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

All right. Good afternoon or good morning from the virtual JPMorgan Healthcare Conference. My name is Cory Kasimov, I'm the senior large-cap biotech analyst, and it's my pleasure to introduce our next company ACADIA Pharmaceuticals and CEO, Steve Davis. Please note that following this presentation, we will have a Q&A session where you have the ability to submit questions via the little blue toggle button in your conference portal. So with that, Steve, thanks for being here today, and let me turn things over to you.

Great. Thanks much, Cory. Hello, everyone. Thank you for joining us today. I'm Steve Davis, CEO of ACADIA Pharmaceuticals. Just a brief reminder that the business of pharmaceutical development and commercialization has certain inherent risks. So please refer to Slide 2 of this presentation and a copy of our most recent SEC filings for a description of those risks as they relate to our business. I'd like to start by reminding everyone why we do what we do at ACADIA. What you see on Slide 3 are the faces of patients and their families and their caregivers that we strive to help every day. If 2020 has taught us anything, it's the importance of cherishing every moment with our loved ones, and at ACADIA, that is reflected in our mission to elevate life. The people you see on this slide represent the individuals to whom we owe our very best and the people who have the most to gain as we fulfill our mission. Please turn to Slide 4. In order to deliver on our mission, we're focused on 3 strategic pillars: one is to drive growth in NUPLAZID; two is to deliver the dementia-related psychosis, or DRP, opportunity; and three is to develop the next wave of breakthroughs in the field of neuroscience. Slide 5 is an illustration of how we view our business. The significant potential of pimavanserin combined with our innovative pipeline will drive meaningful long-term growth. The foundation we're building upon is our continued growth in PDP. For 2020, we expect net sales to be between $430 million and $450 million, and we will continue to drive significant future growth in PDP alone. We're on the cusp of a potential approval in DRP, which represents a much larger market opportunity, it's about 10x the size of PDP. NUPLAZID could be the first and only approved treatment for DRP, and it would certainly represent a true breakthrough for patients and their families. We're focused on developing and expanding a pipeline of innovative new programs. Our Phase III program for trofinetide in Rett syndrome is advancing, and we have top line results coming in the second half of this year in that program. Our Phase III program for pimavanserin in the negative symptoms of schizophrenia was initiated last year. And in addition, we have 2 exciting programs that we added in 2020. First is a novel first-in-class non-opioid pain program entering Phase II and an innovative and differentiated muscarinic receptor program in Phase I. As we look forward, business development continues to be a key priority for our strategy. And with a strong balance sheet, we are well capitalized to advance and expand our pipeline. Let's turn to our first pillar to dive a little deeper on Slide 7. In 2020, we expect to increase net sales of NUPLAZID by 30% year-over-year, delivering consistent linear growth since launch, and we expect this to continue in PDP. The FDA just recently approved a label update to allow NUPLAZID capsule to be sprinkled on certain foods and liquids. This is an important feature for patients who may have difficulty swallowing or due to their psychosis may be reluctant to take their medications. As we look forward, we see further growth in PDP from more and more physicians gaining experience with the product, establishing a higher and higher share of new patients taking NUPLAZID, which continues to drive the overall market share growth and growing clinical evidence supporting the use of NUPLAZID, including presentation of a recent study, highlighting its long-term safety. Let's discuss this last point on Slide 8. Additional analysis supporting the pimavanserin's differentiated safety profile was presented recently at the International Parkinson's and Movement Disorder Society Virtual Congress. The authors included members of FDA, of CMS and Stanford University and their poster described a retrospective cohort study conducted in Medicare Parkinson's patients treated with either pimavanserin or a group of atypical antipsychotics primarily quetiapine. They concluded that pimavanserin treatment was associated with the reduced all-cause mortality compared to treatment with atypical antipsychotics, as shown in this Kaplan-Meier survival curve. Now I'd like to discuss the opportunity for pimavanserin in dementia-related psychosis, the second pillar of our strategy, starting on Slide 10. The symptoms of psychosis hallucinations and delusions are common in dementia and carry significant burden. Patients often experience hallucinations and delusions 2 to 6 times a week, and these symptoms can progress and typically get worse over time. Psychosis in dementia patients is also associated with higher risk of cognitive decline with institutionalization, morbidity and mortality. The cost of the overall health care system are high. For example, the average cost for a newly diagnosed DRP patient compared to a dementia patient without psychosis nearly doubles, reaching almost $90,000 during the first year with psychosis relative to the prior year where they did not have psychosis. And psychosis is a leading reason why dementia patients go to a nursing home or hospitalized. Unfortunately, with no approved treatments today, the off-label options carry significant risk for this often frail in the elderly patient population, including worsening of cognition, worsening of motor function, increased sedation and increased mortality. Turning to Slide 11. Pimavanserin has the potential to be the first treatment approved for DRP, and I'm pleased to report that our sNDA submission is progressing well and as we would expect at this point in the review cycle. Pimavanserin selective serotonergic mechanism is highly differentiated. It's unlike any other antipsychotic on the market. And as I mentioned, the DRP market opportunity is very large and approximately 2/3 of the 1.2 million patients treated for DRP today are treated with off-label atypical antipsychotics, which, as I mentioned, carry significant disease burden or side effect burden. Our sNDA is supported by strong and robust efficacy data. Pimavanserin demonstrated an almost threefold reduction in risk of relapse of psychosis in our pivotal HARMONY study. Our sNDA's also includes positive results from 2 supportive efficacy studies, a positive Phase II study in Alzheimer's Disease psychosis; and positive data from our pivotal Phase III study in Parkinson's disease psychosis in patients with dementia. Our sNDA is also supported by strong safety data. Pimavanserin is well tolerated and notably exhibited, no worsening of cognition, no worsening of motor function and no increase in sedation. As we prepare for the DRP launch, we are well positioned to leverage our established capabilities and expertise. As you can see on Slide 12, NUPLAZID has significant brand awareness with over 30,000 prescriptions since launch. We already have a patient support hub. We've optimized it. That's not an insignificant task to accomplish when you launch a drug. NUPLAZID has broad formulary access in PDP today with a well-recognized value proposition, and we have a dedicated and best-in-class long-term care sales force already in place. I'm confident that we'll be ready for a successful launch and help many more patients and their families upon approval. Please turn to Slide 13. As we expand into DRP, there are some important key similarities and key differences to the PDP marketplace. Let's start with some of the key similarities. PDP had no previously approved FDA treatment with high disease burden, and the same is true for DRP. Use of off-label atypical antipsychotics is problematic in both PDP and DRP. In Parkinson's, they can impair motor function. In dementia, they can impair cognition. In both cases, you're worsening the hallmark of those diseases. What's different between PDP and DRP? The DRP opportunity is much larger. As I mentioned before, it's 10x the size of PDP. And an important difference is in DRP, the treating physicians are focused on cognition and the connectivity between cognition impairment and psychosis is much greater in Parkinson's disease where physicians are focused on motor function and psychosis. Turning to Slide 15. Beyond the significant opportunity in PDP and DRP, we have a growing and significant pipeline. Our Phase III programs are progressing well with trofinetide in Rett syndrome. We expect top line results in the second half of this year. In the Phase III ADVANCE 2 study evaluating pimavanserin for the negative symptoms of schizophrenia is continuing to enroll very well. We added 2 innovative clinical programs in 2020, I referenced earlier. ACP-044 from our CerSci Therapeutics acquisition and ACP-319 from our Vanderbilt University collaboration. I'll talk more about these programs in a few slides. Let's discuss our negative symptoms of schizophrenia program on Slide 16. This remains an area of very high unmet need, and there are no FDA-approved treatment option for the negative symptoms of schizophrenia. Greater than 700,000 patients in the U.S. are treated for schizophrenia and still have persistent and potentially debilitating negative symptoms. Approved antipsychotics today primarily address the positive symptoms and do not control the negative symptoms of the disorder. As part of our ADVANCE program, we have one positive pivotal study already under our belt, ADVANCE-1, and we're enrolling our second pivotal study now. If this study is positive, pimavanserin could be the first and only FDA-approved treatment for negative symptoms of schizophrenia. Now I'd like to discuss our trofinetide program for Rett syndrome, a highly debilitating neurological disorder on Slide 17. Rett syndrome occurs primarily in females following apparent normal development for the first 6 months of life. Between months 6 and 18 of age, patients begin to experience a period of rapid decline with severe impairment, including loss of hand use, speech and independence. Today, there are no approved therapies for the estimated 6,000 to 9,000 patients in the U.S. with Rett syndrome. Our Phase III study, LAVENDER, is progressing well. Top line results are expected in the second half of this year. And in this study, we're seeking to confirm the positive results of the Phase II study previously conducted using the same validated endpoints to show improvement on the core symptoms of Rett syndrome. Based on the end of Phase II meeting with FDA, if this study is positive, we will submit an NDA. Please turn to Slide 18 to discuss ACP-044. With a very novel scientific approach, ACP-044 is a first-in-class, orally administered, nonopioid analgesic. This drug acts by interrupting multiple downstream pain pathways and sensitize neurons to pain, and it does this by accelerating the decomposition of peroxynitrite, a byproduct of tissue damage. So one of the things we really like about this program is with pain, we have redundant pain sensory mechanisms, and this approach by accelerating the decomposition of peroxynitrite operates upstream of many of those pain pathways. This -- our drug candidate ACP-044 has the potential to address an urgent need for new nonopioid approaches to pain management. Specifically, in acute pain, there is a high prevalence of persistent and disabling pain following surgery and the vast majority of surgery patients are prescribed opioids due to lack of better treatment options. Other nonopioid treatments have either inadequate efficacy or additional troubling side effects such as GI bleeding, cardiovascular events and liver toxicity. Chronic pain remains a massive problem, affecting approximately 1 in 5 U.S. adults and remains a leading cause of disability in this country. Available treatments are often lack efficacy and are poorly tolerated and of course, as we all know, opioids are often used when other treatments fail, but have a very high risk of dependence, addiction, abuse and significant side effects. ACP-044 has shown compelling and promising results in several animal models of both acute and chronic pain, and there is a real opportunity here for pain therapy that is efficacious across multiple modalities without the high risk of addiction and abuse. We're very excited to initiate our Phase II program and, as I said, with clinical studies in both acute and chronic pain, and we'll do that in the first half of this year. On Slide 19, I'd like to touch on ACP-319. The muscarinic receptors have been supportive of potential utility and cognition in dementia and psychotic symptoms in schizophrenia. The body of work supporting the muscarinic system is very tantalizing. We see very strong efficacy working through this system, but the challenge has been how to mitigate the unwanted downstream cholinergic side effects that occur when you modulate the muscarinic system. ACP-319 provides allosteric modulation of the M1 receptor. So this M1 PAM approach, based on the animal model data that's been established, could achieve similar levels of efficacy, but without the downstream cholinergic side effects that I referred to earlier. We're currently in Phase I testing, and the preclinical evidence is very compelling. As I mentioned, animal models have already demonstrated improvement in models of cognition in schizophrenia, and importantly, in those models, we do not see the downstream cholinergic side effects that you often see when you modulate the muscarinic system. Slide 20 highlights our ongoing programs and upcoming milestones. To recap what I've shared, near term, we look forward to a potential approval in DRP with a PDUFA date of April 3. Also, in the first half of this year, we will initiate our 2 Phase II programs for ACP-044 in acute and chronic pain. And later this year, we expect top line results from trofinetide's Phase III program in Rett syndrome. I'd like to end on Slide 21, framing the future outlook for ACADIA. NUPLAZID has the potential to help millions of patients and their loved ones. This is going to be a significant and very meaningful therapeutic for patients and physicians aligned. At the same time, we're focused on what's next, continuing to build a company that will generate tremendous value by developing cutting-edge signs in areas where we can deliver meaningful advances for patients. We're very well capitalized to execute on our strategic priorities and fulfill our mission. In closing, I'd like to thank our employees for their impressive and resilient execution in 2020 and their commitment to delivering on our mission to elevate life. And with that, I'll now turn it back over to you, Cory.

Perfect. Thank you, Steve. Thanks for doing that, and just a reminder to our audience that you can ask questions with a little blue button in the conference portal. So just to kick things off, though, obviously, everybody is really focused, I'm sure you are, on your pending PDUFA date for NUPLAZID for DRP. Can you just kind of frame expectations for what you would maybe expect or hope a label would look like, and the importance that will play in the commercialization of the product for the indication?

Yes. Thanks so much, Cory. I'll start and then -- and Serge may want to add some additional color as well. So the indication we'll be seeking as NUPLAZID is indicated for the treatment of dementia-related psychosis. And there are probably 2 key elements that we should touch on here. One is the -- as I mentioned, we're seeking the treatment of dementia-related psychosis. So we're not looking at individual subtypes as they’re often referred to of dementia. The psychosis that we see is very similar between the -- irrespective of the underlying etiology and it responds in a similar way. So we're seeking that broad indication. That's supported by a very both alignment we established with the FDA at our end of Phase II meeting and then again at their pre-sNDA meeting when we submitted our application. The efficacy and safety data that we have that underpins that indication is very strong. We've got a well-established, safety and tolerability profile of the drug. Any time you follow an sNDA, you need to collect all of the safety data you have from either prior or ongoing studies we've done that, all of that data continues to look very positive. If anything, the profile of the drug might look even a little bit cleaner than the very, very clean profile that we observed when we submitted in PDP. When we talk about the label many times, we had questions about the boxed warning that all antipsychotics have, and again, being the first approved treatment for dementia-related psychosis that would put us in a position to further differentiate that as it relates to our drug because the label currently says for all antipsychotics. It points out that those drugs are not approved for dementia-related psychosis, and we'd be the first to have that approval.

Okay. So understanding that DRP is a broad indication. There are obviously the subtypes within. When you think about -- if we go to the other side of the PDUFA and assuming an approval, when you think about potential use, would you expect utilization across the various subtypes of DRP to be comparable?

We would, but Serge, why don't I let you speak a little bit more to them.

Yes. We do expect that utilization would be across all of the subtypes that we included in our clinical research and have data. Of course, this will be proportional to the epidemiological representation of different subtypes. As we know, the most frequently seen dementia subtype is Alzheimer disease for dementia, Parkinson's, Lewy bodies dementia and then frontotemporal dementia. So within those constraints, obviously, we do expect that the utilization will be across all subtypes. As we did see repeatedly in our clinical trials, a consistent improvement in the symptoms of psychosis across various subtypes.

Okay. And then when it comes to the commercial marketplace and the market research you've done and the feedback you've been able to get from physicians, be it your investigators or otherwise, what do you see in terms of willingness to prescribe? How much is the time in the market for PDP help sort of set the stage for the launch into DRP?

Yes. It's a great question. Let me just start by saying we've had very, very positive feedback from KOLs and physicians we've interacted with since we received the HARMONY data, and this includes physicians from our own advisory boards to community practicing physicians and the market research we've conducted. Specifically, physicians are very excited about the opportunity to prescribe NUPLAZID for a few key reasons. One is the relapse prevention study that we ran identifies a clinical outcome to them that's meaningful. Many times, when you get approval of a neuropsychiatric drug, the approval is based upon comparing your drug against placebo using a scale, and you're looking at how many points on the scale you can move, but it's the scale that physicians usually don't use in their individual practice. So with the relapse prevention study, it answers 2 key questions for them that they really care a lot about. One is, can I improve the symptoms? We saw that in the 12-week run-in period, we have where we saw a very significant response. And then two, will this effect be durable? And through the relapse prevention study, we very strongly rang that bell as well. So they're very impressed with the efficacy, including, in particular, the nature of the study design. The other 2 -- a couple of other key things that really jumped out and we get a lot of fee -- very positive feedback on are on the safety profile. And as I mentioned in my prepared remarks, NUPLAZID showed no negative impact on cognition over 9 months of the HARMONY study as measured by the MMSE score. And that's really significant because it's well-known that atypical antipsychotics have a cognitive impairing effect when used in dementia-related psychosis patients. So the fact that we don't see that effect is very meaningful. I might just like to point out that Dr. Clive Ballard just presented at the 2020 CTAD medical Congress in the presentation he made that pimavanserin did not show any of the negative impacts on cognition that we talked about. And then the other thing that really stands out that they indicate to us that they're impressed by is that NUPLAZID also shows no negative impact on motor function. And this is also important because these patients are frail, they're elderly, and you do see motor function or motor impairment with the atypical antipsychotic class. This finding, by the way, was presented -- also presented at the 2020 CTAD medical conference in a poster by Dr. Daniel Weintraub.

Okay. And then for your pre-commercial activities ahead of launch, I mean, what are the key things that you want to do between now and the April PDUFA, and along those lines, just remind us how much you're adding to your existing sales force?

Yes. I'm going to ask Michael to answer the first part of that. I'll let Elena answer the second part.

Thanks for the question, Cory. So our prelaunch activities have been about conditioning the market on disease, education and awareness. We've been engaging the patient and caregiver communities because they're very important constituent in the dementia-related psychosis treatment paradigm. We've been engaged in payer conversations and also in the process of hiring our sales force. It's important to note that we're leveraging an existing infrastructure, Steve indicated in his presentation, with the patient services and our long-term care sales force. So we'll be calling on neurology, psychiatry, geriatric psychiatry, long-term care, and a little bit of primary care physicians who are acting as pseudo-specialist geriatricians in their community. And as such, we'll need to broaden out from the existing 200 or so people that we have in a variety of different functional roles in the field, customer-facing roles to about 450. And so all things are progressing well. We feel really good about where we are. And again, I think the ability to leverage our existing infrastructure and awareness of the market and expanding DRP is a great opportunity for us.

Okay. And then maybe for Elena then too, just thinking about sort of OpEx trends as you get ready for this launch and move into that sort of next phase?

Yes. So we will have some key incremental investments in 20 -- this year in 2021. As Michael mentioned, we'll be expanding the field team as well as some additional resources beyond the field, such as our MSLs and some additional support. We'll be investing in marketing, including DTC. We think to raise awareness unbranded and potentially branded DTC will be an important investment in DRP. We've seen good returns on our investments in PDP from our DTC campaigns. And we'll also be initiating some Phase IV studies that we plan to start post approval so just to continue to build the body of evidence for DRP.

Okay. And then in terms of the market education you kind of alluded to Michael, how well established is the indication? And how well diagnosed? I mean is it pretty obvious with patients who would be the right candidates for a product like NUPLAZID for DRP?

Well, I think one of the things that Serge and Steve touched on and you asked originally around the subtypes, I think one thing that should be noted is the broad label allows us to really get after what is the single largest component, which is dementia not otherwise specified. So there's a lot of folks out there with dementia, but not subtyped. And so that -- our indication, I think, will allow us to really penetrate that opportunity. I think the education around psychosis is a well-known aspect, and it's probably closer to what doctors are treating from a dementia and psychosis point of view than it was even with Parkinson's disease, which was more motor and psychosis. So the connectivity is there. I think the fact that we'll have a lot more psychiatrists involved in this disease state is a very important component. And I would just tell you that it's a target rich environment, whereas in a particular doctor's office or even a nursing home, there might be 2 or 3 patients that are viable PDP candidates, there could be 10 patients in the same basis for doctors to really decide on who to get on therapy. So I think it's going to be a much more fluid marketplace for us to operate in.

Okay. All right. Make sense. And then when we think about NUPLAZID's current commercialization for PDP, can you kind of provide an overview of the impact you're continuing to see with respect to COVID-19, particularly as it relates to kind of the various channels for the product?

Yes, sure.

Michael?

Yes, thanks. The -- as we reported on our last earnings call, in the specialty pharmacy channel, which represents the kind of the doctor office marketplace, which is the largest part of our business, we have returned to pre-COVID levels in regards to new patient starts, and that's been sustained since that last call. So we're seeing that back to normal. Long-term care, which is about 25% of our [ business ] obviously, saw a very significant degradation and impact both operationally, but -- and also from a census perspective, that has stabilized but not return back to a pre-COVID level of census. However, we are performing well in that group as we track our performance relative to a basket of products. I think the long-term care aspect is going to be temporal. I don't think the need for long-term care assisted living is going to abate as the country gets older. So this should be just a temporary shift. Stepping back, given what we've done on a virtual basis, Cory, we're able to capture patients whether they are in the office or in long-term care vis-à-vis our virtual techniques and tactics. You can diagnose a patient. You can sample the patient. We can get reimbursement for the patient and [ ship pay ] the product all virtually. So we're -- our channel distribution strategies and virtual tactics have been very effective.

So I want to follow-up on that point. This is something I know we've talked about in the past, just kind of get your latest thoughts because you have done a good job at adapting specific parts of the business and commercialization strategy during the pandemic. What I'm curious on is kind of how much you think this is going to be continued or maintained when we inevitably or maybe hopefully [ if I want to ] get to this post-COVID world we're all waiting for.

Well, I think telemedicine is going to be here to stay. I think there's a very important need for telemedicine, and I think all commercial companies, all companies on a commercial stage are going to have to have that as a potential arm of their go-to-market strategy. I do think, though, that in-person interactions, especially given the experience we have with physicians is the single best way to engage, education and promotion and appropriate therapy. So I think that will be our best environment. It will be a combination of both. I don't think that the current situation will disintermediate the need for live face-to-face interactions completely.

Okay. And then thinking about the outlook for NUPLAZID. When you think about some of the key levers here, like the rate of refills, increased persistence, how does -- how are you looking at those right now? And are there any specific patient characteristics that you've observed that either help or hurt on that front?

Well, I think that, first of all, psychosis has a very disruptive, debilitating effect and I think that when a patient gets relief, they're highly motivated to maintain that state of equilibrium. So we -- when we get patients on therapy because the drug is effective and because NUPLAZID is still a top grade, we have a very committed patient population. In fact, we still have patients on NUPLAZID in from our launch cohort. So we track the cohort. So we haven't seen anything, if anything, that’s sustained. We've seen as a high sustained rate of persistency and compliance with the product. So I think, thus far, we're very pleased with what we see in that regard.

Okay. And then the question that we get in, when you think about the longevity of this franchise, can you just kind of talk a little bit about the broader IP estate you have now?

Sure. So with a small molecule, the first thing you want to look at is composition of matter. We have composition of matter patents that take us into 2030. We also have formulation patents on the 34 milligram capsule formulation of the drug. Those patents go to 2038. And then for the 10 milligram tablet form of the drug, which is used for those patients who have also taken potent 3, 4 inhibitors, that's about a single digit portion of the market, we have a method use patent for that 10 milligram tablet form. So we have additional IP beyond the composition of matter for the only 2 available forms of the drug today. I think it's -- just state the obvious with something like formulation patents, there's always the potential that someone could develop their own formulation outside of our IP, but we've tried to cut a very wide swath there. Just on a related note -- point, Cory, as we -- we don't talk a lot about it. But we do have an internal program to leverage the learnings we have from pimavanserin, so we have other molecules that we're bringing forward. Those molecules we may develop in indications where pimavanserin’s approved in. We may pursue some of the indications we'll never get to with pimavanserin, but we -- looking for opportunities to both capitalize in and differentiate from pimavanserin itself. And that work, as we progress into the clinic we'll talk more about in the future.

Okay. And then I have a question from the audience about pimavanserin IPR situation, any update?

No. As it relates to the ANDA litigation, we have -- we don't have any IPR litigation yet. But [ with ANDA ] litigation we have 5 firms that filed and we have entered into litigation with them. And I would just say that this is very much a typical process that we have with these -- that we have in our industry. And we have very strong IP, which we will defend vigorously. And this will take as it typically does some years to work out.

Right. Okay. And then on NUPLAZID kind of more on the development front with your negative schizophrenia study of pimavanserin, I should say I guess, what gives you the confidence there given failures and broader schizophrenia studies? And does off-label anti-psychotic use have similar safety concerns that we see there with what they have in DRP?

Well, let me start and then I'll turn it over to Serge. I just wanted to quickly note, negative symptoms of schizophrenia has been probably the most -- the highest unmet need in schizophrenia patients for a couple of decades. There's nothing approved. There's been a lot tried. It's rare to have a positive study. We have a positive pivotal study in negative symptoms, and we're eager to complete the next study, we have to see if we can then support an approval in negative symptoms of schizophrenia. So it has been a tough area. But I think what we've accomplished with pimavanserin is a fairly rare feat in this space. Serge, you want to add additional color?

Yes, I'll just add to what you said, Steve that the level of confidence that we have in our Phase III ADVANCE-2 study is that we applied all this learning from the first Phase II ADVANCE study into this study, mainly we really learned about the dose and learned the 34-milligram dose does yield a substantively better benefit. So we are conducting this trial as a fixed dose 34-milligram trial versus placebo. Second, we are doing this trial ex-U.S. trying to avoid some of the variability and [ defaults ] of the U.S. sites that not only we, as a sponsor, but many sponsors and even FDA pointed out in recent years, present a problem in schizophrenia trial. The trial otherwise is similar in design and the size and power as we did with the previous trial. So we have applying similar measures of quality assurance in terms of ratings and expect that we will be able to maintain the quality that we had in the previous trial. In regard to the second half of your question, I would just add very briefly that in our tolerability overall of pimavanserin and safety across different indications from PDP to DRP to schizophrenia, major depression, whether that's in monotherapy or in adjunctive paradigm -- treatment paradigm such as in schizophrenia and major depression, we have consistently seen a very favorable profile for pimavanserin and there are no, really, in this respect in terms of the adjunctive use with other antipsychotics, we did not observe any potential issues or new observations.

Okay. I was informed that we temporarily cut out here, and so Mark actually asked me to ask you, Steve, if you can repeat your answer to the IP question. Just in terms of an update, a reminder of where you stand on the IP front with NUPLAZID and the ANDA filers and then we’ll wrap up.

Yes, happy to. Small molecule, you want to first look at composition matter patents. We have composition of matter to take us into 2030. In addition to that, we have formulation patents on the 34-milligram capsule form of the drug that take us to 2038. And then we have a method to use patent on the 10-milligram tablet for the drug would take us to 2037. The 10-milligram tablet is used for those patients who are taking potent 3 or 4 inhibitors. That's a single-digit portion of the population. As it relates to ANDA filers, there are 5 companies have filed. We've initiated litigation against all of them. I would just simply describe this as it's the prototypical process that you go through with all drugs in our industry, and we have very, very high confidence in our intellectual property, but this will operate in the background for some period of time.

Okay. Perfect. Sorry about that, too. That's one of the, I guess, the pitfalls of the virtual world we're in. We only have a couple minutes. I did want to ask about trofinetide and the LAVENDER study for Rett. Maybe Serge, what would be a clinically meaningful result from that trial?

Well, the threshold that is set in agreement with the FDA is that we have a co-primary outcome measure. We need to achieve statistically significant separation from placebo, both on the Rett behavioral symptom questionnaire, which is a parent completed questionnaire, and on the global clinical improvement scale, which is a clinician improvement scale. And the meaning of that is that obviously, any movement on the scale would be validated by the clinical observation and validation of the meaningfulness of those changes by the clinician’s judgment. So by virtue of that us achieving these outcomes would actually be a meaningful outcome for the patients.

Okay. Perfect. I think we are -- I'm being told by the operator, we're out of time, so we'll have to end it there. Thank you guys very much for taking the time to speak with us today, and good luck with your meetings the rest of the week.

Thanks, guys.

Thank you, Cory. Take care.

Thank you very much. Bye-Bye.