ACADIA Pharmaceuticals Inc.

as well so absolutely I think you should be thinking about two main factors you know new patient starts and active patients because it's going to be the active patients that we believe that we can continue to grow over time that are really going to be meaningful for the ongoing revenue uptick for this brand into the long term

Liz, do you want to touch on our positioning versus the new Celina product? Sure.

I'll start out with the fact that, I mean, we're delighted for the PWS community that there is now a first therapy available for them. That said, I think we see this as an area of significant high unmet need and complex patients who are dealing with a number of different challenges. It's the kind of space where we think that it's likely that there is going to be absolutely room for multiple agents that are used with different MOAs, with different benefit-risk profiles that physicians can use according to the patient that's in front of them. I don't know if there's anything you want to add here, Tom?

Well, the only thing I would add is we know that the Prada Willy population, you know, they have very complex and distinct needs, and we actually believe that there's going to be an opportunity for more than one product to play here, and I think with therapeutic areas like this, the notion of combination therapy could also be something that plays out into the future as well. So a pretty substantial patient population here in the US, plenty of opportunity for more than one player to play, and we will be ready to launch should the data be positive.

Yeah, and we do spend a lot of time, of course, talking to caregivers, advocacy organizations, and we hear pretty robustly that, again, they are delighted that there is something available for their family members now. And they absolutely think that there needs to be continued therapies and the ability to treat an individual patient for their individual circumstances.

Thanks, guys. Hopefully that answers the question, David. Yes, thank you.

Thank you. Our next question comes from the line of Sean Lehman with Morgan Stanley. Your line is now open.

Hi, good afternoon. This is Catherine on for Sean. Thank you so much for taking our question. Just one from us on your earlier pipeline. For ACP 711, you announced the successful completion of the Phase 1 MAD cohorts earlier this year. We're just curious if you can provide any color on what you observed here, and if you have an update on the status of that study. Thank you.

Yeah, so I think what I'd share there is, you know, consistent with what we put out at the time. We were pleased with the safety and tolerability profile we were seeing in that study. There are some interesting pieces on the biomarker side that we'll be sharing at R&D Day. So please feel free to come in and look for that. Status-wise, we're continuing forward with additional explorations that we think are necessary to get us lined up for the phase two that we're planning to start in 2026. So continued good progress there.

Thanks, Catherine.

Thank you. Our next question comes from the line of Tazin Ahmad with B of A Securities. Your line is now open.

Hi, good afternoon. Thanks for taking my question. For Tricentatide in EU, can you maybe, Catherine, give us a sense on in what ways the launch could be different from the trajectory that Debut has seen in the U.S.? ? I know you bring a lot of experience from launching products outside of the U.S. What kind of, you know, I guess attention to specifics should we be paying as we think about how to model out European launches for your drugs and how we think about debut in general?

Yeah, thanks, Tuzine. So let me start with the European overall population being larger than the U.S. So we are But that is sort of in line with countryside. So there's no specific country that has more or less patience. So as you know, Germany being the largest country in the EU, we will launch first into Germany. As you know, there's a period of free pricing. And then after that, we start to negotiate with Amnog. And then beyond that, we'll look at each of the countries and start those negotiations with the national payers. Yes, both Tom and I are very experienced at launching in Europe. We also have now put in place a really great team who have a lot of rare experience in Europe, and we're building up our dossiers, we're building up our value story, and we're ready to start those discussions with the authorities as soon as we get that regulatory approval. I think to your point about learning from the US launch, you know, as with all global launches, the launch country, which generally tends to be the US, is the one where we can learn a lot, and I think we have learned about the importance of working with families and the importance of making sure that we really are sharing the titration strategies that have been put in place here. So there's a lot of work going on right now with the KOL communities, with the advocacy groups. You know, we had a big bolus of patients in the US that came out the gate pretty strong. We're also getting a lot of inquiries from patients in the European Union, and that's why we put in place our main patient program and managed access program for those physicians that want to access trofinetide in the countries where it is legally and regulatory allowed. Those processes will be in place. We don't expect sort of the same sort of massive bolus of patient dynamic, but each country is going to be slightly different depending on how many of their patients are on those managed access programs. We feel very confident that we understand what we're doing. We understand how to get our product into the markets. And we're also investing appropriately. We're not investing all over the place. We're being very strategic about where we build our teams, about where we put our people, and we will take into account any future administration directives that affect that too. So, you know, we're very We're very conscious about it, but also very excited and mostly excited by the advocacy groups who are very, very interested in accessing trofinetide for their loved ones.

So thanks, Tazeem, for the question.

Thank you. Our next question comes from the line of Gregory Renza with RBC Capital Markets. Your line is now open.

Hi, Catherine and team. It's Anish on for Greg. Congrats on the progress this quarter, and thanks for taking our questions. Firstly, as a follow-on to David's previous question, what unique aspects of your commercial engine or priorities within the target market do you believe you'll be able to leverage to rise above competitors in the PWS market with both respect to Celino and other therapies in development? And secondly, obviously, there's a lot of concern across the sector on macro and policy exposure for companies. I know you commented on inventory already, but maybe if you could just share some thoughts around where Debut and New Placid might be impacted along their respective supply chains and how you're navigating that. Thanks so much.

Great. Thanks, Anisha. Quite a few different subsets of questions there. So let me start... But just giving you an overview of my thoughts around the commercial engine, I'll ask Tom to add, and then we'll throw it to Mark to talk about supply chain and tariffs. So just in terms of commercial engine, you know, we have a very strong team now, both in neuropsych and in rare, who understand the subtleties of launching within a rare space. And we've learned a lot through the debut launch. So we feel very well prepared as a company to work within the Prada Willy community We have strong associations with them already. We have our teams out there right now. And as Liz has already outlined, we feel very strongly that the community is asking for as many options as possible for their patients. These are complicated, complex patients. And we'll see over time the need, I believe, for more than one therapy option for sure. So we feel very confident in our ability to go out there and compete, but also offer patients choices, which we believe are very important. Tom, is there anything you'd bring from that, your previous experience in rare?

Yeah, I mean, I would say that clearly we have already launched a rare product in very recent history, the debut. I think we've learned a great deal as we've gone through that launch. And as Catherine mentioned, I think both Catherine and I have had the privilege of launching products in other rare spaces. And I think being able to continue to kind of build that muscle, make sure that we're pulling through the experiences that we have, and really making sure that as the 101 data reads out, that we're able to leverage the product profile in an appropriate way as quickly as possible, taking all of the learnings that we already have, but also thinking about some of the kind of unique aspects that we bring as Acadia, you know, with a true kind of focus on the patient and on patient advocacy. I think we will have a a significant leg up in making sure that we can be highly competitive, even as a fast follow.

Mike, do you want to talk about the supply chain?

On the supply chain, obviously we're monitoring all the events of the day as it relates potentially to tariffs that may come forth for the industry. I think as our supply chain is set up today, You know, our API for both products is manufactured outside the U.S. The ABU has drug product manufacturing in Canada and the U.S. The drug product manufacturing for Nuplazit is all in the U.S. I think what we've done thus far, you know, in recent months, as I mentioned on the call, is, you know, onshore as much inventory as possible due to investments that the company had made previously in advance of potential DRP approval. The company did make investments in inventory for supply for Covantrin, which is why we have the supply. All of that's in the United States today and can last us into the mid to late 2030s. And we don't own any manufacturing sites, so we don't have any infrastructure. that's set up with our supply, like everybody, we look at our supply chain to make sure we have assurances of supply, redundancy, high quality suppliers, appropriate price. If there are tariffs, that's one cost that will be considered in the overall supply chain. But from a manufacturing standpoint, time and investment can change everything. So nothing's permanent, but nothing changes overnight. I think we feel very comfortable in the position that we are today with our inventories, and we'll keep the supply chain as is until there's an appropriate reason, whatever that may be, to change it. We can do that in the future.

Thank you. Our next question comes from the line of Yatin Suneha with Guggenheim. Your line is now open.

Hey, guys. Thank you for taking my questions. Question on the Prader-Willi study. Are you able to talk about the powering of the study and the kind of size of the study? It's pretty robust. What effect size are you powered for? What is the minimum delta you are able to achieve? Thank you.

Yeah, last list to talk about the effect size and the powering for our study.

Yeah, so I think probably the most important thing to orient here is that We have a study that is substantially larger than the prior study where there was nominal significance, but where if 3.2 had been run by itself, we would have anticipated having a significant p-value. So that is a check in our column. As far as we think about the specifics of the powering that underlies this, we actually looked at a number of different potential powering scenarios to make sure that we were adequately covered for a few possibilities. The one that is most obviously disclosed is a slight increase in terms of the delta between placebo and active, and that's reflective of the fact that we have a slightly longer time point in this trial than we did in the prior study. But I think broadly consistent expectations with what we've seen historically and a number of different scenarios that get us with, you know, strong 80-plus percent powering.

Thanks, Liz. Thanks for the question.

Thank you. Our next question comes from the line of Joel Deedy with Baird. Your line is now open.

Hi, thanks for taking the question. It's a little bit of a math question on Dayview and the ability to find new patients starts faster than patients discontinue. And I guess it's in the context of you're getting close to 1,000 patients on therapy in a quarter now. And then a discontinuation or persistency rate at 12 months of about 50%. So putting those numbers together, I guess the question is, would that mean to expect about 500 patients dropping off over the course of a year? And then if so, how realistic is it to be able to find 500 plus patients of new starts to be able to replace that?

Let me try and reorient the math a bit. And if I get convoluted, somebody can help simplify. But you're right. In terms of the patients actively shipped in the quarter, 954. Now, of those patients, 65% of them, just above actually, have been on therapy for more than a year. So it's important to understand that within that 954, there are different cohorts of patient start times, but more than 65 have been on the product for over a year. We continue to see strong persistency beyond a year, so we're not seeing sort of a sudden drop-off beyond that either. So it's really a cohort question, if I may, in terms of the math, Joel, and in terms of new starts added every quarter and the expected time that that patient stays on therapy. Again, we've given you the 12 months if you like, persistency rate. However, we are seeing patients stay on therapy for much longer than that. So that's sort of maybe a way to think about it, Mark or Tom. I mean, it's like that.

When we talk about 12 months, that's the first 12 months of therapy. It's not each 12 months of therapy. So the rate of the persistency rates are very high kind of after, you know, the curve is like plateauing after as you get out in time. So it's really in that first 12 months that we keep more than 50% of our patients. And then beyond that time, it's a very high rate of persistency. So as Catherine mentioned, we have that stable base of patients that are on therapy more than 12 months, 65% of our current patients. And so then we're adding patients on top of that, and that's how the patient count grows over time.

Maybe I'll just give you one statistic that gives you maybe a... As we went through 2024, we started sort of with 870 or so patients per quarter, and now we're at 954. So again, they don't drop off just at the end of the year. They continue to stay on therapy. Hoping that that helps you out, Joel. If you need some more follow-up, I'm happy to do that too.

Thank you. Our next question comes from the line of Sumant Kulkarni with Canaccord Genuity. Your line is now open.

Good afternoon. Thanks for taking our questions. I have two quick ones. Given post-trial briefing is done on the Pimavacidin 2 case, could you remind us of your latest assumptions on when you might expect generic competition on Linoplacid? And second, on Trophinatide, do you expect to start recognizing European revenue from France via the paid early access program that country allows? And how important might that type of initiative be to give you a good sense of how the product might launch in the rest of Europe?

Okay, I'm going to ask Mark to update you on New Plaza, and then I'll take the front question.

Yes, so on PIL of Answer and IP, we remain kind of in the view that we have bookends, right? The short end of the bookend would be October 2030. The long end of the bookend is February 2038. Really nothing has changed with our reasoning behind that as we've been talking over the last months and year, whatever the timeframe would be. Really the only update since the last time we've talked publicly is that oral arguments for the appeal on our composition of matter is now scheduled for June 6th of this year.

In terms of France, I'll start and Tom can add color. I think you're referring to the ATU program in France, which has now got a different acronym that's currently escaping me, but essentially it's the early access program where the French government pays for product. We're putting in place mechanisms for that program to be activated in France for debut. There are a number of regulatory and legal considerations we need to put in place before that's action, but that's actively going on right now. As you know, once you then get reimbursement through the Transparency Commission, those patients switch over to paid product from the French government, and that's our current plan. Again, we have to understand what the French situation is nearer to the time, but we are planning for the ATU to be activated this year, and we're planning for those patients to transition over to commercial product once those negotiations have completed. Tom, did I miss anything?

No, I think as it relates to France, that's entirely true. I mean, the other thing I would say is obviously Germany, we will be having a managed access program there as well. And actually Germany, if you recall, will be out the gates pretty significantly ahead of where we are in France. So I think if you want to kind of have a good kind of barometer as to what's going to be happening in Europe, the German launch will be the one to watch because We do anticipate having patients enrolled in that early access program. As a reminder, on day one, once we have a European approval, they will be able to be switched over to commercial drug with free drug pricing as well. So more to come, but that's how we expect to see things playing out.

Hopefully that answers the question. Take the next one.

Thank you. Our next question comes from the line of Malcolm Hoffman with BMO Capital Markets. Your line is now open.

Hi, Malcolm Hoffman for Evan from BMO. I wanted to touch on New Plaza gross net. I believe you said gross net for the quarter was roughly 24%, and the guide suggests a range for the year of 22.5 to 25.5. Can you just talk through what pushes and pulls you expect can move this gross net one side or another of the guide? Thank you.

Yeah, I'll let Mark take the gross net question.

Yeah, I think right now, at least the first quarter, is kind of right in the middle of our guidance. It really is just patient mix, which we don't control. It's just the payers for our patient base can change over time, and that can influence quarterly fluctuations and what the gross to net is on the year. The other thing that influences it is if we take any pricing action. We had a small, modest price increase at the beginning of the year. We don't foreshadow when we may or may not take pricing action. We price our medicines to value, and we just announce that when and if we do it over time.

Great.

Thanks, Mark. Thank you. I'm showing no further questions at this time. I would now like to turn it back to Catherine Owen-Adams for closing remarks.

Well, just thanks everybody for your questions this quarter. We look forward to continuing to deliver on our commitments to our patients and updating you on our progress next quarter. Thanks again for your questions.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.