ACADIA Pharmaceuticals Inc (ACAD) 2012 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to ACADIA Pharmaceuticals fourth-quarter 2012 financial results conference call. My name is Darcelle, and I will be your coordinator for today. At this time, all participants are in listen-only mode. We will be facilitating a question-and-answer session towards the end of today's call. (Operator Instructions)

I would now like to turn the presentation over to Tom Aasen, Executive Vice President and Chief Financial Officer at ACADIA. Please proceed.

Thank you. Good afternoon and welcome to ACADIA's fourth-quarter 2012 financial results conference call. This call is being recorded, and an archived copy will be available on our website at www.acadia-pharm through March 26th.

Joining me on the call today from ACADIA are Dr. Uli Hacksell, our Chief Executive Officer, and Dr. Roger Mills, our Executive Vice President of Development and Chief Medical Officer. We will begin our call today with some introductory remarks by Uli, and then I'll briefly comment on our fourth-quarter financial results. Following this, Roger and Uli will provide you with an update on our development programs, 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'll be making a number of forward-looking statements, including statements regarding our and our partners' research and development programs and plans, including the timing, design, and results of clinical trials; the benefits to be derived from, future approval of, and the commercial potential for our product candidates in each case, including pimavanserin; plans regarding the development of and future commercialization of pimavanserin, the value of pimavanserin; and our future expenses, collaboration, and grant payments, cash usage, stock performance, 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, 2012, 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'll now turn the call over to Uli Hacksell, our Chief Executive Officer.

Thank you, Tom, and good afternoon. Let me first take this opportunity to thank all of you for joining us on today's conference call. As many of you know, we had a very exciting and highly productive close to the 2012 year. Most importantly in November, we announced successful topline results from our pivotal -020 Phase III trial with pimavanserin for Parkinson's disease psychosis, or PDP.

These strong data from the -020 study demonstrate that pimavanserin has a clinical profile that we believe is ideal to address this large unmet medical need, and the potential to become the first drug approved in the United States to treat patients with Parkinson's disease psychosis. Following the positive outcome in the -020 study, we significantly strengthened our balance sheet through our successful equity financing in December. This financing has positioned ACADIA with a strong foundation to build significant value in our pipeline of product candidates, led by pimavanserin.

Importantly, we can now pursue the remainder of our Phase III PDP development program from a position of strength, and, at the same time, broaden our pimavanserin program to include other indications to seek to maximize the commercial potential for pimavanserin. While 2012 was clearly a transformational year for ACADIA, we look forward to building on this momentum throughout 2013.

As Roger will share with you later, we are preparing to present data from the -020 study at the American Academy of Neurology annual meeting in March, and we are busy with final preparations for our confirmatory pivotal Phase III trial, the -021 study in our PDP program. We are also preparing for other supporting development studies as part of advancing this program toward registration. Apparently there is no FDA-approved therapy for PDP. We believe that pimavanserin has the potential to be the first safe and effective drug that will treat PDP without compromising motor control, and thereby, improving the quality of life for patients with Parkinson's disease.

Additionally, we believe that pimavanserin has broad potential, and may provide a suitable therapy for a range of other neurological and psychiatric disorders that are poorly served by existing antipsychotic drugs. Towards this end, we plan to initiate a Phase II trial in the second half of this year to evaluate the potential of pimavanserin as a treatment for Alzheimer's disease psychosis.

While pimavanserin provides the foundation of our product pipeline, we have several additional programs in our R&D portfolio. Our pipeline also includes two clinical stage programs in the areas of chronic pain and glaucoma in collaboration with Allergan, and two programs in an advanced preclinical stage is directed at Parkinson's disease and other neurological disorders.

All of our programs have been generated from internal discoveries, and offer what we believe are innovative approaches that may address large potential commercial market opportunities. Overall, our product pipeline or product candidates, led by our Phase III PDP program with pimavanserin, positions ACADIA with multiple product and commercial opportunities and significant growth potential.

Before we review our programs in a bit more detail, let me ask Tom to comment on our fourth-quarter results.

Thank you, Uli. Let's look briefly at some of the components of our fourth-quarter results. Our revenues totaled $380,000 for the fourth quarter, and were derived from our ongoing collaborations with Allergan as well as our research grants.

Our R&D expenses increased to $4.9 million for the fourth quarter from $4.4 million in the comparable quarter of 2011, primarily due to increased personnel costs. External service costs, largely pimavanserin clinical expenses, comprised approximately 2/3 of our total R&D expenses for the quarter and were comparable to the fourth quarter of 2011.

We expect our R&D expenses to increase in 2013 relative to 2012, as we continue to advance our Phase III PDP program, including our planned confirmatory pivotal trial and other supporting development studies in this program, and pursue our Phase II Alzheimer's disease psychosis trial that Uli mentioned. G&A expenses increased to $2.3 million for the fourth quarter from $1.5 million for the comparable quarter of 2011, primarily due to increased personnel costs as well as increased external costs.

Finally, let's turn to our cash position and guidance. We closed the 2012 year with $108 million in cash and investment securities compared to $31 million at December 31, 2011. This increase was primarily due to net proceeds of $80.5 million raised in our December equity financing, as well as $17.1 million in equity proceeds we had raised earlier through our aftermarket agreement. We used an aggregate of $21.6 million in cash during 2012 to fund our operating activities.

Looking ahead, we have a strong cash position that we believe will enable us to continue to advance and build value in our Phase III pimavanserin program, while at the same time broadening the clinical profile of pimavanserin. Consistent with the expected increase in R&D investments, we anticipate using a total of between $26 million and $30 million in cash resources to fund our operating activities during 2013. Importantly, we remain positioned with a strong cash runway.

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

Thank you, Tom, and good afternoon. Following the successful outcome of the -020 study, this remains an exciting and busy time for our team, as we continue to advance our Phase III PDP program.

I'm pleased to report that we've now completed our analysis, the full -020 data set, and have continued to see consistent and robust data aligned with the topline efficacy results. The -020 study showed highly significant improvements on both the primary and secondary anti-psychotic efficacy endpoints. Significant improvements were also demonstrated on nighttime sleep and daytime wakefulness, and on caregiver burden. In addition, the key secondary endpoint of motoric tolerability was met, and the overall safety profile of pimavanserin continued to appear benign.

An initial presentation of the -020 data to the scientific community is scheduled to occur at the American Academy of Neurology annual meeting on March the 20th. At the Emerging Science session at this meeting, Dr. Jeffrey Cummings, who is the Director of the Cleveland Clinic Lou Ruvo Center for Brain Health, and an internationally renowned clinician, will make a brief oral and subsequent poster presentation.

We're also planning additional presentations of the -020 data at subsequent clinical meetings during the year, including the annual meeting of the Movement Disorder Society in June. With the significant and consistent results seen in -020, we are now planning for our confirmatory pivotal Phase III trial, the -021 study, using the same trial design.

Let me take a moment to highlight the -021 study design, which is based on our recently completed -020 study. -021 will be a randomized, multi-center, double-blind, placebo-controlled study, designed to evaluate the efficacy, tolerability, and safety of pimavanserin in about 200 patients with PDP. Once again, we plan to conduct this study exclusively in North America, and use a small centralized group of highly-trained, independent raters to conduct blinded assessments of the primary endpoint at all study sites.

In the two-week period between screening and randomization, patients will participate in a brief psychosocial therapy program designed to help patients adapt to a clinical trial setting, and to poll initial placebo responses ahead of the baseline assessment.

To participate in this study, the patients will be required to have moderate to severe psychosis as measured by the Neuropsychiatric Inventory Scale, or NPI, at screening, and the Scale for the Assessment of Positive Symptoms, or SAPS, at the time of the baseline assessment. The primary endpoint of the study will, once again, be antipsychotic efficacy as measured using the SAPS PD scale, which consists of nine items from the hallucinations and delusions domains of SAPS that best reflect the expressions of psychosis in patients with Parkinson's disease. Motoric tolerability will be a key secondary endpoint in the trial, and measured using Parts 2 and 3 of the Unified Parkinson's Disease Rating Scale, or UPDRS.

We are now in the process of finalizing preparations for the -021 study. We plan to leverage the existing infrastructure from the recent trial, including a core base of clinical sites, to enable us to start up and run the -021 study in an efficient manner. We expect to initiate the -021 study in April.

Let me now turn to another ongoing trial in our PDP program, our Phase III open label safety extension study, referred to as the -015 study. This important trial involves patients who completed the -020 study, as well as patients from earlier trials, and who, in the opinion of the treating physician, may benefit from continued treatment with pimavanserin.

This study, along with a similar extension study from our earlier Phase II trial, has allowed us to generate a large amount of valuable long-term safety data regarding the use of pimavanserin in patients with PDP. Importantly, we have far exceeded ICH guidelines for required one-year exposures, with well over 200 patients having been treated for one year or longer.

We also have well over 100 patients that have been treated with pimavanserin for at least two years, and our longest single patient exposure is over seven years. Our experience to date suggests that the long-term administration of pimavanserin continues to be generally safe and well-tolerated in its often-fragile and elderly patient population. We believe that the favorable safety profile observed to date provides support for the potential of pimavanserin to offer significant advantages, relative to current antipsychotics used off-label for the treatment of PDP.

In addition to our confirmatory pivotal trial and long-term safety extension trials, we are planning for NDA-enabling studies, including drug-drug interaction studies, and supporting CMC development as part of advancing our Phase III PDP program towards registration.

I'll now turn the call over to Uli.

Thank you, Roger. PDP represents a large unmet medical need and what we believe is an ideal lead indication of specialty market opportunity for pimavanserin. PDP is a progressive, persistent condition that occurs in an estimated 40% of Parkinson's patients, and deeply affects their quality of life. It's associated with increased mortality, caregiver burden, and it is the major cause of nursing home placements among Parkinson's patients.

The FDA has not approved any drug to treat PDP, and neurologists currently face overwhelming challenges in managing patients with this debilitating disease. We believe that pimavanserin, with its innovative and well-tolerated non-dopaminergic profile has the opportunity to be a first-in-class therapy that will effectively treat psychosis in Parkinson's patients without compromising motor control.

While our primary focus is on our Phase III PDP development program, we also intend to use this program as a foundation to develop and commercialize pimavanserin for other neurological and psychiatric disorders that are underserved by currently available antipsychotic drugs. One such neurological disorder is Alzheimer's disease psychosis, or ADP, which affects an estimated 25% to 50% of the more than 5 million Alzheimer's patients in the United States. Similar to PDP, there is currently no therapy approved to treat ADP in the United States.

Just like for PDP, physicians frequently resort to off-label use of antipsychotic medications to treat ADP. However, existing antipsychotics may exacerbate the cognitive disturbances associated with Alzheimer's disease, and are also associated with numerous side effects. In addition, all existing antipsychotic medications have a black box warning for use in elderly patients with dementia-related psychosis due to increased mortality and morbidity.

Because of its non-dopaminergic mechanism of action and the favorable safety profile observed to date in elderly patients with Parkinson's disease, we believe that pimavanserin may also be ideally suited to address the need for a novel ADP treatment that is safe, effective, and well-tolerated.

We are planning to initiate a Phase II feasibility study in the second half of this year to evaluate the potential of pimavanserin as a treatment for ADP. In this trial, which we refer to as the -019 study, we plan to evaluate multiple endpoints, and use this to inform us on an optimal design for future studies in this program.

We believe that pimavanserin also has considerable commercial potential in schizophrenia and related psychiatric disorders. Last year, data from our earlier Phase II co-therapy trial was published in the Journal of Schizophrenia Research. This trial demonstrated that co-therapy with pimavanserin and a sub-therapeutic dose of risperidone provided an attractive clinical profile.

The treatment equally effective as a higher standard dose of risperidone, but with a much improved side effect profile and a faster onset of action. As we advance our Phase III PDP program, we will continue to consider additional studies that we may elect to pursue for this indication in the future.

Let me now touch briefly on the other programs in our pipeline. First, through our long-standing alliance with Allergan, we have two clinical stage product candidates in the areas of chronic pain and glaucoma. We are also conducting joint discovery efforts focused on ophthalmology in a third collaboration with Allergan. In addition, we have two advanced preclinical programs, which may offer new disease-modifying approaches to treat Parkinson's disease and other neurological disorders.

In our ER-beta program, we discovered a compound that exhibits neuroprotective and anti-inflammatory properties in preclinical models, and we have the ability to address a range of neurological disorders. We conducted initial research in this program in the area of Parkinson's disease through a grant from the Michael J. Fox Foundation. And we have ongoing preclinical studies for this program as a novel pain treatment supported by a grant from the National Institute of Neurological Disorders and Stroke.

In addition, in December, we announced that we received funding from Fast Forward and EMD Serono, a subsidiary of Merck KG, to evaluate our ER-beta compound as an innovative approach to targeting neurodegeneration associated with multiple sclerosis. We are collaborating on this research with Dr. Rhonda Voskuhl of UCLA, who is a recognized expert in MS and neuroprotection.

In our second preclinical program, Nurr1, our lead program which activates Nurr1-RXR complexes specific in restoring motor function and neuronal health in a preclinical model of Parkinson's disease. We are continuing preclinical studies in this program under a grant from the Michael J. Fox Foundation. We expect to advance the compound from at least one of these two programs into development this year in preparation for future clinical studies.

In closing, we look forward to an exciting year of progress. We believe that our pipeline of product candidates, led by our Phase III pimavanserin program, positions ACADIA with multiple, attractive products and commercial opportunities, and significant growth potential. Finally, before we turn to the question-and-answer session, I would like to take this opportunity to acknowledge the many contributions during 2012 of each of our loyal and valued employees.

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

(Operator Instructions) Jason Butler, JMP Securities.

Thanks for taking the questions and congrats on the progress. First question, could you just give us any more color on what new data we should expect to see in the presentation next week at AAN, in terms of subsets of efficacy or safety data?

Yes, in terms of -- there will be some new views of the data that will be presented by Dr. Cummings. Just in terms of, obviously, the sensitivity around disclosure data with the AAN, we're not going into detail today. But we'll obviously be pleased -- very pleased, in fact, to share it with both the scientific community and, obviously, any of the investment community that are present at the meeting next week and, obviously, subsequent to that meeting. I think it's a very -- you know, be a very nice presentation and the accompanying poster will be very informative.

Okay, great. Thanks. And then, just secondly, you talked about -- a lot about the similarities between the -020 and -021 trial designs. Are there any differences in the design of the two trials? And then could you just maybe comment on your expectations for enrollment timelines compared to the -020 study?

No, the study is, as I say, the same. I mean, the key thing we have is it's the same as anything else -- you don't change a winning team. So I think, importantly, we want to replicate the -020 study as much as we can, to obviously, with the addition of new patients.

When it comes to timing, what we can say is that the previous study -- the -020 study took about two years to complete. We plan a task upstart for the next study, the -021 study. One key role that there will be, not that we can't use manual, the existing sides also in the next study, and we hope that these tasks have start with reduce the time to completion, and we are targeting the near -- of the end of 2014. So hopefully, we can do the next study a little bit faster than the previous one.

Okay, great. Thanks for taking the questions.

Alan Carr, Needham and Co.

Thanks for taking my questions. I've got a couple of them. One of them is, with respect to design of -021, do you plan to elevate any of the exploratory endpoints to secondary? Or do you plan to add any other secondary or new exploratory endpoints that might help with the label down the line?

And then, also, you have -- you know, you've raised a fair amount of cash here, and the PDP trial is relatively small in proportion to that. I'm wondering how you plan to spend that? Do you plan to in-license? Or you hinted, I think, the last time I talked to you, Uli, that you might be thinking more seriously about schizophrenia. So can you give us some thoughts on that?

So in terms of the endpoints, we'll actually keep the same endpoints in the study. It's always tempting to add additional measures in. However, one of the key things we've learned regarding placebo response is to try and minimize the amount of interaction between site staff and patients. And, therefore, we don't want to actually add any scales in there that would actually add to the interactions between the site staff and the patients. So, we'll actually keep the same design throughout and, obviously, the same endpoints.

And, Alan, I can address the second part of the question regarding the cash position. You're right in that we are positioned very nicely with a multi-year, very strong cash position and runway.

As we did indicate, we do expect to increase the R&D investment. We're expecting that, overall, we'll use between $26 million and $30 million this year. And really, as you may expect that, as we continue to pursue the Phase III program, and also, then, initiate the Alzheimer's study in the second half of -- we'll -- you will see, I think, generally speaking, the expenses to step up as we kind of move through the 2013 year.

So that's the priority as we stand to ensure that we're really pushing ahead full speed with the PDP or moving forward with the Alzheimer's. We are, as Uli pointed out earlier, also considering in evaluating the studies that we may decide to pursue in the schizophrenia area, but we would come back to you later with that. So right now, it's just a nice position to be in from a financial strength.

Okay. And I guess a follow-up. How about in terms of out-licensing pimavanserin ex-US? What are your thoughts on that?

Well, currently, first of all, our intention and our focus is on moving forward with the PDP program. We think that's our best way of building value in the pimavanserin program.

When it comes to our strategy, we clearly want to keep our US rights. We think ACADIA should play a major role in the commercialization of the pimavanserin in the US. When it comes to potential partnerships, ex-US, that's something that we may want to discuss over time, but we're not in a rush to do so. As I said, our key thing now is to build value with pimavanserin and not think a lot about partnerships.

All right. Thanks very much.

Juan Sanchez, Ladenburg.

A couple of questions. One is clarification. Which one of your clinical products is likely to have an asset in Stage I this year? And the other one is, the direction of the Alzheimer's trials. I mean, are you going to start the study in the second half of this year, but how long do you think it's going to take to perform? Thank you.

So, hi, Juan. First of all, we have not decided yet which of the two preclinical programs that will move into a formal development phase. But I can say is that both of them are relatively advanced. And we will make that decision at the later stage. And this year, we -- by the way, I'm really excited about both of these programs, which I think have a lot of potential to offer.

So, your question -- your second question was related to the ADP program?

Yes. The timing.

Yes. So, again, it's a little bit early to talk about the timing for that before we have decided exactly how many sites that we're going to include. Because that's something that we have not yet done so far. But what we can think about is the two-year timeframe. But we have to come back to provide more specificity around the trial at a later stage later on this year.

Thank you, guys.

Bert Hazlett, ROTH Capital.

Thank you for taking the question. My question is also on the -019 study in Alzheimer's disease psychosis. I guess, have you -- again, just following up with the previous comments. Maybe you're ready to talk about this; maybe not. But have you decided on a 40 milligram dose for that study? And you did some canny work with secondary endpoints in the -020 study. Can you comment -- maybe if you're ready -- with regard to secondary endpoints you might be considering for -019 in Alzheimer's? Thank you.

So, first of all, we clearly are going to test the 40 mg. dose in the ADP study. When it comes to secondary endpoints, perhaps you can comment on that, Roger?

Yes. I think the key thing with the -019 study is that it is a Phase II proof-of-concept study. And, therefore, we haven't explored pimavanserin in Alzheimer's disease before.

We don't -- the -- around the psychosis in Alzheimer's disease, they're a constellation of broader symptomatology. And at this point, with no experience of the drug in this population, I can't say where we're likely to get our best bang for the buck, in terms of outcome.

So, we're keeping the endpoint relatively broad in order to allow us to explore the potential benefits in these patients. And then, based on the findings from the -019, we'll be able to fire off a Phase III study in Alzheimer's, which is focused around where we would expect to get the best results. And, obviously, we would enrich the population to make sure we achieve that.

Sure. And just one other follow-up. Would you expect the adverse event profile in tolerability of the profile to be similar in that patient group, as compared to the Parkinson's patients?

Yes, we would.

Okay. Thank you.

Jason Napodano, Zacks.

Can you talk a little bit about the challenges of running the -021 study? Now that you've got positive data from -020, I'm wondering if people see that this drug works, they know it works. I'm wondering if that creates a greater desire from clinicians to enroll their patients into the study or for patients to get into the study and get on active drug.

You hit on a couple of good points there. It's something we've clearly considered. I mean, we've got great results out of the -020, and therefore, I do expect it to at least have a positive influence in terms of enrollment into -021.

Obviously, in the life of that, there must be a greater expectation, of anybody coming into the study, of potential benefits. But we will work hard to remind everybody that 50% of the patients who will be entering that study will be on placebo. And we really had great relationship with the sites in the -020 study. And we worked hard with them to really get them to understand the clear nature of the investigative nature of the study, and the importance of minimizing placebo response.

I think one of the things in interacting with sites for -021 will be to really remind them of the responsibility now that the study -021 must be performed in the same manner with the same -- as much as possible, the same expectations that were in -020. And I think it's something we will be working very intensively with the sites to get that message across.

But similar to the -020 or the patients that enroll in -021 can still enroll into the open-label extension study and get drug. Is that correct?

Absolutely, yes. We will -- are keeping -015 open. And as soon as we get -021 underway, then patients who complete the -021 study will be eligible to roll over into -015.

Okay. All right, guys. Thanks a lot.

Thank you.

George Zavoico, MLV & Company.

Thank you and -- for taking the question. And congratulations on the progress and in advance of starting the -021 study. In that regard, a quick, brief question about that. Have you guided at all what the -021 study is expected to cost?

Yes. It's -- these studies take about $15 million in total cost.

Okay. And next question, I was intrigued -- there was a -- you probably saw the recent paper in Lancet Neurology about the progress of Alzheimer's disease, how long it takes using the imaging that the amyloid starts forming almost 20 years before frank dementia. And then you get hippocampal atrophy about 4.5 years ahead, and then memory loss about 3.5 years ahead.

The psychosis -- and I guess another way of looking at it is that you, with the prodromal patients, and then you see lots of executive function, and then memory loss before you get frank dementia. The psychosis -- along that curve of disease progression, where does the psychosis really predominate? Is it toward the end? Is it in the dementia patients or prior to dementia?

Certainly in dementia, it's later; it's similar to Parkinson's with it being a later phenomenon of the disease.

And you have an increasing severity of the psychosis with increasing dementia as well.

Yes.

But it's -- yes, it's clearly worsening over time.

Alzheimer's, dementia, and the psychosis goes sort of very parallel to Parkinson's psychosis, Parkinson's dementia. So hence the similarities in the alignments of the two conditions and why we are focusing on this as the next indication.

I see. Okay. And what intrigued me about what you said before about some of your preclinical program was your increasing attention to neuroprotection, specifically anti-inflammatory effect of some of your preclinical drug candidates. This seems to be an emerging concept that also, as the disease progresses, you end up having an inflammatory component that may actually kill more neurons than does the amyloid then tau of Alzheimer's and perhaps the synuclein deposition in Parkinson's.

With the anti-inflammatory drug, do you expect to see or would you -- I imagine you would like to see, but based on the preclinical studies that you've done, do you expect to see disease progression or symptomatic -- I mean, modification of disease progression or symptomatic relief or both?

With the ER-beta program, clearly, what we are seeing in models of Parkinson's disease so far is a reversal of the neurodegeneration that we have induced with toxic chemicals. So that's what we know about Parkinson's disease models.

We will clearly learn much more when we start the MS studies. We have not yet -- when we say to dose, we'll dose shortly there. And with Dr. Voskuhl from UCLA, I think we will learn a lot about the different components of the activity profile on the ER-beta compound. It is certainly something that is very interesting, if you can receive both neuroprotection and have an anti-inflammatory component on the top of that. We're excited about that as well.

Well, what are the target cells there? Is it the microglia in the brain? As far as you know, does it cross the blood brain barrier? Or is it more of a totally systemic anti-inflammatory effect?

No, this is a drug that passes into the blood brain barrier, and we expect to see anti-inflammatory effects also in the brain.

Okay. That's very exciting, because it's a novel approach and I think it has tremendous promise going forward.

Thank you.

Okay. Thank you very much.

Thanks.

(Operator Instructions) Charles Duncan, Piper Jaffray.

Thanks for taking my question and congratulations on the progress in the quarter.

Thanks, Charles.

My question, first of all, is on pimavanserin and the -021 study. Uli, you mentioned the -020 study having taken about two years, but you would anticipate this one to have a faster upstart. Approximately how much time would you expect -021 to take? Is it still a two-year time frame? Or is it maybe a year and a half?

Well, without providing too much specificity on this, but we can say that by having this task -- already expected task upstart of the -021 study, we're targeting near the end of 2014 for completion of the -021 study. So that will be considerably faster than the two-year time frame. And we'll come back and provide closer and more detailed guidance on that over time. But we feel confident that we can do it faster than the -020 study.

Good deal. That's good information, Uli. And then with regard to the percentage of patients that you would anticipate from sites that are experienced, is that the majority -- call it 80%, 75%, or is it 50% -- what percent of patients would you anticipate from sites that you've used in the past?

I think it's hard to answer that with any degree of certainty there. There are a couple of reasons for bringing sites we've used back to -021. Obviously, a key one is the fact that they were able to enroll patients. But, obviously, a critical part of it is not just enrolling patients, but ensuring that we enroll patients with the appropriate quality to be in the study.

So, there are two factors that went into our decision to bring sites back. And in terms of how many they will contribute, it's difficult to say right now. We're obviously at new sites, and out of the new sites, there will be a mix, and again, some will do very well; some -- most will probably do very average, and there'll be some that don't perform as well.

So, it really is a mix of the sites and a blend of the sites. And as we run the study, we keep very, very close watch on the performance and activity at all the sites. And we're with them to ensure that they are productive, and productive in terms of quality patients.

Okay. And then hopping over to the ADP and the Phase II, I appreciate the insights that you've provided on that and the timing. With regard to ADP versus PDP, you talked a little bit about the two kind of disease states to the last questions, but what about the types of hallucinations that are seen in ADP versus PDP? And, specifically, the kind of endpoints? Or do you see this Phase II really as being exploratory and hypothesis-generating?

I think in terms of the activity of the drug, it is very exploratory, as I mentioned earlier. And we would expect to see potential, certainly, on the psychosis. Once again, we would expect to see improvement in terms of sleep disorders, an important aspect of Alzheimer's disease similar to PD again.

But there are other factors in terms of agitation, anxiety, other factors like that, that we really don't know whether there will be an improvement or not, and how great that improvement is. So we really are in that exploratory mode. But, again, once we get the data from that, we'll be able to design the Phase III study with the best outcome in mind, and obviously, build the entry criteria to enrich the study population to achieve that goal.

So with that, I can add a little bit to what Roger mentioned also, in the sense that there are many similarities between the psychosis in Parkinson's disease and the psychosis in Alzheimer's disease. Just let me give you one example.

The most typical hallucination in both conditions is the visceral hallucination. So that's very different from the psychosis that you see in schizophrenia patients. But the most typical hallucinations are auditory hallucinations. So the schizophrenia patients, they hear things that don't -- well, they hear voices that speak to them. The most typical thing in Alzheimer's and Parkinson's disease is that patients see things, see persons -- for example, may see your deceased relative that really doesn't exist.

That's helpful, Uli and Roger. And then my final question is regarding the non-efficacy studies that are NDA-enabling that you mentioned, including drug-drug interactions. Would you expect that to be completed before, say, the completion of the -021 study? And, also, does that include a cardiovascular tolerability study that you need to complete as well?

Yes, so everything else on the -- in the PDP program will be down at the end of the critical timeline of the -021 study. So we believe that we are in great shape. It will be a lot of work for us, but we will check the boxes and we will get all of this -- these things done before the end of the -021 study. When we have the data from the -021 study, we will be able to start to assemble the NDA.

Very good. Thanks for the added color.

Thanks.

Juan Sanchez, Ladenburg.

Just one brief follow-up. Do you consider running two additional PDP trials as opposed to a single one?

No, we expect that two pivotals will be sufficient. So (multiple speakers) --

But do you ever consider that running a second additional trial -- I mean, a third trial would be a good (multiple speakers) investment?

No. No, we think two will be sufficient. We expect the next one will be pivotal as well, so we think that we have the right formula for success. Now, no reason to run a third one.

Got it, guys. Thank you.

Thanks.

And there are more no further questions at this time. I will now turn the call over to Dr. Hacksell for closing remarks.

So, thanks again to everyone for joining us on today's call and for your continued support. We look forward to an exciting year, and 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. Have a great day.