ACADIA Pharmaceuticals Inc (ACAD) 2013 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the ACADIA Pharmaceuticals first quarter 2013 financial results conference call. My name is Sue, 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 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 21, 2013.

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

Uli will begin our call today with some introductory remarks and then Tom will briefly comment on our first-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 will be making a number of forward-looking statements, including statements regarding our research and development programs and plans, including the timing, design and results of clinical trials; the timing of regulatory filings or approvals; 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 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.

Following an exciting close to the 2012 year, highlighted by the impressive results from our pivotal -020 Phase III trial with pimavanserin for Parkinson's Disease Psychosis or PDP. And our successful financing -- we are off to a very strong start for the 2013 year.

While the last several months have been a transformative period, I believe this is just the beginning for ACADIA as we enter a new phase, in which we're focused on building additional value in our pimavanserin franchise.

During the first quarter data from our -020 Study were presented at the 65th American Academy of Neurology Meeting. The -020 data shows robust and consistent efficacy of pimavanserin across study measures and confirm the positive topline results that we had previously announced.

More recently, in April, we met with the US Food and Drug Administration to discuss the PDP regulatory path. We were delighted to announce that the FDA agreed that the data from our -020 Study, together with supportive data from other studies with pimavanserin, would be sufficient to support the filing of a new drug application or NDA for the treatment of PDP.

This represented another important step forward in the pimavanserin program and it is expected to expedite the path to NDA filing and potential approval of pimavanserin. Most importantly, this may enable pimavanserin to be available earlier than previously expected to help Parkinson's patients suffering from psychosis.

As Roger will share with you later, following this positive outcome we are now busy completing the remainder of our pimavanserin PDP development program needed for NDA submission.

Currently there is no FDA approved therapy for PDP. We are convinced that pimavanserin's clinical profile is ideal to address this large unmet medical need, and that it has the potential to become the first drug approved in the US to treat patients with PDP.

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 antipsychotics.

While pimavanserin provides the foundation of our product pipeline, we have several additional products 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 advanced preclinical stages 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 pipeline of 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 the first-quarter results.

Thank you, Uli. Good afternoon. Our revenues totaled $417,000 for the first quarter compared to $450,000 for the first quarter of 2012 and were derived from our collaborations with Allergan as well as our research grants.

Our R&D expenses decreased to $4.4 million for the first quarter from $5.0 million for the comparable quarter of 2012, primarily due to decreased external costs following the completion of our -020 Study.

We expect our R&D expenses to increase in future quarters as we continue to conduct the remaining supporting studies and CMC development necessary to advance our Phase III PDP program to registration.

G&A expenses increased to $2.2 million for the first quarter from $1.7 million for the comparable quarter of 2012, reflecting increased personnel costs as well as increased professional fees.

Finally, let's turn to our cash position and guidance. We closed the first quarter with $101.5 million in cash and investment securities compared to $108 million at December 31, using $6.5 million of net cash to fund our activities during the quarter.

Looking ahead, following the positive outcome of our FDA meeting last month, we will see a shift in our expenditures in future quarters. While we will save costs as a result of no longer conducting a confirmatory PDP trial, this will be offset by additional costs associated with accelerating the remaining development and precommercial activities as a result of our expedited path to NDA filing.

We currently anticipate using a total of between $28 million and $32 million in cash resources to fund our activities for the 2013 year. Importantly, we remain positioned with a solid cash runway that we believe will enable us to continue to advance and build value in our PDP program, while at the same time beginning to strategically broaden the clinical profile of pimavanserin.

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

Thank you, Tom, and good afternoon. The last several months have been an exciting period for all of us at ACADIA, beginning with the successful results from our -020 Study that we announced late last year. During the first quarter we completed our analysis of the -020 data set in which we continue to see robust data aligned with the topline efficacy results.

Dr. Jeff Cummings, who is the Director of the Cleveland Clinic Lou Ruvo Center for Brain Health and an internationally renowned clinician, presented detailed results from the -020 Study at the 65th American Academy of Neurology Meeting in March.

The -020 data showed robust and consistent efficacy of pimavanserin across a wide array of study measures. Pimavanserin demonstrated highly significant antipsychotic efficacy in patients with PDP and allowed for maintained motor control.

Highly significant improvements were also seen in all secondary efficacy measures. In addition, significant benefits were observed in exploratory measures of nighttime sleep, daytime wakefulness and caregiver burden.

Importantly, regardless of whether assessments were performed by independent blinded raters, site investigators, or caregivers, clear benefits of pimavanserin were observed. Consistent with previous studies, pimavanserin was safe and well tolerated in this Phase III study.

The robust and consistent results observed in a pivotal -020 Study afforded us the opportunity to meet with the FDA to discuss the PDP regulatory path. Meanwhile, in parallel we continued full-scale preparations during the first quarter for what had been planned as a confirmatory PDP trial.

Our objective for the FDA interaction was straightforward. Determine whether the agency would be willing to accept and review a pimavanserin NDA for PDP that was based on the results from our single positive pivotal study, together with supporting data from our other studies.

In April we held a meeting with the FDA. We were delighted the agency agreed that they would file an NDA based on data from the positive -020 Study, together with supportive efficacy and safety data from our other studies. We believe this reflects both the strength and results demonstrated in the -020 Study along with supporting efficacy and safety data and the fact that PDP is a serious, unmet medical need without any approved treatment option.

Importantly, we believe this positive outcome will expedite the path to registration and potential approval for this indication, and potentially enable pimavanserin to be available sooner to help Parkinson's patients suffering from psychosis.

With this expedited path, our team has been focused on completing the remaining elements of our pimavanserin PDP development program that are needed for submission of an NDA. This includes customary supportive studies including drug-drug interaction studies that are intended to provide appropriate label information for doctors to treat patients and its elderly population who are commonly on several medications.

We also have final aspects of the CMC development, including stability testing of pimavanserin registration batches.

I'm pleased to report that we continue to make solid progress with these remaining development activities. We are also continuing to conduct our Phase III open-label safety extension trial referred to as the -015 Study. This trial involves patients who have completed our Phase III efficacy studies and who, in the opinion of the entreating physician, may benefit from continued treatment with pimavanserin.

The 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 who have been treated for pimavanserin for at least two years, and our longest single patient exposure is over seven years.

Our experience to date continues to suggest that the long-term administration of pimavanserin appears to be generally safe and well-tolerated in this often fragile and elderly patient population.

We believe that this safety profile provides support for the potential of pimavanserin to offer significant advantages relative to current antipsychotics used off label for the treatment of PDP. As we move forward we intend to request pre-NDA meetings with the FDA later this year to discuss our plans for the NDA submission.

Subject to changes that could result from our future interactions with FDA or other developments, we continue to target an NDA submission near the end of 2014. I will now turn the call over to Uli.

Thank you, Roger. This important step forward in our pimavanserin program brings us closer to our ultimate goal of bringing innovative compounds like pimavanserin to the market to improve the lives of patients with neurological and related central nervous system disorders. PDP represents a large unmet medical need and what we believe is an ideal lead indication and specialty market opportunity for pimavanserin.

PDP is progressive and it is a persistent condition that recurs in an estimated 40% of Parkinson's patients and deeply affects their quality of life. It is 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 difficult challenges in managing patients with this debilitating disease. We believe that pimavanserin, with its well-tolerated non-dopaminergic profile, has the opportunity to be the 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 program, we also are preparing 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. Alzheimer's Disease Psychosis, or ADP, is one such indication in which we believe pimavanserin may provide important benefits to patients. ADP affects an estimated 25% to 50% of the more than 5 million Alzheimer's patients in the US.

Similar to PDP, there is currently no therapy approved to treat ADP in the United States. And as with PDP, physicians frequently resort to off-label use of antipsychotic medications to treat ADP. However, existing antipsychotic drugs may exacerbate the cognitive disturbances associated with Alzheimer's disease, and are 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 that we plan to evaluate multiple endpoints and use this to explore the potential benefits of pimavanserin in this patient population and 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 Schizophrenia Research. This trial demonstrated that co-therapy with pimavanserin and the sub-therapeutic dose of risperidone provided an attractive clinical profile. The treatment, equally effective at higher standard does smack of risperidone, but with a much improved side effect profile and a faster onset of action.

As we advance our Phase III PDP program and prepare for initiation of our ADP trial, we will plan for additional studies that we may pursue with pimavanserin in schizophrenia.

Let me now touch briefly on the other programs in our pipeline. Through our long-standing alliance with Allergan and we have two clinical stage product candidates in the areas of chronic pain and glaucoma. In addition, we have two advanced preclinical programs which offer -- which may offer new disease-modifying approaches to treat Parkinson's disease and other neurological disorders.

We conducted initial research in our ER-beta 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, we are collaborating with Dr. Rhonda Voskuhl of UCLA, a recognized expert in MS and neuroprotection, on research aimed at evaluating our ER-beta compound as an innovative approach to targeting neurodegeneration associated with multiple sclerosis.

In our second preclinical program Nurr1, our lead program which activates Nurr1-RXR complexes was effective 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 one of these two programs into development this year in preparation for future clinical trials.

In closing, our success of the past several months sets the stage for what we believe will be a new phase for ACADIA. Our pipeline of product candidates led by our Phase III pimavanserin program positions ACADIA with multiple, attractive product and commercial opportunities and significant growth potential.

We are focused on building additional value in our pimavanserin franchise. And, most importantly, all of us at ACADIA remain committed to advancing innovative therapies 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). Jason Butler, JMP Securities.

Just wondering if you could give us any more color with the progress on the manufacturing stability studies. For example, have you now completed the manufacturing of those three commercial lots? And just if you could give us any more color on when you think you will have sufficient stability data to submit the NDA?

First of all, you may recall that the CMC program is on the critical timeline for our NDA submission. We have said that what we will need to do is to do stability testing on the regulatory batches and, of course, we need to manufacture these as well. We haven't provided any specific details on where we are in this program. All we have said is that it is timely meeting for us and it has at the time for NDA submission to near the end of 2014.

Okay, great. Thanks for the added color.

Charles Duncan, Piper Jaffray.

Thanks for taking my question and congratulations on the recent progress. I appreciate all the commentary on the progress to the NDA filing, but I'm wondering if you have had any further discussions with European regulatory authorities, and what your thoughts are on next steps in that region.

Charles, what we have said is that we will initiate contacts with EMA this year. And we expect to have some information about the requirements in Europe next year, so that is clearly very important for us to see if the FDA will -- if the EMA will follow the lead from the FDA or not.

We know that they may do so. They have the opportunity to do so, but we clearly cannot predict what their response will be more than -- I think that what we are convinced about is that our development program that we are preparing for the FDA will provide a very solid foundation for other regulatory submissions as well.

Uli, I know that in the [recently write-off] Phase III all the sites were from the States. I'm wondering if you have any insights into the standard of care. Are patients similarly treated in Europe with atypical antipsychotics as they are here, and do the regulators over there also have a negative bias towards that practice?

Charles, I think it is fair to say that in fact a lot of the recent emergence of concerns around the off label use of atypicals in these elderly patients, actually a lot of it originated in Europe. So I think it is pretty fair to say that there is at least a similar level of concern for the regulators in the EU as there is in the USA.

And, obviously, not just the regulators but in a similar manner to the USA, there are many questions asked at Parliamentary level in the different countries that are regarding how patients are under the chemical cosh, as it is termed, with basically using the sedative properties of the atypicals to knock the patients out and make them more manageable.

So in terms of sites we have, the standard of care is much the same in Europe as here in all aspects of the patient's management. And in fact there are, in a number of countries, restrictions on the use of clozapine as an agent due to the very clear safety concerns regarding the use of that drug.

In our program we have included a good number of European sites in the earlier studies, so we do have good experience of European investigators. And we received a great deal of interest from the leading experts in Europe following the announcement of our data at the end of last year and subsequently.

That is very helpful, Roger. Thank you. Perhaps last question for Tom on the commercial strategy; you folks are very busy getting ready for your first NDA. I am wondering if you're still thinking the US market concentration is still pretty good and, therefore, one in which you might be able to mount a commercial effort. And how is that impacting, if at all, your discussions with potential commercial partners?

Yes, Charles, I think you hit it. I think we believe that this particular market is really ideal for commercialization. It is really a classic specialty neurology market, very centralized and it can be focused and addressed very effectively with a dedicated sales force. So that is clearly our strategy.

Now our focus is on building the value in the pimavanserin program, not only advancing it clearly to the NDA and preparing ourselves with the precommercial activities for a successful launch, but, also, to begin the strategy of life cycle management of the drug to extend it into these other indications since we believe it has broad potential.

So that is clearly the focus we have, and I think we are excited about preparing for that next stage of ACADIA.

Thanks, Tom, Uli, Roger for taking the questions.

Alan Carr, Needham.

(technical difficulty) taking our questions. I just wanted to dig a little bit more into the commercial opportunity that you guys see, and wondering if you could give us some comments on how you see things breaking out between nursing homes versus a more retail opportunity? Which do you guys think you're going to go after first?

So, you can in fact look specifically at the kind of patients that we have recruited for our -020 Study and for previous studies. These are not patients from nursing homes, and we think that is the ideal initial population for pimavanserin. In fact, we believe that we may delay the placement to nursing homes by providing pimavanserin as a therapy for the psychosis.

So, clearly, as you know, eventually these patients are likely to have to enter to nursing homes, and in that case they will clearly continue with their pimavanserin therapy. We believe that pimavanserin will be a daily, chronic therapy for patients with Parkinson's psychosis.

Great. And then just one clarifying question on the cash spend guidance. Was that for the rest of the year, or is that total for the year?

That is total for the year.

Total for the year. Okay. Thanks very much for taking my questions, guys.

(Operator Instructions). Bert Hazlett, ROTH Capital.

(technical difficulty) finished conducting the next Phase III before really considering licensing in Europe. So the question is, now that you don't have to do it, at what point would you be engaging in those types of discussions? Thanks. I also have another question.

So, I think we missed the first part of your questions. So could you please repeat that?

Sure. Sorry about that. The question is really, I believe, in terms of licensing and partnering internationally, the strategy, I believe, was to finish the second Phase III and then engage licensing partners overseas. Now that you don't have to do that, how has that strategy, with regard to international markets, in particular with regard to licensing the compound, how has that changed?

Sure. I think as we said, our current focus right now is on building the value in the program. That is where we are at. So if -- we are clearly moving the program forward for the NDA. As Uli mentioned earlier, we believe that will be a strong foundation for regulatory submissions and the other regions.

We clearly will, as part of our process, go through the dialogue with the EMA to understand how they will view -- again, whether or not we would have the opportunity to submit on the basis of one study, as we have in the US. We will determine that later.

I think it relates to our view, we want to continue to move the program forward, build value in it. As we move toward the NDA, we certainly have the opportunity to consider a partner that could help us position for commercialization ex-US. That is something that we have the flexibility of time to consider.

And, clearly, as we move the program, we believe we are adding additional value. And we will do so not only in the US, but in other regions as well.

Okay, and thank you. Just one on Allergan and the collaborations there; you have mentioned it again. In terms of timing for when we might hear anything with regard to those collaborations, you have long said that Allergan is in control of that data release.

Is there any expectation that we should hear anything for those collaborations in the next 12 months or 24 months? Or can I pin you down at all with regard to any type of data release or movement there? Thanks.

We appreciate that question. In reality, as we have said previously, Allergan is in control of data announcements here. And we will seem to come back to you with more information when we are able to do so.

Thanks very much.

Jason Napodano, Zacks.

With the potential -- can you talk a little bit about the potential for pricing for a drug like pimavanserin? You mentioned the safety concerns with clozapine. We know antipsychotics are used off label with limited efficacy, and the lack of any approved treatment option for PDP or ADP. So it seems like there would be some pretty strong pricing mechanisms here, but I'm wondering if you could talk about that a little.

Yes, so, while we don't want to comment specifically on pricing, what I think we can really say is that we believe that PDP represents a major unmet medical need. And at the same time, there is nothing approved for this indication. We are the first in a completely new class on antipsychotics that represent safe, well-tolerated and effective therapy for this.

So, taking both together, we believe that in itself can be used to make a point for significant pricing. But when it comes to the specific amounts that we expect for the future, we have to come back to that at a later stage. The important thing is that we deal with the major unmet medical need without any available therapy today.

Thanks, guys.

Juan Sanchez, Ladenburg.

The question is what kind of surprises do you think could emerge from the pre-NDA meeting with the FDA? In other words, what kind of topics are you going to discuss that you didn't already discuss in the April meeting, and whether or not -- how much stability work you need to have pre-filing is one of the topics for discussion in the upcoming meeting?

So, just to maybe approach it this way, that in the meeting we have just held with FDA we submitted a substantial briefing package encompassing all the efficacy and safety data we have generated in the program. And it is on the basis of the totality of that briefing package that FDA agreed to file the NDA.

Obviously, in the background with any drug development there are a number of other factors that we need to complete to ensure a complete NDA. We discussed the CMC earlier and also the clinical studies such as the drug-drug interactions.

These are very standard and important in a population such as patients with Parkinson's disease, because there are many other medications to treat various aspects and facets of their Parkinson's disease and, also, the many other issues that they face -- cardiovascular, et cetera, et cetera. So we really do the drug-drug interaction studies to enable the label guidance to facilitate safe prescribing of not only pimavanserin but other agents when using conjunction in these fairly complex patients. So this is pretty standard.

In the meetings with FDA we will go through to ensure that we have got all the boxes checked, and, therefore, that we will be able to file the NDA in the matter that they require. We are not anticipating there will be any issues in that. I think as I started out, the FDA agreed to file the NDA based on the complete fairly comprehensive briefing package that we supplied to them.

Got it. Thank you, guys.

Brian Lian, SunTrust.

Thanks for taking the question. Roger just touched on this a little bit in his last answer, but I'm curious if there are any unique drug-drug interactions studies required ahead of the initiation of the Alzheimer's Disease Psychosis trial?

There are no specific requirements ahead of doing that. It is very similar populations in so many ways.

We have already discussed with FDA the option of combining the databases, because really the challenges faced by patients with late stage Alzheimer's disease is very similar to the challenges faced by late stage Parkinson's disease patients. So we are not anticipating there needs to be any preliminary studies before embarking on that study.

Okay, thanks. And then with the Alzheimer's Disease Psychosis trial initiating, I think Uli mentioned that multiple endpoints were planned. But I just wanted to clarify if the SAPS would still be the primary efficacy measure for Alzheimer's Disease Psychosis?

No, we wouldn't be using the SAPS. We are using the MPI as the primary endpoint in this population. It is well tried and tested in the Alzheimer arena and well validated in that arena.

The SAPS really lent itself very much to the Parkinson's patients that we have looked at. These patients that are far more demented with Alzheimer's, it is impossible for the patient to input into the rating scales. And, therefore, we will use the NPI, which, as I say, is well validated and very nicely offers us a broad array of indicators of potential benefits of the drug in the population.

This is the first opportunity we have had to really explore the potential utility. We would really like to have a look and see where the best bang for the buck would be with the drug in this population.

In the NPI, are some of those components similar to some of the components that were evaluated in the -020 Study or in any of the other studies?

Absolutely. I think in terms of the clinical expression of psychosis in Alzheimer's disease, as Uli mentioned, it is very similar to that that you see in PDP. It is driven by hallucinations and delusions.

It is probably more prominent in respect of delusions to hallucinations in PDP. Certainly earlier on, hallucinations tend to be the dominant element of the psychosis, though even in PDP as patients become more demented, delusional symptoms become more prominent.

So, again, there is a lot of similarities between the two, and the key area we're looking at is the psychosis which is so similar between the two -- hallucinations and delusions.

Okay, thanks very much.

George Zavoico, MLV & Co.

Good afternoon, and congratulations on the tremendous progress you have made in the last quarter and subsequent to that.

As a follow-on to Brian's question, when you did the SAPS in PDP, you clearly found some elements in the SAPS that weren't related to the PD psychosis. Do you expect the same sort of thing in NPI? Is that a measure of more than just the psychosis in Alzheimer's disease patients? And is it something that is -- is that metric applied by caregivers as well as the physician investigators?

The difference between the two is that the NPI was specifically developed for patients with Alzheimer's. SAPS was developed for schizophrenia patients focused around the positive symptoms.

It was, therefore, the adoption of that from schizophrenia meant that inherent within the scale there were still is remaining items that really reflected schizophrenia psychosis as opposed to the neurodegenerative psychosis that we saw with PDP. Hence, as we acquired experience using the SAPS in the PDP population, we are able to adapt that and refine it to really reflect the symptoms that patients with PDP were suffering from.

The NPI, as I mentioned, was developed for patients with dementia. And, therefore, it is more specific, and we wouldn't expect to see -- or wouldn't expect to have the need to further refine the endpoint to reflect the benefits that we expect to see.

Okay, and just like with PDP, I expect you will have a number of other -- I think you already mentioned the secondary endpoints like caregiver burden and that sort of thing for the ADP as well. You're going to be as thorough as you possibly can be, as you were with PDP, I imagine?

Yes. And we want -- as I was saying earlier, in terms of the endpoint it does enable us to look at different aspects of the patient's condition. However, one of the key things we have learned on the way through is that we do try to restrict interaction between the caring staff, the professional staff and the patients, because we found that that actually enhances placebo response, which is clearly something we don't wish to do.

We want to be comprehensive in the way that we look for improvements in symptomatology. But at the same time there is often and frequently -- frequently a great danger of employing too many assessments of patients that actually may not offer a great deal more information, but may actually add to placebo response. So it will be a considered balance in how we rate these patients.

And so having said that, though, I think you mentioned previously that the ADP psychosis -- sorry the AD psychosis differs from PDP in certain respects so the NPI would not have been applicable to Parkinson's disease, in hindsight?

Yes, you can use it in PDP, but it was more developed for patients who have a higher degree of dementia.

Okay. I see. And, finally, just for the --

It is fair to say that both sets of patients, the dementia increases in each of them. Obviously, in Alzheimer's the initial characterization of the disease is by dementia. But even in PDP, as the brain further degenerates, dementia becomes more important in those patients.

Okay, and then a final brief question for the ADP trial that you project to begin in the second half. Would that be just North America or would you include some European sites as well?

We are actually assessing the sites right now, but it will likely certainly include some European.

Okay, thank you very much. Look forward to the next update.

Dr. Hacksell, please proceed to closing remarks.

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 so much.

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