ACADIA Pharmaceuticals Inc.

Good day, ladies and gentlemen, and thank you for standing by. Welcome to Acadia Pharmaceuticals' third quarter 2025 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. Please be advised that today's conference is being recorded. I would now like to hand the conference over to Al Kildani, Senior Vice President of Investor Relations and Corporate Communications at Acadia. Please go ahead.

Good afternoon, and thank you for joining us on today's call to discuss Acadia's third quarter 2025 financial results. Joining me on the call today from Acadia are Catherine Owen-Adams, our Chief Executive Officer, who will provide some opening remarks, followed by Tom Garner, our Chief Commercial Officer, who will discuss our commercial brand, Debut and New Plazit. Also joining us today is Elizabeth Thompson, Ph.D., Executive Vice President, Head of Research and Development, who will provide an update on our pipeline programs, and Mark Schneier, our Chief Financial Officer, who will review the financial highlights. Catherine will then provide some closing thoughts before we open up the call to your questions. We are using supplemental slides which are available on our website's events and presentations section. Before proceeding, I would like to remind you that during our call today, we will be making several forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements, including goals, expectations, plans, prospects, growth potential, timing of events, future results, and 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. Viewer cautions 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 another strong quarter for Acadia, with solid execution across our commercial portfolio and continued momentum, positions as well for a strong finish to 2025, as we lay the foundation for sustained growth into 2026 and beyond. We delivered total revenues of $278.6 million this quarter, up 11% from a year ago, reflecting the strength of our commercial portfolio. This performance underscores our ability to execute on multiple fronts while building for future growth. Starting with debut, we're very pleased with our progress. following the expansion of our field force earlier this year, the benefits of which are now starting to materialize. I'm excited to share that we achieved our largest sequential increase in referrals since launch. This meaningful sequential growth reflects the impact of our expanded team into the community setting, giving us confidence that we will continue to see benefits from our broadened physician reach. During the third quarter, they've generated 101.1 million in net sales, including contributions from both US sales and main patient supply programs outside the US. We ship the highest number of daily bottles ever in a single quarter. In total, we ship to over 1,000 unique patients globally, an exciting milestone for the company. Importantly, patient persistency remains stable. underscoring the sustained benefit they deliver to patients and their families. Moving to New Placid, we delivered an exceptional quarter with net sales of $177.5 million, marking our strongest sales quarter ever. The momentum we are now driving gives us tremendous confidence in New Placid's potential to unlock higher growth in the coming years. To ensure we capture this opportunity, we're making strategic investments in a meaningful field force expansion. The impact of this field team expansion, combined with our direct-to-consumer campaigns, creates a powerful combination that we believe will drive sustained growth and value maximization for Newcastle. We're looking to build on our commercial success by advancing our pipeline of novel product candidates, including the recent initiation of one phase two and one phase three trials. I'll now send the call over to Tom to cover our commercial performance.

Thank you, Catherine. I'll begin with debut, where we delivered another strong quarter of commercial execution. Debut sales were $101.1 million in Q3, representing our highest revenue and total prescription volume in any quarter to date since launch. As Catherine noted, for the first time since approval, the number of unique patients receiving debut worldwide exceeded 1,000 in a single quarter, for an actual count of 1,006. This achievement reflects not only our progress in the US, but also from patients now starting to access Debut through our named patient supply programs internationally. We're seeing strong early indicators from our field force expansion. Referrals are leading the way, with the highest quarter-over-quarter increase since Debut's launch in 2023. This momentum is translating into other key performance indicators, such as broadening prescriber reach, with 956 physicians having now written at least one prescription for debut. Our sales teams are now gaining real traction, with call volumes on our expanded target customer base increasing over 20% versus Q2, supported by a similar increase in the number of educational programs we delivered. both of which are important leaders in helping to educate prescribers on the benefits that Debut has to offer. Importantly, adoption is broadening beyond centers of excellence, or COEs, with community-based physicians accounting for 74% of new prescriptions in Q3. We're also seeing a meaningful uptick in scripts from nurse practitioners and physician assistants, reinforcing that our strategy to expand in-person efforts into the wider RET treating community is working. These trends position us well to reach more RET patients who could benefit from Debut. Even with this progress, overall market penetration remains relatively low at about 40% in the US and only 27% in the community setting where the majority of RET patients are treated. This continues to represent a substantial growth opportunity for the brand. Looking at age demographics, penetration among patients under the age of 11 is over 60%, but amongst older patients is significantly lower, despite growing real-world evidence of DEBU's positive impact in this group. As we expand our reach beyond COEs, we see this segment as a significant growth driver for 2026 and beyond. Long-term persistency remains a key strength for DEBU. reflecting its sustained clinical benefit and strong patient engagement. With another quarter of maturity in our data, persistency rates remain above 50% at 12 months and greater than 45% at 18 months. The strengths of these metrics are important, as they further reinforce not only our confidence in Davey's therapeutic value, but also our outlook for sustainable long-term growth in the US. Internationally, our name patient supply programs continue to gain traction. All three distribution partners are now actively shipping to patients in the EU, Israel, Middle East, and Latin America. Looking ahead, we remain confident in Debu's growth outlook, driven by sustained demand generation supported by our strategic field force investments, strong persistency metrics, and expanding global access. These factors are critical because they are not only validate the long-term value of Debut for patients, but also create a durable foundation for revenue growth. While we began to see the initial positive impact from the Field Force expansion in Q3, we expect meaningful benefits to accelerate through Q4 and into 2026. In summary, Debut is well positioned to capture significant market opportunities in the U.S. and internationally. reinforcing our commitment to delivering both patient impact and shareholder value. Now, turning to New Placid, where we delivered record performance with net sales of $177.5 million, representing 12% year-over-year growth, driven by 9% volume growth. This reflects strong underlying demand for New Placid among patients with Parkinson's disease psychosis, or PDP, and the success of our commercial strategy coupled with the unwavering focus of our customer-facing teams on executional excellence. Referrals were a key driver of this momentum, increasing 21% year over year. This growth signals increasing awareness and confidence among healthcare providers in identifying and treating Parkinson's-related hallucinations and delusions earlier in the course of the disease. New prescription volumes grew 23% in Q3 compared to the same quarter last year, representing the strongest year-over-year increase since 2019, and were up 9% sequentially. This inflection point demonstrates that our patient engagement campaigns and HCP outreach are translating into tangible prescribing behavior. It also underscores their belief in New Plaza's differentiated profile as the first and only FDA-approved therapy for PDP with a well-established safety and efficacy record. Taken together, we believe these trends are an important leading indicator of future prescribing behavior and reinforce the strength of Nuplazid in meeting a critical unmet medical need. As a reminder, the US PDP market represents a significant opportunity. There are approximately 1 million Parkinson's patients with an estimated 50% experiencing hallucinations and delusions at some point during the course of the disease. This translates into a substantial number of patients who could benefit from Nuplasid, underscoring the long runway for growth. Looking ahead, we see significant opportunity to build on this momentum. Our reach and frequency model is driving broader prescribing patterns across a wide range of HCPs, and our direct consumer campaigns are raising awareness of PDP symptoms while highlighting Nuplasid as the first and only approved treatment. To fully realize Nuplasid's long-term potential and capitalize on the brand's strong momentum, we are making strategic investments, including a 30% increase in our customer-facing team starting in the first quarter of 2026. This expansion will allow us to reach newly-activated physicians, and improve pull-through. We are approaching this expansion thoughtfully to maximize near-term efficiency and long-term impact. Our various consumer initiatives are driving awareness and creating demand, with our expanded field force ensuring we efficiently convert that demand into prescriptions. In summary, the new PLASID fundamentals are strong. The market opportunity is substantial, and we have a proven strategy designed to capture it. With a differentiated product profile, accelerating demand indicators, and targeted investments in our commercial model, our ambition is not just to grow, but to become standard of care for these patients. I'll now turn the call over to Liz.

Thank you, Tom. I'm pleased to share some updates on our pipeline, where we continue to make encouraging progress across multiple programs that hold meaningful potential for the future. We've achieved some important milestones recently, including the successful initiation of our Phase II study for ACP204 in Lewy body dementia psychosis, and the initiation of our Phase III study of trofinetide in Japan. Looking ahead, our next expected milestone is the initiation of a Phase II study for ACP211 in the fourth quarter of this year. we are developing ACP211 in major depressive disorder, a common condition with significant unmet needs. Then in Q1, 2026, we expect to initiate our first in human study of ACP271 in healthy volunteers. To our knowledge, this will be the first time a GPR88 agonist enters the clinic, and it moves us along the path of development, targeting the indications of tardive dyskinesia and Huntington's disease. We also have important projected study readouts coming. We anticipate reporting results from four phase two or phase three studies between now and the end of 2027, underscoring both the breadth of our pipeline and the momentum behind our R&D strategy. Our next major readout is expected to be ACP204 in Alzheimer's disease psychosis in mid-2026. We're particularly excited about this opportunity and what success could mean for the future trajectory of our company. The unmet need here is substantial. The market opportunity is large, and we have built this program based on a substantial body of learning from Pima-Vancerin at both the molecule and the trial level. Now, switching gears to our international expansion efforts. First, I wanted to provide an update on the regulatory process in the EU for trofinetide. We've been informed by EMA that the earliest that a scientific advisory group could be held would be January. Given this, we now anticipate a CHMP opinion in the first quarter and the EC regulatory decision following the standard regulatory timeline. Meanwhile, in Japan, we've successfully initiated our phase three study, representing a key step towards potentially bringing Trufinitide to patients in this important market. Now, before I close, I wanted to take a moment to acknowledge and thank everyone involved in our COMPASS Prader-Willi Syndrome Study and the ACP 101 Clinical Development Program. We are so grateful for the dedication and contributions of the patients, families, study site personnel, and physicians who participated. While the outcome wasn't what we hoped for, we hope that learnings from the trial will benefit the Prader-Willi community and we're actively sharing our insights while we work to add the findings to the scientific literature. Our pipeline continues to represent a powerful engine for future growth as we look to advance therapies for underserved neurological disorders and rare disease communities. We anticipate continued activity across our pipeline over the coming years with multiple programs progressing through key stages of development. As a reminder, across our eight disclosed programs, we anticipate initiating five additional Phase II or Phase III studies between now and the end of 2026, demonstrating the depth and diversity of our development portfolio. And of course, we anticipate reporting four Phase II or Phase III study results in 2026 and 2027. And now, I'll pass over to Mark for a review of our financials.

Thank you, Liz. Let me walk you through our third quarter financial results. We delivered an excellent quarter that underscores the robustness of our commercial portfolio, which enables us to generate strong revenue and cash flows while continuing to invest strategically in growth opportunities. The third quarter was strong across the board with $278.6 million in total revenues, up 11% year over year. Debut achieved net sales of $101.1 million, up 11% year-over-year, all of which is attributable to volume growth. The gross to net adjustment for debut in the quarter was 22%. New Plaza delivered net sales of $177.5 million, up 12% year-over-year, with 9% of that growth attributable to volume. The gross to net adjustment for New Placid was 25%. Turning to operating expenses, R&D expenses were $87.8 million in the third quarter, up from $66.6 million in the third quarter of 2024, with the increase primarily attributable to higher clinical trial expenses from our ACP 204 LBDP and ACP 101 programs and personnel expenses. partially offset by lower clinical spend from programs that have completed. SG&A expenses for the third quarter were $133.4 million, essentially flat with the prior year. Turning to the balance sheet, we ended the quarter with $847 million in cash, compared with $762 million at the end of the second quarter. Looking ahead to our full year 2025 guidance, we're making targeted updates that reflect our strong performance and outlook. For New Placid, we're raising the lower end of our guidance range and increasing at the high end to $685 to $695 million, up from $665 to $690 million, reflecting the momentum we're seeing in the business. For Debut, we're modifying to include contribution from our named patient supply programs and narrowing our prior guidance range and now expect $385 to $400 million compared with prior guidance of $380 to $405 million for U.S. only. Regarding operating expenses, we now expect R&D expenses of $335 to $345 million compared with prior guidance of $330 to $350 million. For SG&A expenses, we now expect $540 to $555 million compared with prior guidance of $535 to $565 million. Our financial strength positions us exceptionally well to finish 2025 strong while making the investments necessary to drive sustained growth in 2026 and beyond. I'll now turn the call back to Katherine for closing remarks.

Thank you, Mark. As we wrap up today's call, I wanted to emphasize our commitment to finishing 2025, hitting over $1 billion in total revenues, positioning Acadia for continued growth in 2026 and beyond. We continue to be confident in the stability and growth trajectory driven by our new sales team for debut, reflected by the over 1,000 patients globally who are now on treatment. We're focused on unlocking New Plaza's full potential with our strategic field force expansion and proven patient engagement campaigns. And we now have the elements in place to further accelerate that growth. We are dedicated to advancing our robust pipeline, as Liz has described, and look forward to the four major readouts expected in 2026 and 2027. We also continue to focus on expanding our portfolio through business development, with our strong balance sheet providing flexibility to pursue partnerships and acquisitions. Ultimately, our mission drives everything we do, to turn scientific promise into meaningful innovation that makes a difference for underserved neurological and rare disease communities around the world. We are here to be their difference. I'm excited about what lies ahead for Acadia, and I'm confident that our strategic investments and unwavering focus on our patients will deliver value for all of our stakeholders. And with that, I'll turn the call back to the operator for questions.

Thank you. Ladies and gentlemen, if you wish to ask a question, please press star followed by 1-1 on your touchtone telephone. If it has been answered or if you wish to withdraw your question, press star 1-1 again. Please limit yourself to one question. I'll repeat. Please limit yourself to one question. Press star 1-1 to begin. And stand by for your first question. That first question comes from the line of Ritu Barrow with TD Cowan. Your line is now open.

Good afternoon, guys. Thanks for taking the question this afternoon. I wanted to ask about the expanded New Pleasant client-facing force. Catherine, how is that organized? Is it along the lines of focus on the newly activated prescribers? How should we think about it in terms of community versus long-term care facilities, which is a way that historically Acadia has broken up the population for New Placid? And which of those two has the most likelihood for continued growth as you see the market right now? Thank you.

Thanks, Ritu. Appreciate the question. I'm going to ask Tom to explain. He's been leading this charge for us, so Tom.

Good afternoon, Ritu. Thank you for the question. So as we think about the expansion that, as we mentioned, we plan on executing in Q1 of next year, there's a few different factors, I would say, are playing into our thinking. So as you think about kind of the new writer base, if we look at kind of dynamics during Q3, we actually saw that in terms of our overall prescription volume, 26% actually came from new writers. So I think this really talks to the way that our campaigns are working, the execution of the field force, and it's been that kind of underlying dynamic that we've actually seen throughout the year but actually accelerated in Q3 that's really given us the confidence to pull forward this investment into Q1 of next year. In relation to your question regarding community versus LTC, actually we're seeing growth across all channels. We're seeing growth both in the community setting and in the LTC setting as well. And there are various channels that we see the new passive scripts being pulled through. So in essence, we're investing in both. If you're looking at it from an absolute kind of percentage terms, we're actually investing slightly more on a percentage basis in the community. But at the same time, we are going to be modestly increasing our LTC team, just given the dynamics that we're seeing in that space as well. Long story short, we're investing in both and at the same time making sure that wherever we see a new pleasant script, we're able to pull that through as optimally as possible.

Thank you.

Thank you. Your next question comes to the line of Yigal Notramoffitz with Citigroup. It's now open.

Hi, great. Thank you very much for taking the questions. I have one on ACP 204. With the top line data for Phase 2 coming out middle of next year, I'd be curious if you could comment briefly on what you would see as a clinically meaningful score on the SAPS-HD score, and also if you could just discuss related to that why that particular scale is a good one to use in this context. Thank you.

Thank you, Gal. Liz is leading that for us, so I'm going to ask her to comment on the scales and the confidence around both of them.

Yeah, absolutely. Thank you. So I'll go in reverse order, I suppose, and start with SAS H&D and why we landed there for Alzheimer's disease. So SAS H&D is actually an endpoint that we do have some experience with in our prior PIM of answering trials. It was involved in the Pivotal Study for PDP, and it was also part of the relapse criterion in Harmony. And so overall, we feel like we have a good understanding of that endpoint and its responsiveness. It is well set to measure the domains that we think are important in this patient population. And it's one of several endpoints that are in the literature that are supported as being relevant for this patient population. We are measuring other things as well. So that is how we landed on this as the primary endpoint for the phase two portion of this study. In terms of how we're looking at this, first I'll note the powering piece, and then I'll talk a little bit about what we're looking for in this trial. In terms of how we sized the trial, we actually did this on effect size, and so we're looking for roughly a moderate effect size, a 0.4 effect size on SAP's H&D. But really what we're looking for in the phase two is to continue to understand how we progress towards our overall target product profile for 204. And that certainly has an efficacy component to it, but it also is about making sure that this is appropriate for use in this patient population. I think there are a number of important unmet needs here. Sparing cognition, avoiding daytime sleepiness or sedation, avoiding increasing risk of falls or fractures, avoidance of motoric adverse effects. So there's a number of things we're going to be looking for that we feel good about based on what we know about TRUE or FOUR's profile, but we're sort of holistically going to be looking at the profile of the drug in this trial.

Thanks so much, Liz.

Great. Thank you.

Thank you. Your next question comes to the line of Tess Romero with JP Morgan. Your line is now open.

Hey, Katherine and team. Good afternoon. Thanks for taking our question. So, for Debut, you cited the highest quarter-over-quarter referral growth since launch this quarter. Double-clicking, how do you think new patient starts will look sequentially here over the next few quarters in light of the growth you are seeing? And the second one is just a quick housekeeping. When do you think you will finish enrollment in the Phase II trial in ADP? Thank you.

Thanks, Tess. I'll ask Tom to kick off about the referral dynamics we're seeing, and we saw in the quarter, and then Liz can talk about that as well.

Yeah, good afternoon. So thank you for the question. In terms of debut and referral dynamics, we're really encouraged by what we saw in Q3. We saw actually our highest rate of referrals since essentially launch. And if you look over the last 12 months, you know, we're really growing at a pretty decent rate now, which is very encouraging. In terms of pull through, you know, just given standard dynamics that you would expect, it does take some time for a referral to then become a actual new-to-brand prescription. Given the dynamics that we saw during Q3 and the acceleration that we saw, we would anticipate that we'll continue to see growth in actual patient counts through Q4 into 2026 and beyond.

Melissa, do you want to touch on that? Oh, right. Sorry. 204. So, again, just reiterating the predicting mid-year for top-line results here. We're really keeping a careful eye on enrollment for the right patient populations. I don't have an exact date of final enrollment here, but we anticipate that that would be occurring sort of in the, you know, Q2-ish timeframe to enable that mid-year.

Thank you.

Thanks, Jen.

Thank you. Your next question comes to the line of Brian Abrahams with RBC Capital Markets. Your line is now open.

Hey, good afternoon. Thanks for taking my question. Congrats on the quarter. Maybe another question on 204. Can you talk a little bit about maybe the overall study conduct, how you're feeling about that, and are there any I guess, have there been any or will there be any looks at the blinded safety data that might inform the potential around having the QTC prolongation advantage or anything you could learn about things like risk of falls or some of the other aspects of the profile that you talked about that could give you kind of an early read into that? Thanks.

So the first overall, you know, pleased with how the study is progressing thus far in terms of, you know, behavior of sites, investigators, the patient population that we're getting in there. You know, we are laser focused on making sure that we are getting the right patients in here trying to, not trying to, we are verifying them with biomarkers to make sure that this is a biologically confirmed Alzheimer's diagnosis, which we think is going to be important. You know, from a blinded safety perspective, I'd say a couple of things. You know, we do have a DSMB that looks after this on an ongoing basis, so we would get, you know, any indication of anything that is concerning from that perspective. And thus far, they've been supportive of continuing the study on as planned. And we do monitor on an ongoing basis from just sort of medical monitoring perspective. I don't like to comment on data from ongoing blinded trials because you never really know how that's going to sort out across arms.

Thanks, Liz. Thanks.

Thank you. Your next question comes from Ash Verma with UBS. Your line is now open.

Hi. This is for Ash. Thank you for taking our question. Just wanted to get back to the risk-adjusted peak sales guide that you have provided at your R&D day. What is your latest thought on the 2.5 billion and 12 billion peak sales you provided on risk-adjusted and nominal basis?

It was a little bit difficult to hear, but I think what you asked was how we're commenting on our peak potential that we talked about at R&D day. and our expectations for the commercial portfolio within that same discussion. Let me talk about the overall aspirations for Acadia. R&D day, we shared that we aspire to achieve a $12 billion top line should all of our pipeline programs hit during the next two to three years. And as you know, unfortunately, our 101 program did not hit. And so we would take about $800 to a billion from that top line expectation. So we would now, if we were speaking about the same thing, aspire to achieve the $11 billion total peak sales of our currently shared portfolio within that same group of compounds. In terms of our commercial aspirations, we shared the $1.5 to $2 billion for our commercial brands, New Pleasant and Debut, and we are still absolutely committed to deliver on that and look forward next year to showing a little bit more clarity about both of those brands and our expectations for each of them so that you can understand where we see both of those in the next two to three years.

Thank you.

Thank you. Your next question comes from the line of Sam Beck with Deutsche Bank. Your line is now open.

Hey, team. Sam on for David Wong. Thanks for taking the question. Just a quick one from us on New Placid. If you could just provide a little bit more detail on any drivers you're seeing behind the higher average net selling price in the quarter, that'd be great. Thanks.

Yeah, I'll start to take the net selling price question around New Placid.

Yeah, I think at this point, you know, I think when you take all the puts and takes that go into pricing and the fact that you know, the majority or the super majority of sales for New Plaza or for Medicare-based patients, kind of our year-over-year pricing, you know, is about the rate of inflation. That's been our expectation the whole year, except for the kind of one-time pricing benefit in the first quarter, and that's really what we saw in this quarter.

Thank you, Sam. Thank you.

You're next in the line of Evan Siegerman with BMO Capital Markets. Your line is now open.

Hi, Malcolm Hoffman on for Evan. Thanks for taking our question. For debut with the CHMP opinion expected in the first quarter next year, how can you make sure scripts kind of get off the ground quickly after what could be a positive opinion there? Thanks.

I'll let Tom take that. He's leading our European team. We're all getting ready for that right now. So Tom, why don't you share our plan?

Absolutely. So thank you for the question, Matt. So as you'd imagine, there's a significant amount of energy being put behind our launch readiness planning in Europe. We're going to be following kind of the standard track that you see for any approval in Europe. So we will be out the gate first in Germany. And I can tell you we're already gearing up to make sure that the team is ready to go there. So we already have a small group of key account managers. We have a handful of folks working on the medical side of the organization. And they've been very actively engaged already with prescribers, well, actually with rat treaters from across the universe. I mean, as you'd imagine, each of the European markets looks very different to the US. But we are making sure that we have the right infrastructure in place. right focus in place and I'm pleased to announce that actually in this quarter we opened our compassionate use program in Germany and have already had a number of requests from German HCPs to enroll their RET patients in that program which we think is a very nice kind of early indicator of enthusiasm to use the product and obviously we'll be making sure that that experience is positive as we build out towards the launch.

Do you want to share a little bit more about the other countries who have also opened their programs in the last quarter?

Sure. So I'm also pleased to announce that we have just opened programs in Italy and France. Again, we're pursuing wherever the regulatory and legal frameworks allow us to do so, and early engagement programs. And as we mentioned on the call, we also have our ongoing rest of world patient access programs as well, which again, encouragingly, we continue to see ad hoc requests in an unsolicited fashion coming through to the council.

Thanks, Tom. That's the question.

Thank you.

Your next question comes to the line of Sean Lyman with Morgan Stanley. Your line is now open.

Good afternoon, Catherine and team. Hope everyone's well. I have a question on the 30% increase investment to New Placid. I guess, could you describe in percentage terms how many new prescribers you might be reaching with that investment, and what's the headroom there before you get near saturation? And if you can provide any guide on quantifying what the cost of that investment is, it'd be really useful. Thank you.

Yeah, I'm going to let Tom talk about the increase, and we'll go from there.

So, you know, as I mentioned a few minutes ago, you know, we actually saw a very nice uptick during the quarter in terms of new prescriptions increasing through actual new writers, which is, you know, over 25% in the quarter. As we look ahead to kind of opportunities for growth and as we've really kind of done a deep dive on what that assessment looks like and where we see the opportunity, you know, we see a ton of opportunity across a wider group of customers that we've been actually calling on to date. Just for reference, you know, historically speaking, we've generally called on neurologists, we've called on some movement disorder specialists, and some psychiatrists. But as we look at that 26% who are new to writing prescriptions for New Plazas, you know, a ton of those are now coming from primary care. They're often nurse practitioners or advanced practitioners that are now writing New Plazas. And in reality, we want to ensure that wherever that prescription is written, whether it be for a patient in the community or in the LTC setting that we're really highlighting the benefit that New Glasset can offer. And just as a reminder in terms of headroom, our share in terms of MBRX remains in the mid-20% range. So if you just think about the upside-off opportunity that we have, given the size of the overall PDP population in the U.S., there is still significant headroom for growth, and that's what we're aiming to tap into in 2026.

And I'll let Mark share a little bit more about how we plan to – make that investment.

Yeah, I think in terms of people, it's about 50 customer-facing reps. I think you can certainly use standard benchmarks for what that cost is. We don't dive into the exact cost at this level of detail, but consider 50 reps plus some home office support and other things that go around that for the kind of overall investment. And we'll just share this kind of within you know, our guidance for SGA expenses next year.

Okay. Thank you, everyone.

Thank you. Thanks a lot.

Thank you. Your next question comes to the line of Tezeen Ahmad with Bank of America. Your line is now open.

Hi. Good evening. Thanks for taking my question. I maybe just wanted to ask about Why do you think now is the right time to add to the field force for New Plaza? And how are you deciding, like, what is the right size? Is this the final change or final increase that you think you need to make? Or are there certain targets that you might be monitoring? And if so, can you kind of share a little bit about how you were thinking about needing more or less people as this launch matures, thankfully?

Yeah, Tazine, let me start, and then I'll let Tom dive into a little bit more of the details. You know, I think as I came on board last year in September, the team had just started their DTC communications, both the unbranded and the branded, and we weren't sure how impactful that was going to be. We knew it probably would have some traction, but again, and we hadn't really been in the DTC space for a while since pre-COVID, and we wanted to understand the impact of that type of DTC investment. We've now got a year under our belt, and we can see, and you can see in the numbers, real traction in terms of carers and their families being made aware of what the symptoms of Parkinson's disease can be beyond motor. And then those sort of awareness levels now translating into moving into the physician office, and physicians now Also with our increasing real world evidence and data generation around New Placid being confident in prescribing it for the right patient to treat their hallucinations and delusions. So all of those metrics have come together. And with the important IP win that we had for New Placid allowing us to continue to feel confident about our IP runway in the US, we felt it was time to reassess the opportunity for New Placid. Tom's been leading that reassessment and from that he has made the decision and we have as a management team that it's right to invest now and so maybe Tom you can talk a little bit more about some of those investment decisions.

Yeah I mean I think Catherine captured it really well I mean it's really been a story of momentum this year for New Placid and Q3 in particular has really seen this kind of step change in how we're seeing referrals across the board and you know I think Given that momentum, that gave us the opportunity and the lens to really have another look at what our customer model looked like, especially as you think about the world where we're seeing a number of new prescribers outside of our core kind of target base really beginning to latch on to the benefit that New Mazard can offer and really engaging with this community in terms of where they're engaging with healthcare professionals, which, as a reminder, it can be quite challenging to get time with a neurologist or with a PDP specialist. And we think that with this expanded reach, we'll be able to actually help these patients really understand the benefit that they can afford and see with New Placid beyond what we're doing today. So it's about really capitalizing on momentum and then ensuring that we have the right structure in place for both today and tomorrow, to your question, that we believe will put us in a really very strong position to maximize the opportunity ahead.

And just a final thought, you know, we've been very focused at Acadia on ensuring that we are building a company that's built on a foundation of analytics and insights and data. And within the new expansion, it's been fueled by analytics, data, and insights, and we'll be using both that and AI on top of it to ensure that we really efficiently now find our patients and target them. And so I think the combination of the new data being sort of driven by a focus on analytics, technology, We have a new CIDO in place to help us drive that, and so I feel very confident that it will not only be an efficient focus, but also a very effective one. Thanks for the question.

Thank you. The next question comes from the line of Jack Allen with Baird. Your line is now open.

Great. Thank you so much for taking the questions, and congrats to the team on the progress made over the course of the quarter. I wanted to ask on the European Opportunity for Debut. I just wanted to engage people's opinion on how to think about reimbursement.

Jack, you just cut out the end. I heard reimbursement in Europe. Could you just maybe just repeat the question for us?

Yeah, sorry about that. I hope you have me better now. Yeah, I wanted to ask about reimbursement in Europe. I know there was in Canada over the summer. I don't know what your thoughts are and your early conversations are around payers in Europe ahead of a potential European launch for Debut.

Thanks, Jack. So, yes, we are obviously in the middle of discussions and thinking right now around reimbursement in Europe. And you're right, we did have a disappointing decision in Canada. Tom, do you want to share a little bit more about how we're thinking about reimbursement in terms of the sequential approach to that?

Absolutely. So, as I mentioned a few minutes ago, our plan would be that we launch first in Germany. And as a reminder, in Germany, as we launch, we have six months of free pricing, which we will obviously think very carefully about what that looks like, especially just given some of the other dynamics that we continue to monitor across the board, such as MFN. But, you know, I think given the engagement that we've already started with payers and clinicians, we remain pretty confident, actually, that, you know, our European clinicians and the broader environment are seeing the benefit that Debut can offer. And I think as we continue to generate new real-world evidence in the U.S., you know, we're going to ensure that we leverage that as we go into discussions with European payers and beyond as well. to really ensure that the value of debut is fully understood and realized across the markets where we're launching. So more to come, but again, I think we're excited about the opportunity in Europe and look forward to putting debut into the hands of many more patients who clearly deserve this treatment.

Thanks, Jack.

Thank you. Your next question comes to the line of Paul Matthias with Stifel. Your line is now open.

Hi there. This is Julian Unferpaul. Thanks very much for taking our question. I guess just on ACP204, I was wondering if you guys could clarify the exposure-response relationship you've sort of seen from PIMAvanserine and the work you've done on ACP204. You often allude to, you know, like your learnings that you've you know, learnings that you've had from development as well, you know, from an execution perspective as well as from, you know, scientific and biological perspective, and why you believe greater potency with ACP204 will translate to greater clinical benefit. Thanks very much.

All right. I'll try and get all the things that were in there. So, starting with the exposure response. So, Both in the Alzheimer's disease population as well as in Lewy body, we do have some information from Pimivantrin suggesting that with higher levels of exposure, you are able to get to higher levels of improvement on the clinical endpoints. And that the median exposure that we're able to achieve with Pimivantrin leaves some of that efficacy on the table. So it's sort of midway through that exposure response downward curve. And the reason for that, of course, is that unfortunately with Pimivanturin, there was a tendency towards QT prolongation, which limited the ability that we could dose range. So we were not able to push the average patient up to the near maximal efficacy that you could get with higher exposure levels. With 204, we don't have that problem. So thus far, our non-clinical and our clinical data are supportive of the fact that there is not a signal of QT prolongation here. And overall, our experience has been such that it is supportive of moving to our current clinical doses, which we're looking at in our Alzheimer's and Lewy body programs, where the lower dose is roughly equivalent to the exposure with the marketed dose of New Placid, and the higher dose is roughly twice that. So those are the pieces that give us some optimism that we have the possibility of exploring higher levels of efficacy. But even if we are not able to actually achieve higher levels of efficacy with the higher doses, we do think that there are some program learnings that we're able to apply here. Certainly, in both cases, we have programs that are focused specifically on the disease understudies. The Pimivanserin data in Lewy body is promising, but it's a limited number of patients. And the Alzheimer's program had a single dedicated study and then a subgroup in an overall study. So here we're going to be able to bring to bear much more robust data evaluating both of these disease states. So those are the things that we take together to give us some real enthusiasm about 204, which again we see as potentially having the possibility of really changing the trajectory of this company.

Excellent. Thank you.

Your next question comes to the line of Mark Goodman with Lyric Partners. Your line is now open.

Hi, good afternoon. This is Basma on for Mark. We have a question on debut. You mentioned that the penetration is lower in the patients older than 11 years old. Do you believe that the slower penetration is driven by the higher discontinuation in this older age group? The reason why we're asking this question is we would expect that the improvement in communication skills and other effects may be minimal. in the older patients, and maybe that's a lack of effect to drive greater discontinuations. And also, could you clarify whether the age of red patients in general seeking treatment is skewed to the younger age group, or it's basically uniform across a different age? Thank you. That's it for us.

Thank you. I think there's some important opportunities there to clarify what the data actually says about debut efficacy across the age groups and to share a little bit more about what we're seeing in the field. So Tom, do you want to answer it? And if, Liz, you've got any efficacy points to add on top, that would be good.

Absolutely. So thank you for the question. So, I mean, going back to the original premise, you know, do we think that the reason that we are slightly lower penetrated in patients greater than 11 years and older is just discontinuation? I don't think that that's the case. I mean, essentially what we have to remember is The vast majority of patients who have been treated so far, again, if we look at penetration by age, are those in the two to four age bracket. You know, newly diagnosed patients, they're easy to identify, and they generally fall under the focus of the sense of excellence. And I think that that's a group that we've been able to penetrate very early on. If you look at the last quarter, interestingly, 65% of our patients were actually older than the age of 11. So it's a group of patients that we believe that we can. really begin to penetrate further still. And especially with our Lotus real-world evidence generation, which as a reminder, has patients as old as 60 included in it, we do continue to see a group of, well, we continue to see patients seeing benefit irrespective of age. And this has been part of the strategy as we've extended our reach beyond the Centers of Excellence because many of these patients who are slightly older Unfortunately, you know, they sit within the community setting. They may not be under the care of a COE, and they may not even be aware of debut. In fact, we just heard about a patient's story yesterday for a patient in Kansas who was receiving debut for the first time, but before they came into this center had never even been made aware of debut. So I think it really does talk to the fact that we have more work to be done, both in terms of educating the community about what RET is and what to look for, and at the same time ensuring that they understand the benefit that debut can offer to these patients irrespective of their age.

Liz, do you want to enhance a little bit on that or is there anything you want to add about the data that we've shared?

Sure. I mean, so, you know, agree with everything that Tom said there. I think that, you know, going back even to the original clinical trial, there is supportive data suggesting that there's efficacy in patients above 11 as well as below 11, though, you know, it is a somewhat smaller proportion of our overall patient population. But exactly as Tom said, we've also been tracking these patients in Lotus as well and see evidence of improvement in those patients as well. So I think that it is an increasing body of evidence that supports the fact that Debut does bring benefit to patients in line with the indication, which is not restricted in terms of age and age.

Yeah, I think that's the key. We see a Debut efficacy across age ranges and We want to ensure that neurologists and treating physicians are educated about the data and don't have preconceived notions about specific efficacy and specific age groups. And that's a big focus of Tom and Allison and the team as we move into next year to really ensure that that data is shared specifically to encourage the physicians that aren't so well-versed in RET to really look at the data and think about it for all patients, not just younger patients. So with that, it's a good question.

Thank you. Your next question comes to the line of Amy Fadia with Needham and Company. Your line is now open.

Hi, this is Poole now on for Amy. Thank you for taking our question and congratulations on the quarter. My first question is we're seeing some IRA impact feedback coming for therapies such as Astido. Is there any read-through for New Plaza based on this? Is this more positive than you expected? And my second question is, how is ACP211 differentiated from Spravato and the emerging psychedelic class in depression? Thank you.

I'm going to ask Mark to answer the IRA question first, and then we'll ask Liz to talk about the differentiation of ACP211.

I think on the IRA, there's not a great comp yet. for Nuplazid as Nuplazid is the first and only approved therapy for its indication. And so it doesn't have competition with other branded agents, as well as we haven't seen a comp like that go through the IRA negotiation. So simply speaking, I think we'll see how this evolves as as in if New Plaza goes through negotiations or others in a more comparable situation, and that may or may not have read-through for what a New Plaza negotiation may look like.

And as far as switching gears, quite a lot to 211, as far as 211 is concerned. So we've designed 211 as an oral therapy, and what we're hoping for here is the potential for ketamine-like efficacy or spravato-like efficacy with a very different patient experience in terms of the degree of required in-office monitoring. And the data that we have so far supports that, both in terms of animal models, that suggest efficacy as well as lacking sedative impacts or dissociation. And in Healthy Volunteers, in our Phase 1 study, we've demonstrated the ability to reach high doses with no sedation and minimal dissociation. We think if this reads through in our upcoming clinical trials, we are looking to start this Phase 2 and 2.11 before the end of this year. And we designed this, of course, to look at efficacy, but also, very importantly, to rule out unacceptable levels of sedation and dissociation. So we think that there is a potential for a really appealing product here.

Thanks so much.

Thank you.

Thank you. Your next question comes to the line of Salveen Richter with Goldman Sachs. Your line is now open. Good afternoon. Thanks for taking my question.

On the LBD psychosis study, can you just help us understand the rationale for enrichment of the phase two with the additional patient groups, including LBPP and the PDP population, instead of just focused on Lewy body dementia psychosis specifically?

So, Lewy body dementia psychosis is sort of an umbrella term that actually encapsulates dementia with Lewy bodies as well as Parkinson's disease dementia psychosis. And so what we're looking to do in our Lewy body program is actually ensure that we're looking at roughly equivalent numbers of both of those two patient populations to understand any similarities and differences in terms of how they behave. This will help us in terms of designing what future studies could look like. When we look at the population in the Pimivanserin data set that is specifically that Lewy body dementia psychosis, The numbers are relatively small, but it is very promising data, and that's part of what had us move this program forward and part of what makes us amused about it.

Thanks, Salvi.

Thank you. Your last question comes to the line of Sumant Kulkarni with Canaccord Genuity. Your line is now open.

Grafnan, thanks for taking our question. You're investing more on New Placid and there have been some questions already about that. But we're finally seeing some excitement in the Parkinson's market and AbbVie recently announced a Salesforce expansion on the strength they're seeing for YLF and the potential approval for Tavapadon. So how do you think this additional focus on the Parkinson's market from a relatively large player might influence the market or diagnosis rates for psychosis associated with Parkinson's?

I'll start and then maybe give a perspective from Tom. I think, so let's just start by reminding everybody that Nuclasid is the only branded product approved for Parkinson's disease psychosis. But as we see more activity in an overall Parkinson's market, I think what history would tell us is that once more, once larger companies are in the market talking about Parkinson's disease more fulsomely with more people, there does tend to be an increase in terms of awareness of different elements of the disease. And as Tom has already alluded to, 50% of patients suffer from psychosis or suffer from the hallucinations and delusions of Parkinson's at some point during their journey. And so it wouldn't be unsurprising to sort of see that rate increase. What we do know right now is that there's a relatively low level awareness amongst families and caregivers of those symptoms, which is why we've been putting effort behind the unbranded campaign. And that would still have to be true because those sort of non-motor related symptoms generally go undiscussed and unfocused on by the physicians and their families. And what we have understood is that we need to continue to talk about them to ensure that those questions are raised As we continue to educate physicians with our expansion, Tom, I think we probably hope to see that the physicians are starting to learn more about it themselves. But I don't think without us it's going to be a sort of a natural place for them to go with other companies. What would you say on that?

No, I mean, one thing I would say, I mean, I think it's well recognized that Parkinson's in general is one of the fastest growing neurological disease types in the United States. As a reminder, there's estimated to be about a million patients with With Parkinson's in the US, and as we kind of then take a step down into those patients who are actually diagnosed with hallucinations and delusions, it's somewhere between 40% and 50% of that population at any given time. By our estimate, there's about 130,000 of those patients who are actually diagnosed with antipsychotic during the course of the disease. That's not to say there's more work to be done here, because I think if you look at Most patients, as they go through their Parkinson's journey, to begin with, they are fully focused on the movement elements of the disease. And unfortunately, not everybody is educated on hallucinations and delusions that can commonly concur. And I think one of the key calls to action that we're trying to drive at the moment, that if a patient, even if early in their disease course is experiencing hallucinations or delusions, that that is a trigger point to start treatment. That's a trigger point to make sure that they're engaging with an HCP, whether it be a neuro or it be their primary care physician, to make sure that they're having that dialogue to ensure that appropriate action can be taken. We believe that that's where, quite honestly, New Placid can play a really critical role, just given its profile, given its safety profile, and given the growing body of evidence that Catherine mentioned earlier on. I think taken together, you know, clearly more upside, and I think that that's one of the reasons that we have decided that now is the time to really up-invest in our customer-facing approach to New Placid as we look forward.

Now is the time is a great way, I think, to end that question. Thanks very much.

Thank you. Since there are no further questions, I'll pass it along to Mrs. Owen-Adams to proceed to close her remarks.

Thanks, everybody, for your questions.

We're really excited about what lies ahead for Acadia, and we look forward to our next call.

Thank you for your participation in today's conference call. This concludes the presentation. You may now disconnect.