Acadia Pharmaceuticals at TD Cowen Conference: Strategic Expansion Insights

On Wednesday, 05 March 2025, Acadia Pharmaceuticals (NASDAQ: ACAD) presented at the TD Cowen 45th Annual Healthcare Conference. The discussion highlighted the company’s strategic initiatives, including both opportunities and challenges. Key topics included market penetration for Debut (trofinetide) in Rett syndrome, expansion plans beyond Centers of Excellence (COEs), and the impact of Medicare Part D redesign on financial expectations.

Key Takeaways

• Acadia plans to expand its sales force by 30% to increase Debut’s market penetration outside COEs.
• The company is preparing for the EU launch of Debut, with managed access programs in key European countries.
• Medicare Part D redesign presents mixed financial impacts, benefiting NUPLAZID but challenging Debut.
• Strong Q4 performance for NUPLAZID, with 13% growth versus the prior year quarter.
• Ongoing advancements in Acadia’s pipeline, including ACP-204 and ACP-101, are expected to drive future growth.

Financial Results

Acadia anticipates sequential net sales growth starting in Q2 2025, following a decline in Q1 due to seasonal factors. The company expects US sales for Debut to range between $380 million and $405 million for 2025. Despite a 0.5% projected increase in net price for Debut, volume is expected to drive most of the growth. Medicare Part D redesign will act as a headwind for Debut, increasing rebates. For NUPLAZID, Acadia forecasts a sales range of $650 million to $690 million, with a 300 basis point improvement in gross to net due to Medicare Part D redesign.

Operational Updates

Acadia is focusing on increasing Debut’s market penetration, particularly outside COEs where only 25% of Rett patients are currently treated. The company is investing in peer-to-peer and family-to-family education programs to support community physicians and plans to expand its sales force by 30%. In Europe, Acadia is progressing with its EU application for Debut, with a managed access program launching in Germany, followed by France, Italy, and Spain. For ACP-204, Acadia is conducting a seamless Phase two/three program, while Phase three enrollment for ACP-101 is expected to complete by the end of 2025.

Future Outlook

Acadia is preparing for the EU launch of Debut, with a CHMP opinion expected in Q1 2026. The focus will be on managed access programs in key European countries to gather real-world evidence. For ACP-204, the company is using a seamless Phase two/three design to accelerate enrollment and data generation. The primary endpoint is the SAPS HD total score change from baseline to week six. A long-term extension will assess safety and response durability. ACP-101 enrollment is anticipated to complete by the end of this year.

Q&A Highlights

During the Q&A session, Acadia emphasized efforts to increase Debut’s penetration outside COEs and address GI side effects through new supportive care materials. The Medicare Part D redesign’s impact was discussed, with NUPLAZID benefiting from a 300 basis point improvement in gross to net, while Debut faces challenges due to increased rebates. Acadia’s targeted direct-to-consumer campaign for NUPLAZID is driving patient visits to physicians, contributing to growth.

For more details, readers are encouraged to refer to the full conference call transcript.

Full transcript - TD Cowen 45th Annual Healthcare Conference:

Ritu Baral, Analyst, TD Cowen: I’ll go ahead and get started. Thank you, everyone, for joining us for the Acadia Pharmaceuticals Fireside Chat here at the forty fifth Annual TD Cowen Healthcare Conference. I’m Ritu Baral, covering Analyst. And with us from Acadia, we have, starting on that side, Catherine Owen Adams, CEO Doctor. Poni Subbiah, Chief Medical Officer and Mark Schneier, CFO.

Thank you every thank you everyone for joining us. So let’s start with Debut. I think most of the focus, investor focus on the on the name is still Debut. You’re expanding your sales force by 30% to help drive patient starts, specifically outside Rett Centers of Excellence. Can you review for us the current penetration rates in Centers of Excellence as you see it, high volume institutions and community practices respectively?

Sure. So right now, we believe there

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: are about five thousand five hundred to five thousand eight hundred Rett patients in The U. S. And from the data that we’ve gathered, we believe about thirty five percent of those patients are treated in the 21 or 22 now COEs that exist in The U. S, which means about sixty five percent of them obviously are treated outside those centers of excellence. And up until now, we’ve had a very strong focus, as you would imagine, in a rare launch, you do focus on the Centers of Excellence to get the KOL community engaged in the product, understanding it and writing it because those are the people that the community physicians look to for guidance.

We’re sort of now coming into our second full year of launch, and we believe there’s a lot of opportunity outside of the Centers of Excellence to drive volume growth for debut. Within the Centers of Excellence, we’re about it’s varied, but we’re about fifty percent penetrated in terms of patients that have tried Debut. Outside, so the sixty five percent of patients that are treated outside, we have a twenty five percent penetration. So in terms of that opportunity to drive volume growth, it’s definitely sitting outside the centers of excellence. Up until now, our reach and frequency back to the old fashioned reach and frequency model with Salesforce has been that we haven’t been able to get to those physicians with the right frequency.

And so on average, those physicians have seen an Acadia rep maybe once or twice. And that’s not enough to get them confident to prescribe debut. They might see one, two, three patients a year and it’s just not top of mind when you’ve only seen that many representatives. So really the logical focus now is to ensure that we have enough representatives to reach that group at the right frequency. So you mentioned something interesting.

You said now 23 centers of excellence. 22. Yeah. Oh, it’s it’s 22. Okay.

Is there a new one? Or I think Miami is just big.

Ritu Baral, Analyst, TD Cowen: Yes. There were Okay.

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: The three that were added last year including

Ritu Baral, Analyst, TD Cowen: Miami. Okay. Is is that something is that something we should watch out for? Are there increasing centers of excellence for for a broad swath of care? One thing we noticed when we were doing our, tracking surveys is that there was this giant hole in the, like, Northwest, like, over here.

We because we were trying to survey a good geographical distribution, and there seemed to be

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: giant holes in parts of the country. The IRS? Centers.

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: Yeah. So IRSF, I think, in collaboration with the directors of the current COEs Mhmm. They’re very much committed to ensuring there’s centers of excellence across the country. But each of the centers have to meet a certain criteria and experience to get there. And and that’s why they do have to fit in applications, it gets reviewed.

And so it is encouraging that now they’ve added more centers in different parts of the country, which is helpful because not all patients are able to travel Exactly. Those distances.

Ritu Baral, Analyst, TD Cowen: Exactly. Okay. Great. And then, going back to what you said, Catherine, about the community setting, Are you guys developing new materials, supportive care products such that that are more tailored to a community setting in managing the GI side effects because the more community you go, the less time these

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: The less time and the less infrastructure. So the COEs generally have a lot more infrastructure in terms of additional physicians, nurse practitioners, etcetera, that can manage the other parts of the patient care. Outside of those centers, it’s maybe one or two physicians in the practice. And so what we’re doing, and Poni’s team are responsible for this is putting in place peer to peer education programs. We’re putting in place family to family education programs so that we can sort of start to talk about best practices.

I don’t know if you can talk about anything else we’re putting in place to help those extra community physicians.

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: I think as Catherine mentioned, you know, in the community, we need to be able to educate because they’re seeing maybe one, maybe two patients in their practice. So what we’ve done is in addition to publishing the GI management strategies, for example, most recently, the anti epilepsy meeting, we did a survey of the COE directors, like how were they managing debut. We have presented that poster so that one of the things we hear from these community physicians is they wanna learn from these experienced practitioners. So through publications, through our medical team, through our Salesforce team, we are going to be able to share this information so they can leapfrog from the learnings from the COE directors. Got it.

Got it.

Ritu Baral, Analyst, TD Cowen: In the non COE setting right now, is it really just the mind share question that is the gating factor? Or are they I guess, are they hesitant to use Debut because of the manpower burden of managing the patient early on in titration?

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: I think that they are they very much I mean, clinicians in the community, when they do see them, they want to be able to provide best of care. Right? At the same time, they are more constrained in the resources like Catherine said. Like, they don’t have a GI specialist that may be there. And so one of the things that’s gonna be important is we become a very important source of information for these physicians.

And that’s why expanding our field team members to be able to, you know, have more frequent contact with them is going to be very important.

Ritu Baral, Analyst, TD Cowen: Is assistance with insurance coverage and back office support also an element of this?

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: Yes. So we’re investing in more reimbursement specialists to support the offices.

Ritu Baral, Analyst, TD Cowen: Is this part of the 30%

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: It is. Yeah. So we now have dedicated reimbursement specialists that are aligned to different parts of the country. So that offices who are having, maybe they’re doing a PA to label that they’ve been asked for additional documentation, that our reimbursement team will sort of help them through that. We’ve learned over the last two years that that it depends on the payer.

It can be a little bit of a paperwork burden. So we are investing in more people to help support the back office. Got it.

Ritu Baral, Analyst, TD Cowen: And are these doctors managing towards a different goal than COEs? I know you mentioned, you know, they wanna be able to offer and they wanna be able to help their patients. But, you know, what is I guess, as we think about dose titration, what are they dosing towards versus what centers of excellence dose towards?

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: Yeah. So I think, so first, you know, I think the the main thing is that we’re focusing on right now is the early experience for these patients. So, one of the things we’re sharing is, first of all, they need to better understand what debut is and how it is used and, also sharing, as I mentioned earlier, from what the experience of the COE directors. Mhmm. And the other important thing is we want them to be able to articulate what the benefits of the drug is.

It’s not just about GI management. Right? So and we need to have them have a successful conversation.

Ritu Baral, Analyst, TD Cowen: What’s the point of titrating it up in order to even, you know, risk

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: that time to see. So they need to give time to see the benefit. It’s a very it’s a chronic neurodevelopmental disorder. And so to be able to it’s very important the clinician helps set those expectations with the parent.

Ritu Baral, Analyst, TD Cowen: Mhmm. Got it. And and so going back to the COEs for a second, are there any additional resources or support that you think makes sense to deploy towards the COEs?

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: So we’re not taking our focus off the COEs. The expansion allows us to it’s an and strategy. So it’s the COEs now and outside. So what we’re doing right now is Poni said, a lot of the COEs have had quite deep experience in terms of managing these patients. So we’re using their experience to publish an additional sort of papers around GI management strategies.

We’re also using them to help teach through peer to peer programs, best practices. But there are physicians within the COEs that still maybe are a little bit on the sidelines. And so again, we’re going out to the maybe each CUI has three or four physicians that might prescribe, maybe one or two have. So we’re now focusing on maybe the others that maybe haven’t tried it yet or need just a little bit more information. Got it.

Ritu Baral, Analyst, TD Cowen: And then given these efforts in the expansion, how much debut growth should we expect in the second half?

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: Mark, do you want to take that one?

Mark Schneier, CFO, Acadia Pharmaceuticals: Yeah. I think for maybe we’ll split it between operational and financial and and we all talk qualitatively. So I think for for all the efforts that Catherine and Poni have been talking about, we expect, and I would you should expect kind of more operational pickup in the second half of the year Mhmm. Than the first half of the year. And when we talked about guidance, you know, on our last earnings call, you know, it’s the top of the funnel.

It’s referrals in the top of the funnel that are really make the difference within, you know, our range over the course of the year while we’re looking to continue to improve, like, as Catherine likes to send and, right, continue to improve all the other metrics, all the other metrics have kind of settled into a more narrow band at the moment, you know, roughly two years into launch. But if you’re thinking about for financial models, you know, how our quarterly net sales sequence could be, Keep in mind, we do expect a sequential decline in the first quarter due to mostly seasonal and net price impact. Right. So so once you factor that in, I would say if you look to q two, q ’3, q ’4 from a net sales standpoint, it should be more consistent growth starting from where we come out of Q1.

Ritu Baral, Analyst, TD Cowen: Got it. Actually, that leads to a very interesting question on Q1 seasonality given the changes in Medicare, Medicaid, out of pocket caps and the way that Wall Street is usually modeled Q1, but down Q1, increased gross to net, lower percentage lower market share due to patients switching and also greater gross to net because of the doughnut hole. How should we think about that going forward with the redesign? Is is it should should it be an amplification of what we had previous years? Or It’s

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: actually quite a different way of thinking about it, I think, Mark.

Mark Schneier, CFO, Acadia Pharmaceuticals: And I think there’s it’s it’s both debut and new plaza, but it’s slightly different for for both metrics.

Ritu Baral, Analyst, TD Cowen: We’ll go back to debut in Europe in a second, But if you could address that

Mark Schneier, CFO, Acadia Pharmaceuticals: So I think for us, right, on so the Medicare Part d would deal let me kind of expand from there, but start with your specific question. So for for for NUPLAZID, it’ll be a tailwind and for Debut, it will be a headwind. And the reason why I say that for the difference is is NUPLAZID, on Debut, we’re starting there. We do have less than ten percent of our patients are Medicare kind of primary payer responsibility. But what’s happened between the Medicare Part d redesign for DaVue, since DaVue was launched after August 2020, even though we as a company qualify as a small manufacturer, DaVue doesn’t.

Oh. Right? So they’re

Ritu Baral, Analyst, TD Cowen: Oh, because it’s your second product?

Mark Schneier, CFO, Acadia Pharmaceuticals: No. Because the the drug launched after a cutoff in the leg in the legislation.

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: Gotcha.

Mark Schneier, CFO, Acadia Pharmaceuticals: So because of that, our actual rebates on Debut will increase year over year.

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: Okay.

Mark Schneier, CFO, Acadia Pharmaceuticals: So when we’re thinking when we talked about overall net price for Debut year over year on our quarterly guidance call, midpoint of our range, we expect about a half a percentage point increase in net price. The vast majority of our increase in guidance is volume. Right? And so I think that’s those dynamics flow through for debut. And I think what you’ll think see for both medicines, while the impact of inflation having kind of a general net realized price increasing over the year, there won’t be the seasonal quarterly changes amongst either drug.

There actually wasn’t on debut historically, but it still won’t be. On NUPLASID, it’s the other way. Right? So we do qualify as a small manufacturer, you know, under the legislation. NUPLASID qualifies.

We’ve talked with the investment community. We expect to just isolating the Medicare Part d redesign, we expect a 300 basis point improvement, so reduction in gross to net which

Ritu Baral, Analyst, TD Cowen: For 2025 and and the net sliding scale.

Mark Schneier, CFO, Acadia Pharmaceuticals: Right. And so and and and then but our overall gross to net is not quite 300 basis points down just due to other changes in normal mix. And and then but then for New Plaza, as I said for Debut, New Plaza, we saw this big seasonal adjustment for for first quarter being the highest, second and third quarter being lower, and fourth quarter gross to net being slightly higher, we don’t we won’t see that going forward. DayView will the new plaza will be more consistent gross to net throughout the year.

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: Got it.

Mark Schneier, CFO, Acadia Pharmaceuticals: And so any seasonality in the first quarter for both medicines will be volume driven insurance reauthorization, kind of typical Q1 seasonality for a volume basis, not necessarily, the gross to that price impact that you’ve seen in past years.

Ritu Baral, Analyst, TD Cowen: Understood. Understood. Okay. Let’s move back to trofenatide or debut in the EU. You’ve guided to expected CHMP, I believe, in the first quarter of twenty twenty six.

How is that application going? First of all, have you gotten the first round of questions back?

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: Not yet. So our day 120 questions come in Q2 and we’re preparing for that. We put in our package of the lilac and lavender data. What was nice about the EU application was we were able to put a little bit more in terms of our real world evidence with LOTUS. So it’s a little bit more of an expanded package of data that the EU will appreciate because obviously there’s a strong focus in HTA markets on that sort of real world evidence.

So the team are expecting that to come in Q2. So everything is tracking according to plan. Who are your rapporteurs?

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: So I’m Pauline

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: from The Netherlands. Yes. Okay. With Netherlands having extensive experience with rare disease. I think all of our our rapporteurs appear to be very experienced and, we we we’re very confident and and happy with our rapporteur interaction so far.

Yeah.

Ritu Baral, Analyst, TD Cowen: Great. As we think about centers of excellence and concentration of care in The EU versus U. S, how should we be thinking about that?

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: Unfortunately, it’s a little bit of a country by country situation. But let me talk about the larger markets to help sort of guide the thinking. Unusually for Germany, we actually don’t have a COE structure in Germany. It’s much more of a diffuse care of patients in what they are they describe with a German acronym that I won’t summarize, but they have about 120 centers that treat children with neurological disorders throughout the country, and that’s where our rep patients are treated. Contrast that to France, where we have four or five key centers of excellence around the large cities as you would expect.

So those two countries just out the bat are very, very different. Italy and Spain seem to be much more along the lines of of France in terms of more centers of yes. And then as you sort of move out to the, what we call, the mid sized the mid sized countries, it’s it’s a little bit much more of one or two centers of excellence. So Germany is probably the the biggest outlier in terms of treatment in Europe.

Mark Schneier, CFO, Acadia Pharmaceuticals: Where does

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: UK right now, is more of a centers of excellence approach, and and we’re examining The UK in terms of our our overall strategy, whether we will or will not launch in The UK because of the NICE

Ritu Baral, Analyst, TD Cowen: pre launch activities, what do you have going on in Europe and what geographies will you be concentrating commercial investment in even before?

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: So we’re building up our team in Zug in Switzerland. We’ll have a sort of small European core there. We’ve just hired quite a few new people, but we’ve actually had our MSL team out in the field for about six months. Six months. And Poni and I were out there in January to meet with them.

So they’re out there right now mapping all the centers of excellence, giving us this insight that I’ve just shared with you.

Ritu Baral, Analyst, TD Cowen: Mhmm.

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: And I would just say that the interest in Europe is very strong. And we have a lot of centers that are very keen to use debut. And so that’s why we have decided, as we announced on our call, to go ahead with a managed access program in Europe and allow access to debut prior to approval.

Ritu Baral, Analyst, TD Cowen: And what geographies is that allowed in? I think it’s France and Italy.

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: Right now, Germany will go first, France, Italy, and Spain.

Ritu Baral, Analyst, TD Cowen: Germany has a managed access

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: They do. They do. And so we we are able to to tap into all the different regulatory and legal systems. And, you know, some is charged, some is free of charge. It’s it’s it’s different by country, but we are responding to clinician interests and ensuring that patients have access to debut before we launch.

And we think that’s important because the physicians in Europe were not part of our clinical trial program. And so we’re really trying to ensure that the experiences that they have are guided by our learnings in The U. S. And that we have our MSLs out there able to support them prior to launch. So that when we do launch, we feel very confident about the uptake and the ability for those physicians to prescribe with knowledge.

Ritu Baral, Analyst, TD Cowen: For the part of it that is charged, will you be keeping, like, will you be keeping a reserve on the revenues? Mike, do you

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: want to talk about how we’re gonna?

Mark Schneier, CFO, Acadia Pharmaceuticals: Treat? Well, most of it for what’s charged will just be

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: revenue. Okay.

Mark Schneier, CFO, Acadia Pharmaceuticals: Right? There’s some maybe in some particular jurisdiction, if there’s, you know, future rebates regarding, you know, final price, there’ll be some, you know reserve or net sales adjustment because of that, but that’s like the minority.

Ritu Baral, Analyst, TD Cowen: So there’s no clawback in the majority of these measures?

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: There is, but we understand the clawback system and how it works. We will reserve according to that. I think just to be clear, our guidance this year, the 380s to the 405s is U. S. Only sales.

We’re not guiding to include any outside of U. S. Sales because we just sort of don’t know right now. And as we proceed through the year, we all sort of give more clarity to that, but our guidance is excluding any sales outside The US. Got it.

And then as you approach these health technology assessments, will

Ritu Baral, Analyst, TD Cowen: the patients on these expanded access programs and, you know, your relationships with the KOLs assist in final pricing procedures?

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: Can you talk to some of

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: that? Yeah. So so we’re actively right now interacting with thought leaders in Europe. So for example, as Catherine mentioned, when we were in Europe in January, we met with one of the top leaders in France. Mhmm.

And she’s very supportive, very excited about having debut for as a treatment option for her patients.

Ritu Baral, Analyst, TD Cowen: Mhmm.

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: In addition, we’re actively interacting with the patient advocacy groups, just as we have done in The US. They are also going to play a key part in ensuring that their voices are heard and they’re very, you know, very supportive of having a debut as an option for their loved ones. Got it.

Ritu Baral, Analyst, TD Cowen: Great. So we’re gonna move on to 204. Unfortunately, we have less than ten minutes left already. Yeah. We’re gonna move on to 204.

So this is your next generation neuplexa, essentially, five HT HT2A agonist in development for ADP and now also Lewy body dementia. Can you walk us through the design of the seamless Phase twothree ADP study and timelines for enrollment and data as you see them right now?

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: Okay. Yeah. So, again, as you mentioned, ACP two zero four is our next generation of the five H2A inverse agonist antagonist. Now, we’ve really leveraged a lot of the learnings to develop two zero four. So right now, the phase two, three program is divided into two parts.

So part one has the phase two study, which is a dose confirming and efficacy confirming study. Part two has two three phase three studies, which are efficacy confirming studies. Now we intently, intentionally designed these studies to be very similar to accelerate enrollment and for a seamless design. So all three studies are six weeks in duration. They are double blind placebo controlled.

They have three parallel arms, placebo, thirty milligrams and sixty milligrams. And we’re targeting approximately 318 patients for enrollment in each of these studies. And the primary endpoint is the SAPS HND, also called the scale for positive symptoms, assessment of positive symptoms, specifically hallucinations and delusions. And that’ll be a total score change from baseline to week six.

Ritu Baral, Analyst, TD Cowen: Got it. What informed your decision to use tau based serum biomarkers during patient enrollment?

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: Yep. So, you know, as a neurologist, I’m very excited with how much the science has advanced in Alzheimer’s disease. And one of that is actually in the area of diagnosis. So when I was practicing and even some of the clinical trials we have done, the enrollment of patients into the trials were based purely on clinical criteria that was set by the National Institutes of Aging and Alzheimer’s Association. But now with the advancement of the science and biomarkers, the field is definitely enlarging in research as well as in clinical practice.

And even the FDA is very much, you know, asking companies that are going to work in Alzheimer’s disease to include biomarkers to ensure the patients that are including in the trials are actually true Alzheimer’s disease. And so that’s one of the reasons we’ve included that as screening criteria. Got it.

Ritu Baral, Analyst, TD Cowen: Can you talk to the buy in that you have from FDA on the SAPS HD? And can you talk a little bit about powering of the study?

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: Yes. So, the SAPS HD, again, it specifically targets the symptoms that of psychosis, which is hallucinations and delusions. Yep. And, so we have been aligned with the FDA on the design of the study, including using the total the total score, the change from baseline. Also, the design of the study is six weeks for the double blind phase followed by a one year long term extension look at looking at the safety, tolerability, and the durability of the response.

And this was felt to be sufficient to meet our goals in terms of getting approval. Got it.

Ritu Baral, Analyst, TD Cowen: And and the effect size in powering?

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: Yeah. So we don’t specifically share specific assumptions related to powering. But what I can say is, you know, we have a lot of learnings and data from the pimavanserin study and we’ve done extensive work in the phase one study with two zero four that has really helped us design the study both from the duration as well as the endpoints that we selected as well as the dosing. So could the prior Pima studies provide a

Ritu Baral, Analyst, TD Cowen: fair assumption of what placebo is expected in these studies?

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: Yes. Okay. Both in this as well as in other Alzheimer’s studies just in terms of

Ritu Baral, Analyst, TD Cowen: the disease progression. Got it. Well, HARMONY was a randomized withdrawal study. Why why not pursue randomized withdrawal with two zero four?

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: Well, I think, learnings from that experience, I think we we felt that having a single withdrawal study would probably not lead to approval. Mhmm. And I think, what we’ve learned is you need to have parallel group design. And as I mentioned earlier, because we want to have accelerated enrollment, we intentionally decided to do a seamless design and with three studies that are very similar in endpoints and duration. Got it.

Ritu Baral, Analyst, TD Cowen: How do you think of the three studies as registrational studies? You’re basically saying if one Phase III fails that you could file on the Phase IIIII together as the two pivotals. Is that first of all, is that correct? Like, does the Phase two generate all the data points needed? And also within the trials, are you generating any sort of durability data that FDA might be looking for?

Yeah. So first, the

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: let me answer the second question first. The durability, as I mentioned earlier, we are going to be have a long term extension of one year, so that’ll allow us to see the safety, tolerability, and exploratory efficacy.

Ritu Baral, Analyst, TD Cowen: Exploratory efficacy. So you’re still taking the SAPS HD

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: out that long term? But the primary part of the long term extension is usual as safety. Mhmm. Yeah.

Ritu Baral, Analyst, TD Cowen: Are there any requirements from FDA or questions from FDA on that twelve month SAPS safety data?

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: No. It’s definitely having intermittent assessments. And with regards to your first part of that question, you know, whether, you know, we’re gonna you know, what if one study fails? Yep. Well, that’ll you know, the data will bear that out.

Mhmm. But, you know, it is not unprecedented in the neuropsych space even if there is failure to be expected. That that we are able to get approval. So so we will be running these studies, as I mentioned, seamlessly. But, you know, we will definitely have learnings from phase two.

So that that will help us. So if need to, we can modify phase three studies if needed.

Ritu Baral, Analyst, TD Cowen: Alright. I’ve left myself one minute on day I’m sorry. You place it in one minute on ACP one zero one. Okay. Let’s let’s do one zero one first, lightning round.

This is your Prader Willi compound. Can you quickly review where you are on Phase three enrollment and the key efficacy endpoints and when that data will come?

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: I’ll start on where we’re at. We’re actively enrolling. We’re doing very well, very pleased with the interest and the support of the community. And as we guided, we’re going to, we expect to complete enrollment by the end of this year. And if you want to just talk a little bit more about the study design?

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: Yes. So it is a twelve week study and it’s a parallel randomized double blind study. It includes two arms. One is the active arm with three point two milligrams of intranasal carbutosin three times a day versus placebo. Mhmm.

And the primary endpoint is a is called HQCT, is the hyperphagia questionnaire and clinical trials.

Ritu Baral, Analyst, TD Cowen: And that is caregiver based, correct?

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: That is a caregiver assessment, yes.

Ritu Baral, Analyst, TD Cowen: Got it. And then in our last minute, there’s a new new place at DTC campaign. There is you see, we see sort of renewed growth, which, at least from the investment community sort of came out of nowhere. How do we see those two interplaying? And what’s going to drive continued growth?

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: Yes. So we had a very strong Q4, as you heard on the earnings call with 13% growth versus the prior year quarter and 11% year on year growth, so very strong. In terms of the DTC, we see that NUPLAZID is highly promotionally sensitive as I would say from a commercial point of view. And what we’re seeing is that patients are actively looking for information after seeing the direct to consumer campaign. They’re coming onto our website.

But more than that, we’re not looking for clicks. We’re looking for actual patients going to their doctors. We can track that. And what we’re seeing is increased number of patients actually going to their physicians and asking about NUPLAZID. So with that confidence, we are continuing to invest in the direct to consumer campaign as we move into this year.

It’s very targeted, very specific. It’s not blanket national. It’s, it’s very specific to where the patients are. And as a result, we’re looking for continued growth. As you know, we’ve guided to from six fifty to six ninety this year, which is, I think, above most consensus expectations, and that’s because we believe this growth will continue because it’s highly sensitive.

And I know consensus had not modeled significant growth going forward.

Ritu Baral, Analyst, TD Cowen: Great. Well, thank you so much, Catherine, Renee, Mark, for joining us.

Catherine Owen Adams, CEO, Acadia Pharmaceuticals: This is very helpful. Appreciate it.

Poni Subbiah, Chief Medical Officer, Acadia Pharmaceuticals: Thank you. Thank you.

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