Welcome, everyone, to the 44th Annual JPMorgan Healthcare Conference. My name is Tess Romero, and I'm one of the Senior Biotech Analysts here at JPMorgan. Our next presenting company is ACADIA Pharmaceuticals, and presenting on behalf of the company, we have CEO Catherine Owen Adams. Catherine, over to you.
Thanks so much, Tess. Good morning, everybody, and thank you for joining us at the 44th Annual JPMorgan Healthcare Conference. As Tess said, my name is Catherine Owen Adams, and I'm the CEO of ACADIA Pharmaceuticals, and today, I'm really delighted to share our progress building a leading neurological and rare disease company. I'll be making forward-looking statements in this presentation, so please refer to our SEC filings for the risks and uncertainties relevant to our business. At ACADIA, our mission is to deliver meaningful innovation to underserved patients with neurological and rare disease, and this slide illustrates how we intend to deliver on that with products that are either first in class or best in class. Starting with our neurological franchise, the momentum of NUPLAZID is leading the way and expected to continue this year and beyond.
We're advancing exciting pipeline candidates that I'll give more detail about in a minute, anchored by our new 5-HT2A agonist, Remlifanserin, formerly known as ACP-204. Also, our phase II program with ACP-211, which has deuterated R- ketamine, our program in major depressive disorder. With ACP-711, we have the opportunity to move into essential tremor, and with ACP-271, to move into tardive dyskinesia. In rare disease, we're making great progress with DAYBUE and have the opportunity in 2026 to serve many more patients in the U.S. and beyond into the EU, including the launch of our new powder-for-oral formulation, DAYBUE STIX. Beyond that, we have ACP-2591, ACP-271, and an association with our colleagues at Stoke Therapeutics for a SYNGAP1 program. We're actively evaluating additional areas of rare disease expansion, primarily through our business development activities.
Importantly for the company, we're also investing in areas of core capability: that of precision medicine, where we intend to continue driving biomarkers used across all of our trials, data innovation with the introduction of AI across many of the areas of our business, globalization with the intent to serve patients both in the U.S. and beyond, and finally, patient empowerment, ensuring that our patient voices come into both our R&D and commercial functions. Several recent and upcoming milestones underscore the momentum that we're building across our pipeline. Recent milestones are the start of our phase II ACP-211 study initiated already in major depressive disorder, the initiation of our ACP-204 Lewy body dementia psychosis, and the initiation of our phase III trofinetide trial in Japan.
Important upcoming milestones: In Q1 of 2026, we expect to start our first in-human study of ACP-271, which is our GPR88. We also expect to get a CHMP opinion for trofinetide, and we also have announced today more specific timing for our Remlifanserin top-line results, now guiding to between August and October of this year. From our eight disclosed and undisclosed programs, we expect five additional phase II or phase III study starts between now and the end of 2027, and four phase II and phase III study readouts by the end of 2027. We are building a really strong foundation for growth with our two commercial brands, now delivering more than $1 billion in sales in 2025.
Sharing for the first time today our expectation for these commercial brands, which we believe can grow to about $1.7 billion in 2028, with about $1 billion coming from NUPLAZID and $700 million from DAYBUE. In addition, we see substantial future sales opportunity for the key programs in our development pipeline. Our pipeline includes four molecules entering larger markets with higher unmet need, and we believe these molecules have the full peak sales potential to reach $11 billion combined if they were all to reach market. Importantly, within this, we're highlighting the specifics of a $4 billion potential peak sales opportunity from Remlifanserin across both indications that we're pursuing. Now, we understand that this is not guidance.
We all understand that drug development carries risk, and not every program will succeed, but we felt it important to illustrate the value that we see in our programs, and we understand it's our responsibility to build our case and unlock that value. In 2025, we developed a very strong focus on building AI in all that we do at ACADIA. We appointed a new Chief Information and Data Officer and are now leveraging AI throughout key areas of our business to accelerate growth of the enterprise. Within the commercial business, we're looking to better target and engage customers and drive quicker uptake. Within R&D, we're excited to announce a new clinical command center, which we will use to monitor trials on an ongoing basis to enable us to drive quicker decisions.
In our regulatory group, we expect to use AI to develop documents more quickly and expand our internal capacity. We're committed to utilizing data and technology to grow our business and advance our pipeline as quickly as we can. We're also focused on being the difference to patients everywhere around the world, and 2026 will be a critical year for our global expansion. Focusing on DAYBUE, we're now approved in three markets, as we announced Israel approval today, and anticipate CHMP opinion in the first quarter of this year. I've already said we've initiated our phase III study in Japan. We also will continue to make DAYBUE available to patients around the globe through our named patient supply programs, where we have patients from countries in the EU, the Middle East, and Latin America.
Turning to R&D, our development pipeline leverages clinical trial sites across the globe to ensure we're suited to meet the needs of our diverse patient population, and now for a deeper dive into neurology and Parkinson's disease. Just to level set, in the U.S. , there's about a million patients with Parkinson's, and about 50% of them are expected to develop the symptoms of hallucinations and/or delusions during the course of their disease. These symptoms place a tremendous strain on families and caregivers, and even with a high-profile, successful, unbranded campaign with Ryan Reynolds, still less than 20% of patients and caregivers are aware of these symptoms, so there continues to be a major educational opportunity for us. Currently, there are about 130,000 patients treated for hallucinations and delusions with off-label antipsychotics, and so we believe there's really a potential growth opportunity here for NUPLAZID.
NUPLAZID is still the first and only approved treatment for Parkinson's disease, hallucinations, and delusions. Since launch, we've treated 97,000 patients, and we estimate we currently have about a 25% market share of those 130,000 patients who are treated. We also now have patent protection through 2038, which we achieved following the successful defense of our patents in 2025. We're excited to share today that we do believe we can achieve $1 billion for NUPLAZID in 2028, which will be driven by our investment and our excellence in commercial execution. We're going to continue our direct-to-consumer campaigns, which are accelerating patient and caregiver awareness. I shared a moment ago that the awareness has been driven from about 10% to 20% through our campaign with Ryan Reynolds, and we will continue to leverage this highly successful campaign.
We announced last year that we're also going to increase the size of our commercial field force for NUPLAZID. Starting this quarter, we intend to increase it by about 30%, at the same time leveraging AI to ensure precision execution across this larger field force, and our goal is to become the standard of care in patients treated for hallucinations and delusions of Parkinson's disease. Now for DAYBUE and Rett syndrome. Rett syndrome is a rare disease, highly debilitating, caused by mutations in the MECP2 gene, primarily affecting females. These girls develop normally until the age of about 18 months to two when they see developmental deterioration. Our latest figures indicate that there are about 6,000 diagnosed patients with Rett in the U.S. This is up from our recent ranges that we've been talking about, which has been between 5,500 and 5,800.
That diagnosed population has increased by about 30% since the launch of DAYBUE. As we look to EU and our possible approval there, we see a prevalent population in the EU, even larger than the U.S., between 9,000-12,000 patients. Again, with DAYBUE, we have the first and only treatment for Rett syndrome. Since its launch in 2023, we've treated over 2,000 patients. We've seen really strong persistency with now 55% of patients still on treatment at 12 months, underscoring the sustained benefit that families and patients see from DAYBUE therapy. We now have over 300 patients in our real-world evidence LOTUS study, which continues to develop and publish data. Looking ahead to our global ambitions, as I've said, we anticipate our European approval in Q1 of 2026.
Again, for the first time today, we're giving you ambition for DAYBUE in 2028 at $700 million in global sales. We see that there are three drivers of this ambitious growth. The first is the approval of DAYBUE STIX in the U.S. I'll give you a little bit more about that in a second. The second is the continued impact of the expansion of our U.S. sales team, which we initiated in Q2 of last year. And the third is our continued international expansion. We're really excited for the approval of DAYBUE STIX that we received on December the 12th, which is a new powder-for-oral solution. DAYBUE STIX, as you can see here, is in a small packet, a little bit like the Liquid I.V. that you get.
And the key attributes of this STIX formulation are primarily the ability for patients and their caregivers to mix with different liquids to potentially reduce the volume, no refrigeration required, highly portable as a result of that. And importantly, for our patients in the Rett community, many of them are on a keto diet to control their seizures. DAYBUE STIX has a much lower sugar and carbohydrate content. It offers us several potential benefits, including that customization of the taste. You can formulate this in many different fluids, from apple juice to orange juice to Gatorade. We believe this will enable patient growth from families who have previously declined to try the liquid formulation for whatever reason, and enable growth from patients who will restart DAYBUE with this new option now available.
As we've said in the press release this morning, we're rolling this out on a limited basis as we build up stock through the first quarter, with full availability by the beginning of Q2 this year. And now a deeper dive into our pipeline. As we've already outlined, we have a series of molecules in both our neurological and rare disease portfolios, and I'm going to take a few minutes to highlight some of those for you now. I'm going to start with Alzheimer's disease psychosis, a condition where a person with Alzheimer's disease experiences hallucinations and delusions. This is a huge unmet need with no approved treatments as yet. Of the seven million patients who suffer from Alzheimer's disease in the U.S. , about 30% of them will experience some kind of psychosis during the course of their disease.
We're excited for the opportunity for Remlifanserin, our next 5-HT2A agonist that's been built on the knowledge of our previous pimavanserin. And we're very excited about our potential to transform this disease area if our clinical development program is successful. The Remlifanserin program was designed and developed based on significant learnings from our pimavanserin studies, and the program and the molecule are differentiated in a few critical ways. From the molecule perspective, we've designed it so that the structural differences minimize or eliminate the QT prolongation. We've designed it to generate a faster time-to-study state, as well as the ability to give patients higher doses and exposures to hopefully drive increased efficacy. From the program perspective, we've learned, and we're really ensuring that we have an appropriate study patient population included in our two or four studies with the use of biomarkers.
Remlifanserin has also been designed with patient-centric dosing in mind, once-daily dosing, the ability to be taken with or without food, which we believe is really important in this elderly and frail population, and importantly, few drug-drug interactions. Our Remlifanserin study in Alzheimer's disease psychosis is our RADIANT study. It's a global, double-blind, placebo-controlled phase II trial currently enrolling 318 subjects. We're looking at two doses, 60 milligram and 30 milligram versus placebo, and our primary endpoint is SAPS-H+D at six weeks. This is an operationally seamless but statistically separate trial that's moving into two phase III studies with similar design, and again, from our press release this morning, top-line results expected from our phase II portion of these seamless studies between August and October of Lewy body dementia psychosis holds great opportunity for Remlifanserin.
Lewy body dementia is a progressive brain disorder that affects thinking, movement, mood, and behavior. And essentially, the difference between this and Alzheimer's is it's associated with abnormal alpha-synuclein deposits in the brain. It's thought that over a million patients in the U.S. suffer from Lewy body dementia, with 50%-75% of those patients experiencing some kind of psychosis during the course of their disease. Again, there Lewy body dementia psychosis, but there are 200,000 patients currently treated for this with off-label antipsychotics, so a significant Lewy body dementia psychosis includes two distinct patient populations with highly related symptomatology, both related by alpha-synuclein biology and both displaying hallucinations and delusions associated with it. In dementia with Lewy body, the cognitive symptoms in the patient tend to precede the motor symptoms.
Conversely, in Parkinson's disease psychosis, motor symptoms precede cognitive impairment. As mentioned, with Remlifanserin, we are leveraging our learnings from our pimavanserin studies. A subset of data from the HARMONY study supports the Lewy body dementia psychosis. in harmony, patients who achieved a response were randomized to continue treatment with pimavanserin or to have treatment withdrawn for up to 26 weeks. Of those patients, there was a notable difference in the patients experiencing relapse between the two groups, as you can see here, with only 5.3% of patients relapsing with pimavanserin compared to 55% relapsing for those patients receiving placebo. With that in mind, we've recently initiated our Remlifanserin study in this patient population. It's a global, double-blind, randomized, placebo-controlled phase II study, again looking at the same two doses, 60% and 30% versus placebo.
We're enrolling both of those two subpopulations, patients with Parkinson's disease dementia Lewy body dementia psychosis. As i've said already, both patients share that alpha-synuclein biology. The primary endpoint here is SAPS-LBDP at six weeks, which is identical to the endpoint that I just mentioned in the pimavanserin HARMONY study. We look forward to updating you on our progress with this trial. Turning next to our candidate for major depressive disorder. Major depressive disorder, we probably all know fairly well, a pervasive loss of sadness, loss of interest, multiple symptoms. Current treatments are there, but we believe are limited by their efficacy and particularly the onset of treatment requiring extensive monitoring in a physician's office. ACP-211 has been designed for ketamine-like efficacy, but with minimal in-office monitoring. It's orally dosed, and we believe addresses a significant treatment gap.
There are 21 million patients in the U.S. with major depressive disorder, but only 9 million of those are treated. Within that, 3 million are actually treated for treatment-resistant depression. It's the second highest cause of disability in the U.S. economy, and there remains substantial unmet need, both clinically and obviously economically. We've recently initiated our phase II study of ACP-211 in major depressive disorder. This is a four-week randomized, double-blind, placebo-controlled study enrolling 153 patients with a primary endpoint looking at a change in MADRS score at week four. We look forward to providing you updates on this study as we proceed through the year. Essential tremor is a movement disorder. It's a high-frequency postural and/or kinetic tremor, mainly affecting the upper limbs.
It represents a huge unmet need as current treatments are very often ineffective, and there have been no new approved therapies for the last 50 years. ACP-711 is a selective GABA alpha-3 modulator targeting cerebellar GABA. We have phase I data starting to support, so we already have phase I data to support the potential absence of cognitive or sedative effects and a potential negative impact on sleep. Essential tremor affects about 7 million patients in the U.S. , so about 2% of the U.S. population, so it's 10x more prevalent than Parkinson's disease, and of those patients, about a million sought treatment between 2015 and 2019, and those are really those that are affected by the more moderate to severe tremors.
Currently, we have a phase I elderly cohort underway to look at this molecule in the elderly population, and we project a phase II study initiation in the fourth quarter of 2026. The plan right now is to enroll 150 patients in a double-blind, placebo-controlled study, and we look forward to giving you more information as we develop details on the program. Finally, turning to ACP-271, which we view as one of the most novel chemistries in our pipeline. It's a GPR88 agonist that we believe may modulate the balance of D1 and D2 signaling without affecting dopamine levels. We're about to initiate a healthy volunteer study in Q1 2026 and plan to develop this candidate for both tardive dyskinesia and Huntington's disease. Looking ahead, we're really excited for a number of important milestones in 2026.
In the near term, the next quarter, we have the CHMP opinion on the initiation of ACP-271 in healthy volunteers. The highly anticipated top-line results of Remlifanserin in Alzheimer's disease psychosis will come between August and October of this year. Between Q4 and Q1 of next year, we expect the top-line results of our Japanese phase III trial with trofinetide. In Q4, we expect the initiation of our phase II study in ACP-711 in essential tremor. Beyond that, in 2027, the results of our phase II study in major depressive disorder with ACP-211. We have a continued strong focus on business development fueled by our strong balance sheet, looking for partnerships and acquisitions within these two focus spaces for ACADIA. I conclude by reiterating our mission as a company, turning scientific promise into meaningful innovation for underserved communities with neurological and rare disease.
We're excited to have shared this today with you. Thanks for your attention. And Tess, I think we've got some time for questions. Should there be any from the audience?
Yep. Brilliant. Thank you, Catherine, so much for the presentation. Would you like to invite the rest of your team?
Sure. We have Liz, Tom, and Mark here. Head of R&D, our Chief Commercial Officer, and our Chief Financial Officer.
Okay. Okay. Great. Well, welcome, team. So I thought I might start the conversation here with a couple of kind of overall business questions. As you think specifically about your commercial franchises in 2026, what are the specific priorities that you have for the year, and how should we be thinking about the key drivers for revenue growth this year?
Yeah. I'm going to let Tom have a go at that question.
Yeah, certainly.
I think Catherine's probably laid out the case for both brands pretty clearly. Starting with DAYBUE, obviously near term, we're excited about the approvability in Europe, which we think provides an additional leg up for DAYBUE and us to help more patients outside of the U.S.. Within the U.S., we're going to be very much focused on building on the expansion of the field team that we pulled through Q2 of last year, really maximizing the opportunity that we see with DAYBUE STIX. We've already seen significant interest from both the patient and the HCP and advocacy communities around this new formulation because it really addresses some of the unmet needs that we believe exist for DAYBUE today, just having that greater flexibility, removal of some of the ingredients that they don't necessarily like in terms of the liquid formulation.
Worth noting that we will continue to promote both moving forward. For NUPLAZID, really, it's a story of continuing the momentum that we built in 2025. I think we had a very, very solid year in terms of growth. We're seeing new writers come to the fore, as Catherine mentioned, significant amounts of engagement with the broader PDP community. And we think that that gives us a tremendous platform to build from with our expanded field footprint in 2026.
Okay. And maybe I know it was kind of a hot off the presses today, so maybe you could just talk a little bit about that combined net sales outlook that you outlined for 2028. What are the key underlying assumptions to that and any key risks?
Yeah, I'll take that, and then maybe ask Tom to add some.
We felt it important for us to put out there our ambition for both NUPLAZID and DAYBUE. We have strong conviction that we can grow both of these brands to the $1.7 billion that we've stated. And so just a couple of assumptions within those growth trajectories. With the DAYBUE assumption, we are assuming that we get approval in Europe, so it does include that. And with NUPLAZID, we're continuing to see that growth. And so we assume that that continues to grow as we move through the next three years. Anything additional, Tom?
No, absolutely. I think for DAYBUE, clearly, ex-US is going to be an opportunity with STIX. We do anticipate that that's going to help us unlock additional growth, both in terms of patients who may be considering DAYBUE and unsure based upon formulation, but also those who have discontinued.
We think that there's a real opportunity for those who may have stopped due to formulation concerns that we can re-engage with those families as well. And then for NUPLAZID, really, it's a case of continuing that building on that momentum, really maximizing the opportunity that we've seen in 2025. I mean, 40% of our writers in 2025 were new to brand. And I think that that's a really nice indicator of not only commercial execution, but also how our campaigns are working for us. And that's an opportunity that we continue to lean in heavily as we move into 2026.
Okay. Okay, that's helpful.
And then over this timeframe, however you kind of want to kind of lay it out for us, how should we be thinking about your OpEx line and how it's going to be evolving over the next couple of years on both the R&D and SG&A lines? Mark?
Thanks for the question. I think so we'll give guidance for expenses this year when we announce our fourth quarter results. But qualitatively, to think about it, we've talked about the investments that we've made and are making. So you'll see an uptick in OpEx certainly this year, year over year, as we have an expansion of the NUPLAZID field force that we talked that's starting now, making investments to continue to advance in Europe as well as STIX.
Just annualization of some expenses like the DAYBUE field force that came in the second quarter of last year that will be involved in our OpEx for the full year this year. It'll be a year of investment. The pipeline's advancing with all the excitement and additional work that we're doing. You'll see further investment there. I think as you think about over the next coming years, up till 2028, you'll see operating leverage in the business. I think from a commercial and SG&A perspective, you'll see modest growth from where we kind of go in 2026. The pipeline obviously is dependent upon how it advances. I think the more success that we have, the greater the expense will go forward, but that will be with value creation and advancement of the pipeline.
And then, of course, there's just normal attrition that ultimately happens in a pipeline. So we'll see how that evolves with the R&D line going forward, independent of whether or not, but how we add to the pipeline through business development.
Okay. Okay. You kind of beat me to the punch on my next question. Just on the business development front, what types of products is ACADIA interested in for 2026?
So I think just starting with therapeutics, it's very clear we're a neurological and rare disease company. We have an ambition to expand our rare disease aperture beyond just neuro. So we're looking at opportunities in other rare diseases, cardiac rare, endocrine rare, metabolic rare, etc. In terms of the type of opportunity we're really interested in, we have really thought through where we believe a strong fit would be from a BD perspective.
And I think something late stage is something that we're really looking at very hard right now. We would love to have something that we can commercialize in the next few years added into the portfolio. But we continue to look for pipeline innovation. I know Liz and I are very keen to look at larger molecule opportunities and again, back into the rare disease beyond neuro. So we have a very wide aperture. Tina and her team are very active right now. We have a nice strong balance sheet, and we're looking forward to bringing some business development deals to the fore in 2026.
Okay. Okay. Okay, great. So maybe turning to the pipeline here, there is a lot of data that has been generated for NUPLAZID across dementia-related psychoses. And now you're exploring the potential for, okay, I'm going to try it out, Remlifanserin for ACP-204.
Liz, can you maybe give us a little bit of your broad strokes for why you think this study has a reasonable probability of success? And how confident are you that you picked the right doses here and the right primary endpoint?
Absolutely. So Remlifanserin, very well done. We're all getting used to saying that instead of 204. It is informed at both the molecule level and the programmatic level by a wealth of information from pimavanserin. So Catherine mentioned this in her presentation, but just to touch on it very briefly, NUPLAZID is a great drug that has done really good things and continues to do really good things for many patients out there. It does have some QT, some suggestions of a QT signal.
Certainly, if you get at doses above the marketed dose, it gets to the point where we were not able to dose range higher with NUPLAZID. So minimizing or eliminating the QT signal, which we've been able to do with Remlifanserin, is important in and of itself, but it's also important because it lets us explore higher exposures. And there is a suggestion in the PIM data set that suggests that there is an exposure response relationship from an efficacy perspective, such that if we're able to go to higher exposures, we might actually be able to get more efficacy out of this mechanism.
The final thing is that we were looking for a faster time to steady state, which we'll have to prove it out in the clinic, but there is the possibility that that gets you faster onset of efficacy and maybe more robust and similar efficacy across time points. So those are the things we did from a molecule perspective that make us feel good about Remlifanserin's profile. In terms of how we translate that to the program itself, we do have several points of data with pimavanserin in Alzheimer's disease psychosis. First of those is a positive phase II study. It was on a different endpoint that we think is less sensitive to change than SAPS-H+D, so we think we've maximized our probability there. There was also a subpopulation in the HARMONY trial where really we didn't design the study to look specifically at the Alzheimer's population.
That's one of the other big learnings we've taken forward into our program here is that it's important to be able to really look at the disease that you want the eventual approval in. So our study is not just clinically diagnosed Alzheimer's that we're focusing on, but also further biomarker confirming it. We think that that gives us a better likelihood of regulatory success in the instance of a positive program. Hopefully, that addressed what you were looking for.
Yeah, it does. It does. It's a much longer conversation. I think that was helpful.
I tried to make it as short as I could.
No, no, that was helpful. So this morning, you announced that when you expect the data to be this year, I think it's a little bit later than what we thought previously.
Just on getting the patient population right in the study, can you just maybe help us understand that element and what might have driven the delay or slight delay here?
Yeah, so I'd say that we really refined our estimates of what this timing could look like as we got further into the trial. So I don't think of it as a delay necessarily as much as a refinement. That said, there are some things that do play into this. We were very keen to make sure we were getting the right patient population in this study. So again, looking not just for that clinical Alzheimer's diagnosis, but also biomarker confirmation. And the part that is helpful for our hypothesis is that that did actually help us identify some patients who were not biomarker positive for Alzheimer's.
So we feel better about the patient population we have compared with what we would have gotten if we hadn't put that criterion in. Otherwise, we did learn from our prior PIM work for some moderate refinements of patient population looking for slightly more severe psychosis at baseline as an example. But really, this has been a focus on making sure that the patients that are in there are Alzheimer's in a way that we can very, very clearly document and defend to agencies.
Okay. Liz, any other key pipeline milestones for 2026 that we should have an eye on?
So in terms of readouts, there is a possibility. We're putting out at this point a six-month time horizon for our Japan phase III for trofinetide. So that six-month horizon does span a portion of 2026.
But what we were trying to give you all a flavor for was what the next couple of years could evolve into. And the fact that 211 phase II data falls within that span, we thought was important to make sure people were aware of.
Okay. And in terms of relative risk across your key pipeline, how do you see that over the next several years? How do you think there how much balance do you think there is?
Yeah. We've got a couple of very important de-risking events that come over the course of the next couple of years with our phase II data coming out of both the Remlifanserin ADP program as well as 211.
I mean, to make a massive overgeneralization, the earlier you get in the pipeline, the more risk you're going to have just associated with how much we know about the molecule itself as well as the biology. I think it's certainly fair to say that 271 is the riskiest thing in our pipeline because it is also the most novel biology we have. So we've been working over the last year and a half that I've been here to try to have a real diversification of risk profiles, some riskier things as well as things where we think we have important pieces of data that help us de-risk them. And of course, as you heard from Catherine, we are keen to continue to expand that pipeline, potentially diversifying our risk into some larger molecules as well.
Okay, great. Well, I think we are just about at time here.
So I think this might be a good place to close our conversation. Thank you so much, team.
Thank you so much.