ACADIA Pharmaceuticals Inc (ACAD) 2014 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the ACADIA Pharmaceuticals first-quarter 2014 financial results conference call. My name is Sue, and I will be your coordinator for today. (Operator Instructions).

I would now like to turn the presentation over to Lisa Barthelemy, Director of Investor Relations at ACADIA. Please proceed.

Good afternoon and welcome to ACADIA's first-quarter financial results conference call. This call is being recorded, and an archived copy will be available on our website at www.acadia-pharm.com through May 20, 2014.

Joining me on the call today from ACADIA are Dr. Uli Hacksell, our Chief Executive Officer; Dr. Roger Mills, our Executive Vice President of Development and Chief Medical Officer; and Terry Moore, our Executive Vice President and Chief Commercial Officer.

We will begin our call today with some introductory remarks and brief comments regarding our recently announced financial results. Following this, we will provide you with an update on our development programs and business, and we will then open the floor to your questions.

Before we proceed, I would first like to remind you that during our call today we will be making a number of forward-looking statements, including statements regarding our research and development programs and plans and our strategy, including the timing, results or implications of clinical trials or CMC development; the benefits to be derived from, future approval of and the commercial potential for our product candidates in each case including pimavanserin; the timing, content or likelihood of regulatory meetings, filings or approvals; future development and commercialization of pimavanserin; the expansion of the pimavanserin franchise and its value; and our future expenses, cash position and usage and growth potential.

These forward-looking statements are based on current information, assumptions and expectations that are inherently subject to change and involve a number of risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements.

These factors and other risks associated with our business can be found in our filings made with the SEC, including our annual report on Form 10-K for the year ended December 31, 2013 and other filings. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of today's date. ACADIA disclaims any obligation to update these forward-looking statements.

I will now turn the call over to Uli Hacksell, our Chief Executive Officer.

Thank you, Lisa, and good afternoon. Let me first take this opportunity to thank all of you for joining us on today's conference call.

The first quarter of 2014 was another busy and productive period for ACADIA, helping to set the stage for what we expect will be a very exciting year.

Most importantly, we have continued to make outstanding progress in advancing our Phase III Parkinson's disease psychosis or PDP program toward registration. With this progress, I'm delighted to report today that we remain on track for our planned submission of a new drug application or NDA near the end of this year.

Currently no drug is approved in the United States to treat PDP, a debilitating disorder that can have devastating effects on patients, as well as their caregivers and families. Pimavanserin offers them innovative, non-dopaminergic therapy and has the potential to be the first safe and effective medicine to treat PDP without compromising motor control.

Concurrently with advancing toward our NDA submission, we recruited additional professionals to round out our core commercial team during the first quarter. This highly experienced team is busy progressing with a wide range of precommercial activities designed to position ACADIA for success in the planned PDP launch.

Meanwhile and in parallel with completing our PDP program, we are pursuing an aggressive lifecycle management program to strategically broaden our pimavanserin franchise. Because of pimavanserin's selective mechanism of action and its efficacy and safety profile observed to date in elderly patients with PDP, we believe that it also may be ideally suited to address other major neurological and psychiatric disorders that are poorly served by currently available therapeutics.

Our initial focus in our lifecycle program is Alzheimer's disease psychosis or ADP where we are conducting the Phase II trial that we initiated late last year. As is the case with PDP, no drug is currently approved in the United States to treat ADP, and the off-label use of existing antipsychotics is linked to increased mortality, serious adverse events and cognitive decline in elderly patients with dementia-related psychosis.

Behind ADP, we're actively planning additional studies designed to further characterize aspects of pimavanserin's clinical profile in our core neurological indication areas and to expand to additional indications, including schizophrenia. Roger will provide you with additional information on our lifecycle management program later on in the call.

Before we review our programs in a bit more detail, let me highlight another very important first-quarter event, the public stock offering that we completed in March. Through this financing, we raised net proceeds of approximately $197 million, which significantly bolstered our financial position. This included proceeds from the underwriters full exercise of the overallotment option.

Following the financing, we closed the first quarter with $369.3 million in cash on the investment securities. This positions ACADIA with a robust balance sheet as we pursue our strategy to build a leading US specialty neurology franchise using pimavanserin as a foundation.

We used a total of approximately [$14.2] million in cash during the first quarter to fund our operating activities. In future periods, we expect our cash used in operations to increase as we continue to advance our PDP program to an NDA, conduct commercial activities and execute on our pimavanserin lifecycle management program.

Importantly, we have a strong cash runway that we believe will enable us to expand and build additional value in our pimavanserin franchise and fund planned commercial activities. We think those precommercial activities are designed to optimize positioning for the planned PDP launch, as well as subsequent sales and marketing efforts through and beyond the projected time period of our market launch.

We currently anticipate that our cash and the investment securities will be greater than $300 million at December 31, 2014, and that our cash resources will be sufficient to fund our operations at least into 2017.

Let me now turn the call over to Roger who will provide you with an update on our pimavanserin program.

Thank you, Uli, and good afternoon. As Uli mentioned, we're off to a great start to what we expect will be another exciting year for ACADIA. Our team has remained focused on completing the remaining activities in our pimavanserin PDP development program that are needed for submission of our NDA. This includes aspects of the CMC development, including stability testing of pimavanserin registration batches and supportive studies including customary drug-drug interaction studies.

Once again, I am pleased to report that we remain on track for planned NDA submission near the end of 2014.

Firstly, we have made steady progress in our CMC program. You may recall that are three required registration batches of pimavanserin were successfully manufactured at the commercial launch scale, and registration stability testing on these drug product batches was initiated last October.

During the first quarter, we completed an assessment on the initial three months of stability data from these registration lots and importantly confirmed that these data are consistent with historical data observed with our clinical trial formulation.

Registration batches use the same manufacturing suppliers and general processes of our clinical trial formulation for which we have previously established long-term stability of pimavanserin covering a three-year period.

The initial three-month stability data on our registration batches provides an important bridge between our regulatory and clinical formulations and increases our confidence in the performance and stability of our pimavanserin commercial scale batches.

We are continuing to accumulate data in our registration stability program and expect to have six-month stability data on our registration lots available this quarter. This program is designed to comply with ICH guidelines amid the regulatory filing requirements for major markets worldwide.

Secondly, we have also made substantial progress with supportive studies, which include customary short duration drug-drug interaction or DDI studies.

I am pleased to report that we are now in the process of finalizing our planned DDI program and that the profile of pimavanserin appears consistent with what we have observed in our long-term PDP safety extension studies.

Because patients with PDP are frequently on a number of concomitant medications, we have had the opportunity to gain a significant amount of real life clinical experience in this patient population through our clinical trials, in particular our open-label extension studies.

Importantly, we have continued to observe that pimavanserin is generally safe and well tolerated in PDP patients. Our Phase III PDP open-label safety extension trial referred to as the -015 Study is designed to continue until pimavanserin is commercially available. This ongoing study has allowed us to generate a large amount of valuable long-term safety data regarding the use of pimavanserin in patients with PDP.

We have already far exceeded the ICH guidelines for required one-year exposures with well over 250 patients having been treated for one year or longer. In fact, through our -015 Study and a similar extension study tied to our earlier Phase II trial, we have well over 100 patients who have been treated with pimavanserin for at least two years, and our longest single patient exposure exceeds eight years.

Our long-term safety data provides support for the potential of pimavanserin to offer significant advantages relative to current antipsychotics frequently used off label for the treatment of PDP.

In parallel with completing the remaining development activities, our regulatory team has made significant progress in preparation for the NDA.

As part of this process, we are scheduled to hold routine pre-NDA meetings with the FDA this quarter. These interactions will enable us to outline and discuss our plan submission and how the NDA will be organized. While our priority is clearly on our planned NDA submission, we've also moved forward with efforts to outline the path to registration in the EU.

We have completed an initial series of interactions with regulatory authorities from several EU member states. These initial interactions were very informative. We believe it is clear that the -020 Study was seen as a strong study and that the unmet medical need for PDP is appreciated in the EU and that there were significant concerns surrounding the current off-label use of atypicals in this patient population.

We are continuing this process designed to clarify the pathway for registration in the EU.

Let me now turn to our lifecycle management program for pimavanserin. As Uli mentioned earlier, our initial focus in this program is on our Alzheimer's disease psychosis or ADP Phase II trial that we initiated last year.

This is a randomized, double-blind, placebo-controlled trial referred to as the -019 Study designed to examine the efficacy and safety of pimavanserin in about 200 patients with ADP. We are conducting this study through a large network of research care facilities established as part of the National Institute for Health Research Biomedical Research Centre for Mental Health at King's College, London.

The principal investigator is Dr. Clive Ballard, Professor of Age Related Diseases at King's College and a renowned clinician in the field of Alzheimer's disease. We believe that conducting the study at this high quality medical institution with its network of nursing care homes and its experience in this patient population provides several advantages in study execution.

Firstly, we were able to incorporate many design features from our successful pivotal PDP trial into the -019 Study design. Importantly, a geographically focused network of care facilities enables the use of a small group of highly trained raters, which we expect will enhance study precision.

Secondly, we believe this unique clinical research infrastructure and expertise provides access to a pool of well-characterized ADP patients and facilitates data management and monitoring.

Let me take a moment to highlight key aspects of the -019 Study protocol. In this study patients are randomized on a one-to-one basis to receive either 40 milligrams of pimavanserin or placebo once daily for 12 weeks following an initial three-week screening period that includes brief psychosocial therapy.

This brief nonpharmacologic therapy is designed to help patients adapt to participating in a clinical trial setting, help manage symptoms during the screening phase and pull initial placebo responses ahead of the baseline assessment.

The study is designed to assess several efficacy endpoints, including use of the Neuropsychiatric Inventory - Nursing Home or NPI-NH scale to measure psychosis, agitation, aggression and sleep nighttime behavior, as well as additional exploratory endpoints.

The key efficacy endpoints will be based on the change at week six from baseline, which is a standard duration for psychosis studies. The full 12-week treatment period will allow us to explore additional endpoints, including the cognitive status of patients.

We will be looking to show that we do not worsen cognition relative to placebo-treated patients. In contrast, currently marketed antipsychotics have been linked to cognitive decline in elderly patients with dementia-related psychosis. The 12-week treatment period will also provide the opportunity for demonstration of durability response for pimavanserin beyond the six-week placebo-controlled period tested in our pivotal PDP efficacy trial and the key efficacy endpoints in the -019 Study.

We are very excited with the -019 Study and continue to believe that this study provides us with the unique opportunity to demonstrate the potential benefits of pimavanserin in this patient population.

In addition to ADP, we are actively planning additional studies in our lifecycle management program designed to further characterize and highlight aspects of pimavanserin's clinical profile in our core neurological indication areas. One area of keen interest for us is sleep disturbance, which represents a frequent problem for patients with neurological disorders, including both PD and AD patients.

Poor nighttime sleep quality and excessive daytime sleepiness are associated with a lower quality of life for PD subjects and their caregivers. Benefits from sleep in this population are of particular importance, because sleep disturbance in PD can exacerbate psychosis, worsen cognition, lead to more falls and increase caregiver burden.

We have observed very intriguing, non-sedating, sleep-related benefits of pimavanserin in clinical studies, including our pivotal Phase III -020 PDP study. In the -020 Study, pimavanserin demonstrated a significant improvement in nighttime sleep, and this improvement was not accompanied by any sedation or hangover effect.

In fact, pimavanserin produced a significant improvement in daytime wakefulness in PDP patients. Moreover, those patients in the -020 Study with severe nighttime disturbances benefited the most from pimavanserin therapy and showed highly significant nighttime sleep improvements throughout the study.

Interestingly, the positive effects of pimavanserin nighttime sleep and daytime wakefulness did not correlate with psychosis measures, thus indicating that sleep and wakefulness improvements of pimavanserin may represent independent treatment benefits.

We believe that additional studies in sleep disturbances area may allow us to further characterize and highlight these potentially important clinical benefits.

We're also planning a health economic observational study involving patient caregiver payers to demonstrate the economic and resource burden of PDP. This may complement important findings from our -020 Study in which we observed a significant reduction in caregiver burden.

Another key focus of our lifecycle program is to broaden the pimavanserin clinical program to pursue other major indications, including schizophrenia. We have done considerable planning in this area and believe that pimavanserin's selected mechanism of action and attractive clinical profile may enable it to be used in multiple ways to improve the therapy for patients with schizophrenia.

Firstly, as demonstrated in our earlier Phase II trial, pimavanserin may be used as a co-therapy, together with low doses of existing atypical antipsychotic drugs such as risperidone to enhance the clinical profile.

A second intriguing approach that we are very excited about is the potential to use pimavanserin as monotherapy in the maintenance phase of schizophrenia treatments. In this application, we believe that pimavanserin's selective 5-HT2A blockade may allow for effective symptom control whilst avoiding interactions with dopamine and other receptors that are linked to many of the side effects caused by existing antipsychotics.

We, therefore, believe that pimavanserin has the potential to provide a novel, well-tolerated maintenance therapy that may result in better compliance for schizophrenia patients.

Our commercial assessment has reinforced our belief that this is an area of large unmet medical need for patients with schizophrenia and represents a considerable commercial opportunity. We are now reviewing study designs for the schizophrenia program and look forward to sharing further details on this and other planned studies in our lifecycle management program later this year.

I will now turn the call back over to Uli.

Thank you, Roger. We continue to be excited with the progress in our PDP program, which moves us closer to our ultimate goal of bringing innovative medicines like pimavanserin to market to improve the lives of patients with neurological and related central nervous disorders. PDP represents what we believe is an ideal lead indication in our specialty market opportunity for pimavanserin.

Our strategy is to commercialize pimavanserin for this indication in the US by establishing a specialty sales force focused primarily on neurologists. During the first quarter, our core commercial team continued to conduct precommercial activities in preparation for the planned future launch of pimavanserin in PDP.

These ongoing efforts are designed to ensure that a robust commercialization process and optimal strategy are in place to position ACADIA for success in the planned US market launch.

As part of these efforts, we conducted extensive market research with over 700 PDP-treating physicians, including a thorough review of the market landscape to provide us with a deep understanding of the PDP patient journey.

Importantly, this assessment of the PDP patient journey has confirmed our prior insights into the market, highlighting the large unmet medical need and reinforcing our understanding that prescribers are in need of safe and effective alternatives to the off-label use of antipsychotics.

PDP substantially contributes to the burden of Parkinson's disease. As a result, patients frequently suffer from limitations in daily activities, strained relationships with family members and social isolation. PDP is also recognized as a key contributor to nursing home admissions.

In addition to disturbing hallucinations and delusions, our research indicates that over half of PDP patients also suffer from sleep disturbances, often including daytime sedation. Caregivers also observed that the drugs currently prescribed for psychosis exacerbated this problem, often causing patients to sleep throughout the day.

The psychosis and other comorbid conditions often have a profound impact on PDP patients, as well as their families and caregivers.

One of our interviews with a professional PDP caregiver really highlighted the challenges faced by caregivers and families. She noted and I quote, we are generally called when the family can no longer cope. They often describe the patient seeing things that are not there, not sleeping, restless, and up all night. The family doesn't know what to do. The burden to care for someone 24 hours a day can be totally draining, end of quote.

Because no drugs are approved to treat PDP in the United States, today physicians frequently resort to off-label use of existing antipsychotic drugs, even though they carry a black box warning for use in elderly patients with dementia-related psychosis due to increased mortality and morbidity.

Many physicians have indicated that they will only consider initiating treatment with current therapies when the patient's symptoms become disruptive to the caregiver and/or the patient's family. Our market research uncovered that physicians currently devote considerable extra time and effort related to prescribing and administering existing atypical antipsychotics due to their pronounced safety concerns.

In addition, physicians face a dilemma because current antipsychotics worsen motor symptoms in PDP patients by contracting the customary dopamine replacement therapy for Parkinson's disease.

Because of its innovative non-dopaminergic mechanism of action, pimavanserin avoids this dopamine dilemma and has the potential to be the first safe and effective medicine to treat PDP without compromising motor control, thereby significantly improving the quality of life for patients with Parkinson's disease.

The profile of pimavanserin has been well received by physicians in our market research. Among the themes we have heard from them was that if it were to be approved by the FDA for the treatment of PDP, pimavanserin would provide them with an alternative that they would be more comfortable prescribing than the current antipsychotics.

Our market research also indicated that the ability to date to be able to use optimal doses of customary Parkinson's disease medications while maintaining motor function and treating the PDP symptoms would be factors in favor of the use of pimavanserin.

Consequently, with pimavanserin available, physicians would have a treatment option that they could initiate at the onset of PDP symptoms without the burden of safety concerns and off-label use of currently available atypicals.

In early April, we held an advisory board meeting involving several of the world's leading PDP experts. It was encouraging to hear the positive feedback on our pimavanserin PDP program.

In addition, these leading clinicians clearly agreed that an appropriate and proven treatment for PDP remains a large unmet medical need and suggested that there was a potential for pimavanserin to become a new first-line therapy and to be widely adopted by neurologists and psychiatrists.

Overall, the more our team examines the PDP market, the more excited we become with the potential for pimavanserin to improve the lives of people impacted by the disease. We believe that if approved, pimavanserin has the profile to be a game changer in the treatment paradigm for PDP.

Let me now touch briefly on several other programs we have in our R&D portfolio behind pimavanserin. Together with Allergan, we have clinical stage programs in the areas of chronic pain and glaucoma. Allergan also is pursuing preclinical development of an additional compound, which was advanced last year from our collaborative research as a potential new treatment for glaucoma.

In addition, we have two advanced preclinical programs -- our ER-beta and Nurr1 programs, which may offer novel approaches to treating Parkinson's disease and other neurological disorders.

Preclinical studies in our ER-beta program as a novel pain treatment are supported by grants from the National Institute of Neurological Disorders and Stroke, and we are also conducting preclinical studies with our ER-beta compound as an innovative approach to targeting neurodegeneration associated with multiple sclerosis.

Preclinical studies in our Nurr1 program directed at Parkinson's disease had been supported by a grant from the Michael J. Fox Foundation.

Finally, before I close out, once again I would like to acknowledge and thank our employees. ACADIA's extraordinary progress has been the direct result of the hard work, dedication and passion of our talented team.

Looking forward, I'm confident that we have the right team and strategy in place to capitalize on the vast opportunities ahead. Our priorities remain clear. We are focused on building additional value in our pimavanserin franchise and establishing the foundation to transform ACADIA into a successful development and commercial organization.

We believe that our pipeline of product candidates led by our Phase III pimavanserin program positions ACADIA with multiple attractive commercial opportunities and significant growth potential. And, most importantly, all of us at ACADIA remain committed to advancing innovative medicines that will improve the lives of patients suffering from neurological and psychiatric disorders.

Operator, you may now proceed with the Q&A session.

(Operator Instructions). Charles Duncan, Piper Jaffray.

Hi, Uli. Thanks for taking the question, and thanks for the update today. My first question is on the European strategy, regulatory strategy. I appreciate that you have been meeting with member states, but I am wondering when if you have a goal, not date or timeframe, but when do you think that you can provide additional clarity on steps forward for Europe?

We have guided that we expect to have that clarity by the end of this year. We have initiated the process as we have talked about publicly by meeting with country representatives and learned about their views. We have interactions with our European advisors, which are top advisers in the regulatory area, and as we have said, we expect to have a clear path forward established near the end of this year.

Okay. That's helpful. And then what is your perspective on Asia? We have never really talked about that, but it seems like there is an opportunity there as well.

Yes, it's a good question, Charles. Obviously, Asia is a very different thing. We have not yet approached Asian regulatory authorities. It is something that we intend to do probably together with a partner.

Asia is a scenario where we don't expect ACADIA to have to play a commercial role, in particular not in Japan. So, eventually, you'll see that we will seek help to both go through the regulatory process in Asian countries, in particular in Japan, and also to get help on the commercial side.

What I can say is also that obviously in Japan in particular, we will need to conduct a bridging program, and that's another reason why we think that we would benefit from having a partner that helps us with that.

Okay. And then, finally, my last question on the Alzheimer's psychosis study, lots of information provided, but wondering how is enrollment going in terms of patient -- the characterization of patients? Are you getting the kind of patients you thought you would do and any update in terms of number of patients -- if not numbers, just timelines to that trial being fully enrolled? Thanks.

Hi, Charles. This is Roger. Just to -- as you probably know, we don't give guidance on enrollment in the studies. However, we are actually really pleased with the way the study is going. We purposely placed the study in a center of excellence, in a center that is well-versed in doing nursing home studies and also in using the NPI-NH. And as we have outlined before, it is important that we were able to build in a number of the factors that we believe really helped with the success of our -020 PDP study.

It is what we -- I am happy to say is that in working with the team at King's, it's very clear that they understand the nature and the exact patients that we want in the study, and they are performing the study to a high level as we fully expected they would do.

Okay. And with regard to that, is it at all possible that could serve as a label expansion study or really just inform the next study, a broader study?

I think right now the important thing is this is the first time we've explored potential utility of pimavanserin in Alzheimer patients, and I think we need to run the study, get the data, look at it and then decide next steps.

Okay. Great. Thanks for the added color, guys.

Thomas Wei, Jefferies.

On the US filing strategy, I just wanted to clarify, I know you had said you were last time you were in the midst of meeting with the agency about your filing. Have you had the discussions with the FDA on how much stability data would be required, and we know now that the definitive answer is 12 months of stability data, or are you still waiting to clarify or finalize that point with them?

Tom, we have not yet had our pre-NDA meetings with the agency. We have scheduled them and will have them later on this quarter. So we don't have an answer for that question currently.

Okay. That's helpful. And then I wanted to ask about the QT prolongation profile. Just to double check, we all know from The Lancet paper you had disclosed a 7.3 millisecond increase in the QT interval. But I can't remember what you had said about your thorough QT study and whether or not you can share with us the specifics on the data of what happened at both a therapeutic dose and the super therapeutic dose that you tested? Thanks very much.

Yes, I think we saw the QT signal that we saw in the -020 Study we feel is very much in line with the drugs that are currently approved in the antipsychotic arena and certainly at the lower end of the QT signal seen there.

In terms of the thorough QT study, we did complete that. It was a good study, and that study is done in healthy volunteers, and the signal that we saw in patients was perfectly in line with what is expected from that study. So, that really fits with the high predictability of the PK of patients with not a great deal of inter-patient or intra-patient PK variability.

In terms of the implications of it, at our meeting with FDA last year, all our data, including the QT data, were in the package, the briefing package that we sent to FDA in order for them to make an informed decision around our request to submit an NDA for the PDP. And they were very clear in their response that they were comfortable in us moving forward with that NDA submission in the light of all the data, both the short term, the long term and importantly the volunteer studies that we've done, including the QT.

Can you share with us what the super therapeutic exposure was that you tested, like what fold over the therapeutic dose does it represent?

So, the -- in terms of the actual dosage, we explored 80 milligrams at the top end. And, as I say, in terms of modeling the data that we saw in the PDP population, which bear in mind is an elderly, very fragile population, was perfectly in line. We have not seen any concerns from QT in our programs.

Great. Thank you.

Alan Carr, Needham.

Thanks for taking my questions. Wondered if you could, I guess, specify exactly what the next step is in dealing with the -- your EU process there? And then, also, are you considering with respect to business development bringing something into the Company, and what is the timing for bringing those early stage preclinical programs into the clinic? Thanks.

So let me start with the first part of your question, Alan. That was related to Europe, and what we have said is that we currently are interacting with our European advisers to establish the next step, and that following that if there were processes that will lead to clarity later on this year.

When it comes to your other questions, shall we come back to the second part?

In terms of -- so you will submit a protocol to the EMA after you meet with the -- after your discussions with the advisers or --?

We have not yet decided exactly how we are going to proceed, so this is a process that we really want to deal with quite carefully and in the best possible way, and so we will certainly over the rest of this year work through that process carefully, and the intention is to have the clarity on how to proceed in Europe before the end of this year.

Okay. Fair enough. The other question was around business development, potential for inbound (multiple speakers).

Yes, so that is clearly something that we want to think about over time. Obviously, we think that in order to really keep our sales force busy, we will need eventually something that will complement pimavanserin, that can be used to -- with the same prescribers, but prescribed pimavanserin ideally. So this is something that we have started to try to look at. We are not in a rush to do anything because we are not on the market with pimavanserin yet.

But, obviously, it becomes more and more interesting over time, and long-term it is a popular strategy to complement pimavanserin with additional assets.

(multiple speakers).

The other -- yes -- when you count all the programs that we have in our portfolio, obviously Allergan has the rights to the glaucoma and the chronic pain programs. So we don't consider to commercialize those programs. But when it comes to the early stage programs, they are still not yet in formal development. So it will take quite some time before we think about commercializing those programs.

So, I think in terms of bringing other programs to help pimavanserin on the market, we will need to access such assets by other means.

One other question I have is around your plans for sleep. What sort of extra work would you need to do to build a label around improvements to sleep?

Roger, can you take that?

Yes, sure. Sleep will be run under a separate IND. The PDP and ADP is overseen by the psychosis division of FDA. Sleep is everything (technical difficulty). And, obviously, as part of this process, we will be interacting with that division to determine the path with sleep.

But I think it's very clear that the great -- we have seen really consistent benefits in these populations, which concern the improvements in sleep that we saw much earlier in our healthy, normal volunteer sleep study. And what's nice now is that we have seen a very clear, consistent benefits study for study in terms of improvement in sleep in a population for which sleep disturbance is not simply annoyance, it is something which can really lead to clinical outcomes to patients that are not good.

So, I think there is a pretty good recognition, certainly, from the physicians and the experts in the area, and quite a -- it really is, I think a little bit excited that we are going to explore this area.

Is your thought at this point that you would start with a population with some sort of disorder that also have sleep disturbance? Is that -- how are you approaching it? (multiple speakers)

I think we are not outlining the design of the study, but it's fair to say that inherent with Parkinson's disease and actually with Alzheimer's disease as well, sleep disturbances are pretty common through the patient populations. In fact, in the studies we have done on PDP, there were no entry criteria that were embedded in the protocols to enroll patients for sleep disturbances. The entry criteria were all around psychosis.

So, the studies were in no way enriched for sleep disturbance, but very clearly there are a large number of patients in the studies that did exhibit sleep disturbances, and hence we were able to show that very clear benefit. So, I think we will be really looking at one of these populations, probably most likely going to be the PD population.

Okay. Thanks very much.

(Operator Instructions). Jason Butler, JMP Securities.

Thanks for taking the question. Just wanted to follow up on the sleep disturbance work. So, it makes sense that the drug might not have the same detrimental impact on sleep and wake that other antipsychotics do, but do you have any mechanistic rationale as to why there would actually be improvements in sleep and wake? For example, is there any impact on circadian regulation?

Perhaps I can take that. It is well-known that molecules with the mechanism of action that we have with pimavanserin, the 5-HT2A inverse agonist mechanistic, that you have an impact on sleep architecture in such a way that you increase the time spent in deep sleep and that you decrease the time spent in superficial sleep. You do not affect REM sleep or other sleep parameters. You do not increase or speed up the onset of sleep, and you don't sedate patients at all.

So the only thing is that you reset the sleep architecture so that you sleep more like a baby and less like an older person, who frequently tends to wake up at night. This can be seen both in animals experiments and in clinical trials.

Great. Thanks for the added color.

Dr. Hacksell, please proceed to closing remarks.

Well, thanks, again, to everyone for joining us on today's call and for your continued support. We look forward to updating you in the future on our ongoing progress. Thank you.

Thank you for your participation in today's conference call. This concludes the presentation. You may now disconnect. Good day.