ACADIA Pharmaceuticals Inc. (ACAD) Earnings Call Transcript & Summary

Good afternoon, everyone. Thanks for joining us. I'm Salveen Richter, biotechnology analyst at Goldman Sachs. And we're pleased to have ACADIA with us this afternoon. We have Steve Davis, CEO; and Elena Ridloff, CFO. And with that, I'm going to turn it over to Steve to make some opening comments.

Great. Thanks so much, Salveen, and thanks to each of you for joining today. I just need to start with a brief reminder that the business of pharmaceutical development and commercialization has certain inherent risks, so please see a copy of our most recent SEC filings for a description of just how those risks relate to our business. I'd like to briefly highlight today some of our key accomplishments so far this year, which will be a transformational year for ACADIA as we execute on our 3 strategic pillars. First, we will drive NUPLAZID growth in PDP. Our first quarter 2020 net sales were $90.1 million, representing 43% year-over-year growth. We continue to add new patients and see high adherence amongst continuing patients, and as a result, we expect our 2020 net sales to be between $420 million and $450 million, representing a 28% year-over-year growth at the midpoint of the range. Beyond 2020, the long-term opportunity for NUPLAZID in PDP is very significant and growing. Second pillar is to deliver the DRP opportunity to the market. So there is no approved treatment for DRP today. And the opportunity, as you all recall, is about 10x the size of the PDP opportunity. There are serious consequences associated with DRP, for example, repeated hospital admissions, increased likelihood of nursing home placement, progression of dementia and increased risk of morbidity and mortality. We held our pre-sNDA meeting with the FDA in the first quarter, and we remain on track to submit an sNDA for DRP this summer. Pimavanserin was previously granted breakthrough therapy designation, and as such, we would expect the 6-month priority review with the potential approval or PDUFA date around the end of the year. And we're laser-focused on the potential to bring pimavanserin to patients suffering from DRP. Finally, our third pillar is to develop innovative treatments for unmet needs. Near term, we're excited about the opportunity for pimavanserin in adjunctive major depressive disorder. We're currently in an ongoing Phase III program with the top line results coming next quarter. We recently received positive feedback from the FDA regarding our strategy for the Phase III CLARITY MDD program. Our 2 Phase III studies, CLARITY-2 and 3 were identically designed at just over 50% enrolled, and we're now in the process of stopping these studies and combining them into 1 Phase III study with a prespecified analysis plan. We'll talk more about that, I'm sure, on this call. If the results of that are positive along with positive results from our previously announced pivotal CLARITY-1 study, would form the basis of an sNDA in adjunctive MDD. For the negative symptoms of schizophrenia program, we have one positive pivotal study. We're preparing to initiate a second pivotal study in the second half of this year. In addition, we initiated a Phase III program late last year evaluating trofinetide as a treatment for Rett syndrome, and we expect results next year. Finally, on the BD front, we recently announced a licensing and collaboration agreement with Vanderbilt University, adding a muscarinic receptor program to our pipeline. This M1 PAM program is a portfolio of early-stage candidates with the lead compound in early Phase I and several preclinical compounds. So as you can see, we're executing on our 3 strategic pillars. This sets us up to deliver long-term growth with a multiyear cadence of potential product approvals in DRP, MDD, Rett syndrome and the negative symptoms of schizophrenia. And in parallel, we're growing our pipeline through business development in the CNS space. And with that, I'll now turn it back over to you, Salveen.

Great, Steve. Thank you. So 2020, as you just mentioned, look to be a key year in terms of NUPLAZID expansion from Parkinson's disease psychosis to potentially dementia-related psychosis and major depressive disorder. On DRP, can you just give us an update on where you stand with your sNDA regulatory strategy? Are you still on track here for mid-2020? And then with regard to your MDD program, have you started the process of combining these 2 data sets here ahead of data in the third quarter?

Yes. Great. So the short answer is, on both programs, we made 100% on track. For DRP, we've indicated that we'll be submitting this summer, and we expect a PDUFA date around the end of the year, with a 6-month priority review expected. Working backwards from there, you can see that we're -- we should be very close to announcing an sNDA submission. As it relates to MDD, as I mentioned in my prepared remarks, based upon positive feedback we received from FDA, we're now in the process of stopping the 2 studies and combining it into one study with a prespecified statistical analysis, and we look forward to announcing results from this in the third quarter of this year. And just as a reminder, on MDD, we already have one positive pivotal study. So if this combined study is positive, that would put us in a position to prepare an sNDA filing in adjunctive MDD.

Great. And then kind of just in light of the recent deal that you did, what is your strategy here for business development transactions in the context of the prior ones you've done with Neuren and Vanderbilt? What areas do you see as most attractive here? What stage assets, in terms of leveraging your infrastructure and complementing your R&D efforts?

Great. So a couple of questions there. If I don't hit everything, please let me know. But I'll start with strategy. So look, I think the starting point for this discussion is pimavanserin, for NUPLAZID, is going to be a very large and important drug. And as a result of the development and commercialization of pimavanserin, we've built a first-class R&D organization that is -- you've heard me say before, I would put up against anyone in our industry in the CNS space. And I feel just as strong about our commercial organization, where we've established a very strong footprint in -- again, in the CNS space. We needed to build this strong organization in order to fully leverage the pimavanserin opportunity. And it puts us in a great position to continue to grow the company transactionally. Business development, as you've heard me say many times, is a critical strategic pillar. And currently, I hope -- I probably spend more of my time thinking about what our business -- what we're going to be doing in our business in 2025 and 2030 than any other single thing. I spend my time on a whole lot of things, but that's one that is very important to us and a very important pillar in our strategic plan. You asked about the Vanderbilt and Neuren examples. And I think both of those are great examples of the kinds of deals that we're interested in. They -- obviously, one is a very early stage deal and one is a late-stage deal, and both of them fully leverage our capability and commercial infrastructure that we built. So we have -- today, we have a very strong team involved in business development. It's multifunctional. The kinds of things we look at, that is -- our -- it's a multifaceted type of assessment. But among the things that we look at are, first and foremost, do we believe in the science? And could it address a significant unmet need? I know that phrase gets used a lot in our industry, but it's really critical for us that we pursue things that have -- that advance both significantly from a medical and scientific perspective. And we look at -- as the program is set up in a way to maximize the likelihood of success, sometimes we assess opportunities where we think that is not the case. And sometimes, those are the kind of more interesting opportunities you run across in business development, if you feel like you can take a more valuable approach than is currently being taken. And of course, just to state the obvious, finally, we look for what's the right place, right time, right price to ensure that we maximize value for our shareholders. And I guess I'll just sum up by saying, you know that we said many times, we started early. We started before we actually launched pimavanserin. We did that for a reason. We wanted to be in a position where we could be very strategic and judicious about the kinds of things that we acquire. There are a lot of things in the CNS space that we -- probably wouldn't be a good fit for us. And there are some things that we think are very interesting, but maybe mispriced. And I think today, we have a very strong team and a very good -- very well informed view of the assets in this space and the -- and what I see is a very attractive opportunity for us to continue to grow the business.

Do you think that you'll be mostly focused on the field of neuropsychiatry? And then just thoughts on other modalities. I think, you've mentioned gene therapy before, but how are you thinking about just expansion here?

Yes. Of course, pimavanserin is a small molecule. But internally, we have a lot of expertise in other modalities as well because we really have built the company in the last 5 years. We have brought in a lot of expertise from other organizations, and we like to think that we've been able to take the best practices from other organizations and distill them into our own culture. But in bringing people from other -- we'll look at these things from other sides. But I feel like we brought in a really, really heavy-hitting team. And this team brings expertise in other areas as well, historical work that they've done. So we're open to other modalities. We're not just focused on small molecules. And in the CNS space, unfortunately, there remains a really dramatic unmet need in many of the areas that we work in. So there's -- or many of the areas that we assess, and so there's ample opportunity. I mean, I'll just give you a couple of quick examples. Depression, of course, is a major one. Patients more often than not do not respond adequately to their initial depression therapy. And the additional treatment choices we have today are very problematic. They're very, very imperfect drugs. They are the same class of dopaminergic antipsychotics that are not approved for PDP or DRP. But in some respects, the liabilities of the drugs can be even more problematic in an MDD population, where the metabolic effects that those -- side effects those drugs can have can be very problematic in younger population. So it's just an example of where there's, I think, a significant unmet need in a very large market. Pain management is another area of high unmet need. The opioid crisis and addiction has affected many families across the country and hit every socioeconomic group. There are a lot of interesting areas in orphan space that are similar to what we're doing in Rett syndrome in the neurology space. So we're fortunate to be working in a space where there are a lot of interesting opportunities and where the science is really beginning to bear some meaningful fruit in terms of therapies that are a significant advance over the types of drugs we've had in the past. And so as we think about modalities, we can be fairly agnostic because we have a lot of internal expertise. When we think about specific areas that we want to focus on, there's a fairly long list of things that are interesting areas with interesting approaches. And as I mentioned, we're being very judicious and strategic. But you will see more deals. It's an important part of our business.

And then what are your updated thoughts here on the ex U.S. strategy? Has that evolved with the advent of these additional indications?

So as we said before, we have frame-shifted our ex U.S. strategy. I'd just like to remind everyone that the bulk, the significant majority of the value pie for pimavanserin and the indications that we're pursuing is in the United States. And that's just a simple function of pricing of these kinds of drugs in other countries being basically heavily subsidized by the U.S. pharmaceutical industry. And so there is a piece of the pie that has value outside the U.S., but it is a relatively small piece of the pie. In order to make it feasible for us to pursue these other markets, we frame-shifted our strategy so that we could try to combine multiple indications into a common 10-year period of data exclusivity that we'll have in Japan and in Europe. And so we're not at a point yet where we are ready to start that process and then ultimately start that clock. But I think as we get read out in more of these indications and get them closer to the finish line, then we'll come back and speak more to that.

And then just one last, kind of, big picture question here. But can you -- Elena, can you remind us on your cash balance and expected runway? And what activities this is anticipated to cover before just in terms of the opportunities in the pipeline?

Sure, Salveen. So we ended Q1 with just over $650 million in cash. And with that strong cash balance, we're well positioned to launch in DRP and progress the rest of our pipeline. Any additional cash needs at this juncture would likely be driven by additional business development.

Got it. So first, moving to NUPLAZID in PDP. Could you just talk about the dynamics that you're seeing as a result of COVID-19? I think you mentioned on the last EPS call that new patient starts were down as in-person physician visits decreased. And has this been a trend that has been continuing through May and into June?

Sure. So we did see an impact to the rate of growth of our new patient starts in March. And we modestly reduced our guidance -- our revenue guidance by about 5% to reflect the impact we saw at that time. What we're seeing is, we're continuing to see very strong fulfillment rates for our continuing patients. We continue to add patients, albeit at a little slower rate following the COVID impact that started in March. And we are seeing NUPLAZID new patient starts outpace the overall market new-to-brand trends, and we're continuing to add new prescribers. We saw the biggest impact to in-person physician visits and new patient starts in March. And as we saw physicians adapt to telemedicine and virtual visits in our engagement, we started to see those trends improved in April, which were sustaining into May and now into early June.

Great. And then how has the impact played out in long-term care facilities, given at least about 75% of your specialty distribution channel? Could you just comment on the trends you're seeing here?

Sure. So maybe just to level set, long-term care makes up about 25% of our total business. And we are continuing to see a strong fulfillment in that channel as well as new patient starts. Our growth assumptions for the full year has seen both growth in specialty pharmacy and specialty distribution. And we see similar dynamics in our ability to operate in those 2 settings. One important piece to note is, in long-term care, a lot of the prescribing comes from physicians that are not physically located in the long-term care center. They visit and they are consulting physicians. And so we have ability to engage with them outside of the facility virtually as well.

And then you have noted penetration into the PDP market has grown steadily with time. Can you just comment where you are in terms of penetration now -- penetration rates now? And what the key drivers are that you see here for continued growth? Where you think you can go in terms of capturing share over the long term?

Sure. Sure. I'll start, and then Elena, please add any additional color, if you like. So since launch, we expected this product to have a -- in PDP, we expected this to have a very linear sales trajectory and that's exactly what we've seen. So we thought it would have -- provide an opportunity for very attractive revenue growth quarter-over-quarter year after year. And that is the way it's played out. So we're currently in the high teens for our market share. This is out of about 125,000 or so patients in the U.S. who are currently being treated for PDP. We're continuing to gain share. And the key initiatives to help us drive further share and drive adoption are first, continuing to establish NUPLAZID as the standard of care by communicating The Movement Disorder Society guidelines and new data sets that we have on patient safety and efficacy and the impact on caregiver burden. We're continuing to increase PDP awareness and stimulating patient and caregiver conversations with health care professionals about their PD psychosis with our direct-to-consumer programs, and then focusing on new patient identification by optimizing our sales and medical education, by leveraging technology to conduct peer-to-peer educational programs and product theaters, et cetera. So we continue to press on all fronts. And while we haven't given specifics around the potential peak market for NUPLAZID, as I've said before, we believe this can be a very big drug just in the PDP indication alone.

Great. And then moving to the DRP indication. You've noted that an AdCom is likely ahead of the FDA's decision. Could you just walk us through your expectations here? And what are the likely points of discussion?

Yes. So maybe the starting point is, typically, with an sNDA, you wouldn't anticipate AdCom. However, we think there it is likely that we will have one, because this is the -- would be the first drug approved in this indication. And the existing drugs that are used off-label are actually contraindicated for use in this population. So we think there -- it is likely. We're well prepared to have an AdCom. If we have one, great. If we don't have one, that's fine, too. And we'll find out from FDA as they get -- they'll probably need to be a couple of months into the review of our sNDA before we'll have a sense as to whether we'll have an AdCom or not. If we do have an AdCom, of course, the topics for AdComs are efficacy, safety and then benefit risk. And as I mentioned, we're well prepared on all fronts. And we were extremely well prepared for our AdCom -- an AdCom we had with PDP, and we will be for DRP as well.

And then can you also walk through the preparations you're making here on the commercial side and the effort you've made for the identification.

Sure. So we'll be making key investments this year as we prepare for the DRP launch, including ongoing disease awareness activities and our plan to expand our commercial footprint. As we've indicated, we plan to do that towards the end of the year from approximately 200 FTEs today to between 450 and 500 at the end of the year to support the DRP launch. Look, we continue to advance our plans focused on market research, disease awareness, education, focusing on the high burden of disease. And these are all things that we do very effectively virtually, including virtual advisory boards, payer engagements, et cetera. So I feel very good about our preparations in that regard. Just maybe another point on disease education. I should have pointed out that we began this well before we received our positive HARMONY results. And every day, we're seeing greater HCP interest in learning more about DRP. For example, our disease education website MoreThanCognition.com has attracted tens of thousands of visitors since launch late last year, and it's continued to grow steadily. So in a nutshell, when we think about where we stand in PDP versus where we need to be in DRP, one of the great things about this launch is we already have an established brand. We already have an established infrastructure. So we've got a hub that's up and running. We have relationships that we've already built. We're already in long-term care facilities, where about 25% of the PDP patients reside, but up to 50% of the DRP patients reside. So we're very well positioned for a successful launch here. We're prepared to launch virtually if we need to. We're operating that way today, that's working very well. We're obviously prepared to launch in-person and multiple variations in between.

And Steve, can you speak to the pseudo specialists with regard to the learnings and the requirements needed to bring these practitioners into the mix?

Yes. Sure. So I'll take a little bit of a running start at it. So today, we currently call on neurologists, psychiatrists, long-term care physicians, which generally tend to be more geriatric psychiatrists as well as a group of physicians that sometimes we refer to as pseudo specialists. And so these are typically the CNS and geriatric focused primary care physicians that you find in all regions, but they either are more common in more rural areas where population density is not as great. You may have someone that acts kind of as a -- in that capacity. So as we prepare for DRP, we'll leverage their current infrastructure in each of those prescribing populations in neurology, psychiatry -- well, neurology will continue to be an important part in DRP as it is in PDP. The psychiatry piece will be bigger in DRP. The long-term care piece is bigger, as I mentioned. And the pseudo specialists will be bigger as well. So we'll do a lot of the same things we're doing now, but of course, we need to expand to cover the entire waterfront in DRP. As it relates to the pseudo specialists' group and kind of how they operate, I would say that we'll pay close attention to activities such as speakers bureaus. They pay close attention to them, and they'd like to learn what the specialists are saying about new therapies. So this will be an important part of our direct outreach and consumer campaigns in that regard. And just as we're talking about the translation from -- or the transition from PDP to now encompassing DRP as well. I'd be remiss if I didn't point out a couple of key points here. One is there's a key similarity between PDP and DRP, and there's a key difference between those 2. The key similarity is, in both cases, there was nothing approved before NUPLAZID. So it's nothing approved -- there was nothing approved in PDP. Today, there is nothing approved in DRP. And the off-label use of dopaminergic drugs is very problematic in both cases. And in both cases, they exacerbate the key symptoms that these patients suffer from or the predominant symptoms. In Parkinson's, the dopaminergic antipsychotics can impair motor function. In dementia, it's been well-established that those same drugs, when used off-label in dementia patients, accelerate cognitive decline. So that dynamic is very similar between the 2 indications. A key difference between them is because Parkinson's is predominantly treated by neurologists, and neurologists, of course, are the center of the bulls eye for them, is motor function. They certainly encounter psychosis. They know how to deal with it, but it is not as high on the priority scale for them as getting a patient so that they can walk to the bathroom and they can feed themselves and all that. Whereas if you frame shift over to dementia-related psychosis, the connectivity between cognitive impairment and confusion and hallucinations and delusions is much tighter. And so we're much closer to the center of the bulls eye for physicians that treat dementia. And I think that will be an important dynamic that will support the launch in DRP as well.

That's very helpful. And how do you think about pricing here? I don't know if you've made any comments about the pricing side, just given the DRP indication is about 10x the size of PDP.

Yes. Thanks. So you're right, it is about -- it's 10x the size, and it's a little bit premature for us to comment on the pricing today. But I would say that payers get what I just described. So we've had a lot of interactions with payers. Some of the key interactions will happen when we have a label, and we're talking about the precise wording label. So it's premature for us to say precisely where we'll be on price today. But I would say that the dynamics are very similar and payers get that. They understand there's nothing approved. They understand the use of these dopaminergic antipsychotics in this patient population is very complicating. It requires compromises and it can impair the patients further in terms of their cognitive abilities. They also impair motor function in dementia patients as well. And so there are some really important key considerations that we -- and very important as we continue these payer discussions. But today, I'll just simply say, as we think about the 2 indications, we think the dynamics are very similar.

Okay. And then moving to major depressive disorder here. So the rationale behind combining the 2 Phase III trials makes sense. But could you help us understand the risk here in combining the trials? While they're identical, you've got an ex U.S. and a U.S. base heavy, so how are you thinking about that?

Yes. Sure. So the -- just to level set, so with 2 Phase III studies that were ongoing when COVID-19 hit, they're identical studies. One is U.S.-based, one is ex U.S.-based. And with the pandemic, we stopped enrolling new patients in the study in March. And so at that point in time, we were a little bit past halfway enrolled in each of the 2 studies. We only need 1 of those studies to combine with our previous positive pivotal study in MDD to submit an sNDA. We ran 2 studies as an insurance policy. So we're still committed to taking 2 bites of the apple if we need it, we'll just do it sequentially now as opposed to doing it in parallel. So what we're doing is we're combining the 2 studies into 1 study based upon positive feedback we have from FDA. We requested a Type A meeting and got the request, and they were in full support of this plan. We'll combine those 2 studies into 1 study. As a consequence, we'll wind up with a little bit more -- a little bit higher number of patients in that combined study than we would have had in a single individual study. We will also have a larger number of sites. So we'll have almost double the number of sites that we would have had in a single study. And so a question that always comes up in that kind of a situation is when you increase the number of sites, will you increase the variability? And what I can say to that today is we looked at all of the blinded -- of course, we're still blinded. We don't know who's on drug and who's on placebo. But looking at all of the blinded data that we have available to us, we didn't see anything that would indicate to us a higher degree of variability. So when we looked at each study individually and we looked at change from baseline, we looked at standard deviations, unchanged from baseline, outlier analysis, et cetera. Both studies looked very similar. They also looked very similar to what we saw in our previous positive pivotal study. So we saw no indication that we shouldn't follow this strategy. I think this strategy is a great one. I think it's the right one to pursue, and we'll have data from this combined study and combined analysis again in the third quarter.

Great. And what effect size here would be meaningful as we look to just kind of understand, firstly, how this trial compared to the prior Phase II? And whether there were differences in in-patient baseline characteristics? But secondly, just versus the competitive landscape here, what we'll be able to see?

So thanks for asking the question. The -- we powered these studies to show an effect size that would be considered clinically meaningful. In this case, we had the benefit of a very large effect size in our CLARITY-1 study, our previous positive pivotal study. In that study, we had an effect size of 0.63. What you often see with antidepressants is an effect size that's more in the 0.3 to 0.35 range. So we had a very significant -- a very robust antipsychotic effect. And so we powered these studies recognizing that we had a very large effect size there. But you never want to count on being able to replicate that precisely. So we powered them assuming Rett actually had an appropriate effect size that would be clinically meaningful. As I mentioned, now combining the studies we'll have slightly more than the number of patients that we would have had. So perhaps we get a little bit of additional power from that, but we feel good about -- we just happen to be in a position where this strategy was really ideally situated to execute on this strategy. And I'll just really quickly just make nuances around MDD of -- since we're talking about effect size, as you recall, in the previous pivotal study that we did, we saw a very robust effect. We saw a quick onset of action. We saw separation from placebo within a week. What we didn't see is we didn't see sexual dysfunction, in fact, we saw sexual improvement. We didn't see daytime sedation, in fact, we saw increase in daytime wakefulness. The issues around weight gain that you see with the metabolic effects from dopaminergic drugs, we don't have. We don't have the -- we've never seen anything to indicate we'd have the potential for target dyskinesias and other things that are typically associated with dopaminergic drugs. And so when we think about MDD and the profile that we observed in the previous pivotal study, if we get anywhere near that profile in our Phase III program, I think that will be a profile that will move right to the head of the class in MDD. It is a very large population that are already taking adjunctive therapy and these very imperfect drugs that they're taking. So we're very excited about the opportunity here. And as I mentioned before, we're eager to have results of this study, and we'll have those in the third quarter. If we do need to run another study, we're poised to do that and already prepared to run it.

And Steve, how do you think about where NUPLAZID would be positioned in the current treatment paradigm or the evolving treatment paradigm?

In the MDD?

Yes. In MDD.

Yes, yes, in MDD. Today, a majority of patients with -- there's 17 million depression patients in the U.S. So it's a vast medical need. A majority of them do not adequately respond to front-line therapy. So what we're not doing is we're not trying to displace the cheap generics that you take as a front-line therapy. We've developed pimavanserin as adjunct therapy for those patients -- those majority of patients that don't adequately respond. Today, as I mentioned, about 2.5 million of those patients are taking adjunctive therapy on top of the SSRIs or SNRIs. We see us fitting into that spot. And that part of the market, in particular, has a very high unmet need. Again, the drugs that are approved to treat depression adjunctively are the same dopaminergic antipsychotics with all of the side effect burden that those drugs carry with them. And we sometimes see quite a bit of Wellbutrin being used too. So Wellbutrin is not approved for adjunctive therapy. It's not thought of as being the most highly efficacious antidepressant. But I think it's a reflection of the reticence that a lot of physicians have in using these dopaminergic antipsychotics. And so I think we -- with a robust efficacy that we've seen versus what you would expect with Wellbutrin and with a dramatically improved side effect profile or the very favorable side effect profile that we have, I think we'll be -- just as I mentioned, we'll be well positioned to move -- route to being the preferred drug to treat depression adjunctively.

Maybe then, Steve, moving over to the rest of the pipeline. So you do have 2 other programs that are entering or in pivotal states. So the NUPLAZID in schizophrenia negative symptoms as well as a Rett syndrome study. So on the schizophrenia negative symptoms trial, could you help us understand your learnings from Phase II and how they're informing the plan for the pivotal travel here and including the use of only EU clinical sites? And then just if you could give us an update on the Rett syndrome trial, just given the pause related to COVID-19.

Yes. So you're breaking up a little bit, Salveen, but I think I caught it all. So let me -- if I didn't, just let me know. So as it relates to the negative symptoms of schizophrenia, I think the most important learning from the ADVANCE study that we did where we saw positive results in that large pivotal study is the dose. So in that study, we wanted to do a little bit of dose-ranging to make sure that we've zeroed in on the right dose. And what we saw there in the 34-milligram dose, which is the only dose approved today in PDP, it is also the dose that we'll be seeking approval for in DRP and in MDD. At that dose, we saw a very highly statistically significant result with a p-value of 0.0065 and an effect size of 0.34. So the most important learning from that study that we're carrying forward into the next pivotal study is that dose. Otherwise, there are a lot of things in that study that we want to continue and leverage in the next study. And then there are always some learnings that you have that will apply as well. But I think given the results of that study and the very positive results we have at that 34 milligram -- I mean positive overall results, but particularly at the 34-milligram result -- 34-milligram dose, we're well positioned now to execute the next study. You're also asking about Rett syndrome. So we -- last year, we initiated our Phase III program in Rett syndrome with trofinetide. And we also stopped enrollment there in the second week of March. We are very near to the point of enrollment -- beginning enrollment again. It is going to be a little bit staged. We have to be just mindful of the medical condition of these patients as well as the fact that -- because it's a rare disease, many of them have to travel to see their physician. And so we just want to be mindful of those things as we advance enrollment there. All said and done, we continue to expect results of that study next year. They'll be a little bit later in the year than they would have been otherwise, but we expect to have results of the study next year.

And one last question here. You recently, through the Vanderbilt collaboration, are bringing an M1 PAM into your portfolio here. How do you think about where this will fit in? And how does it coexist with NUPLAZID? And could you think about a combinatorial approach here for some indications?

Yes. So we really like this program. It's an early stage program. So as I mentioned before, you want to have a battery of compounds. That was key for us in this collaboration to make sure we had battery compounds, because there is a high attrition rate with small molecules in the early stages of development. The potential of this program, though, is very, very intriguing. There's been a lot of work done in the muscarinic system. The key hurdle that we faced as an industry is how to get the benefits of modulating the muscarinic system without getting the downstream side effects through the cholinergic system. And so the M1 PAM approach that Vanderbilt has pursued, we found very, very interesting. And the hypothesis is that modulating M1 with a positive allosteric modulator, a PAM, very selective compound, that you can get those kind of muscarinic benefits without the downstream cholinergic side effects. And in in-vitro testing that hypothesis is holding up and in in-vivo testing, the hypothesis is holding up. The key now will be getting into humans in Phase II to see if those results are able to confirm in humans. And if so, we think that has a great potential, both in potential cognition enhancement as well as in schizophrenia. And when we look at the body of data that's supported, it's a substantial support that mechanism or that -- the M1 receptor subtype, there's a substantial body of evidence. There's also a lot for M4. We think that they're about equal bodies of evidence, and we're eager to advance the program. You asked about ways that it could be -- coexist with pimavanserin. Look, we operate with pimavanserin in areas where they're very large markets, and there's room for multiple drugs, including multiple drugs from us. There's also the potential, always, of combining pimavanserin with other drugs, and it's a little bit premature for us to say that, that would be an appropriate approach here, but it's certainly the kind of thing that we would take into consideration.

Great. Well with that, thank you so much, Steve and Elena. Really appreciate it.

Thanks, Salveen.

Thank you, Salveen.

Thank you. Good bye.

Take care. Bye.