Good afternoon. Welcome back to the Bank of America Global Healthcare Conference. I'm Tazeen Ahmad, one of the biotech analysts here at the bank. It's my pleasure to have our next presenting company, Acadia Pharmaceuticals. Sitting up here on stage with me are a couple members from the management team. Of course, Catherine Owen Adams, who is CEO of the company. Welcome, Catherine. Also Liz Thompson, who is Head of Research and Development. Nice to see you again, Liz.
We'll go into the specifics of a couple of data catalysts that people have their eye on, but maybe Catherine can start off by giving us an overview of the company. You know, you brought in a new era to Acadia, and maybe talk to us about changes that have happened to the company since you became CEO.
Sure. I've been in role now just over 18 months, and, you know, the initial focus for us was to stabilize the commercial business and also look for new growth opportunities. Bringing in Thomas Garner as the CCO, I think we've looked at the business through new eyes and reassessed the opportunity, and have made some significant changes to both NUPLAZID and DAYBUE in terms of the field force sizing and the commercial strategy. As a result of that improved marketing, we were able to guide to almost a $1 billion opportunity for both commercial brands by 2028.
Liz, who came in about two months, three months ahead of me, we've been working together particularly building her team and looking at how we can invigorate the pipeline, both looking at how we can accelerate the phase II to phase III opportunities, but also look at the whole pipeline and start to make decisions on where we're going to invest.
In terms of BD, we've definitely got a nice balance sheet, $851 million, no debt. We've been looking out of it the opportunities and in really two areas, one is later stage that we could add to our commercial portfolio within the next couple of years. We've been looking, as many other people are, in the areas of rare disease to try and sort of ensure that we can have something beyond DAYBUE and look to build on the great commercial infrastructure we have there. We're also looking slightly earlier in the pipeline to add to that. We're looking at sort of, pre-clinical. We really have a nice bonus of phase II, phase III trials which I'm sure we're going to spend time today which are gonna come into fruition in the next couple of years.
Okay, great. Maybe let's talk about currently marketed products just for a couple of minutes. For NUPLAZID, that's a, you know, a maturing launch. It's been on the market now for some time, but you felt it important to continue to focus attention and time on this launch. You had a sales force increase in order to focus on areas that could increase demand. Can you talk to us about how that's been going?
Yeah.
What early indications of upside you're seeing.
You know, when I came into role, the peak sales, depending on the analyst, was, you know, $650 million-$700 million for NUPLAZID. As I said earlier, Tom and I looked at it again, and we felt we could really drive some incremental growth into that figure, and we've guided now to $1 billion in 2028. The confidence behind that is based on the fact that we have a great brand that has a strong clinical profile, and we didn't feel that it had really been looked at in terms of its commercial opportunity through the lens that we wanted to see. We have increased the field force by 30%, and the focus of that is to really get to about 4,000-5,000 new physicians.
We have been looking at the impact of our direct-to-consumer campaigns, and they've really raised the awareness of hallucinations and delusions amongst the caregiver population. We've been seeing new types of prescribers for NUPLAZID beyond neurologists, and that's in sort of PCPs and NPs and PAs that are now treating more patients with Parkinson's disease. We've really almost doubled our physician population that we're going after with the field force, as well as revamping our direct-to-consumer campaign, working with a new agency, and signing Ryan Reynolds for the unbranded campaign, which has been incredibly impactful. We've had a fourfold increase in the awareness of hallucinations and delusions since we started working with Ryan. We have a new campaign coming out next week, which we're really excited about.
Both of those two things together gives us confidence that we really have a lot of room to grow NUPLAZID in this market. We're roughly, depending on how you look at the market basket, about 20%-25% share, and we think we have the ability to go way beyond that.
Okay. As you think about, you know, the IP runway, so you did win some important cases on patent challenges.
Yeah.
How should The Street be modeling sales in terms of just strict IP expiry now?
We have, composition of matter out to, October 2030, and, MoU out to 2038. We're looking at our runway to 2038.
The biggest inflection point for NUPLAZID over the next five years or so will be the 2029 to 2031 timeframe, where we will highly likely get IRA price reductions. We do qualify for the small company benefit, so we step into those price reductions over the first two years. We do expect those price reductions to come to NUPLAZID. Even so, we still think there's a strong runway beyond that in terms of having NUPLAZID on the market. That's how we're looking at it in terms of out to 2038.
Okay. For DAYBUE and Rett syndrome, the launch had started off with a lot of enthusiasm and demand.
Yeah.
from the community and from physicians. Talk to us about, you know, sort of like the intermediate stage of the launch, what tweaks you think were needed and what you're seeing as a result of making some changes?
One of the initial tweaks was to increase the size of the field force. We didn't feel we were getting to enough of the community physicians. 65% of Rett patients are treated outside of centers of excellence, and we really didn't have enough reach and frequency on those physicians to get to them. We increased our field force initially, and then we've also been evolving our patient support model to ensure that we're really thinking about the patient journey right from actually prior to the prescription starting to all the way through and beyond. We've really increased our focus from our family support educators and our MSLs in terms of educating the physicians. We've seen a nice stabilization in terms of those initial sort of first, I think, few quarters post the launch hump.
Where we saw this sort of increase in dropouts on DAYBUE due to the GI side effects. We've learned a lot through the process. We've got a white paper now out on how to titrate patients, looking at how you can increase patients over time. We've got a very steady persistency rate now, which has actually increased a little bit since we first came on, which is 55% at 12 months. We've just launched DAYBUE STIX, we've had a lot of community interest and physician interest in that, we're really excited to see what incremental opportunities that now gives us to penetrate the market.
Yeah, maybe explain what DAYBUE STIX is for those who may not know.
Yeah. It's a powder for oral solution. It comes in a sachet a little bit like a Liquid I.V. that you get to add to your water. It's much more flexible for our caregivers, so it doesn't have to be refrigerated. It's obviously a lot smaller in terms of the size. It can be importantly mixed with any liquid apart from dairy that the child prefers, so apple juice, lemonade, iced tea, whatever it might be. Importantly, also the volume that the caregiver can choose to mix it to is about half of the volume of the liquid. We've also removed Red Dye 40 and maltitol. From an overall patient experience perspective, it's just got a lot more to offer the patient and the caregiver.
Because of that, we're seeing three types of patients now coming back to DAYBUE. First of all is switch patients that are currently on liquid who are looking to switch over. The second is new patients who would not start DAYBUE because of mainly, the maltitol and Red Dye 40. A lot of these girls are on a keto diet, the parents didn't want to start them. The final group is patients that have discontinued DAYBUE in the past who are now coming back to try DAYBUE STIX. Those are the three groups we're now seeing who have a lot of strong interest in the oral solution.
Is there one of those groups that's more represented?
In terms of the first quarter, we launched mainly in the centers of excellence because we wanted to get experience with physicians who understood how to use DAYBUE. We had 250 prescriptions for DAYBUE STIX, of which 30% were either new to DAYBUE or restarts on DAYBUE. The rest of them were switchers, so 70-30. For [sybil, three years, we've guided to about 450 incremental patients that we believe will come to DAYBUE as a result of the powder for oral solution. We're tracking slightly ahead of that right now, and we'll see how Q2 plays out.
Okay. Maybe let's just move to the pipeline. ACP-204, remlifanserin, Liz, I'm sure this is now super near and dear to your heart with all the questions that you're getting. Just remind us, this is a study that's phase II that we're expecting to see top-line data for between August and October of this year. Just remind us of that study design, and then we'll go into a few more questions.
Briefly, just sort of set the stage of remlifanserin, ACP-204 is a cousin of pimavanserin. It was informed by a pretty vast amount of data on pimavanserin, both from a molecule perspective and from a program perspective. You know, NUPLAZID is a good drug, does good things for people. It does have a QT prolongation signal. That can be important in and of itself in an elderly patient population, but it also limited our ability dose range with pimavanserin. That's important because we've seen some indication that there's an exposure-response relationship for pimavanserin with efficacy in Alzheimer's disease from some of our many prior studies there. Here with remlifanserin, we have the opportunity to look at higher exposures and see if we're able to get more efficacy.
Also we have a faster time to steady state, which could translate into quicker onset of efficacy. We've also focused our Alzheimer's program, now I'll talk a little bit more about the study design aspects. One of the main learnings from our prior history in Alzheimer's was the importance from a regulatory perspective about having a study that is devoted entirely to the patient population you're looking to get indicated in. In our phase II and the follow-on phase IIIs, we're requiring a clinical diagnosis of Alzheimer's, but we're then confirming that with biomarkers, which we think is gonna be hopefully helpful from a technical perspective, but I think very important from an eventual regulatory perspective to be able to prove that we have the population that we want. Our primary endpoint is at week six.
It's something called the SAPS-H+D, which focuses in on hallucinations and delusions. It is an instrument we have used in the past with pimavanserin. What other things are important to note? The three-arm study placebo-controlled, the lower dose that we're using of remlifanserin is roughly equivalent to the exposures you get with the currently marketed dose of NUPLAZID, and the higher dose that we're using is roughly twice that exposure. It's gonna give us the opportunity to see if we can get more efficacy out of higher exposures.
Okay. A couple of things. Is six weeks enough time to detect if you're seeing efficacy?
I will say, if we look back at the pimavanserin dataset, in Alzheimer's in a phase II study, we did have a positive primary endpoint at week six.
That was part of what led us to choose this. We've seen efficacy by week six in other aspects of the NUPLAZID program. Hopefully, with a faster time to steady state and potentially faster onset of efficacy, we will see more consistency efficacy across that timeframe, but we think week six gives this mechanism time to work.
Okay. As far as the doses that you've chosen, for the higher dose where you have double the exposure, is there any concern about safety profile that comes into play there?
Yeah, I mean, you always have to think about the, there's exposure response for efficacy in. There's exposure response for safety. What I can say is a couple of things. You know, overall, aside from the QT prolongations and signal, the NUPLAZID safety database has been fairly reassuring, but of course, that's the exposure for the lower dose. We've used remlifanserin in a variety of phase I trials, and some of them have gone as high as 180 mg of dosing, but of course, that is in short-term and limited numbers of patients, but seemed to be generally supportable there. Always it's a blinded thing.
You know, it's gonna depend how things sort out, but at least at a blinded aggregate level, so far the safety profile appears to be, we're not seeing anything concerning in blinded data. We'll see how that sorts out eventually. Thus far, we think there are promising signs.
Anything on QT prolongation?
We feel pretty good about the QT prolongation based on the phase I work that we've done. I feel pretty confident from that perspective.
Okay. Now, what should we be expecting to see when you release that data, you know, later this year, level of data to expect in the press release, assuming it's on a press release, and what are you gonna hold for, let's say, a medical meeting?
I don't know exactly what we're going to hold for a medical meeting. What I can say is that we're currently anticipating that we would be sharing a comment on the primary endpoint, that week six SAPS-H+D, as well as general commentary on the safety profile. That's sort of the minimum set that you should expect. We may very well share additional information as needed to sort of contextualize what we're seeing. There's a number of aspects of the clinical data that we're looking at in terms of thinking about what a successful product could be and what we wanna see.
Have you talked about what effect size you would think would be clinically meaningful?
Well, what we've talked about is the effect size that we're currently powered for. I will say that I think that something a little bit below that probably would also be clinically meaningful. What we're powered for at this point is a 0.4 effect size or a moderate effect size, 80% power. Again, this is a phase II. Our primary goal here is phase III-enabling. We feel confident in the KOLs we worked with as we put the program together, felt that if we saw the level of data we're powering for, that would be a win.
Okay. You get your data, you top line it. What would be the next steps? Making arrangements to go talk to FDA, or have you already had some preliminary discussions about what a phase III would look like?
Yeah. We have a bit of an unusual situation here in that we have a master protocol that covers a phase II and two phase IIIs.
It's operationally seamless. What that means is once we stop enrolling in the phase II, we start enrolling in the phase III. I'm saying, but it is statistically separate, so we're able to evaluate the phase II and apply learnings to phase III. The reason I'm saying this is we talked to FDA before we went into the phase II, phase III program.
We have the opportunity to learn from the phase II and potentially make modifications to the phase III. Depending on those modifications, we may want to go talk to FDA again to make sure those are still in line with thinking. That's gonna depend a little bit on the scope of what they are. I'll say in general terms, the kinds of things I think about that we might consider modifying, right now we do have, I said, the zero the placebo 30 mg and 60 mg. If there were evidence that made us feel really good that one of those doses was the right one to take forward, we might well consider dropping one of those doses.
That has a number of advantages, but one would be presumably speed. There is the possibility that we may need to modify our estimates around effect size, and that could have sample size implications. There could be things that we would think about from an endpoint perspective. We are looking at SAPS- H + D, but we are considering other endpoints as well.
I guess why choose to kind of have a outline already as opposed to wait to see this phase II and then figure out what phase III looks like?
Yeah. I think part of it was we felt good about many aspects of this. While I'm saying these are things we could do, that doesn't mean these are things that we definitely think we're going to have to do.
Right.
The intent was to have the benefit of the time savings of starting up that enrollment directly, but t hen the opportunity to make modifications if we need to.
Okay. How are you thinking about the competitive landscape for ADP?
I'll make a couple comments and then hand it over. I mean, I think one thing is that this is a pretty substantial unmet need. There's a large amount of patients out here. I think that there are some, you know, there are some other later stage programs also at psychosis. There are some related but separate things that are looking at agitation. We think we have something that's mechanistically distinct in terms of those agents that are currently looking at the psychosis component, actually overall. I think that if we have the kind of profile out of remlifanserin that we're hoping for, we think that could be a really powerful agent for patients.
Okay. You bring up a good point on agitation, and I wanted to talk about agitation versus psychosis. Do people use these terms interchangeably and are antipsychotic drugs viewed by physicians as eligible to treat psychosis?
They may use the terms interchangeably, but they are not interchangeable.
Right.
Agitation can come from a number of different sources. It's a pretty complex phenomenon. It can be driven by pain. It can be driven by confusion. It can be driven by psychosis. It can be driven by just separate mechanistic anxiety-related behaviors. By and large, the agents that are targeting agitation don't generally target the underlying driver of that agitation. I think that, you know, as I think about it, something that is effective in agitation may or may not be, and frankly probably isn't, effective in treating the underlying manifestations.
On the flip side of the coin, as we look at psychosis, we I don't expect that we would be able to address agitation broadly. What I do think, and we've got some data from NUPLAZID that this suggests that in patients who have significant psychosis, and associated with that they also have significant agitation, in those patients, when their psychosis got better, their agitation got better.
I think that we have that within the psychosis realm, I think we could treat the underlying and the resultant agitation potentially, but again, not agitation more broadly. The agitation agents are by and large not going to positively impact psychosis, and some of them, based on mechanism, may actually have not helpful impacts on psychosis.
Catherine?
I think just as a market as a whole, I think probably people are very well aware, but, you know, there are 7 million patients with Alzheimer's in the U.S., and about 30% of those will have a psychosis episode during their diagnosis. For us, there's a large market of patients who currently don't have an approved medication. Because of that, I think there's a lot of competitive focus on the space and that's great because patients need choice, and we all know that within just psychiatry generally, different MOAs, different patient types, that there's co-prescribing, there's all sorts of ways to treat these patients. Just in terms of the competitive environment, of course we expect competition, but there's a lot of patients.
We believe that we hold a specific space in terms of the type of patient that we can treat. We'll see with the data what that looks like. I feel confident that there's room for quite a few players in this space, and it will be better for patients to have those different choices.
Okay. Now, several years ago, pimavanserin did do an umbrella study where ADP was looked at, and we've talked about this a few times. Just to put a, you know, a bow on this conversation, if you will, the difference in what you're doing with 204, mechanistically, what gives you more confidence that it will have the desired effect that pima did not?
I would say that for me at least, it's a little bit less a mechanistic question and more a little bit of the molecule parameters we talked about with the potential for greater efficacy, greater speed to efficacy, et cetera. A lot is about the, you know, the umbrella DRP trial wasn't powered for any of the individual subpopulations. I think that, you know, I'm not trying to condense all of the challenges in that indication down to that one thing, but I think that was a pretty substantial component. The biggest thing that we're doing differently here is having a very Alzheimer's specific program that then, again, goes that sort of extra mile with the biomarker confirmation.
Okay. The flip side of the argument is that Lewy body did work, even though that umbrella study wasn't powered. You know, we feel particularly bullish on that study being positive in 2027, I believe is the readout. Wanted to get your thoughts about, you know, is that observation from Pima the reason why you chose to do a Lewy body study for this asset as well?
Yeah. The Lewy body study is the first program I started when I got to Acadia.
Yeah.
I was very intrigued by the data. Small patient population exactly as you know. Pretty striking data. I think that that is a really exciting opportunity for remlifanserin. I will note that it is also, while it is a smaller patient population than Alzheimer's, it's about a million patients.
Still quite large.
It's still quite large, and they are disproportionately impacted by psychosis. 50%-75% of patients with Lewy body are gonna have psychosis as part of their journey. From a clinical development perspective, there's less going on there. I think this is a really impactful constellation of something where I have some good data to believe in from a mechanism perspective and some really substantial unmet medical need.
What do patients with Lewy body take now, if anything?
It is a lot of off-label.
Antipsychotic.
Yeah.
Yeah.
Yeah.
Which, you know, given that they do have motor impact, can be very problematic for them. The cognition impact can be really difficult. Yeah.
Yeah.
There aren't good options.
In terms of sites that you use, what was the overlap in ADP sites versus Lewy body sites, and can you compare the pace with which these enrollments occurred?
We haven't yet shared our expectations on when Lewy body's going to be done.
Yeah.
What I can say is, you know, we are looking at a somewhat smaller study for Lewy body.
In part that is because we're expecting a somewhat larger effect size. I anticipate that it will probably not take as long as the Alzheimer's program, but part of that may be sample size. There is some overlap in sites, and some distinct sites that we're working with.
Okay. Is it the case that for studies where you're looking at these types of indications, the same concerns might pop up as for study sites for, let's say, schizophrenia, where there's concern about, you know, certain patients being enrolled in too many studies, for example?
I think that we see maybe not to the same extent those dynamics, but I think we are very cognizant of doing everything we can to ensure data quality, that the patients are, you know, appropriate patients. I think in the Alzheimer's trial in particular, the fact that we're biomarker confirming these, we're pretty confident t hese are the right people to have in here. There can be some of that dynamic, but I don't think it's as significant as you see in some of these other spaces.
Okay. In the few minutes we have, maybe let's talk about 211 in major depressive disorder.
Sure. Yep. Okay. Okay. ACP-211 is our selectively deuterated R-ketamine. We are looking at this in major depressive disorder. It is in a phase II trial right now. The sort of promise of this is ketamine-like efficacy with a different patient experience. We base our expectations of that on preclinical and early clinical data. Preclinical data suggesting efficacy and absence of sedation. It's kind of hard to measure dissociation in preclinical studies. In early phase I, we have seen no sedation and only low levels of dissociation at the highest doses. That's in healthy volunteers, which can be a little bit more sensitive to these things.
We design our phase II in part, of course, to look at efficacy, but also to try to help us rule out unacceptable levels of sedation and dissociation. We are looking for the proof of concept readout in that in roughly mid-year next year.
Okay. On that, just because there's so many mechanisms that are being developed for MDD, how are you thinking about where this could fit in?
I mean, I think that, you're right, there is a lot going at this. I think that this is widely understood all the way up to, the President's executive order around psychedelics, widely understood as a massive unmet medical need space with huge numbers of patients suffering. I think that a profile that is consistent with what we're hoping that 211 can be, could be pretty impactful for patients, and I think that's true, again, to Catherine's point earlier about the, these are spaces where having a variety of mechanisms handy is a good thing for patients. I think that's gonna be true here. I think this profile's pretty compelling.
Yeah. I think the oral nature of the product is an additional benefit to patients. To the point that Liz just made, there's plenty of competition already. The ketamine-like efficacy without the dissociation of the monitoring requirement, t he total patient experience is something that we're really holding out hope that we can launch into this market.
I did wanna ask you, I mean, there are companies that are leaning into psychedelics, and so how do you think that this is, you know, a type of disruptive treatment, you know, to go against the grain on traditional, you know, antidepressants? There's obviously a certain subset of patients that don't respond to any treatment so far, and do you think that, you know, allowing things like psychedelics could also in the longer term also help, you know, products like what you're trying to develop become a little bit more seamless in how FDA chooses to look at data?
You know, I think psychedelics are obviously the flavor of the moment a little bit right now, both with the administration and also, the companies that are in that space. I think for us, there's room for many opportunities, and I don't wanna talk specifically about whether I think psychedelics are good or bad, other than there's obviously a high unmet medical need.
Yeah.
What is kind of important about getting these products to patients is the schedule and the control nature of getting drugs to patients. Psychedelics will be highly controlled no matter what happens, and so that's gonna be a very specific channel in terms of commercialization. You know, having had quite a lot of experience with fentanyl, from my Duragesic days, it's a specific commercial execution opportunity that you have to really be very careful about. You have to have high ethics and high monitoring of the whole supply chain to get these products to patients. It's quite a complex-
A complex area. I feel like the ketamine-like efficacy with the patient experience that we're aiming for is something that we can achieve both clinically, through our clinical study, but also commercially. I think those two things together are actually quite important. You need both to be successful.
Okay. I guess last question, based on today's update, there looks like there's gonna be staffing changes at the FDA again. Does that impact any of your expected interactions with the agency near term?
Yeah. I guess what I'd say is, you know, putting on my just biotech hat. I think that getting to a place where we've got a little bit more stability in the agency is going to be a good thing for all of us. Wearing just my Acadia hat. I will say that a good part of our portfolio has been we've had pretty consistent review teams sort of throughout. We've been, most of our products, certainly our later stage ones, are in the Division of Psychiatry, and Tiffany's been a pretty consistent force throughout, and the review team's been pretty consistent. Thus far, not expecting an Acadia specific impact, but it would be great to get to a little more stability.
Okay. With that, I'll say thank you for joining us here today. Thanks everybody for listening.