously, that's when we were actually talking to STIX more broadly beyond just the center of excellence. In terms of returning patients, I mean, we are seeing a very diverse mix. One of the things that has been different to what we had assumed before we launched is that it would primarily be patients who have discontinued due to formulation concerns that we return to the brand. We're actually seeing that a far broader group of patients are willing to return, which, again, I think just talks to the community's interest in trying DAYBUE again based upon the efficacy that they know that patients can see with this treatment. And I think the new formulation will potentially give us an avenue to unlock that opportunity further.

And our next question comes from the line of Ananda Ghosh with H.C. Wainwright.

Congrats on the quarter. I have 2 questions on ADP. The first one is where do enroll patients of RADIANT compared to prior trials, as mentioned, like the Ballard et al paper? And what instrument was chosen on that criteria? The second follow-up question is, we noted that Study 19 was using NPI-NH, both for screening as well as on the endpoint determination. But the RADIANT, I think the screening tool is different than the endpoint. And what's the rationale behind that?

So Anand, the first part of your question was a little bit unclear. So maybe we'll get to start the Study 19 response and then you can reask it so that we can answer the right question.

Sure. So what I'll say is on the screening criteria that we used -- well, let me phrase this carefully. So when we are considering patients that we're including in the analysis, we're taking into account both the NPI-NH values as well as the SAPS-H+D values in terms of who qualifies for the primary analysis. So we are actually including a component of the endpoint as well as another criterion. And again, the goal here is to sort of edge up that overall population level psychosis severity because we do think that slightly more severe patient population does seem to have a greater effect size that's shown.

The first part of the question was around enrolled patients, but perhaps you could just ask it again so we can understand it properly.

Yes. No, that was helpful. So I think this answers a part of that question. My question was, given that one of the ideas from the Study 19 was that you need to have much more severe patients. So given the baseline of RADIANT, where do they sit with respect to the overall Study 19 population? That was the question.

So we're not, at this point, disclosing what baseline characteristics of the population look like. So what I can say is we did have enrollment criteria that should be consistent with edging up that overall population level of severity, but we're not currently disclosing what the actual baseline values are.

And our next question comes from the line of Uy Ear with Mizuho.

Congrats on the quarter. Just going back to the RADIANT study. I was wondering if you can provide a little more color in terms of the number of patients enrolled and whether all the patients have been dosed? And what are the gating factors, I guess, to getting the data in September versus October? And my second question is, are you able to share for which program the milestone payment in R&D was shifted to 2027?

Sure. So again, hopefully, I got all my notes down here. In terms of complete enrollment in the RADIANT program, in particular, in the Phase II portion of it, that was 363 patients that were enrolled. The main gating factor between September and October is going to be the 30-day safety follow-up if patients don't roll over. The study is still -- it is still ongoing. Everybody has gotten past randomization, but there are still patients on study. So I cannot answer today whether all patients are going to go into the open-label extension or whether we may need that 30-day follow-up, which would move us out later. In terms of the milestone question, so sorry. So as we have been -- as we've been progressing 711 forward, one of the things that we've been pleased actually is from both a -- from a nonclinical perspective, we found that we both have the ability from a tox perspective and also the potential benefit of higher dosing. And so accordingly, we added in some additional higher dosing that we're going to be exploring in Phase I before we go into Phase II. That did shift out our timing a little bit such that the milestone is not going to hit this year. I do look forward to updating more with some specifics around time lines and study impact as we get through that Phase I dosing, but we wanted to reflect reality of when we thought milestone would hit.

And our next question comes from the line of Paul Matteis with Stifel.

This is Julian on for Paul. In thinking about DAYBUE STIX with the reversal of the CHMP opinion, you sort of set this like 15% threshold for contribution. Just thinking about like the peak opportunity, I guess, is that a reasonable sort of like benchmark? Or do you have any analogs that you can point to in the rare disease space that can sort of set expectations to what contribution ex U.S. that DAYBUE could potentially have to your franchise? And then one quick question also on remlifanserin. There have been some studies published out there that -- from independent authors that suggest that pimavanserin at approved doses can get to 90% receptor occupancy after only a couple of weeks of dosing. I guess just with the improvements to your molecule, what do you think is -- is it fair to expect that it's going to be driving greater efficacy due to receptor occupancy? Or is it going to be elucidating an effect due to the improvements you made to the clinical trial?

Thanks, Julian. I'll just make a quick comment around the peak opportunity for DAYBUE outside the U.S. As we talked about already, we've guided to $700 million in 2028. That is definitely not the peak opportunity that we see. That is the 2028 number, just to be clear about that. And right now, we're talking about around 15% of those sales to be from outside the U.S. That's obviously highly dependent on the reimbursement decisions that we get as we move through the reimbursement discussions that we've already sort of talked about. I would say that's an average analog for other rare disease opportunities. As we progress through the reimbursement discussions and we get those decisions and we get the first view of prices in the EU, we will be better able to articulate what percentage of our 2028 sales as well as further future peak opportunities would be. But I think for right now, that's a fairly normal analog for rare disease. But as rare disease is very heterogeneous. There is really not a normal analog. So it's one that we are sticking with for right now, and we will update you as we go through. And I'm going to hand the other question back to Liz.

Yes. Briefly, I suspect that the data that you were referring to is in young healthy volunteers because that's where most of the receptor occupancy information is. And I'll say that, that is true that we get to near full receptor occupancy even with pimavanserin at marketed doses. It is our expectation and belief that in elderly and diseased patients, this is a bit of a different animal and higher levels are going to be necessary to get to the same receptor occupancy. And to sort of support this, I would point again to the exposure response analyses that we've done out of prior data sets in both Alzheimer's and Lewy body that do suggest that levels that are higher than what you can get to with the marketed dose of pimavanserin on average do seem to be associated with higher efficacy. So again, I think that, that is a strong reason to believe there's a potential for greater efficacy. But I will say that even if the degree of efficacy we saw with remlifanserin winds up being more similar to what we've seen with pimavanserin, we're structuring our programs in such a way by being focused on the individual diseases and properly powered such that I think that we have an increased likelihood of technical and regulatory success even if the effect were to be similar to the pimavanserin in terms of its scope.

Ladies and gentlemen, that concludes our question-and-answer session. I will now turn the conference back over to Catherine Owen Adams for closing remarks.

I'd just like to thank you all for your questions and continued support of ACADIA and look forward to reporting on our next quarter where we will have an exciting set of results for remlifanserin. Thank you all for your attention today.

This concludes today's call, and we thank you for your participation. You may now disconnect.